Pulmonary oxidative stress is increased in cyclooxygenase-2 knockdown mice with mild pulmonary hypertension induced by monocrotaline.

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Francesca Seta

Full Text Available The aim of this study was to examine the role of cyclooxygenase-2 (COX-2 and downstream signaling of prostanoids in the pathogenesis of pulmonary hypertension (PH using mice with genetically manipulated COX-2 expression. COX-2 knockdown (KD mice, characterized by 80-90% suppression of COX-2, and wild-type (WT control mice were treated weekly with monocrotaline (MCT over 10 weeks. Mice were examined for cardiac hypertrophy/function and right ventricular pressure. Lung histopathological analysis was performed and various assays were carried out to examine oxidative stress, as well as gene, protein, cytokine and prostanoid expression. We found that MCT increased right ventricular systolic and pulmonary arterial pressures in comparison to saline-treated mice, with no evidence of cardiac remodeling. Gene expression of endothelin receptor A and thromboxane synthesis, regulators of vasoconstriction, were increased in MCT-treated lungs. Bronchoalveolar lavage fluid and lung sections demonstrated mild inflammation and perivascular edema but activation of inflammatory cells was not predominant under the experimental conditions. Heme oxygenase-1 (HO-1 expression and indicators of oxidative stress in lungs were significantly increased, especially in COX-2 KD MCT-treated mice. Gene expression of NOX-4, but not NOX-2, two NADPH oxidase subunits crucial for superoxide generation, was induced by ∼4-fold in both groups of mice by MCT. Vasodilatory and anti-aggregatory prostacyclin was reduced by ∼85% only in MCT-treated COX-2 KD mice. This study suggests that increased oxidative stress-derived endothelial dysfunction, vasoconstriction and mild inflammation, exacerbated by the lack of COX-2, contribute to the pathogenesis of early stages of PH when mild hemodynamic changes are evident and not yet accompanied by vascular and cardiac remodeling.

Arterial morphology responds differently to Captopril then N-acetylcysteine in a monocrotaline rat model of pulmonary hypertension

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Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary

2010-03-01

Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.

Toxicokinetic comparison of 14C-monocrotaline and 14C-senecionine in the rat

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Estep, J.E.; Lame', M.W.; Morin, D.; Segall, H.J.; Wilson, D.W.

1990-01-01

Two commonly studied macrocyclic pyrrolizidine alkaloids (PAs) are monocrotaline (MCT) and senecionine (SEN). Both PAs exhibit hepatic, renal and pulmonary toxicity, but SEN primarily causes centrol lobular necrosis of the liver while MCT promotes the development of pulmonary hypertension with decreased liver necrosis. Previous work in our laboratory has shown that MCT (60mg/kg IV) is sequestered in the red blood cell (RBC). To determine if this retention could play a role in MCT pulmonary toxicity, we compared the toxicokinetics of MCT with SEN. Both compounds exhibited a similar decline in plasma concentration (as measured by carbon 14) by the end of seven hours. The decrease in radioactivity associated with RBC's differed significantly with MCT declining from 144.34 to 81.46 nmol MCT-equivalents/gm of RBC's, while SEN decreased from 108.55 to 26.18 nmol SEN-equivalents/gm. Fortyfour versus 12 percent of the radioactivity was excreted in the bile for SEN and MCT dosed rats, respectively. In the absence of bile duct cannulation, plasma and RBC levels of radioactivity were identical to cannulated animals receiving MCT while SEN dosed animals exhibited almost twice the radioactivity associated with the RBC's, suggesting enterohepatic recirculation. The results of these studies suggest that the RBC-MCT complex is involved in MCT pulmonary toxicity

Paracrine effects of bone marrow-derived endothelial progenitor cells: cyclooxygenase-2/prostacyclin pathway in pulmonary arterial hypertension.

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Dong-Mei Jiang

Full Text Available BACKGROUND: Endothelial dysfunction is the pathophysiological characteristic of pulmonary arterial hypertension (PAH. Some paracrine factors secreted by bone marrow-derived endothelial progenitor cells (BMEPCs have the potential to strengthen endothelial integrity and function. This study investigated whether BMEPCs have the therapeutic potential to improve monocrotaline (MCT-induced PAH via producing vasoprotective substances in a paracrine fashion. METHODS AND RESULTS: Bone marrow-derived mononuclear cells were cultured for 7 days to yield BMEPCs. 24 hours or 3 weeks after exposure to BMEPCs in vitro or in vivo, the vascular reactivity, cyclooxygenase-2 (COX-2 expression, prostacyclin (PGI2 and cAMP release in isolated pulmonary arteries were examined respectively. Treatment with BMEPCs could improve the relaxation of pulmonary arteries in MCT-induced PAH and BMEPCs were grafted into the pulmonary bed. The COX-2/prostacyclin synthase (PGIS and its progenies PGI2/cAMP were found to be significantly increased in BMEPCs treated pulmonary arteries, and this action was reversed by a selective COX-2 inhibitor, NS398. Moreover, the same effect was also observed in conditioned medium obtained from BMEPCs culture. CONCLUSIONS: Implantation of BMEPCs effectively ameliorates MCT-induced PAH. Factors secreted in a paracrine fashion from BMEPCs promote vasoprotection by increasing the release of PGI2 and level of cAMP.

MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

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Bi, Rui; Bao, Chunrong; Jiang, Lianyong; Liu, Hao; Yang, Yang; Mei, Ju; Ding, Fangbao, E-mail: dbcar126@126.com

2015-05-01

Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAH associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.

Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

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Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

2017-08-15

Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

Fasudil and DETA NONOate, Loaded in a Peptide-Modified Liposomal Carrier, Slow PAH Progression upon Pulmonary Delivery.

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Rashid, Jahidur; Nahar, Kamrun; Raut, Snehal; Keshavarz, Ali; Ahsan, Fakhrul

2018-05-07

We investigated the feasibility of a combination therapy comprising fasudil, a Rho-kinase inhibitor, and DETA NONOate (diethylenetriamine NONOate, DN), a long-acting nitric oxide donor, both loaded in liposomes modified with a homing peptide, CAR (CARSKNKDC), in the treatment of pulmonary arterial hypertension (PAH). We first prepared and characterized unmodified and CAR-modified liposomes of fasudil and DN. Using individual drugs alone or a mixture of fasudil and DN as controls, we studied the efficacy of the two liposomal preparations in reducing mean pulmonary arterial pressure (mPAP) in monocrotaline (MCT) and SUGEN-hypoxia-induced PAH rats. We also conducted morphometric studies (degree of muscularization, arterial medial wall thickness, and collagen deposition) after treating the PAH rats with test and control formulations. When the rats were treated acutely and chronically, the reduction in mPAP was more pronounced in the liposomal formulation-treated rats than in plain drug-treated rats. CAR-modified liposomes were more selective in reducing mPAP than unmodified liposomes of the drugs. Both drugs, formulated in CAR-modified liposomes, reduced the degree of muscularization, medial arterial wall thickness, and collagen deposition more than the combination of plain drugs did. As seen with the in vivo data, CAR-modified liposomes of fasudil or DN increased the levels of the vasodilatory signaling molecule, cGMP, in the smooth muscle cells of PAH-afflicted human pulmonary arteries. Overall, fasudil and DN, formulated in liposomes, could be used as a combination therapy for a better management of PAH.

Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.

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Moreira-Gonçalves, Daniel; Ferreira, Rita; Fonseca, Hélder; Padrão, Ana Isabel; Moreno, Nuno; Silva, Ana Filipa; Vasques-Nóvoa, Francisco; Gonçalves, Nádia; Vieira, Sara; Santos, Mário; Amado, Francisco; Duarte, José Alberto; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

2015-11-01

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

Possible involvement of mitochondrial energy-producing ability in the development of right ventricular failure in monocrotaline-induced pulmonary hypertensive rats.

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Daicho, Takuya; Yagi, Tatsuya; Abe, Yohei; Ohara, Meiko; Marunouchi, Tetsuro; Takeo, Satoshi; Tanonaka, Kouichi

2009-09-01

The present study was undertaken to explore the possible involvement of alterations in the mitochondrial energy-producing ability in the development of the right ventricular failure in monocrotaline-administered rats. The rats at the 6th week after subcutaneous injection of 60 mg/kg monocrotaline revealed marked myocardial hypertrophy and fibrosis, that is, severe cardiac remodeling. The time-course study on the cardiac hemodynamics of the monocrotaline-administered rat by the cannula and echocardiographic methods showed a reduction in cardiac double product, a decrease in cardiac output index, and an increase in the right ventricular Tei index, suggesting that the right ventricular failure was induced at the 6th week after monocrotaline administration in rats. The mitochondrial oxygen consumption rate of the right ventricular muscle isolated from the monocrotaline-administered animal was decreased, which was associated with a reduction in myocardial high-energy phosphates. Furthermore, the decrease in mitochondrial oxygen consumption rate was inversely related to the increase in the right ventricular Tei index of the monocrotaline-administered rats. These results suggest that impairment of the mitochondrial energy-producing ability is involved in the development of the right ventricular failure in monocrotaline-induced pulmonary hypertensive rats.

Characterization of hepatic DNA damage induced in rats by the pyrrolizidine alkaloid monocrotaline

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Petry, T.W.; Bowden, G.T.; Huxtable, R.J.; Sipes, I.G.

1984-04-01

Hepatic DNA damage induced by the pyrrolizidine alkaloid monocrotaline was evaluated following i.p. administration to adult male Sprague-Dawley rats. Animals were treated with various doses ranging upward from 5 mg/kg, and hepatic nuclei were isolated 4 hr later. Hepatic nuclei were used as the DNA source in all experiments. DNA damage was characterized by the alkaline elution technique. A mixture of DNA-DNA interstrand cross-links and DNA-protein cross-links was induced. Following an injection of monocrotaline, 30 mg/kg i.p., DNA-DNA interstrand cross-linking reached a maximum within 12 hr or less and thereafter decreased over a protracted period of time. By 96 hr postadministration, the calculated cross-linking factor was no longer statistically different from zero. No evidence for the induction of DNA single-strand breaks was observed, although the presence of small numbers of DNA single-strand breaks could have been masked by the overwhelming predominance of DNA cross-links. These DNA cross-links may be related to the hepatocarcinogenic, hepatotoxic, and/or antimitotic effects of monocrotaline.

Nicorandil prevents right ventricular remodeling by inhibiting apoptosis and lowering pressure overload in rats with pulmonary arterial hypertension.

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Xiang-Rong Zuo

Full Text Available BACKGROUND: Most of the deaths among patients with severe pulmonary arterial hypertension (PAH are caused by progressive right ventricular (RV pathological remodeling, dysfunction, and failure. Nicorandil can inhibit the development of PAH by reducing pulmonary artery pressure and RV hypertrophy. However, whether nicorandil can inhibit apoptosis in RV cardiomyocytes and prevent RV remodeling has been unclear. METHODOLOGY/PRINCIPAL FINDINGS: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT. RV systolic pressure (RVSP was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochemical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD reversed these beneficial effects of nicorandil in MCT-injected rats. CONCLUSIONS/SIGNIFICANCE: Nicorandil inhibits PAH-induced RV remodeling in rats not only by reducing RV pressure overload but also by inhibiting apoptosis in cardiomyocytes through the activation of mitochondrial ATP-sensitive K(+ (mitoK(ATP channels. The use of a mitoK(ATP channel opener such as nicorandil for PAH-associated RV remodeling and dysfunction may represent a new therapeutic strategy for the amelioration of RV

Tier-2 studies on monocrotaline immunotoxicity in C57BL/6 mice.

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Deyo, J A; Kerkvliet, N I

1991-01-01

Monocrotaline (MCT) is a member of a class of naturally occurring phytotoxins known as pyrrolizidine alkaloids, and is a toxicological concern to both man and his livestock. The purpose of these studies was to evaluate the effect of a 14-day oral MCT (0-100 mg/kg per day) exposure on the functional integrity of various immunocyte effector systems in C57BL/6 mice, as well as to investigate potential mechanisms for its immunotoxicity. Decreases in lymphoid organ weights and cellularity, and resident peritoneal exudate cell (PEC) number were only observed after exposure to the highest dose of 100 mg/kg MCT. This dose also inhibited NK cell cytotoxicity, while the total number of NK lytic units per spleen was decreased (-53%) after exposure to 50 mg/kg MCT. Following i.p. injection of SRBC, the percentage of PEC macrophages containing engulfed SRBC was significantly increased in MCT-exposed mice, while the percentage of large vacuolated (activated) macrophages was decreased in a dose-dependent manner. Exposure to MCT significantly decreased the total number of Ig+ cells without altering the number of CD4+ and CD8+ cells. The antibody responses (PFC/10(6) spleen cells) to two T cell-independent antigens, TNP-LPS and DNP-Ficoll, were significantly decreased at all MCT doses, and the degree of suppression of both responses was identical at coincident doses. MCT exposure (25 mg/kg) significantly suppressed the blastogenic response to the T cell mitogen concanavalin A (-38%), and to the B cell mitogen lipopolysaccharide (-58%). These results indicate that exposure to MCT can alter the functional integrity of various immune effector responses in a dose-dependent manner, and suggest that the B cell may be a relatively more sensitive target of MCT immunotoxicity compared to T cells, macrophages and NK cells.

The Role of Astrocytes in Metabolism and Neurotoxicity of the Pyrrolizidine Alkaloid Monocrotaline, the Main Toxin of Crotalaria retusa

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Pitanga, Bruno Penas Seara; Nascimento, Ravena P.; Silva, Victor Diógenes A.; Costa, Silvia L.

2012-01-01

The metabolic interactions and signaling between neurons and glial cells are necessary for the development and maintenance of brain functions and structures and for neuroprotection, which includes protection from chemical attack. Astrocytes are essential for cerebral detoxification and present an efficient and specific cytochrome P450 enzymatic system. Whilst Crotalaria (Fabaceae, Leguminosae) plants are used in popular medicine, they are considered toxic and can cause damage to livestock and human health problems. Studies in animals have shown cases of poisoning by plants from the genus Crotalaria, which induced damage to the central nervous system. This finding has been attributed to the toxic effects of the pyrrolizidine alkaloid (PA) monocrotaline (MCT). The involvement of P450 enzymatic systems in MCT hepatic and pulmonary metabolism and toxicity has been elucidated, but little is known about the pathways implicated in the bioactivation of these systems and the direct contribution of these systems to brain toxicity. This review will present the main toxicological aspects of the Crotalaria genus that are established in the literature and recent findings describing the mechanisms involved in the neurotoxic effects of MCT, which was extracted from Crotalaria retusa, and its interaction with neurons in isolated astrocytes. PMID:22876233

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats.

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Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; Almeida, Francine Maria de; Silva, Bárbara Soares da; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

2014-01-01

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats*

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Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; de Almeida, Francine Maria; da Silva, Bárbara Soares; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

2014-01-01

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation. PMID:25210965

Monocrotaline pyrrole-induced megalocytosis of lung and breast epithelial cells: Disruption of plasma membrane and Golgi dynamics and an enhanced unfolded protein response

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Mukhopadhyay, Somshuvra; Shah, Mehul; Patel, Kirit; Sehgal, Pravin B.

2006-01-01

The pyrrolizidine alkaloid monocrotaline (MCT) initiates pulmonary hypertension by inducing a 'megalocytosis' phenotype in target pulmonary arterial endothelial, smooth muscle and Type II alveolar epithelial cells. In cultured endothelial cells, a single exposure to the pyrrolic derivative of monocrotaline (MCTP) results in large cells with enlarged endoplasmic reticulum (ER) and Golgi and increased vacuoles. However, these cells fail to enter mitosis. Largely based upon data from endothelial cells, we proposed earlier that a disruption of the trafficking and mitosis-sensor functions of the Golgi (the 'Golgi blockade' hypothesis) may represent the subcellular mechanism leading to MCTP-induced megalocytosis. In the present study, we investigated the applicability of the Golgi blockade hypothesis to epithelial cells. MCTP induced marked megalocytosis in cultures of lung A549 and breast MCF-7 cells. This was associated with a change in the distribution of the cis-Golgi scaffolding protein GM130 from a discrete juxtanuclear localization to a circumnuclear distribution consistent with an anterograde block of GM130 trafficking to/through the Golgi. There was also a loss of plasma membrane caveolin-1 and E-cadherin, cortical actin together with a circumnuclear accumulation of clathrin heavy chain (CHC) and α-tubulin. Flotation analyses revealed losses/alterations in the association of caveolin-1, E-cadherin and CHC with raft microdomains. Moreover, megalocytosis was accompanied by an enhanced unfolded protein response (UPR) as evidenced by nuclear translocation of Ire1α and glucose regulated protein 58 (GRP58/ER-60/ERp57) and a circumnuclear accumulation of PERK kinase and protein disulfide isomerase (PDI). These data further support the hypothesis that an MCTP-induced Golgi blockade and enhanced UPR may represent the subcellular mechanism leading to enlargement of ER and Golgi and subsequent megalocytosis

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

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Igor Bastos Polonio

2014-08-01

Full Text Available We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH. Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model; and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days Mean pulmonary artery pressure (mPAP was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

Methods to obtain radiolabelled monocrotaline

International Nuclear Information System (INIS)

Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J.

1996-01-01

Crotalaria spectabilis, a plant found in many areas of the world is associated with the pyrrolizidine alkaloid monocrotaline. Monocrotaline when injected subcutaneously in Sprague Dawley rats has been utilized for years to create a condition known to mimic pulmonary hypertension in humans. We attempted to determine the optimum conditions for the biosynthesis of radiolabelled monocrotaline. Our work describes the plant growth conditions and the time periods associated with the production of radiolabelled monocrotaline. In addition, the incorporation of 14 CO 2 or [2,3- 3 H]-putrescine dihydrochloride and the specific activity plus the amount(s) of recovered radiolabelled monocrotaline are discussed. We conclude that the most efficient and cost effective method for the biosynthesis of radiolabelled monocrotaline is still the utilization of 14 CO 2 . (author)

Methods to obtain radiolabelled monocrotaline

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Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J. [University of California, Davis, CA (United States)

1996-12-01

Crotalaria spectabilis, a plant found in many areas of the world is associated with the pyrrolizidine alkaloid monocrotaline. Monocrotaline when injected subcutaneously in Sprague Dawley rats has been utilized for years to create a condition known to mimic pulmonary hypertension in humans. We attempted to determine the optimum conditions for the biosynthesis of radiolabelled monocrotaline. Our work describes the plant growth conditions and the time periods associated with the production of radiolabelled monocrotaline. In addition, the incorporation of {sup 14}CO{sub 2} or [2,3-{sup 3}H]-putrescine dihydrochloride and the specific activity plus the amount(s) of recovered radiolabelled monocrotaline are discussed. We conclude that the most efficient and cost effective method for the biosynthesis of radiolabelled monocrotaline is still the utilization of {sup 14}CO{sub 2}. (author).

Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

International Nuclear Information System (INIS)

Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei

2014-01-01

Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

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Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Deng, Wei [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072 (China); Han, Hui; Wang, Hao [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Chen, Yuguo [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China); Li, Yu, E-mail: qlliyu@126.com [Department of Respiratory, Qilu Hospital of Shandong University, Jinan 250012 (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012 (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan 250012 (China)

2014-07-18

Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

The role of astrocytes in metabolism and neurotoxicity of the pyrrolizidine alkaloid monocrotaline, the main toxin of Crotalaria retusa.

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Bruno Penas Seara Pitanga

2012-08-01

Full Text Available The metabolic interactions and signalling between neurons and glial cells are necessary for the development and maintenance of brain functions and structures and for neuroprotection, which includes protection from chemical attack. Astrocytes are essential for cerebral detoxification and present an efficient and specific cytochrome P450 enzymatic system. Whilst Crotalaria (Fabaceae, Leguminosae plants are used in popular medicine, they are considered toxic and can cause damage to livestock and human health problems. Studies in animals have shown cases of poisoning by plants from the genus Crotalaria, which induced damage to the central nervous system. This finding has been attributed to the toxic effects of the pyrrolizidine alkaloid (PA monocrotaline (MCT. The involvement of P450 enzymatic systems in MCT hepatic and pulmonary metabolism and toxicity has been elucidated, but little is known about the pathways implicated in the bioactivation of these systems and the direct contribution of these systems to brain toxicity. This review will present the main toxicological aspects of the Crotalaria genus that are established in the literature and recent findings describing the mechanisms involved in the neurotoxic effects of MCT, which was extracted from C. retusa, and its interaction with neurons in isolated astrocytes.

CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.

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Le Floch, Renaud; Chiche, Johanna; Marchiq, Ibtissam; Naiken, Tanesha; Naïken, Tanesha; Ilc, Karine; Ilk, Karine; Murray, Clare M; Critchlow, Susan E; Roux, Danièle; Simon, Marie-Pierre; Pouysségur, Jacques

2011-10-04

Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H(+)/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res(-)) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res(-) cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H(+) symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basigin(high) cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy.

Effects of bone marrow-derived cells on monocrotaline- and hypoxia-induced pulmonary hypertension in mice

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Vainchenker William

2007-01-01

Full Text Available Abstract Background Bone marrow -derived cells (BMDCs can either limit or contribute to the process of pulmonary vascular remodeling. Whether the difference in their effects depends on the mechanism of pulmonary hypertension (PH remains unknown. Objectives We investigated the effect of BMDCs on PH induced in mice by either monocrotaline or exposure to chronic hypoxia. Methods Intravenous administration of the active monocrotaline metabolite (monocrotaline pyrrole, MCTp to C57BL/6 mice induced PH within 15 days, due to remodeling of small distal vessels. Three days after the MCTp injection, the mice were injected with BMDCs harvested from femurs and tibias of donor mice treated with 5-fluorouracil (3.5 mg IP/animal to deplete mature cells and to allow proliferation of progenitor cells. Results BMDCs significantly attenuated PH as assessed by reductions in right ventricular systolic pressure (20 ± 1 mmHg vs. 27 ± 1 mmHg, P ≤ 0.01, right ventricle weight/left ventricle+septum weight ratio (0.29 ± 0.02 vs. 0.36 ± 0.01, P ≤ 0.03, and percentage of muscularized vessels (26.4% vs. 33.5%, P ≤ 0.05, compared to control animals treated with irradiated BMDCs. Tracking cells from constitutive GFP-expressing male donor mice with anti-GFP antibodies or chromosome Y level measurement by quantitative real-time PCR showed BMDCs in the lung. In contrast, chronically hypoxic mice subjected to the same procedure failed to show improvement in PH. Conclusion These results show that BMDCs limit pulmonary vascular remodeling induced by vascular injury but not by hypoxia.

Development of occlusive neointimal lesions in distal pulmonary arteries of endothelin B receptor-deficient rats: a new model of severe pulmonary arterial hypertension.

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Ivy, D Dunbar; McMurtry, Ivan F; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2005-06-07

Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ET(B) receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ET(B) receptor-deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT(+/+)) and ET(B) receptor-deficient (MCT(sl/sl)) rats at 6 weeks of age were assessed. MCT(sl/sl) rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCT(sl/sl) rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCT(sl/sl) rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ET(B) receptors was decreased in MCT(sl/sl) rat lungs, ET(A) receptor expression increased. Deficiency of the ET(B) receptor markedly accelerates the progression of

Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

International Nuclear Information System (INIS)

Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

2006-01-01

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH

High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension.

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Brown, Mary Beth; Neves, Evandro; Long, Gary; Graber, Jeremy; Gladish, Brett; Wiseman, Andrew; Owens, Matthew; Fisher, Amanda J; Presson, Robert G; Petrache, Irina; Kline, Jeffrey; Lahm, Tim

2017-02-01

Exercise is beneficial in pulmonary arterial hypertension (PAH), although studies to date indicate little effect on the elevated pulmonary pressures or maladaptive right ventricle (RV) hypertrophy associated with the disease. For chronic left ventricle failure, high-intensity interval training (HIIT) promotes greater endothelial stimulation and superior benefit than customary continuous exercise training (CExT); however, HIIT has not been tested for PAH. Therefore, here we investigated acute and chronic responses to HIIT vs. CExT in a rat model of monocrotaline (MCT)-induced mild PAH. Six weeks of treadmill training (5 times/wk) were performed, as either 30 min HIIT or 60 min low-intensity CExT. To characterize acute hemodynamic responses to the two approaches, novel recordings of simultaneous pulmonary and systemic pressures during running were obtained at pre- and 2, 4, 6, and 8 wk post-MCT using long-term implantable telemetry. MCT-induced decrement in maximal aerobic capacity was ameliorated by both HIIT and CExT, with less pronounced pulmonary vascular remodeling and no increase in RV inflammation or apoptosis observed. Most importantly, only HIIT lowered RV systolic pressure, RV hypertrophy, and total pulmonary resistance, and prompted higher cardiac index that was complemented by a RV increase in the positive inotrope apelin and reduced fibrosis. HIIT prompted a markedly pulsatile pulmonary pressure during running and was associated with greater lung endothelial nitric oxide synthase after 6 wk. We conclude that HIIT may be superior to CExT for improving hemodynamics and maladaptive RV hypertrophy in PAH. HIIT's superior outcomes may be explained by more favorable pulmonary vascular endothelial adaptation to the pulsatile HIIT stimulus.

Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

OpenAIRE

Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; Almeida, Francine Maria de; Silva, Bárbara Soares da; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

2014-01-01

We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and...

Liposomal Fasudil, a Rho-Kinase Inhibitor, for Prolonged Pulmonary Preferential Vasodilation in Pulmonary Arterial Hypertension

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Gupta, Vivek; Gupta, Nilesh; Shaik, Imam H.; Mehvar, Reza; McMurtry, Ivan F.; Oka, Masahiko; Nozik-Grayck, Eva; Komatsu, Masanobu; Ahsan, Fakhrul

2013-01-01

Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH. However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes. In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles. Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient. Liposomes were then characterized for various physicochemical properties. Optimized formulations were tested for pulmonary absorption and their pharmacological efficacy in a monocrotaline (MCT) induced rat model of PAH. The entrapment efficiency of optimized liposomal fasudil formulations was between 68.1±0.8% and 73.6±2.3%, and the cumulative release at 37°C was 98–99% over a period of 5 days. Compared to intravenous (IV) fasudil, a ~10 fold increase in the terminal plasma half-life was observed when liposomal fasudil was administered as aerosols. The t1/2 of IV fasudil was 0.39±0.12 h. and when given as liposomes via pulmonary route, the t1/2 extended to 4.71±0.72 h. One h after intratracheal instillation of liposomal fasudil, mean pulmonary arterial pressure (MPAP) was reduced by 37.6±5.7% and continued to decrease for about 3 h, suggesting that liposomal formulations produced pulmonary preferential vasodilation in MCT induced PAH rats. Overall, this study established the proof-of-principle that aerosolized liposomal fasudil is a feasible option for a non-invasive, controlled release and pulmonary preferential treatment of PAH. PMID:23353807

Red blood cells augment transport of reactive metabolites of monocrotaline from liver to lung in isolated and tandem liver and lung preparations

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Pan, L.C.; Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J. (Department of Veterinary Pharmacology, University of California, Davis (United States))

1991-09-01

Monocrotaline (MCT) is a pyrrolizidine alkaloid that causes pulmonary hypertension in rats by mechanisms which remain largely unknown. MCT is thought to be activated in the liver to a reactive intermediate that is transported to the lung where it causes endothelial injury. The authors previous pharmacokinetic work demonstrated significant sequestration of radioactivity in red blood cells (RBCs) of rats treated with (14C)MCT. To determine whether this RBC sequestration might be important in the transport of reactive MCT metabolites, they compared the effect of inclusion of RBCs in the perfusion buffer on the extent of covalent binding of (14C)MCT to rat lungs in tandem liver-lung preparations. The potential effect of RBCs in stabilizing reactive intermediates was evaluated by preperfusion of isolated liver preparations with (14C)MCT with and without RBCs, separation and washing of the RBC fraction, and subsequent (90 min later) perfusion of washed RBCs or buffer alone in isolated perfused lungs. Covalent binding to lung tissues was determined by exhaustive methanol/chloroform extractions of unbound label from homogenized lung tissue followed by scintillation counting of residual 14C. Covalent binding was expressed as picomole MCT molecular weight equivalents/mg protein. Comparison of the relative capability of these isolated organ preparations for conversion of MCT to polar metabolites was done by extraction and HPLC analysis of perfusate at the end of the experiment. Isolated livers converted 65-85% of MCT to polar metabolites compared with less than 5% conversion in the isolated lungs. Inclusion of RBCs in the buffer of tandem lung liver preparations perfused with 400 microM (14C)MCT increased the covalent binding to the lung from 97 {plus minus} 25 (buffer alone) to 182 {plus minus} 36 (buffer + RBC) pmol/mg protein.

Red blood cells augment transport of reactive metabolites of monocrotaline from liver to lung in isolated and tandem liver and lung preparations

International Nuclear Information System (INIS)

Pan, L.C.; Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J.

1991-01-01

Monocrotaline (MCT) is a pyrrolizidine alkaloid that causes pulmonary hypertension in rats by mechanisms which remain largely unknown. MCT is thought to be activated in the liver to a reactive intermediate that is transported to the lung where it causes endothelial injury. The authors previous pharmacokinetic work demonstrated significant sequestration of radioactivity in red blood cells (RBCs) of rats treated with [14C]MCT. To determine whether this RBC sequestration might be important in the transport of reactive MCT metabolites, they compared the effect of inclusion of RBCs in the perfusion buffer on the extent of covalent binding of [14C]MCT to rat lungs in tandem liver-lung preparations. The potential effect of RBCs in stabilizing reactive intermediates was evaluated by preperfusion of isolated liver preparations with [14C]MCT with and without RBCs, separation and washing of the RBC fraction, and subsequent (90 min later) perfusion of washed RBCs or buffer alone in isolated perfused lungs. Covalent binding to lung tissues was determined by exhaustive methanol/chloroform extractions of unbound label from homogenized lung tissue followed by scintillation counting of residual 14C. Covalent binding was expressed as picomole MCT molecular weight equivalents/mg protein. Comparison of the relative capability of these isolated organ preparations for conversion of MCT to polar metabolites was done by extraction and HPLC analysis of perfusate at the end of the experiment. Isolated livers converted 65-85% of MCT to polar metabolites compared with less than 5% conversion in the isolated lungs. Inclusion of RBCs in the buffer of tandem lung liver preparations perfused with 400 microM [14C]MCT increased the covalent binding to the lung from 97 ± 25 (buffer alone) to 182 ± 36 (buffer + RBC) pmol/mg protein

A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats

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Conotte, R.; Colet, J.-M.

2014-01-01

The main curative treatment of colorectal cancer remains the surgery. However, when metastases are suspected, surgery is followed by a preventive chemotherapy using oxaliplatin which, unfortunately, may cause liver sinusoidal obstruction syndrome (SOS). Such hepatic damage is barely detected during or after chemotherapy due to a lack of effective diagnostic procedures, but liver biopsy. The primary objective of the present study was to identify potential early diagnosis biomarkers of SOS using a metabonomic approach. SOS was induced in rats by monocrotaline, a prototypical toxic substance. 1 H NMR spectroscopy analysis of urine samples collected from rats treated with monocrotaline showed significant metabolic changes as compared to controls. During a first phase, cellular protective mechanisms such as an increased synthesis of GSH (reduced taurine) and the recruitment of cell osmolytes in the liver (betaine) were seen. In the second phase, the disturbance of the urea cycle (increased ornithine and urea reduction) leading to the depletion of NO, the alteration in the GSH synthesis (increased creatine and GSH precursors (glutamate, dimethylglycine and sarcosine)), and the liver necrosis (decrease taurine and increase creatine) all indicate the development of SOS. - Highlights: • Urine metabonomic profiles of SOS have been identified. • Urine osmoprotectants and anti-oxidants indicated an initial liver protection. • Liver necrosis was demonstrated by increased urine levels of taurine and creatine. • NO depletion was suggested by changes in ornithine and urea

Pulmonary artery remodeling differs in hypoxia- and monocrotaline-induced pulmonary hypertension

NARCIS (Netherlands)

van Suylen, R. J.; Smits, J. F.; Daemen, M. J.

1998-01-01

In the present study we analyzed structural characteristics of muscular pulmonary arteries and arterioles in two classic models of pulmonary hypertension, the rat hypoxia and monocrotaline models. We hypothesized that an increase in medial cross-sectional area would result in reduction of the lumen

A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats

Energy Technology Data Exchange (ETDEWEB)

Conotte, R.; Colet, J.-M., E-mail: jean-marie.colet@umons.ac.be

2014-04-15

The main curative treatment of colorectal cancer remains the surgery. However, when metastases are suspected, surgery is followed by a preventive chemotherapy using oxaliplatin which, unfortunately, may cause liver sinusoidal obstruction syndrome (SOS). Such hepatic damage is barely detected during or after chemotherapy due to a lack of effective diagnostic procedures, but liver biopsy. The primary objective of the present study was to identify potential early diagnosis biomarkers of SOS using a metabonomic approach. SOS was induced in rats by monocrotaline, a prototypical toxic substance. {sup 1}H NMR spectroscopy analysis of urine samples collected from rats treated with monocrotaline showed significant metabolic changes as compared to controls. During a first phase, cellular protective mechanisms such as an increased synthesis of GSH (reduced taurine) and the recruitment of cell osmolytes in the liver (betaine) were seen. In the second phase, the disturbance of the urea cycle (increased ornithine and urea reduction) leading to the depletion of NO, the alteration in the GSH synthesis (increased creatine and GSH precursors (glutamate, dimethylglycine and sarcosine)), and the liver necrosis (decrease taurine and increase creatine) all indicate the development of SOS. - Highlights: • Urine metabonomic profiles of SOS have been identified. • Urine osmoprotectants and anti-oxidants indicated an initial liver protection. • Liver necrosis was demonstrated by increased urine levels of taurine and creatine. • NO depletion was suggested by changes in ornithine and urea.

Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

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Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

2018-01-01

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

Development of Occlusive Neointimal Lesions in Distal Pulmonary Arteries of Endothelin B Receptor–Deficient Rats: A New Model of Severe Pulmonary Arterial Hypertension

Science.gov (United States)

Ivy, D. Dunbar; McMurtry, Ivan F.; Colvin, Kelley; Imamura, Masatoshi; Oka, Masahiko; Lee, Dong-Seok; Gebb, Sarah; Jones, Peter Lloyd

2007-01-01

Background Human pulmonary arterial hypertension (PAH) is characterized by proliferation of vascular smooth muscle and, in its more severe form, by the development of occlusive neointimal lesions. However, few animal models of pulmonary neointimal proliferation exist, thereby limiting a complete understanding of the pathobiology of PAH. Recent studies of the endothelin (ET) system demonstrate that deficiency of the ETB receptor predisposes adult rats to acute and chronic hypoxic PAH, yet these animals fail to develop neointimal lesions. Herein, we determined and thereafter showed that exposure of ETB receptor–deficient rats to the endothelial toxin monocrotaline (MCT) leads to the development of neointimal lesions that share hallmarks of human PAH. Methods and Results The pulmonary hemodynamic and morphometric effects of 60 mg/kg MCT in control (MCT+/+) and ETB receptor–deficient (MCTsl/sl) rats at 6 weeks of age were assessed. MCTsl/sl rats developed more severe PAH, characterized by elevated pulmonary artery pressure, diminished cardiac output, and right ventricular hypertrophy. In MCTsl/sl rats, morphometric evaluation revealed the presence of neointimal lesions within small distal pulmonary arteries, increased medial wall thickness, and decreased arterial-to-alveolar ratio. In keeping with this, barium angiography revealed diminished distal pulmonary vasculature of MCTsl/sl rat lungs. Cells within neointimal lesions expressed smooth muscle and endothelial cell markers. Moreover, cells within neointimal lesions exhibited increased levels of proliferation and were located in a tissue microenvironment enriched with vascular endothelial growth factor, tenascin-C, and activated matrix metalloproteinase-9, factors already implicated in human PAH. Finally, assessment of steady state mRNA showed that whereas expression of ETB receptors was decreased in MCTsl/sl rat lungs, ETA receptor expression increased. Conclusions Deficiency of the ETB receptor markedly

Inhalable delivery of AAV-based MRP4/ABCC4 silencing RNA prevents monocrotaline-induced pulmonary hypertension

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Caroline Claude

Full Text Available The ATP-binding cassette transporter MRP4 (encoded by ABCC4 regulates membrane cyclic nucleotides concentrations in arterial cells including smooth muscle cells. MRP4/ABCC4 deficient mice display a reduction in smooth muscle cells proliferation and a prevention of pulmonary hypertension in response to hypoxia. We aimed to study gene transfer of a MRP4/ABCC4 silencing RNA via intratracheal delivery of aerosolized adeno-associated virus 1 (AAV1.shMRP4 or AAV1.control in a monocrotaline-induced model of pulmonary hypertension in rats. Gene transfer was performed at the time of monocrotaline administration and the effect on the development of pulmonary vascular remodeling was assessed 35 days later. AAV1.shMRP4 dose-dependently reduced right ventricular systolic pressure and hypertrophy with a significant reduction with the higher doses (i.e., >1011 DRP/animal as compared to AAV1.control. The higher dose of AAV1.shMRP4 was also associated with a significant reduction in distal pulmonary arteries remodeling. AAV1.shMRP4 was finally associated with a reduction in the expression of ANF, a marker of cardiac hypertrophy. Collectively, these results support a therapeutic potential for downregulation of MRP4 for the treatment of pulmonary artery hypertension.

MCT1 modulates cancer cell pyruvate export and growth of tumors that co-express MCT1 and MCT4

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Hong, Candice Sun; Graham, Nicholas A.; Gu, Wen; Camacho, Carolina Espindola; Mah, Vei; Maresh, Erin L.; Alavi, Mohammed; Bagryanova, Lora; Krotee, Pascal A. L.; Gardner, Brian K.; Behbahan, Iman Saramipoor; Horvath, Steve; Chia, David; Mellinghoff, Ingo K.; Hurvitz, Sara A.; Dubinett, Steven M.; Critchlow, Susan E.; Kurdistani, Siavash K.; Goodglick, Lee; Braas, Daniel; Graeber, Thomas G.; Christofk, Heather R.

2016-01-01

SUMMARY Monocarboxylate Transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest MCT1 expression is elevated in glycolytic cancers to promote pyruvate export, which when inhibited enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors further supporting their use as anti-cancer therapeutics. PMID:26876179

Propylthiouracil Attenuates Experimental Pulmonary Hypertension via Suppression of Pen-2, a Key Component of Gamma-Secretase.

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Ying-Ju Lai

Full Text Available Gamma-secretase-mediated Notch3 signaling is involved in smooth muscle cell (SMC hyper-activity and proliferation leading to pulmonary arterial hypertension (PAH. In addition, Propylthiouracil (PTU, beyond its anti-thyroid action, has suppressive effects on atherosclerosis and PAH. Here, we investigated the possible involvement of gamma-secretase-mediated Notch3 signaling in PTU-inhibited PAH. In rats with monocrotaline-induced PAH, PTU therapy improved pulmonary arterial hypertrophy and hemodynamics. In vitro, treatment of PASMCs from monocrotaline-treated rats with PTU inhibited their proliferation and migration. Immunocyto, histochemistry, and western blot showed that PTU treatment attenuated the activation of Notch3 signaling in PASMCs from monocrotaline-treated rats, which was mediated via inhibition of gamma-secretase expression especially its presenilin enhancer 2 (Pen-2 subunit. Furthermore, over-expression of Pen-2 in PASMCs from control rats increased the capacity of migration, whereas knockdown of Pen-2 with its respective siRNA in PASMCs from monocrotaline-treated rats had an opposite effect. Transfection of PASMCs from monocrotaline-treated rats with Pen-2 siRNA blocked the inhibitory effect of PTU on PASMC proliferation and migration, reflecting the crucial role of Pen-2 in PTU effect. We present a novel cell-signaling paradigm in which overexpression of Pen-2 is essential for experimental pulmonary arterial hypertension to promote motility and growth of smooth muscle cells. Propylthiouracil attenuates experimental PAH via suppression of the gamma-secretase-mediated Notch3 signaling especially its presenilin enhancer 2 (Pen-2 subunit. These findings provide a deep insight into the pathogenesis of PAH and a novel therapeutic strategy.

MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4

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Hong, Candice Sun; Graham, Nicholas A.; Gu, Wen; Espindola Camacho, Carolina; Mah, Vei; Maresh, Erin L.; Alavi, Mohammed; Bagryanova, Lora; Krotee, Pascal A.L.; Gardner, Brian K.; Behbahan, Iman Saramipoor; Horvath, Steve; Chia, David; Mellinghoff, Ingo K.; Hurvitz, Sara A.

2016-01-01

Monocarboxylate Transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but ...

Effect of training and detraining on monocarboxylate transporter (MCT) 1 and MCT4 in Thoroughbred horses.

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Kitaoka, Yu; Masuda, Hiroyuki; Mukai, Kazutaka; Hiraga, Atsushi; Takemasa, Tohru; Hatta, Hideo

2011-03-01

The aim of this study was to investigate the effects of training and detraining on the monocarboxylate transporter (MCT) 1 and MCT4 levels in the gluteus medius muscle of Thoroughbred horses. Twelve Thoroughbred horses were used for the analysis. For 18 weeks, all the horses underwent high-intensity training (HIT), with running at 90-110% maximal oxygen consumption (VO2 max ) for 3 min, 5 days week(-1). Thereafter, the horses either underwent detraining for 6 weeks by either 3 min of moderate-intensity training (MIT) at 70% VO2 max, 5 days week(-1) (HIT-MIT group) or stall rest (HIT-SR group). The horses underwent an incremental exercise test, VO2 max was measured and resting muscle samples were obtained from the middle gluteus muscle at 0, 18 and 24 weeks. The content of MCT1 and MCT4 proteins increased after 18 weeks of HIT. At the end of this period, an increase was noted in the citrate synthase activity, while phosphofructokinase activity remained unchanged. After 6 weeks of detraining, all these indexes returned to the pretraining levels in the HIT-SR group. However, in the HIT-MIT group, the increase in the MCT1 protein content and citrate synthase activity was maintained after 6 weeks of MIT, while the MCT4 protein content decreased to the pretraining value. These results suggest that the content of MCT1 and MCT4 proteins increases after HIT in Thoroughbred horses. In addition, the increase in the MCT1 protein content and oxidative capacity induced by HIT can be maintained by MIT of 70% VO2 max, but the increase in the MCT4 protein content cannot be maintained by MIT.

Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.

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Prins, Kurt W; Tian, Lian; Wu, Danchen; Thenappan, Thenappan; Metzger, Joseph M; Archer, Stephen L

2017-05-31

Pulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV-targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin-2 (JPH2) expression, resulting in t-tubule derangements. Conversely, we assessed whether colchicine, a microtubule-depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline-induced PAH. Immunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t-tubule localization and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t-tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV-pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity. Monocrotaline-induced PAH causes RV-specific derangement of microtubules marked by reduction in JPH2 and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t-tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV-directed therapy for PAH

Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

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Rui-Xing Wang

2015-03-01

Full Text Available Background: Pulmonary hypertension (PH is characterized by sustained vasoconstriction, enhanced vasoreactivity and vascular remodeling, which leads to right heart failure and death. Despite several treatments are available, many forms of PH are still incurable. Ginsenoside Rb1, a principle active ingredient of Panax ginseng, exhibits multiple pharmacological effects on cardiovascular system, and suppresses monocrotaline (MCT-induced right heart hypertrophy. However, its effect on the pulmonary vascular functions related to PH is unknown. Methods: We examined the vasorelaxing effects of ginsenoside Rb1 on endothelin-1 (ET-1 induced contraction of pulmonary arteries (PAs and store-operated Ca2+ entry (SOCE in pulmonary arterial smooth muscle cells (PASMCs from chronic hypoxia (CH and MCT-induced PH. Results: Ginsenoside Rb1 elicited concentration-dependent relaxation of ET-1-induced PA contraction. The vasorelaxing effect was unaffected by nifedipine, but abolished by the SOCE blocker Gd3+. Ginsenoside Rb1 suppressed cyclopiazonic acid (CPA-induced PA contraction, and CPA-activated cation entry and Ca2+ transient in PASMCs. ET-1 and CPA-induced contraction, and CPA-activated cation entry and Ca2+ transients were enhanced in PA and PASMCs of CH and MCT-treated rats; the enhanced responses were abolished by ginsenoside Rb1. Conclusion: Ginsenoside Rb1 attenuates ET-1-induced contractile response via inhibition of SOCE, and it can effectively antagonize the enhanced pulmonary vasoreactivity in PH.

Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver.

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Narita, Masato; Hatano, Etsuro; Tamaki, Nobuyuki; Yamanaka, Kenya; Yanagida, Atsuko; Nagata, Hiromitsu; Asechi, Hiroyuki; Takada, Yasutsugu; Ikai, Iwao; Uemoto, Shinji

2009-06-01

Sinusoidal obstruction syndrome (SOS) is drug-induced liver injury that occurs in patients who receive hematopoietic cell transplantation and oxaliplatin-contained chemotherapy. The aim of study was to investigate the pharmacological treatment of SOS using a traditional Japanese medicine, Dai-kenchu-to (DKT). Male Sprague-Dawley rats were treated with monocrotaline (MCT) to induce SOS. The rats were divided into three groups: control, MCT and MCT+DKT groups. In the MCT+DKT group, DKT was gavaged at 12 h after MCT treatment and given every 12 h until the end of the protocol. The rats of MCT group were treated with water instead of DKT. At 48 h after MCT treatment, blood and liver samples were collected. In the MCT+DKT group, the macroscopic and histological findings revealed liver congestion, sinusoidal alteration and the destruction of sinusoidal lining, which were comparable with those of the MCT group. However, the area of hepatic necrosis and serum AST levels significantly decreased in the MCT+DKT group compared with those of the MCT group. Treatment with DKT resulted in the reduction of neutrophil accumulation, myeloperoxidase activity and the expression of cytokine-induced neutrophil chemoattractant (CINC) and intracellular adhesion molecule-1 (ICAM-1) mRNA in the liver compared with those of the MCT group. Treatment with processed ginger, one of the ingredients in DKT, resulted in similar effects to those shown by DKT. Dai-kenchu-to attenuates MCT-induced liver injury by preventing neutrophil-induced liver injury through blockage of upregulation of CINC and ICAM-1 mRNA level.

Effects of a series of acidic drugs on L-lactic acid transport by the monocarboxylate transporters MCT1 and MCT4.

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Leung, Yat Hei; Belanger, Francois; Lu, Jennifer; Turgeon, Jacques; Michaud, Veronique

2018-03-07

Drug-induced myopathy is a serious side effect that often requires removal of a medication from a drug regimen. For most drugs, the underlying mechanism of drug-induced myopathy remains unclear. Monocarboxylate transporters (MCTs) mediate L-lactic acid transport, and inhibition of MCTs may potentially lead to perturbation of L-lactic acid accumulation and muscular disorders. Therefore, we hypothesized that L-lactic acid transport may be involved in the development of drug-induced myopathy. The aim of this study was to assess the inhibitory potential of 24 acidic drugs on L-lactic acid transport using breast cancer cell lines Hs578T and MDA-MB-231, which selectively express MCT1 and MCT4, respectively. The influx transport of L-lactic acid was minimally inhibited by all drugs tested. The efflux transport was next examined: loratadine (IC50: 10 and 61 µM) and atorvastatin (IC50: 78 and 41 µM) demonstrated the greatest potency for inhibition of L-lactic acid efflux by MCT1 and MCT4, respectively. Acidic drugs including fluvastatin, cerivastatin, simvastatin acid, lovastatin acid, irbesartan and losartan exhibited weak inhibitory potency on L-lactic acid efflux. Our results suggest that some acidic drugs, such as loratadine and atorvastatin, can inhibit the efflux transport of L-lactic acid. This inhibition may cause an accumulation of intracellular L-lactic acid leading to acidification and muscular disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mct8 and trh co-expression throughout the hypothalamic paraventricular nucleus is modified by dehydration-induced anorexia in rats.

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Alvarez-Salas, Elena; Mengod, Guadalupe; García-Luna, Cinthia; Soberanes-Chávez, Paulina; Matamoros-Trejo, Gilberto; de Gortari, Patricia

2016-04-01

Thyrotropin-releasing hormone (TRH) is a neuropeptide with endocrine and neuromodulatory effects. TRH from the paraventricular hypothalamic nucleus (PVN) participates in the control of energy homeostasis; as a neuromodulator TRH has anorexigenic effects. Negative energy balance decreases PVN TRH expression and TSH concentration; in contrast, a particular model of anorexia (dehydration) induces in rats a paradoxical increase in TRH expression in hypophysiotropic cells from caudal PVN and high TSH serum levels, despite their apparent hypothalamic hyperthyroidism and low body weight. We compared here the mRNA co-expression pattern of one of the brain thyroid hormones' transporters, the monocarboxylate transporter-8 (MCT8) with that of TRH in PVN subdivisions of dehydration-induced anorexic (DIA) and control rats. Our aim was to identify whether a low MCT8 expression in anorexic rats could contribute to their high TRH mRNA content.We registered daily food intake and body weight of 7-day DIA and control rats and analyzed TRH and MCT8 mRNA co-expression throughout the PVN by double in situ hybridization assays. We found that DIA rats showed increased number of TRHergic cells in caudal PVN, as well as a decreased percentage of TRH-expressing neurons that co-expressed MCT8 mRNA signal. Results suggest that the reduced proportion of double TRH/MCT8 expressing cells may be limiting the entry of hypothalamic triiodothyronine to the greater number of TRH-expressing neurons from caudal PVN and be in part responsible for the high TRH expression in anorexia rats and for the lack of adaptation of their hypothalamic-pituitary-thyroid axis to their low food intake.

Lack of effect of deferoxamine, dimethyl sulfoxide, and catalase on monocrotaline pyrrole pulmonary injury

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Bruner, L.H.; Johnson, K.; Carpenter, L.J.; Roth, R.A.

1987-01-01

Monocrotaline pyrrole (MCTP) is a reactive metabolite of the pyrrolizidine alkaloid monocrotaline. MCTP given intravenously to rats causes pulmonary hypertension and right ventricular hypertrophy. Lesions in lungs after MCTP treatment contain macrophages and neutrophils, which may contribute to the damage by generation of reactive oxygen metabolites. Rats were treated with MCTP and agents known to protect against oxygen radical-mediated damage in acute models of neutrophil-dependent lung injury. Rats received MCTP and deferoxamine mesylate (DF), dimethyl sulfoxide (DMSO), or polyethylene glycol-coupled catalase (PEG-CAT). MCTP/vehicle-treated controls developed lung injury manifested as increased lung weight, release of lactate dehydrogenase into the airway, and sequestration of 125 I-labeled bovine serum albumin in the lungs. Cotreatment of rats with DF, DMSO, or PEG-CAT did not protect against the injury due to MCTP. These results suggest that toxic oxygen metabolites do not play an important role in the pathogenesis of MCTP-induced pulmonary injury

Lack of effect of deferoxamine, dimethyl sulfoxide, and catalase on monocrotaline pyrrole pulmonary injury

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Bruner, L.H.; Johnson, K.; Carpenter, L.J.; Roth, R.A.

1987-01-01

Monocrotaline pyrrole (MCTP) is a reactive metabolite of the pyrrolizidine alkaloid monocrotaline. MCTP given intravenously to rats causes pulmonary hypertension and right ventricular hypertrophy. Lesions in lungs after MCTP treatment contain macrophages and neutrophils, which may contribute to the damage by generation of reactive oxygen metabolites. Rats were treated with MCTP and agents known to protect against oxygen radical-mediated damage in acute models of neutrophil-dependent lung injury. Rats received MCTP and deferoxamine mesylate (DF), dimethyl sulfoxide (DMSO), or polyethylene glycol-coupled catalase (PEG-CAT). MCTP/vehicle-treated controls developed lung injury manifested as increased lung weight, release of lactate dehydrogenase into the airway, and sequestration of SVI-labeled bovine serum albumin in the lungs. Cotreatment of rats with DF, DMSO, or PEG-CAT did not protect against the injury due to MCTP. These results suggest that toxic oxygen metabolites do not play an important role in the pathogenesis of MCTP-induced pulmonary injury.

Monocarboxylate transporters MCT1 and MCT4 regulate migration and invasion of pancreatic ductal adenocarcinoma cells

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Kong, Su Chii; Nøhr-Nielsen, Asbjørn; Zeeberg, Katrine

2016-01-01

, localization, activity, and function were explored in human PDAC cells (MIAPaCa-2, Panc-1, BxPC-3, AsPC-1) and normal human pancreatic ductal epithelial (HPDE) cells, by quantitative polymerase chain reaction, immunoblotting, immunocytochemistry, lactate flux, migration, and invasion assays. RESULTS: MCT1......, or knockdown of MCT1 or MCT4. PDAC cell migration was largely unaffected by MCT1/MCT2 inhibition or MCT1 knockdown but was reduced by 4-CIN and by MCT4 knockdown (BxPC-3). Invasion measured in Boyden chamber (BxPC-3, Panc-1) and spheroid outgrowth (BxPC-3) assays was attenuated by 4-CIN and AR-C155858...

Selective Activation of At₂ Receptor Attenuates Progression of Pulmonary Hypertension and Inhibits Cardiopulmonary Fibrosis

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Bruce, E; Shenoy, V; Rathinasabapathy, A

2015-01-01

. However, the role of the angiotensin type II receptor (AT2 receptor) in PH has not been fully elucidated. We have taken advantage of a recently identified non-peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well-established monocrotaline (MCT) rat model of PH....... EXPERIMENTAL APPROACH: A single subcutaneous injection of MCT (50 mg/kg) was used to induce PH in 8-week-old male Sprague Dawley rats. After 2-weeks of MCT administration, a subset of animals began receiving, either 0.03mg/kg C21, 3mg/kg PD-123319, 0.5mg/kg A779 for an additional 2-weeks, after which right......-ventricular hemodynamic parameters were measured and tissues collected for gene expression and histological analyses. KEY RESULTS: Initiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT-induced PH. Most notably, C21 reversed pulmonary fibrosis and prevented right ventricular...

MCT4 Defines a Glycolytic Subtype of Pancreatic Cancer with Poor Prognosis and Unique Metabolic Dependencies

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GuemHee Baek

2014-12-01

Full Text Available KRAS mutation, which occurs in ∼95% of pancreatic ductal adenocarcinoma (PDA, has been shown to program tumor metabolism. MCT4 is highly upregulated in a subset of PDA with a glycolytic gene expression program and poor survival. Models with high levels of MCT4 preferentially employ glycolytic metabolism. Selectively in such “addicted” models, MCT4 attenuation compromised glycolytic flux with compensatory induction of oxidative phosphorylation and scavenging of metabolites by macropinocytosis and autophagy. In spite of these adaptations, MCT4 depletion induced cell death characterized by elevated reactive oxygen species and metabolic crisis. Cell death induced by MCT4-depletion was augmented by inhibition of compensatory pathways. In xenograft models, MCT4 had a significant impact on tumor metabolism and was required for rapid tumor growth. Together, these findings illustrate the metabolic diversity of PDA described by MCT4, delineate pathways through which this lactate transporter supports cancer growth, and demonstrate that PDA can be rationally targeted based on metabolic addictions.

Natural and experimental poisoning of goats with the pyrrolizidine alkaloid-producing plant Crotalaria retusa L

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Crotalaria retusa L. (rattleweed), estimated to contain about 4.96% monocrotaline (MCT) in the seed, was associated with a natural poisoning outbreak in goats. The poisoning was experimentally reproduced by the administration of C. retusa seeds containing approximately 4.49% of MCT. Thus, 1 of 3 goa...

Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

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Doyen, J. [Department of Radiation Oncology, Centre A. Lacassagne, Nice (France); Trastour, C. [Department of Gynecology, Archet II Hospital, 06202 Nice (France); Ettore, F.; Peyrottes, I.; Toussant, N. [Department of Pathology, Centre A. Lacassagne, Nice (France); Gal, J. [Department of Medical Statistics, Centre A. Lacassagne, Nice (France); Ilc, K.; Roux, D. [Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France); Parks, S.K. [Centre Scientifique de Monaco (CSM) (Monaco); Ferrero, J.M. [Department of Medical Oncology, Centre A. Lacassagne, Nice (France); Pouysségur, J., E-mail: jacques.pouyssegur@unice.fr [Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France); Centre Scientifique de Monaco (CSM) (Monaco)

2014-08-15

Highlights: • Glycolytic markers are highly expressed in triple negative breast cancers. • Lactate/H{sup +} symporter MCT4 demonstrated the strongest deleterious impact on survival. • MCT4 should serve as a new prognostic factor in node-negative breast cancers. - Abstract: Background: {sup 18}Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. Methods: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. Results: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients. Conclusion: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H{sup +} symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

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Weissmann Norbert

2005-11-01

Full Text Available Abstract Background The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH in rats. Methods CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii the anti-remodeling effect of long-term inhalation of tolafentrine (iii the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated. Results Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks, cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers, after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery

Synergistic effects of pyrrolizidine alkaloids and lipopolysaccharide on preterm delivery and intrauterine fetal death in mice.

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Guo, Yu; Ma, Zhenguo; Kou, Hao; Sun, Rongze; Yang, Hanxiao; Smith, Charles Vincent; Zheng, Jiang; Wang, Hui

2013-08-29

Preterm birth is the leading cause of death for newborn infants, and lipopolysaccharide (LPS) is commonly used to induce preterm delivery in experimental animals. Pyrrolizidine alkaloids (PAs) are widespread and occur in foods, herbs, and other plants. This study was to investigate the synergistic effects of LPS and two representative PAs, retrorsine (RTS) and monocrotaline (MCT), on preterm delivery and fetal death. Pregnant Kunming mice were divided into seven groups: control, RTS, MCT, LPS, RTS+LPS and two MCT+LPS groups. Animals in PAs and PAs+LPS groups were dosed intragastrically with RTS (10mg/kg) or MCT (20 mg/kg or 60 mg/kg) from gestational day (GD) 9 to GD16; mice given LPS were injected intraperitoneally with 150 μg/kg on GD15.5. Latencies to delivery, numbers of pups live and dead at birth were recorded, and livers of live neonates were collected. The incidence of LPS-induced preterm birth was enhanced in dams pretreated with MCT, and combination of PAs and LPS increased fetal mortality from PAs. The enhancement of LPS-induced preterm delivery and fetal demise in animals exposed chronically to PAs and other substances found in foods and beverages consumed widely by humans merits further focused investigation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

MCT1 and MCT4 expression and lactate flux activity increase during white and brown adipogenesis and impact adipocyte metabolism

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Petersen, Charlotte; Nielsen, Mette D.; Andersen, Elise S.

2017-01-01

RNA and protein levels of the lactate-H+ transporter MCT1 and the Na+,HCO3 - cotransporter NBCe1 were upregulated in mouse interscapular brown and inguinal white adipose tissue upon cold induction of thermogenesis and browning. MCT1, MCT4, and NBCe1 were furthermore strongly upregulated at the mRNA and protein...... level upon differentiation of cultured pre-adipocytes. Adipocyte differentiation was accompanied by increased plasma membrane lactate flux capacity, which was reduced by MCT inhibition and by MCT1 knockdown. Finally, in differentiated brown adipocytes, glycolysis (assessed as ECAR), and after...... noradrenergic stimulation also oxidative metabolism (OCR), was decreased by MCT inhibition. We suggest that upregulation of MCT1- and MCT4-mediated lactate flux capacity and NBCe1-mediated HCO3 -/pH homeostasis are important for the physiological function of mature adipocytes....

MCT expression and lactate influx/efflux in tanycytes involved in glia-neuron metabolic interaction.

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Christian Cortés-Campos

Full Text Available Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes.

The MCT4 Gene: A Novel, Potential Target for Therapy of Advanced Prostate Cancer.

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Choi, Stephen Yiu Chuen; Xue, Hui; Wu, Rebecca; Fazli, Ladan; Lin, Dong; Collins, Colin C; Gleave, Martin E; Gout, Peter W; Wang, Yuzhuo

2016-06-01

The management of castration-resistant prostate cancer (CRPC) is a major challenge in the clinic. Androgen receptor signaling-directed strategies are not curative in CRPC therapy, and new strategies targeting alternative, key cancer properties are needed. Using reprogrammed glucose metabolism (aerobic glycolysis), cancer cells typically secrete excessive amounts of lactic acid into their microenvironment, promoting cancer development, survival, and progression. Cellular lactic acid secretion is thought to be predominantly mediated by MCT4, a plasma membrane transporter protein. As such, the MCT4 gene provides a unique, potential therapeutic target for cancer. A tissue microarray of various Gleason grade human prostate cancers was stained for MCT4 protein. Specific, MCT4-targeting antisense oligonucleotides (MCT4 ASO) were designed and candidate MCT4 ASOs checked for effects on (i) MCT4 expression, lactic acid secretion/content, glucose consumption, glycolytic gene expression, and proliferation of human CRPC cells and (ii) growth of PC-3 tumors in nude mice. Elevated MCT4 expression was associated with human CRPC and an earlier time to relapse. The treatment of PC-3, DU145, and C4-2 CRPC cultures with candidate MCT4 ASOs led to marked inhibition of MCT4 expression, lactic acid secretion, to increased intracellular lactic acid levels, and markedly reduced aerobic glycolysis and cell proliferation. Treatment of PC-3 tumor-bearing nude mice with the MCT4 ASOs markedly inhibited tumor growth without inducing major host toxicity. MCT4-targeting ASOs that inhibit lactic acid secretion may be useful for therapy of CRPC and other cancers, as they can interfere with reprogrammed energy metabolism of cancers, an emerging hallmark of cancer. Clin Cancer Res; 22(11); 2721-33. ©2016 AACR. ©2016 American Association for Cancer Research.

Perinatal and early postnatal changes in the expression of monocarboxylate transporters MCT1 and MCT2 in the rat forebrain.

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Baud, Olivier; Fayol, Laurence; Gressens, Pierre; Pellerin, Luc; Magistretti, Pierre; Evrard, Philippe; Verney, Catherine

2003-10-20

In addition to glucose, monocarboxylates including lactate represent a major source of energy for the brain, especially during development. We studied the immunocytochemical expression of the monocarboxylate transporters MCT1 and MCT2 in the rat brain between embryonic day (E) 16 and postnatal day (P) 14. At E16-18, MCT1-like immunoreactivity was found throughout the cortical anlage, being particularly marked medially in the hippocampal anlage next to the ventricle. In a complementary pattern, MCT2-like immunoreactivity was expressed along the medial and ventral border of the ventricle in the medial septum and habenula before birth. The hypothalamic area exhibited MCT2 and MCT1 positive areas from E18 on. These transient labelings revealed four main sites of monocarboxylate and/or glucose exchange: the brain parenchyma, the epithelial cells, the ependymocytes, and the glia limitans. During the first postnatal week, MCT1 immunoreactivity extended massively to the vessel walls and moderately to the developing astrocytes in the cortex. In contrast, MCT2 immunoreactivity was faint in blood vessels but massive in developing astrocytes from P3 to P7. Neither MCT2 nor MCT1 colocalized with neuronal, microglial, or oligodendrocytic markers during the first postnatal week. At P14, a part of the scattered punctate MCT2 staining could be associated with astrocytes and postsynaptic dendritic labeling. The transient pattern of expression of MCTs throughout the perinatal period suggests a potential relationship with the maturation of the blood-brain barrier. Copyright 2003 Wiley-Liss, Inc.

MCT-1 protein interacts with the cap complex and modulates messenger RNA translational profiles

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Reinert, Line; Shi, B; Nandi, S

2006-01-01

MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and has been shown to induce cell proliferation as well as activate survival-related pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain that is found in several tRNA and rRNA modification...... enzymes. Here, we established that MCT-1 protein interacts with the cap complex through its PUA domain and recruits the density-regulated protein (DENR/DRP), containing the SUI1 translation initiation domain. Through the use of microarray analysis on polysome-associated mRNAs, we showed that up......-regulation of MCT-1 was able to modulate the translation profiles of BCL2L2, TFDP1, MRE11A, cyclin D1, and E2F1 mRNAs, despite equivalent levels of mRNAs in the cytoplasm. Our data establish a role for MCT-1 in translational regulation, and support a linkage between translational control and oncogenesis....

Repair of DNA damage induced by anthanthrene, a polycyclic aromatic hydrocarbon (PAH) without bay or fjord regions

DEFF Research Database (Denmark)

Madsen, Claus Desler; Johannessen, Christian; Rasmussen, Lene Juel

2009-01-01

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants, formed during incomplete burning of coal, oil and gas. Several PAHs have carcinogenic and mutagenic potencies, but these compounds must be activated in order to exert their mutagenic effects. One of the principal pathways...... proposed for metabolic activation of PAHs involves the cytochrome P450 enzymes. The DNA damaging potential of cytochrome P450-activated PAHs is generally associated with their bay and fjord regions, and the DNA repair response of PAHs containing such regions has been thoroughly studied. However, little...... in response to DNA damage induced by cytochrome P450-activated anthanthrene. In cell extracts, functional nucleotide excision repair (NER) and mismatch repair (MMR) activities were necessary to trigger a response to anthanthrene metabolite-induced DNA damage. In cell cultures, NER was responsible...

Impact of MCT1 Haploinsufficiency on the Mouse Retina

KAUST Repository

Peachey, Neal S.

2018-05-02

The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

Impact of MCT1 Haploinsufficiency on the Mouse Retina

KAUST Repository

Peachey, Neal S.; Yu, Minzhong; Han, John Y. S.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Philp, Nancy J.

2018-01-01

The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1+/− heterozygotes, which express half of the normal complement of MCT1. The MCT1+/− retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

Cerivastatin Nano-Liposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension.

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Lee, Young; Pai, S Balakrishna; Bellamkonda, Ravi V; Thompson, David H; Singh, Jaipal

2018-04-25

In this study, we have investigated nano-liposome as an approach to tailor the pharmacology of cerivastatin as a disease modifying drug for pulmonary arterial hypertension (PAH). Cerivastatin encapsulated liposomes with an average diameter of 98±27 nm were generated by thin film and freeze-thaw process. The nano-liposomes demonstrated sustained drug release kinetics in vitro and inhibited proliferation of pulmonary artery smooth muscle cells with significantly less cellular cytotoxicity as compared to free cerivastatin. When delivered by inhalation to a rat model of monocrotalin induced PAH, cerivastatin significantly reduced pulmonary artery pressure from 55.13±9.82 mmHg to 35.56±6.59 mmHg (P < 0.001) and diminished pulmonary artery wall thickening. Echocardiography showed that cerivastatin significantly reduced right ventricle thickening (0.34±0.02 cm monocrotalin vs. 0.26±0.02 cm cerivastatin; P < 0.001) and increased pulmonary artery acceleration time (13.98±1.14 ms monocrotalin vs. 21.07±2.80 ms cerivastatin; P < 0.001). Nano-liposomal cerivastatin was equally effective or slightly better than cerivastatin in reducing pulmonary artery pressure (67.06±13.64 mmHg monocrotalin; 46.31±7.64 mmHg cerivastatin vs. 37.32±9.50 mmHg liposomal cerivastatin) and improving parameters of right ventricular function as measured by increasing pulmonary artery acceleration time (24.68±3.92 ms monocrotalin; 32.59±6.10 ms cerivastatin vs. 34.96±7.51 ms liposomal cerivastatin). More importantly, the rate and magnitude of toxic cerivastatin metabolite lactone generation from the intratracheally administered nano-liposomes was significantly lower as compared to intravenously administered free cerivastatin. These studies show that nano-liposome encapsulation improved in vitro and in vivo pharmacological and safety profile of cerivastatin and may represent a safer approach as a disease modifying therapy for PAH. The American Society for Pharmacology and Experimental

MCT1 and MCT4 Expression During Myocardial Ischemic-Reperfusion Injury in the Isolated Rat Heart

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Yi Zhu

2013-09-01

Full Text Available Background/Aims: Myocardium ischemia-reperfusion (I/R injury can be caused by imbalances in cellular metabolism. Lactate, transported by monocarboxylate transporters (MCTs, has been implicated as a mechanism in this process. The present study was designed to investigate the expression and functional role of MCTs in rat hearts during ischemia and reperfusion. Methods: Langendorff-perfused rat hearts were subjected to 20 minutes stabilization, 30 minutes of global ischemia and 60 minutes reperfusion. Hearts were collected serially for detecting expression changes in MCT1, MCT4 during myocardial I/R injury and lactate concentration was measured. Post-ischemic left ventricular function and infract size were determined at end-point, followed by the pretreatment of D-lactate, a competitive inhibitor of MCTs. Results: MCT4 was significantly increased following global ischemia and MCT1 expression was increased during the early stages of reperfusion in isolated rat hearts, while the expression of the ancillary protein CD147 was increased during I/R injury. We determined increases in AMPK phosphorylation status, which was significantly elevated following ischemia and early reperfusion. Blocking monocarboxylate transport by competitive inhibition with D-lactate caused decreased left ventricular performance and increased infarct size. Conclusion: Increased MCT4 expression facilitates lactate extrusion during the ischemic period, while increased MCT1 may facilitate lactate transport into and out of cells simultaneously during early reperfusion, with increases in AMPK phosphorylation status during the myocardial I/R period. Lactate transport by MCTs has a profound protective effect during myocardial ischemia reperfusion injury.

Synergistic interaction between a PDE5 inhibitor (sildenafil) and a new adenosine A2A receptor agonist (LASSBio-1359) improves pulmonary hypertension in rats.

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Alencar, Allan K; Carvalho, Fábio I; Silva, Ananssa M; Martinez, Sabrina T; Calasans-Maia, Jorge A; Fraga, Carlos M; Barreiro, Eliezer J; Zapata-Sudo, Gisele; Sudo, Roberto T

2018-01-01

Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats. An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured. Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats. The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.

Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice

KAUST Repository

Chatel, Benjamin; Bendahan, David; Hourdé , Christophe; Pellerin, Luc; Lengacher, Sylvain; Magistretti, Pierre J.; Le Fur, Yann; Vilmen, Christophe; Bernard, Monique; Messonnier, Laurent A.

2017-01-01

The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1(+/-) mice). Twenty-four MCT1(+/-) and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1(+/-) mice had lower MCT1 (-61%; P < 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1(+/-) mice at rest (P < 0.001), the mice showed higher acidosis during the first minute of exercise (P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1(+/-) mice had higher specific peak (P < 0.05) and maximum tetanic (P < 0.01) forces and lower fatigability (P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1(+/-) mice remain unexplained.-Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice.

Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice

KAUST Repository

Chatel, Benjamin

2017-03-03

The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1(+/-) mice). Twenty-four MCT1(+/-) and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1(+/-) mice had lower MCT1 (-61%; P < 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1(+/-) mice at rest (P < 0.001), the mice showed higher acidosis during the first minute of exercise (P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1(+/-) mice had higher specific peak (P < 0.05) and maximum tetanic (P < 0.01) forces and lower fatigability (P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1(+/-) mice remain unexplained.-Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice.

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

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Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

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Bárbara Núñez

Full Text Available Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2 cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8, in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

Construction of PAH-degrading mixed microbial consortia by induced selection in soil.

Science.gov (United States)

Zafra, German; Absalón, Ángel E; Anducho-Reyes, Miguel Ángel; Fernandez, Francisco J; Cortés-Espinosa, Diana V

2017-04-01

Bioremediation of polycyclic aromatic hydrocarbons (PAHs)-contaminated soils through the biostimulation and bioaugmentation processes can be a strategy for the clean-up of oil spills and environmental accidents. In this work, an induced microbial selection method using PAH-polluted soils was successfully used to construct two microbial consortia exhibiting high degradation levels of low and high molecular weight PAHs. Six fungal and seven bacterial native strains were used to construct mixed consortia with the ability to tolerate high amounts of phenanthrene (Phe), pyrene (Pyr) and benzo(a)pyrene (BaP) and utilize these compounds as a sole carbon source. In addition, we used two engineered PAH-degrading fungal strains producing heterologous ligninolytic enzymes. After a previous selection using microbial antagonism tests, the selection was performed in microcosm systems and monitored using PCR-DGGE, CO 2 evolution and PAH quantitation. The resulting consortia (i.e., C1 and C2) were able to degrade up to 92% of Phe, 64% of Pyr and 65% of BaP out of 1000 mg kg -1 of a mixture of Phe, Pyr and BaP (1:1:1) after a two-week incubation. The results indicate that constructed microbial consortia have high potential for soil bioremediation by bioaugmentation and biostimulation and may be effective for the treatment of sites polluted with PAHs due to their elevated tolerance to aromatic compounds, their capacity to utilize them as energy source. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biodegradation of Mixed PAHs by PAH-Degrading Endophytic Bacteria

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Xuezhu Zhu

2016-08-01

Full Text Available Endophytic bacteria can promote plant growth, induce plant defence mechanisms, and increase plant resistance to organic contaminants. The aims of the present study were to isolate highly PAH-degrading endophytic bacteria from plants growing at PAH-contaminated sites and to evaluate the capabilities of these bacteria to degrade polycyclic aromatic hydrocarbons (PAHs in vitro, which will be beneficial for re-colonizing target plants and reducing plant PAH residues through the inoculation of plants with endophytic bacteria. Two endophytic bacterial strains P1 (Stenotrophomonas sp. and P3 (Pseudomonas sp., which degraded more than 90% of phenanthrene (PHE within 7 days, were isolated from Conyza canadensis and Trifolium pretense L., respectively. Both strains could use naphthalene (NAP, PHE, fluorene (FLR, pyrene (PYR, and benzo(apyrene (B(aP as the sole sources of carbon and energy. Moreover, these bacteria reduced the contamination of mixed PAHs at high levels after inoculation for 7 days; strain P1 degraded 98.0% NAP, 83.1% FLR, 87.8% PHE, 14.4% PYR, and 1.6% B(aP, and strain P3 degraded 95.3% NAP, 87.9% FLR, 90.4% PHE, 6.9% PYR, and negligible B(aP. Notably, the biodegradation of PAHs could be promoted through additional carbon and nitrogen nutrients; therein, beef extract was suggested as the optimal co-substrate for the degradation of PAHs by these two strains (99.1% PHE was degraded within 7 days. Compared with strain P1, strain P3 has more potential for the use in the removal of PAHs from plant tissues. These results provide a novel perspective in the reduction of plant PAH residues in PAH-contaminated sites through inoculating plants with highly PAH-degrading endophytic bacteria.

The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

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Lin Tai-Du

2010-12-01

Full Text Available Abstract Background MCT-1 oncoprotein accelerates p53 protein degradation via a proteosome pathway. Synergistic promotion of the xenograft tumorigenicity has been demonstrated in circumstance of p53 loss alongside MCT-1 overexpression. However, the molecular regulation between MCT-1 and p53 in tumor development remains ambiguous. We speculate that MCT-1 may counteract p53 through the diverse mechanisms that determine the tumorigenic outcomes. Results MCT-1 has now identified as a novel target gene of p53 transcriptional regulation. MCT-1 promoter region contains the response elements reactive with wild-type p53 but not mutant p53. Functional p53 suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback regulation, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. The apoptotic events are also significantly prevented by oncogenic MCT-1 in a p53-dependent or a p53-independent fashion, according to the genotoxic mechanism. Moreover, oncogenic MCT-1 promotes the tumorigenicity in mice xenografts of p53-null and p53-positive lung cancer cells. In support of the tumor growth are irrepressible by p53 reactivation in vivo, the inhibitors of p53 (MDM2, Pirh2, and Cop1 are constantly stimulated by MCT-1 oncoprotein. Conclusions The oppositions between MCT-1 and p53 are firstly confirmed at multistage processes that include transcription control, mRNA metabolism, and protein expression. MCT-1 oncogenicity can overcome p53 function that persistently advances the tumor development.

An Essential Physiological Role for MCT8 in Bone in Male Mice.

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Leitch, Victoria D; Di Cosmo, Caterina; Liao, Xiao-Hui; O'Boy, Sam; Galliford, Thomas M; Evans, Holly; Croucher, Peter I; Boyde, Alan; Dumitrescu, Alexandra; Weiss, Roy E; Refetoff, Samuel; Williams, Graham R; Bassett, J H Duncan

2017-09-01

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance.

Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

Science.gov (United States)

2015-10-01

AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

Virus-Like Particle (VLP Plus Microcrystalline Tyrosine (MCT Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei/vivax

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Gustavo Cabral-Miranda

2017-05-01

Full Text Available Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT is a well described depot used in licensed allergy immunotherapy products and in clinical development. However, its proof of concept in prophylactic vaccines has only recently been explored. MCT has never been used in combination with virus-like particles (VLPs, which are considered to be one of the most potent inducers of cellular and humoral immune responses in mice and humans. In the current study we assessed the potential of MCT to serve as an adjuvant in the development of a vaccine against malaria either alone or combined with VLP using Plasmodium vivax thrombospondin-related adhesive protein (TRAP as a target antigen. We chemically coupled PvTRAP to VLPs derived from the cucumber mosaic virus fused to a universal T-cell epitope of the tetanus toxin (CMVtt, formulated with MCT and compared the induced immune responses to PvTRAP formulated in PBS or Alum. The protective capacity of the various formulations was assessed using Plasmodium berghei expressing PvTRAP. All vaccine formulations using adjuvants and/or VLP increased humoral immunogenicity for PvTRAP compared to the antigen alone. The most proficient responder was the group of mice immunized with the vaccine formulated with PvTRAP-VLP + MCT. The VLP-based vaccine formulated in MCT also induced the strongest T cell response and conferred best protection against challenge with recombinant Plasmodium berghei. Thus, the combination of VLP with MCT may take advantage of the properties of each component and appears to be an alternative biodegradable depot adjuvant for development of novel prophylactic vaccines.

The effect of extracellular alkalinization on lactate metabolism of breast cancer stem cells: Overview of LDH-A, LDH-B, MCT1 and MCT4 gene expression

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Neolaka, G. M. G.; Yustisia, I.; Sadikin, M.; Wanandi, S. I.

2017-08-01

Changes in the metabolic status of cancer cells are presumed to be correlated with the adjustment of these cells to extracellular changes. Cell glycolysis increases the production of intracellular lactate catalyzed by the lactate dehydrogenases, both LDH-A and LDH-B. An increase in intracellular lactate can affect extracellular pH balance through monocarboxylate transporters, particularly MCT1 and MCT4. This study aimed to analyze the effects of extracellular alkalinization on the lactate metabolism of human breast cancer stem cells (BCSCs). In this study, human primary BCSCs (CD24-/CD44+ cells) were treated with 100 mM sodium bicarbonate for 0.5, 24, and 48 h in DMEM F12/HEPES. After incubation, extracellular pH was measured and cells were harvested to extract the total RNA and protein. The expression of LDH-A, LDH-B, MCT1, and MCT4 mRNA genes were analyzed using qRT-PCR method. Our study shows that administration of sodium bicarbonate in the BCSC culture medium could increase extracellular pH. To balance the increase of extracellular pH, BCSCs regulated the expression of LDH-A, LDH-B, MCT1, and MCT4 genes. As the extracellular pH increases, the expression of LDH-A that converts pyruvate to lactate increased along with the increase of MCT 4 and MCT 1 expression, which act as lactate transporters. As the incubation time increases, the pH decreases, leading to the suppression of LDH-A and increase of LDH-B expression that converts lactate into pyruvate. Therefore, we suggest that the extracellular alkalinization by sodium bicarbonate in BCSCs affected the genes that regulate lactate metabolism.

Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity.

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Shotaro Sasaki

Full Text Available Monocarboxylate transporter 4 (MCT4 is a pH-dependent bi-directional lactate transporter. Transport of lactate via MCT4 is increased by extracellular acidification. We investigated the critical histidine residue involved in pH regulation of MCT4 function. Transport of lactate via MCT4 was measured by using a Xenopus laevis oocyte expression system. MCT4-mediated lactate transport was inhibited by Zn2+ in a pH physiological condition but not in an acidic condition. The histidine modifier DEPC (diethyl pyrocarbonate reduced MCT4 activity but did not completely inactivate MCT4. After treatment with DEPC, pH regulation of MCT4 function was completely knocked out. Inhibitory effects of DEPC were reversed by hydroxylamine and suppressed in the presence of excess lactate and Zn2+. Therefore, we performed an experiment in which the extracellular histidine residue was replaced with alanine. Consequently, the pH regulation of MCT4-H382A function was also knocked out. Our findings demonstrate that the histidine residue His382 in the extracellular loop of the transporter is essential for pH regulation of MCT4-mediated substrate transport activity.

MCT/MOSFET Switch

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Rippel, Wally E.

1990-01-01

Metal-oxide/semiconductor-controlled thyristor (MCT) and metal-oxide/semiconductor field-effect transistor (MOSFET) connected in switching circuit to obtain better performance. Offers high utilization of silicon, low forward voltage drop during "on" period of operating cycle, fast turnon and turnoff, and large turnoff safe operating area. Includes ability to operate at high temperatures, high static blocking voltage, and ease of drive.

Regorafenib suppresses sinusoidal obstruction syndrome in rats.

Science.gov (United States)

Okuno, Masayuki; Hatano, Etsuro; Nakamura, Kojiro; Miyagawa-Hayashino, Aya; Kasai, Yosuke; Nishio, Takahiro; Seo, Satoru; Taura, Kojiro; Uemoto, Shinji

2015-02-01

Sinusoidal obstruction syndrome (SOS), a form of drug-induced liver injury related to oxaliplatin treatment, is associated with postoperative morbidity after hepatectomy. This study aimed to examine the impact of regorafenib, the first small-molecule kinase inhibitor to show efficacy against metastatic colorectal cancer, on a rat model of SOS. Rats with monocrotaline (MCT)-induced SOS were divided into two groups according to treatment with either regorafenib (6 mg/kg) or vehicle alone, which were administered at 12 and 36 h, respectively, before MCT administration. Histopathologic examination and serum biochemistry tests were performed 48 h after MCT administration. Sinusoidal endothelial cells were evaluated by immunohistochemistry and electron microscopy. To examine whether regorafenib preserved remnant liver function, a 30% hepatectomy was performed in each group. The rats in the vehicle group displayed typical SOS features, whereas these features were suppressed in the regorafenib group. The total SOS scores were significantly lower in the regorafenib group than in the vehicle group. Immunohistochemistry and electron microscopy showed that regorafenib had a protective effect on sinusoidal endothelial cells. The postoperative survival rate after 7 d was significantly better in the regorafenib group than that in the vehicle group (26.7% versus 6.7%, P Regorafenib reduced the phosphorylation of extracellular signal-regulated kinase, which induced matrix metalloproteinase-9 (MMP-9) activation and decreased the activity of MMP-9, one of the crucial mediators of SOS development. Regorafenib suppressed MCT-induced SOS, concomitant with attenuating extracellular signal-regulated kinase phosphorylation, and MMP-9 activation, suggesting that regorafenib may be a favorable agent for use in combination with oxaliplatin-based chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Dissipation of phenanthrene and pyrene at the aerobic-anaerobic soil interface: differentiation induced by the rhizosphere of PAH-tolerant and PAH-sensitive rice (Oryza sativa L.) cultivars.

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He, Yan; Xia, Wen; Li, Xinfeng; Lin, Jiajiang; Wu, Jianjun; Xu, Jianming

2015-03-01

A pot experiment was conducted to reveal the removal of two polycyclic aromatic hydrocarbons (PAHs) (phenanthrene, PHE, and pyrene, PYR) during rice cultivation in a paddy field. The rhizosphere effect on facilitating dissipation of PAHs varied simultaneously as a function of soil properties, PAH types, cultivation time, and genotypes within rice cultivars, with differences performed for PYR but not PHE. Changes in soil PLFA profiles evidenced that the growth of rice roots modified the dominant species within rhizosphere microbial communities and induced a selective enrichment of Gram-negative aerobic bacteria capable of degrading, thereby resulting in the differentiated dissipation of PYR. While the insignificant differences in PHE dissipation might be attributed to its higher solubility and availability under flooded condition that concealed the differences in improvement of bioavailability for microorganisms between rhizosphere and non-rhizosphere, and between both soils and both rice cultivars. Our findings illustrate that the removal of PAHs in paddy soils was more complex relative to those in dryland soils. This was possibly due to the specialty of rice roots for oxygen secretion that provides development of redox heterogeneous microbial habitats at root-soil interface under flooded condition.

Bevacizumab exacerbates sinusoidal obstruction syndrome (SOS) in the animal model and increases MMP 9 production.

Science.gov (United States)

Jafari, Azin; Matthaei, Hanno; Wehner, Sven; Tonguc, Tolga; Kalff, Jörg C; Manekeller, Steffen

2018-04-24

Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. After MCT administration 67% of animals developed SOS. GOT serum concentration significantly increased in animals developing SOS ( p SOS. In contrast, animals receiving VEGF developed SOS merely in 40% while increasing the VEGF dose led to a further decrease in SOS development to 25%. MMP 9 concentration in animals developing SOS was significantly higher compared to controls ( p SOS paralleled by MMP 9 production. Therefore, OX-Bevacizumab combination therapies should be administered with caution, especially if liver parenchyma damage is apparent. Male Sprague-Dawley rats were gavaged Monocrotaline (MCT) to induce SOS. Recombinant VEGF or an Anti-VEGF antibody was administered to MCT-treated rats and the hepatotoxic effect monitored in defined time intervals. MMP 9 expression in the liver was measured by ELISA.

Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

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Marte Eilertsen

Full Text Available INTRODUCTION: Monocarboxylate transporters (MCTs 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS in both cancer and tumor stromal cells in NSCLC. METHODS: Tissue micro arrays (TMAs were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. RESULTS: In univariate analyses; ↓ MCT1 (P = 0.021 and ↑ MCT4 (P = 0.027 expression in cancer cells, and ↑ MCT1 (P = 0.003, ↓ MCT2 (P = 0.006, ↓ MCT3 (P = 0.020 expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001, ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001, ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031 and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016 were significant independent poor prognostic markers for DSS. CONCLUSIONS: We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

Metabolic markers in relation to hypoxia; staining patterns and colocalization of pimonidazole, HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4

International Nuclear Information System (INIS)

Rademakers, Saskia E; Lok, Jasper; Kogel, Albert J van der; Bussink, Johan; Kaanders, Johannes HAM

2011-01-01

The cellular response of malignant tumors to hypoxia is diverse. Several important endogenous metabolic markers are upregulated under hypoxic conditions. We examined the staining patterns and co-expression of HIF-1α, CAIX, LDH-5, GLUT-1, MCT1 and MCT4 with the exogenous hypoxic cell marker pimonidazole and the association of marker expression with clinicopathological characteristics. 20 biopsies of advanced head and neck carcinomas were immunohistochemically stained and analyzed. All patients were given the hypoxia marker pimonidazole intravenously 2 h prior to biopsy taking. The tumor area positive for each marker, the colocalization of the different markers and the distribution of the markers in relation to the blood vessels were assessed by semiautomatic quantitative analysis. MCT1 staining was present in hypoxic (pimonidazole stained) as well as non-hypoxic areas in almost equal amounts. MCT1 expression showed a significant overall correlation (r = 0.75, p < 0.001) and strong spatial relationship with CAIX. LDH-5 showed the strongest correlation with pimonidazole (r = 0.66, p = 0.002). MCT4 and GLUT-1 demonstrated a typical diffusion-limited hypoxic pattern and showed a high degree of colocalization. Both MCT4 and CAIX showed a higher expression in the primary tumor in node positive patients (p = 0.09 both). Colocalization and staining patterns of metabolic and hypoxia-related proteins provides valuable additional information over single protein analyses and can improve the understanding of their functions and environmental influences

Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension.

Science.gov (United States)

Yang, Peiran; Read, Cai; Kuc, Rhoda E; Buonincontri, Guido; Southwood, Mark; Torella, Rubben; Upton, Paul D; Crosby, Alexi; Sawiak, Stephen J; Carpenter, T Adrian; Glen, Robert C; Morrell, Nicholas W; Maguire, Janet J; Davenport, Anthony P

2017-03-21

Elabela/toddler (ELA) is a critical cardiac developmental peptide that acts through the G-protein-coupled apelin receptor, despite lack of sequence similarity to the established ligand apelin. Our aim was to investigate the receptor pharmacology, expression pattern, and in vivo function of ELA peptides in the adult cardiovascular system, to seek evidence for alteration in pulmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate attenuation of PAH severity with exogenous administration of ELA in a rat model. In silico docking analysis, competition binding experiments, and downstream assays were used to characterize ELA receptor binding in human heart and signaling in cells expressing the apelin receptor. ELA expression in human cardiovascular tissues and plasma was determined using real-time quantitative polymerase chain reaction, dual-labeling immunofluorescent staining, and immunoassays. Acute cardiac effects of ELA-32 and [Pyr 1 ]apelin-13 were assessed by MRI and cardiac catheterization in anesthetized rats. Cardiopulmonary human and rat tissues from PAH patients and monocrotaline- and Sugen/hypoxia-exposed rats were used to show changes in ELA expression in PAH. The effect of ELA treatment on cardiopulmonary remodeling in PAH was investigated in the monocrotaline rat model. ELA competed for binding of apelin in human heart with overlap for the 2 peptides indicated by in silico modeling. ELA activated G-protein- and β-arrestin-dependent pathways. We detected ELA expression in human vascular endothelium and plasma. Comparable to apelin, ELA increased cardiac contractility, ejection fraction, and cardiac output and elicited vasodilatation in rat in vivo. ELA expression was reduced in cardiopulmonary tissues from PAH patients and PAH rat models, respectively. ELA treatment significantly attenuated elevation of right ventricular systolic pressure and right ventricular hypertrophy and pulmonary vascular remodeling in

Quantitative comparison of PET performance—Siemens Biograph mCT and mMR

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Karlberg, Anna M.; Sæther, Oddbjørn [Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Olav Kyrres gt 17, 7006 Trondheim (Norway); Eikenes, Live [Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Postbox 8905, 7491 Trondheim (Norway); Goa, Pål Erik [Department of Radiology and Nuclear Medicine, St. Olavs Hospital, Olav Kyrres gt 17, 7006 Trondheim (Norway); Department of Physics, Norwegian University of Science and Technology, Trondheim (Norway)

2016-02-25

Integrated clinical whole-body PET/MR systems were introduced in 2010. In order to bring this technology into clinical usage, it is of great importance to compare the performance with the well-established PET/CT. The aim of this study was to evaluate PET performance, with focus on image quality, on Siemens Biograph mMR (PET/MR) and Siemens Biograph mCT (PET/CT). A direct quantitative comparison of the performance characteristics between the mMR and mCT system was performed according to National Electrical Manufacturers Association (NEMA) NU 2-2007 protocol. Spatial resolution, sensitivity, count rate and image quality were evaluated. The evaluation was supplemented with additional standardized uptake value (SUV) measurements. The spatial resolution was similar for the two systems. Average sensitivity was higher for the mMR (13.3 kcps/MBq) compared to the mCT system (10.0 kcps/MBq). Peak noise equivalent count rate (NECR) was slightly higher for the mMR (196 kcps @ 24.4 kBq/mL) compared to the mCT (186 kcps @ 30.1 kBq/mL). Scatter fractions in the clinical activity concentration range yielded lower values for the mCT (34.9 %) compared to those for the mMR (37.0 %). Best image quality of the systems resulted in approximately the same mean hot sphere contrast and a difference of 19 percentage points (pp) in mean cold contrast, in favour of the mCT. In general, point spread function (PSF) increased hot contrast and time of flight (TOF) increased both hot and cold contrast. Highest hot contrast for the smallest sphere (10 mm) was achieved with the combination of TOF and PSF on the mCT. Lung residual error was higher for the mMR (22 %) than that for the mCT (17 %), with no effect of PSF. With TOF, lung residual error was reduced to 8 % (mCT). SUV was accurate for both systems, but PSF caused overestimations for the 13-, 17- and 22-mm spheres. Both systems proved good performance characteristics, and the PET image quality of the mMR was close to that of the mCT

Endothelial and Smooth Muscle Cell Interaction via FoxM1 Signaling Mediates Vascular Remodeling and Pulmonary Hypertension.

Science.gov (United States)

Dai, Zhiyu; Zhu, Maggie M; Peng, Yi; Jin, Hua; Machireddy, Narsa; Qian, Zhijian; Zhang, Xianming; Zhao, You-Yang

2018-04-17

Angioproliferative vasculopathy is a hallmark of pulmonary arterial hypertension (PAH). However, little is known how endothelial cell (EC) and smooth muscle cell (SMC) crosstalk regulates the angioproliferative vascular remodeling. We aimed to investigate the role of EC and SMC interaction and underlying signaling pathways in PH development. SMC-specific Foxm1 or Cxcr4 knockout mice, EC-specific Foxm1 or Egln1 knockout mice, as well as EC-specific Egln1/Cxcl12 double knockout mice were used to assess the role of FoxM1 on SMC proliferation and PH. Lung tissues and cells from PAH patients were employed to validate clinical relevance. FoxM1 inhibitor Thiostrepton was used in Sugen 5416/hypoxia- and monocrotaline-challenged rats. FoxM1 expression was markedly upregulated in lungs and pulmonary arterial SMCs of idiopathic PAH patients and 4 discrete PH rodent models. Mice with SMC- (but not EC-) specific deletion of Foxm1 were protected from hypoxia- or Sugen 5416/hypoxia-induced PH. The upregulation of FoxM1 in SMCs induced by multiple EC-derived factors (PDGF-B, CXCL12, ET-1 and MIF) mediated SMC proliferation. Genetic deletion of endothelial Cxcl12 in Egln1Tie2Cre mice or loss of its cognate receptor Cxcr4 in SMCs in hypoxia-treated mice inhibited FoxM1 expression, SMC proliferation and PH. Accordingly, pharmacological inhibition of FoxM1 inhibited severe PH in both Sugen 5416/hypoxia and monocrotaline-challenged rats. Multiple factors derived from dysfunctional ECs induced FoxM1 expression in SMCs and activated FoxM1-dependent SMC proliferation which contributes to pulmonary vascular remodeling and PH. Thus, targeting FoxM1 signaling represents a novel strategy for treatment of IPAH.

Pharmacological treatment and BBB-targeted genetic therapy for MCT8-dependent hypomyelination in zebrafish

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David Zada

2016-11-01

Full Text Available Hypomyelination is a key symptom of Allan-Herndon-Dudley syndrome (AHDS, a psychomotor retardation associated with mutations in the thyroid-hormone (TH transporter MCT8 (monocarboxylate transporter 8. AHDS is characterized by severe intellectual deficiency, neuromuscular impairment and brain hypothyroidism. In order to understand the mechanism for TH-dependent hypomyelination, we developed an mct8 mutant (mct8−/− zebrafish model. The quantification of genetic markers for oligodendrocyte progenitor cells (OPCs and mature oligodendrocytes revealed reduced differentiation of OPCs into oligodendrocytes in mct8−/− larvae and adults. Live imaging of single glial cells showed that the number of oligodendrocytes and the length of their extensions are reduced, and the number of peripheral Schwann cells is increased, in mct8−/− larvae compared with wild type. Pharmacological analysis showed that TH analogs and clemastine partially rescued the hypomyelination in the CNS of mct8−/− larvae. Intriguingly, triiodothyronine (T3 treatment rescued hypomyelination in mct8−/− embryos before the maturation of the blood–brain barrier (BBB, but did not affect hypomyelination in older larvae. Thus, we expressed Mct8-tagRFP in the endothelial cells of the vascular system and showed that even relatively weak mosaic expression completely rescued hypomyelination in mct8−/− larvae. These results suggest potential pharmacological treatments and BBB-targeted gene therapy that can enhance myelination in AHDS and possibly in other TH-dependent brain disorders.

Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

International Nuclear Information System (INIS)

Cheng Wei; Oike, Masahiro; Hirakawa, Masakazu; Ohnaka, Keizo; Koyama, Tetsuya; Ito, Yushi

2005-01-01

The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation in response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca 2+ transients and cellular uptake of L-[ 3 H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[ 3 H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine

Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis

NARCIS (Netherlands)

Mayerl, Steffen; Müller, Julia; Bauer, Reinhard; Richert, Sarah; Kassmann, Celia M.; Darras, Veerle M.; Buder, Katrin; Boelen, Anita; Visser, Theo J.; Heuer, Heike

2014-01-01

Allan-Herndon-Dudley syndrome (AHDS), a severe form of psychomotor retardation with abnormal thyroid hormone (TH) parameters, is linked to mutations in the TH-specific monocarboxylate transporter MCT8. In mice, deletion of Mct8 (Mct8 KO) faithfully replicates AHDS-associated endocrine abnormalities;

Monocarboxylate transporter 4 (MCT4 and CD147 overexpression is associated with poor prognosis in prostate cancer

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Pereira Helena

2011-07-01

Full Text Available Abstract Background Monocarboxylate transporters (MCTs are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma. Methods Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171, adjacent non-neoplastic tissues (n = 135, PIN lesions (n = 40 and normal prostatic tissue (n = 14. Protein expression was correlated with patients' clinicopathologic characteristics. Results In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence. Conclusions Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and

Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer

International Nuclear Information System (INIS)

Pértega-Gomes, Nelma; Lopes, Carlos; Baltazar, Fátima; Vizcaíno, José R; Miranda-Gonçalves, Vera; Pinheiro, Céline; Silva, Joana; Pereira, Helena; Monteiro, Pedro; Henrique, Rui M; Reis, Rui M

2011-01-01

Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma. Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs) blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171), adjacent non-neoplastic tissues (n = 135), PIN lesions (n = 40) and normal prostatic tissue (n = 14). Protein expression was correlated with patients' clinicopathologic characteristics. In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence. Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and both MCT4 and CD147 as markers of poor prognosis in

Effects of intermittent training on anaerobic performance and MCT transporters in athletes.

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Grégoire Millet

Full Text Available This study examined the effects of intermittent hypoxic training (IHT on skeletal muscle monocarboxylate lactate transporter (MCT expression and anaerobic performance in trained athletes. Cyclists were assigned to two interventions, either normoxic (N; n = 8; 150 mmHg PIO2 or hypoxic (H; n = 10; ∼3000 m, 100 mmHg PIO2 over a three week training (5×1 h-1h30 x week(-1 period. Prior to and after training, an incremental exercise test to exhaustion (EXT was performed in normoxia together with a 2 min time trial (TT. Biopsy samples from the vastus lateralis were analyzed for MCT1 and MCT4 using immuno-blotting techniques. The peak power output (PPO increased (p<0.05 after training (7.2% and 6.6% for N and H, respectively, but VO2max showed no significant change. The average power output in the TT improved significantly (7.3% and 6.4% for N and H, respectively. No differences were found in MCT1 and MCT4 protein content, before and after the training in either the N or H group. These results indicate there are no additional benefits of IHT when compared to similar normoxic training. Hence, the addition of the hypoxic stimulus on anaerobic performance or MCT expression after a three-week training period is ineffective.

Characterization and snubbing of a bidirectional MCT in a resonant ac link converter

Science.gov (United States)

Lee, Tony; Elbuluk, Malik E.; Zinger, Donald S.

1993-01-01

The MOS-Controlled Thyristor (MCT) is emerging as a powerful switch that combines the better characteristics of existing power devices. A study of switching stresses on an MCT switch under zero voltage resonant switching is presented. The MCT is used as a bidirectional switch in an ac/ac pulse density modulated inverter for induction motor drive. Current and voltage spikes are observed and analyzed with variations in the timing of the switching. Different snubber circuit configurations are under investigation to minimize the effect of these transients. The results will be extended to study and test the MCT switching in a medium power (5 hp) induction motor drive.

Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

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Cory D. Bovenzi

2015-01-01

Full Text Available Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p<0.001 for all analyses. Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p<0.0001 for both analyses. Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.

Chronic intratracheal application of the soluble guanylyl cyclase stimulator BAY 41-8543 ameliorates experimental pulmonary hypertension.

Science.gov (United States)

Amirjanians, Matthieu; Egemnazarov, Bakytbek; Sydykov, Akylbek; Kojonazarov, Baktybek; Brandes, Ralf; Luitel, Himal; Pradhan, Kabita; Stasch, Johannes-Peter; Redlich, Gorden; Weissmann, Norbert; Grimminger, Friedrich; Seeger, Werner; Ghofrani, Hossein; Schermuly, Ralph

2017-05-02

Dysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP synthesis via sGC are important therapeutic options for treatment of PH patients. An unwanted effect of this novel class of drugs is their systemic hypotensive effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the sGC stimulator BAY41-8543 could diminish its systemic vasodilating effect.Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal delivery was tested in healthy rats. Four weeks after a single injection of monocrotaline (MCT, 60 mg/kg s.c.), rats were randomized to a two-week treatment with either placebo, BAY 41-8543 (10 mg/kg per os (PO)) or intra-tracheal (IT) instillation (3 mg/kg or 1 mg/kg).Circulating concentrations of the drug 10 mg/kg PO and 3 mg/kg IT were comparable. BAY 41-8543 was detected in the lung tissue and broncho-alveolar fluid after IT delivery at higher concentrations than after PO administration. Systemic arterial pressure transiently decreased after oral BAY 41-8543 and was unaffected by intratracheal instillation of the drug. PO 10 mg/kg and IT 3 mg/kg regimens partially reversed pulmonary hypertension and improved heart function in MCT-injected rats. Minor efficacy was noted in rats treated IT with 1 mg/kg. The degree of pulmonary vascular remodeling was largely reversed in all treatment groups.Intratracheal administration of BAY 41-8543 reverses PAH and vascular structural remodeling in MCT-treated rats. Local lung delivery is not associated with systemic blood pressure lowering and represents thus a further development of PH treatment with sGC stimulators.

Electrical field stimulation-induced excitatory responses of ...

African Journals Online (AJOL)

effect of the endothelium on electrical field stimulation (EFS)-induced excitatory responses of pulmonary artery segments from pulmonary hypertensive rats. Methods: Pulmonary hypertension was induced in rats with a single dose of monocrotaline (60 mg/kg) and 21 days later, arterial rings were set up for isometric tension ...

The influence of PAH concentration and distribution on real-time in situ measurements of petroleum products in soils using laser induced fluorescence

International Nuclear Information System (INIS)

Douglas, G.S.; Lieberman, S.H.; McGinnis, W.C.; Knowles, D.; Peven, C.

1995-01-01

Real-time laser induced fluorescence (LIF) in situ measurements of soil samples provide a reliable and cost-effective screening tool for hydrocarbon site assessments. The site characterization and analysis penetrometer system (SCAPS), is a truck-mounted cone penetrometer probe modified with a sapphire window and connected to a laser by fiber optics. The pulsed nitrogen laser 337-nm excitation source induces fluorescence in polynuclear aromatic hydrocarbons (PAHs), which are present in petroleum products. The fluorescence response of these compounds is measured with a fluorometer. The SCAPS can provide continuous hydrocarbon screening measurements to soil depths greater than 100 feet. Discrete soil samples collected from the SCAPS boreholes were extracted and analyzed for total petroleum hydrocarbons (TPH), by gas chromatography with flame ionization detection (GC/FID), and 16 parent and over 100 alkyl substituted PAH compounds by gas chromatography with mass spectrometry detection (GC/MS). This method provides a basis for evaluating the relationship between TPH and PAH concentrations in the soil samples and laser induced fluorescence measurements from the soil borings

PAH EMISSION AT THE BRIGHT LOCATIONS OF PDRs: THE grandPAH HYPOTHESIS

International Nuclear Information System (INIS)

Andrews, H.; Tielens, A. G. G. M.; Boersma, C.; Allamandola, L. J.; Werner, M. W.; Livingston, J.

2015-01-01

The polycyclic aromatic hydrocarbon (PAH) emission observed in the Spitzer Infrared Spectrograph spectra of bright mid-IR locations of NGC 7023, NGC 2023, and NGC 1333 was analyzed. These objects show large variations in PAH band ratios when studied through spectral mapping. Nevertheless, the mid-IR spectra at these bright spots show a remarkably similar PAH emission. We used the NASA Ames PAH IR Spectroscopic Database to fit the observations and analyze the derived PAH populations. Our results show that PAH emission in the 5–15 μm range appears to be rather insensitive to variations of the radiation field. Similar PAH populations of neutral small to medium-sized PAHs (∼50%), with ionized species contributing in slightly less than 50%, provide very good fits. Analyzing the degeneracy of the results shows that subtle (but intrinsic) variations in the emission properties of individual PAHs lead to observable differences in the resulting spectra. On top of this, we found that variations of <30% in the PAH abundances would lead to noticeable spectral differences between the three photodissociation regions (PDRs). Therefore, PAH populations must be remarkably similar at these different lines of sight. To account for this, we suggest the concept of grandPAHs as a unique mixture of the most stable PAHs emitting at these spots. Using NGC 7023 as an example, the grandPAHs refer to the robust PAH population that results from the intense processing of PAHs at the border limit between the PDR and the molecular cloud, where, due to the UV radiation that destroys the PAH population, the abundance of PAHs starts decreasing as we move toward the star

PAH EMISSION AT THE BRIGHT LOCATIONS OF PDRs: THE grandPAH HYPOTHESIS

Energy Technology Data Exchange (ETDEWEB)

Andrews, H.; Tielens, A. G. G. M. [Leiden Observatory, Leiden University, P.O. Box 9513, 2300 RA Leiden (Netherlands); Boersma, C.; Allamandola, L. J. [NASA Ames Research Center, MS 245-6, Moffett Field, CA 94035 (United States); Werner, M. W.; Livingston, J., E-mail: heandrew@strw.leidenuniv.nl, E-mail: Christiaan.Boersma@nasa.gov [Jet Propulsion Laboratory, MC 264-767, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States)

2015-07-01

The polycyclic aromatic hydrocarbon (PAH) emission observed in the Spitzer Infrared Spectrograph spectra of bright mid-IR locations of NGC 7023, NGC 2023, and NGC 1333 was analyzed. These objects show large variations in PAH band ratios when studied through spectral mapping. Nevertheless, the mid-IR spectra at these bright spots show a remarkably similar PAH emission. We used the NASA Ames PAH IR Spectroscopic Database to fit the observations and analyze the derived PAH populations. Our results show that PAH emission in the 5–15 μm range appears to be rather insensitive to variations of the radiation field. Similar PAH populations of neutral small to medium-sized PAHs (∼50%), with ionized species contributing in slightly less than 50%, provide very good fits. Analyzing the degeneracy of the results shows that subtle (but intrinsic) variations in the emission properties of individual PAHs lead to observable differences in the resulting spectra. On top of this, we found that variations of <30% in the PAH abundances would lead to noticeable spectral differences between the three photodissociation regions (PDRs). Therefore, PAH populations must be remarkably similar at these different lines of sight. To account for this, we suggest the concept of grandPAHs as a unique mixture of the most stable PAHs emitting at these spots. Using NGC 7023 as an example, the grandPAHs refer to the robust PAH population that results from the intense processing of PAHs at the border limit between the PDR and the molecular cloud, where, due to the UV radiation that destroys the PAH population, the abundance of PAHs starts decreasing as we move toward the star.

Changes in the electro-physical properties of MCT epitaxial films affected by a plasma volume discharge induced by an avalanche beam in atmospheric-pressure air

Science.gov (United States)

Grigoryev, D. V.; Voitsekhovskii, A. V.; Lozovoy, K. A.; Tarasenko, V. F.; Shulepov, M. A.

2015-11-01

In this paper the influence of the plasma volume discharge of nanosecond duration formed in a non-uniform electric field at atmospheric pressure on samples of epitaxial films HgCdTe (MCT) films are discussed. The experimental data show that the action of pulses of nanosecond volume discharge in air at atmospheric pressure leads to changes in the electrophysical properties of MCT epitaxial films due to formation of a near-surface high- conductivity layer of the n-type conduction. The preliminary results show that it is possible to use such actions in the development of technologies for the controlled change of the properties of MCT.

Polycyclic aromatic hydrocarbons and PAH-related DNA adducts.

Science.gov (United States)

Ewa, Błaszczyk; Danuta, Mielżyńska-Švach

2017-08-01

Investigations on the impact of chemicals on the environment and human health have led to the development of an exposome concept. The exposome refers to the totality of exposures received by a person during life, including exposures to life-style factors, from the prenatal period to death. The exposure to genotoxic chemicals and their reactive metabolites can induce chemical modifications of DNA, such as, for example, DNA adducts, which have been extensively studied and which play a key role in chemically induced carcinogenesis. Development of different methods for the identification of DNA adducts has led to adopting DNA adductomic approaches. The ability to simultaneously detect multiple PAH-derived DNA adducts may allow for the improved assessment of exposure, and offer a mechanistic insight into the carcinogenic process following exposure to PAH mixtures. The major advantage of measuring chemical-specific DNA adducts is the assessment of a biologically effective dose. This review provides information about the occurrence of the polycyclic aromatic hydrocarbons (PAHs) and their influence on human exposure and biological effects, including PAH-derived DNA adduct formation and repair processes. Selected methods used for determination of DNA adducts have been presented.

Effect of Medium-chain Triglyceride (MCT on Growth Performance, Nutrient Digestibility, Blood Characteristics in Weanling Pigs

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S. M. Hong

2012-07-01

Full Text Available One hundred and twenty weanling pigs in experiment 1 (Exp. 1 (6.91±0.99 kg; 21 d of age and Exp. 2 (10.20±1.09 kg; 28 d of age were used in two 42-d and 35-d experiments to evaluate the effect of medium-chain-triglyceride (MCT on growth performance, apparent total tract digestibility (ATTD of nutrients and blood profile. In both of Exp. 1 and Exp. 2, the same dietary treatments were utilized as follows : i negative control (NC, ii positive control (PC, NC+antibiotics (40 mg/kg Tiamulin, 110 mg/kg Tylosin, and 10 mg/kg Enramycin, iii MCT3, NC+0.32% (phase 1, 2 and 3 MCT, and iv MCT5, NC+0.55% (phase 1, 0.32% (phase 2 and 3 MCT. In Exp. 1, the pigs fed MCT5 diets had higher (p<0.05 ADG compared to NC treatment during the first 2 wk. From d 15 to 28, the ATTD of energy was improved (p<0.05 by MCT3 compared to the PC treatment. No effect has been observed on the blood profiles [red blood cell (RBC, white blood cell (WBC, immunoglobulin-G (IgG, lymphocyte concentration] measured in this study. In Exp. 2, the ADG were increased (p<0.05 by the MCT5 treatment than the PC treatment from d 0 to 14. Pigs fed PC treatment diet had lower ADFI (p<0.05 and better FCR (p<0.05 than NC treatment, whereas no differences were shown between MCT treatments and NC or PC treatment from d 15 to 35 and overall phase. The ATTD of DM and nitrogen were improved (p<0.05 by the effect of MCT5 related to the NC and PC treatment at the end of 2nd and 5th wk. The pigs fed MCT3 had higher (p<0.05 energy digestibility than PC treatment. No effects were seen in the blood profiles we measured (WBC, RBC, lymphocyte and immunoglobulin-G. In conclusion, the addition of MCT in the weanling pigs diet can improve the ADG and digestibility during the earlier period (first 2 wks, but had little effect on the blood characteristics.

Effects of milk from goat fed Crotalaria spectabilis seeds on growing rats

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Rosane Maria Trindade de Medeiros

1999-01-01

Full Text Available Seeds of Crotalaria spectabilis, containing the pyrrolizidine alkaloid (PA monocrotaline (MCT, were fed to a lactating dairy goat. Milk from this goat was fed to rats for 8 weeks to determine whether MCT or its toxic metabolites are transferred into the goat’s milk. Rats from the experimental group showed significantly higher (p<0.05 serum levels of ALT, AST, GGT and LDH and less weight gains (p<0.05 than control rats. The most significant lesions in rats consuming the experimental ration were mild to moderate interstitial pneumonia and a vacuolar degeneration and occasionally necrosis of periportal hepatocytes. The results of this study indicate that the PA and/or its metabolites are eliminated in milk.

CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance.

Science.gov (United States)

Afonso, Julieta; Santos, Lúcio L; Miranda-Gonçalves, Vera; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

2015-11-01

The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpressions of the microenvironment-related molecules CD147, monocarboxylate transporters (MCTs) 1 and 4, CD44 and CAIX in tumor tissue sections from 114 UBC patients. The presence of MCT1 and/or MCT4 expressions was significantly associated with unfavorable clinicopathological parameters. The incidence of CD147 positive staining significantly increased with advancing stage, grade and type of lesion, and occurrence of lymphovascular invasion. Similar associations were observed when considering the concurrent expression of CD147 and MCT1. This expression profile lowered significantly the 5-year disease-free and overall survival rates. Moreover, when selecting patients who received platinum-based chemotherapy, the prognosis was significantly worse for those with MCT1 and CD147 positive tumors. CD147 specific silencing by small interfering RNAs (siRNAs) in UBC cells was accompanied by a decrease in MCT1 and MCT4 expressions and, importantly, an increase in chemosensitivity to cisplatin. Our results provide novel insights for the involvement of CD147 and MCTs in bladder cancer progression and resistance to cisplatin-based chemotherapy. We consider that the possible cooperative role of CD147 and MCT1 in determining cisplatin resistance should be further explored as a potential theranostics biomarker. © 2014 Wiley Periodicals, Inc.

The genetic variation in Monocarboxylic acid transporter 2 (MCT2 has functional and clinical relevance with male infertility

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Jinu Lee

2014-10-01

Full Text Available Monocarboxylic acid transporter 2 (MCT2 transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 (+28201A > G, rs10506398 and 3' untranslated region (UTR single nucleotide polymorphism (SNP (+2626G > A, rs10506399 of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility (n = 471, P A had a strong association with the oligoasthenoteratozoospermia (OAT group. The +2626GG type had an almost 2.4-fold higher sperm count than that of the +2626AA type (+2626GG; 66 × 10 6 vs +2626AA; 27 × 10 6 , P < 0.0001. The MCT2-3' UTR SNP may be important for expression, as it is located at the MCT2 3' UTR. The average MCT2 protein amount in sperm of the +2626GG type was about two times higher than that of the +2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.

Functional analysis of human aromatic amino acid transporter MCT10/TAT1 using the yeast Saccharomyces cerevisiae.

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Uemura, Satoshi; Mochizuki, Takahiro; Kurosaka, Goyu; Hashimoto, Takanori; Masukawa, Yuki; Abe, Fumiyoshi

2017-10-01

Tryptophan is an essential amino acid in humans and an important serotonin and melatonin precursor. Monocarboxylate transporter MCT10 is a member of the SLC16A family proteins that mediates low-affinity tryptophan transport across basolateral membranes of kidney, small intestine, and liver epithelial cells, although the precise transport mechanism remains unclear. Here we developed a simple functional assay to analyze tryptophan transport by human MCT10 using a deletion mutant for the high-affinity tryptophan permease Tat2 in Saccharomyces cerevisiae. tat2Δtrp1 cells are defective in growth in YPD medium because tyrosine present in the medium competes for the low-affinity tryptophan permease Tat1 with tryptophan. MCT10 appeared to allow growth of tat2Δtrp1 cells in YPD medium, and accumulate in cells deficient for Rsp5 ubiquitin ligase. These results suggest that MCT10 is functional in yeast, and is subject to ubiquitin-dependent quality control. Whereas growth of Tat2-expressing cells was significantly impaired by neutral pH, that of MCT10-expressing cells was nearly unaffected. This property is consistent with the transport mechanism of MCT10 via facilitated diffusion without a need for pH gradient across the plasma membrane. Single-nucleotide polymorphisms (SNPs) are known to occur in the human MCT10 coding region. Among eight SNP amino acid changes in MCT10, the N81K mutation completely abrogated tryptophan import without any abnormalities in the expression or localization. In the MCT10 modeled structure, N81 appeared to protrude into the putative trajectory of tryptophan. Plasma membrane localization of MCT10 and the variant proteins was also verified in human embryonic kidney 293T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and characterisation of MCT detectors for space astrophysics at CEA

Science.gov (United States)

Boulade, O.; Baier, N.; Castelein, P.; Cervera, C.; Chorier, P.; Destefanis, G.; Fièque, B.; Gravrand, O.; Guellec, F.; Moreau, V.; Mulet, P.; Pinsard, F.; Zanatta, J.-P.

2017-11-01

The Laboratoire Electronique et Traitement de l'Information (LETI) of the Commissariat à l'Energie Atomique (CEA, Grenoble, France) has been involved in the development of infrared detectors based on HgCdTe (MCT) material for over 30 years, mainly for defence and security programs [1]. Once the building blocks are developed at LETI (MCT material process, diode technology, hybridization, …), the industrialization is performed at SOFRADIR (also in Grenoble, France) which also has its own R&D program [2]. In past years, LETI also developed infrared detectors for space astrophysics in the mid infrared range - the long wave detector of the ISOCAM camera onboard ISO - as well as in the far infrared range - the bolometer arrays of the Herschel/PACS photometer unit -, both instruments which were under the responsibility of the Astrophysics department of CEA (IRFU/SAp, Saclay, France). Nowadays, the infrared detectors used in space and ground based astronomical instruments all come from vendors in the US. For programmatic reasons - increase the number of available vendors, decrease the cost, mitigate possible export regulations, …- as well as political ones - spend european money in Europe -, the European Space Agency (ESA) defined two roadmaps (one in the NIR-SWIR range, one in the MWIR-LWIR range) that will eventually allow for the procurement of infrared detectors for space astrophysics within Europe. The French Space Agency (CNES) also started the same sort of roadmaps, as part of its contribution to the different space missions which involve delivery of instruments by French laboratories. It is important to note that some of the developments foreseen in these roadmaps also apply to Earth Observations. One of the main goal of the ESA and CNES roadmaps is to reduce the level of dark current in MCT devices at all wavelengths. The objective is to use the detectors at the highest temperature where the noise induced by the dark current stays compatible with the photon

Comparison of diet-induced thermogenesis of foods containing medium- versus long-chain triacylglycerols.

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Kasai, Michio; Nosaka, Naohisa; Maki, Hideaki; Suzuki, Yoshie; Takeuchi, Hiroyuki; Aoyama, Toshiaki; Ohra, Atsushi; Harada, Youji; Okazaki, Mitsuko; Kondo, Kazuo

2002-12-01

The purpose of this study was to investigate the effect of 5-10 g of medium-chain triacylglycerols (MCT) on diet-induced thermogenesis in healthy humans. The study compared diet-induced thermogenesis after ingestion of test foods containing MCT and long-chain triacylglycerols (LCT), using a double-blind, crossover design. Eight male and eight female subjects participated in study 1 and study 2, respectively. In both studies, the LCT was a blend of rapeseed oil and soybean oil. In study 1, the liquid meals contained 10 g MCT (10M), a mixture of 5 g MCT and 5 g LCT (5M5L), and 10 g LCT (10L). In study 2, the subjects were given a meal (sandwich and clear soup) with the mayonnaise or margarine containing 5 g of MCT or LCT. Postprandial energy expenditure was measured by indirect calorimetry before and during the 6 h after ingestion of the test meals. Diet-induced thermogenesis was significantly greater after 5M5L and 10M Ingestion as compared to 10L ingestion. Ingestion of the mayonnaise or margarine containing 5 g MCT caused significantly larger diet-induced thermogenesis as compared to that of LCT. These results suggest that, in healthy humans, the intake of 5-10 g of MCT causes larger diet-induced thermogenesis than that of LCT, irrespective of the form of meal containing the MCT.

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

KAUST Repository

Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothsteinb, Jeffrey D.

2015-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21. days in wild-type mice to greater than 38. days in MCT1 heterozygote mice. In fact, half of the MCT1 heterozygote mice have no recovery of CMAP at 42. days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42. days post-crush in the MCT1 heterozygote mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote mice at 4. weeks and tibial mixed sensory and motor nerve at 3. weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush.

Effects of low concentration biodiesel blends application on modern passenger cars. Part 3: Impact on PAH, nitro-PAH, and oxy-PAH emissions

International Nuclear Information System (INIS)

Karavalakis, Georgios; Fontaras, Georgios; Ampatzoglou, Dimitrios; Kousoulidou, Marina; Stournas, Stamoulis; Samaras, Zissis; Bakeas, Evangelos

2010-01-01

This study explores the impact of five different types of methyl esters on polycyclic aromatic hydrocarbon (PAH), nitrated-PAH and oxygenated PAH emissions. The measurements were conducted on a chassis dynamometer, according to the European regulation. Each of the five different biodiesels was blended with EN590 diesel at a proportion of 10-90% v/v (10% biodiesel concentration). The vehicle was a Euro 3 compliant common-rail diesel passenger car. Emission measurements were performed over the NEDC and compared with those of the real traffic-based Artemis driving cycles. The experimental results showed that the addition of biodiesel led to some important increases in low molecular-weight PAHs (phenanthrene and anthracene) and to both increases and reductions in large PAHs which are characterised by their carcinogenic and mutagenic properties. Nitro-PAHs were found to reduce with biodiesel whereas oxy-PAH emissions presented important increases with the biodiesel blends. The impact of biodiesel source material was particularly clear on the formation of PAH compounds. It was found that most PAH emissions decreased as the average load and speed of the driving cycle increased. Cold-start conditions negatively influenced the formation of most PAH compounds. A similar trend was observed with particulate alkane emissions. - This investigation is a contribution to the understanding the impact of different biodiesels on the formation of PAHs, nitro-PAHs and oxy-PAHs over different driving conditions.

Parenteral medium-chain triglyceride-induced neutrophil activation is not mediated by a Pertussis Toxin sensitive receptor.

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Versleijen, Michelle W J; van Esterik, Joantine C J; Roelofs, Hennie M J; van Emst-de Vries, Sjenet E; Willems, Peter H G M; Wanten, Geert J A

2009-02-01

Lipid-induced immune modulation might contribute to the increased infection rate that is observed in patients using parenteral nutrition. We previously showed that emulsions containing medium-chain triglycerides (LCT/MCTs or pure MCTs), but not pure long-chain triglycerides (LCTs), impair neutrophil functions, modulate cell-signaling and induce neutrophil activation in vitro. It has recently been shown that medium-chain fatty acids are ligands for GPR84, a pertussis toxin (PT)-sensitive G-protein-coupled receptor (GPCR). This finding urged us to investigate whether MCT-induced neutrophil activation is mediated by PT-sensitive GPCRs. Neutrophils isolated from blood of healthy volunteers were pre-incubated with PT (0.5-1 microg/mL, 1.5 h) and analyzed for the effect of this pre-incubation on LCT/MCT (2.5 mmol/L)-dependent modulation of serum-treated zymosan (STZ)-induced intracellular Ca(2+) mobilization and on LCT/MCT (5 mmol/L)-induced expression of cell surface adhesion (CD11b) and degranulation (CD66b) markers and oxygen radical (ROS) production. PT did not inhibit the effects of LCT/MCT on the STZ-induced increase in cytosolic free Ca(2+) concentration. LCT/MCT increased ROS production to 146% of unstimulated cells. However, pre-incubation with PT did not inhibit the LCT/MCT-induced ROS production. Furthermore, the LCT/MCT-induced increase in CD11b and CD66b expression (196% and 235% of unstimulated cells, respectively) was not inhibited by pre-incubation with PT. LCT/MCT-induced neutrophil activation does not involve the action of a PT-sensitive G-protein-coupled receptor.

Human mesenchymal stem cell osteoblast differentiation, ECM deposition, and biomineralization on PAH/PAA polyelectrolyte multilayers.

Science.gov (United States)

Pattabhi, Sudhakara Rao; Lehaf, Ali M; Schlenoff, Joseph B; Keller, Thomas C S

2015-05-01

Polyelectrolyte multilayer (PEMU) coatings built layer by layer with alternating pairs of polyelectrolytes can be tuned to improve cell interactions with surfaces and may be useful as biocompatible coatings to improve fixation between implants and tissues. Here, we show that human mesenchymal stromal cells (hMSCs) induced with bone differentiation medium (BDM) to become osteoblasts biomineralize crosslinked PEMUs built with the polycation poly(allylamine hydrochloride) (PAH) and the polyanion poly(acrylic acid) (PAA). Degrees of hMSC osteoblast differentiation and surface biomineralization on the smooth PAH-terminated PEMUs (PAH-PEMUs) and microstructured PAA-terminated PEMUs (PAA-PEMUs) reflect differences in cell-deposited extracellular matrix (ECM). BDM-induced hMSCs expressed higher levels of the early osteoblast differentiation marker alkaline phosphatase and collagen 1 (COL1) sooner on PAA-PEMUs than on PAH-PEMUs. Cells on both types of PEMUs proceeded to express the later stage osteoblast differentiation marker bone sialoprotein (BSP), but the BDM-induced cells organized a more amorphous Collagen I and denser BSP localization on PAA-PEMUs than on PAH-PEMUs. These ECM properties correlated with greater biomineralization on the PAA-PEMUs than on PAH-PEMUs. Together, these results confirm the suitability of PAH/PAA PEMUs as a substrate for hMSC osteogenesis and highlight the importance of substrate effects on ECM organization and BSP presentation on biomineralization. © 2014 Wiley Periodicals, Inc.

Phenylacetylene and PAH

Indian Academy of Sciences (India)

During the last decades, polycyclic aromatic hydrocarbons (PAHs) and other related aromatic compounds, such as ionized PAHs, have received considerable attention from astronomers, astrobiologists, environmentalists, and the combustion community. In the interstellar medium, PAH like species account for up to 10% of ...

Development of Musical Creativity of Higher Class Pupils Using Musical Computer Technologies (MCT

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Sandra Rimkutė-Jankuvienė

2014-03-01

Full Text Available Purpose – to find out possibilities of development of musical creativity by using MCT in the music education of senior pupils.Design/methodology/approach – literature review, qualitative survey methodology (interview with music teachers.Findings – implementation of MCT, like any other innovation (as well as ICT in different spheres of education, including pre-school education, bring forth a certain positive effect. The results of the interview showed that in the praxis of music education, MCT is used for different development purposes (to make a lesson original, help pupils memorize music, expand their imagination not only by listening, but also by watching and evaluating performance of music, listen to music recordings, understand music and evaluate its quality, etc.. But for the development of musical creativity, MCT has been used very poorly.Research limitation/implications – musical creativity’s concept has not been uniquely defined so far. The aim of scientific literature review is to show that musical creativity is not meant to be separated from general creativity. Moreover, this is compounded by the search of the possibilities to the development of musical creativity. Analysis of scientific literature shows that the use of MCT can make an influence on musical creativity. However, empirical researches on this subject are still missing.Practical implications – the results of the interviews about using MCT in music lessons in order to develop musical creativity could be significant in formulating strategies of the development of musical creativity, preparing methodological instruments as well as in teacher training programs.Originality/value – the object of the survey in the chosen theme has never been explored in Lithuania, while the comparison of the obtained data with foreign scientists’ discoveries could contribute to a musical creativity’s definition.Research type: literature review, interview review.

Deciphering the roles of Arabidopsis LPCAT and PAH in phosphatidylcholine homeostasis and pathway coordination for chloroplast lipid synthesis.

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Wang, Liping; Kazachkov, Michael; Shen, Wenyun; Bai, Mei; Wu, Hong; Zou, Jitao

2014-12-01

Phosphatidylcholine (PC) is a key intermediate in the metabolic network of glycerolipid biosynthesis. Lysophosphatidylcholine acyltransferase (LPCAT) and phosphatidic acid phosphatase (PAH) are two key enzymes of PC homeostasis. We report that LPCAT activity is markedly induced in the Arabidopsis pah mutant. The quadruple pah lpcat mutant, with dual defects in PAH and LPCAT, had a level of lysophosphatidylcholine (LPC) that was much higher than that in the lpcat mutants and a PC content that was higher than that in the pah mutant. Comparative molecular profile analysis of monogalactosyldiacylglycerol and digalactosyldiacylglycerol revealed that both the pah and pah lpcat mutants had increased proportions of 34:6 from the prokaryotic pathway despite differing levels of LPCAT activity. We show that a decreased representation of the C16:0 C18:2 diacylglycerol moiety in PC was a shared feature of pah and pah lpcat, and that this change in PC metabolic profile correlated with the increased prokaryotic contribution to chloroplast lipid synthesis. We detected increased PC deacylation in the pah lpcat mutant that was attributable at least in part to the induced phospholipases. Increased LPC generation was also evident in the pah mutant, but the phospholipases were not induced, raising the possibility that PC deacylation is mediated by the reverse reaction of LPCAT. We discuss possible roles of LPCAT and PAH in PC turnover that impacts lipid pathway coordination for chloroplast lipid synthesis. © 2014 National Research Council Canada. The Plant Journal © 2014 Society For Experimental Biology and John Wiley & Sons.

Improvements of MCT MBE Growth on GaAs

Science.gov (United States)

Ziegler, J.; Wenisch, J.; Breiter, R.; Eich, D.; Figgemeier, H.; Fries, P.; Lutz, H.; Wollrab, R.

2014-08-01

In recent years, continuous progress has been published in the development of HgCdTe (MCT) infrared (IR) focal plane arrays (FPAs) fabricated by molecular beam epitaxy on GaAs substrates. In this publication, further characterization of the state-of-the art 1280 × 1024 pixel, 15- μm pitch detector fabricated from this material in both the mid-wavelength (MWIR) and long-wavelength (LWIR) IR region will be presented. For MWIR FPAs, the percentage of defective pixel remains below 0.5% up to an operating temperature ( T OP) of around 100 K. For the LWIR FPA, an operability of 99.25% was achieved for a T OP of 76 K. Additionally, the beneficial effect of the inclusion of MCT layers with a graded composition region was investigated and demonstrated on current-voltage ( IV) characteristics on test diodes in a MWIR FPA.

Renal handling of drugs in renal failure. I: Differential effects of uranyl nitrate- and glycerol-induced acute renal failure on renal excretion of TEAB and PAH in rats

International Nuclear Information System (INIS)

Lin, J.H.; Lin, T.H.

1988-01-01

Two etiologically different models of experimental acute renal failure were induced in rats by administration of either glycerol or uranyl nitrate. Both compounds caused a substantial decrease in the glomerular filtration rate (GFR) and the net tubular secretion of tetraethylammonium bromide (TEAB) and para-aminohippuric acid (PAH). The degree of renal impairment induced by uranyl nitrate and glycerol appeared to be dose related. Deprivation of drinking water 24 hr before the administration of glycerol potentiated the renal damage. In uranyl nitrate-induced renal failure, the decline of the net tubular secretion for TEAB and PAH was not proportional to the decrease in GFR; the secretion process deteriorated faster than the GFR. For example, when 0.5 mg/kg uranyl nitrate was administered, GFR fell to approximately 65% of normal, whereas the net tubular secretion was decreased to 30% of normal. These results suggest that the tubular transport was preferentially affected by uranyl nitrate. In contrast, in glycerol-induced renal failure, the decline of TEAB secretion fell in a parallel fashion with the GFR, suggesting that the glomeruli and the proximal tubules were equally damaged by glycerol. However, in this latter model, the decline of PAH secretion did not parallel the decrease in GFR, contradicting the proposal that glycerol affects equally the glomeruli and the proximal tubules. This discrepancy may be due to the selective competitive inhibition of PAH secretion by the accumulation of naturally occurring organic acids

Effects of altered platelet number on pulmonary hypertension and platelet sequestration in monocrotaline pyrrole-treated rats

International Nuclear Information System (INIS)

White, S.M.; Wagner, J.G.; Roth, R.A.

1989-01-01

To study the role of platelets in monocrotaline pyrrole (MCTP)-induced pulmonary hypertension, pulmonary sequestration of 111In-labeled platelets in rats treated with MCTP and anti-rat platelet serum (PAS) was examined. Lung injury from a single, intravenous injection of MCTP (3.5 mg/kg) at Day 8 was evident as elevated lung weight and lavage fluid protein and lactate dehydrogenase activity. Additionally, right ventricular hypertrophy and elevated pulmonary arterial pressures (PAP) occurred. Treatment with PAS on Days 6-8 did not affect the lung injury but resulted in an attenuation of the pulmonary hypertensive response. Pulmonary platelet sequestration was also decreased in PAS-treated rats, yet the sequestration in the lungs of MCTP-treated rats that received PAS was significantly higher than that in the lungs of N,N-dimethylformamide (DMF) controls. MCTP-treated rats receiving control serum (CS) tended to sequester more 111In-labeled platelets than respective DMF controls, but this was not statistically significant. Blood platelet half-life was unaltered in rats receiving CS. When rats were treated similarly with MCTP and PAS and were killed at 18 days, the attenuation of the pulmonary hypertensive response previously described was not observed, and lung injury was more extensive than when CS was given. Apparently, platelet depletion delayed the development of the pulmonary hypertensive response. Supranormal platelet numbers produced by splenectomy did not affect MCTP-induced lung injury or the elevation in PAP. These results support the hypothesis that the development of MCTP-induced pulmonary hypertension is mediated in part by platelets

The Chemical Chaperone Phenylbutyrate Rescues MCT8 Mutations Associated With Milder Phenotypes in Patients With Allan-Herndon-Dudley Syndrome.

Science.gov (United States)

Braun, Doreen; Schweizer, Ulrich

2017-03-01

Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) prevent appropriate entry of thyroid hormones into brain cells during development and cause severe mental retardation in affected patients. The current treatment options are thyromimetic compounds that enter the brain independently of MCT8. Some MCT8-deficient patients (e.g., those carrying MCT8delF501) will not be as severely affected as most others. We have shown that the MCT8delF501 protein has decreased protein stability but important residual function once it reaches the plasma membrane. We were able to rescue protein expression and the function of MCT8delF501 in a Madin-Darby canine kidney cell model by application of the chemical chaperone sodium phenylbutyrate (NaPB), a drug that has been used to treat patients with cystic fibrosis and urea cycle defects for extended periods of time. In the present study, we have extended our previous study and report on the NaPB-dependent rescue of a series of other pathogenic MCT8 mutants associated with milder patient phenotypes. We show that NaPB can functionally rescue the expression and activities of Ser194Phe, Ser290Phe, Leu434Trp, Arg445Cys, Leu492Pro, and Leu568Pro mutations in MCT8 in a dose-dependent manner. The soy isoflavone genistein, a dietary supplement, which was effective in MCT8delF501, was also effective in increasing the expression and transport of these MCT8 mutants; however, the effect size differed among mutants. Kinetic analyses revealed that the Michaelis constants of the mutants toward the primary substrate 3,3',5-triiodothyronine were not much different from the wild-type value, suggesting that these mutants are not impaired in their interaction with substrate but rather destabilized by the mutation and degraded. Copyright © 2017 by the Endocrine Society.

A PAH growth mechanism and synergistic effect on PAH formation in counterflow diffusion flames

KAUST Repository

Wang, Yu

2013-09-01

A reaction mechanism having molecular growth up to benzene for hydrocarbon fuels with up to four carbon-atoms was extended to include the formation and growth of polycyclic aromatic hydrocarbons (PAHs) up to coronene (C24H12). The new mechanism was tested for ethylene premixed flames at low (20torr) and atmospheric pressures by comparing experimentally observed species concentrations with those of the computed ones for small chemical species and PAHs. As compared to several existing mechanisms in the literature, the newly developed mechanism showed an appreciable improvement in the predicted profiles of PAHs. The new mechanism was also used to simulate PAH formation in counterflow diffusion flames of ethylene to study the effects of mixing propane and benzene in the fuel stream. In the ethylene-propane flames, existing experimental results showed a synergistic effect in PAH concentrations, i.e. PAH concentrations first increased and then decreased with increasing propane mixing. This PAH behavior was successfully captured by the new mechanism. The synergistic effect was predicted to be more pronounced for larger PAH molecules as compared to the smaller ones, which is in agreement with experimental observations. In the experimental study in which the fuel stream of ethylene-propane flames was doped with benzene, a synergistic effect was mitigated for benzene, but was observed for large PAHs. This effect was also predicted in the computed PAH profiles for these flames. To explain these responses of PAHs in the flames of mixture fuels, a pathway analysis has been conducted, which show that several resonantly stabilized species as well as C4H4 and H atom contribute to the enhanced synergistic behaviors of larger PAHs as compared to the small ones in the flames of mixture fuels. © 2013 The Combustion Institute.

Chemical and bioanalytical characterisation of PAHs in risk assessment of remediated PAH-contaminated soils.

Science.gov (United States)

Larsson, Maria; Hagberg, Jessika; Rotander, Anna; van Bavel, Bert; Engwall, Magnus

2013-12-01

Polycyclic aromatic hydrocarbons (PAHs) are common contaminants in soil at former industrial areas; and in Sweden, some of the most contaminated sites are being remediated. Generic guideline values for soil use after so-called successful remediation actions of PAH-contaminated soil are based on the 16 EPA priority pollutants, which only constitute a small part of the complex cocktail of toxicants in many contaminated soils. The aim of the study was to elucidate if the actual toxicological risks of soil samples from successful remediation projects could be reflected by chemical determination of these PAHs. We compared chemical analysis (GC-MS) and bioassay analysis (H4IIE-luc) of a number of remediated PAH-contaminated soils. The H4IIE-luc bioassay is an aryl hydrocarbon (Ah) receptor-based assay that detects compounds that activate the Ah receptor, one important mechanism for PAH toxicity. Comparison of the results showed that the bioassay-determined toxicity in the remediated soil samples could only be explained to a minor extent by the concentrations of the 16 priority PAHs. The current risk assessment method for PAH-contaminated soil in use in Sweden along with other countries, based on chemical analysis of selected PAHs, is missing toxicologically relevant PAHs and other similar substances. It is therefore reasonable to include bioassays in risk assessment and in the classification of remediated PAH-contaminated soils. This could minimise environmental and human health risks and enable greater safety in subsequent reuse of remediated soils.

MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma.

Science.gov (United States)

Fisel, Pascale; Stühler, Viktoria; Bedke, Jens; Winter, Stefan; Rausch, Steffen; Hennenlotter, Jörg; Nies, Anne T; Stenzl, Arnulf; Scharpf, Marcus; Fend, Falko; Kruck, Stephan; Schwab, Matthias; Schaeffeler, Elke

2015-10-13

Cluster of differentiation 147 (CD147/BSG) is a transmembrane glycoprotein mediating oncogenic processes partly through its role as binding partner for monocarboxylate transporter MCT4/SLC16A3. As demonstrated for MCT4, CD147 is proposed to be associated with progression in clear cell renal cell carcinoma (ccRCC). In this study, we evaluated the prognostic relevance of CD147 in comparison to MCT4/SLC16A3 expression and DNA methylation. CD147 protein expression was assessed in two independent ccRCC-cohorts (n = 186, n = 59) by immunohistochemical staining of tissue microarrays and subsequent manual as well as automated software-supported scoring (Tissue Studio, Definien sAG). Epigenetic regulation of CD147 was investigated using RNAseq and DNA methylation data of The Cancer Genome Atlas. These results were validated in our cohort. Relevance of prognostic models for cancer-specific survival, comprising CD147 and MCT4 expression or SLC16A3 DNA methylation, was compared using chi-square statistics. CD147 protein expression generated with Tissue Studio correlated significantly with those from manual scoring (P CD147 in ccRCC. Association of CD147 expression with patient outcome differed between cohorts. DNA methylation in the CD147/BSG promoter was not associated with expression. Comparison of prognostic relevance of CD147/BSG and MCT4/SLC16A3, showed higher significance for MCT4 expression and superior prognostic power for DNA methylation at specific CpG-sites in the SLC16A3 promoter (e.g. CD147 protein: P = 0.7780,Harrell's c-index = 53.7% vs. DNA methylation: P = 0.0076, Harrell's c-index = 80.0%). Prognostic significance of CD147 protein expression could not surpass that of MCT4, especially of SLC16A3 DNA methylation, corroborating the role of MCT4 as prognostic biomarker for ccRCC.

Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.

Science.gov (United States)

Geng, Shanshan; Zhu, Weiwei; Xie, Chunfeng; Li, Xiaoting; Wu, Jieshu; Liang, Zhaofeng; Xie, Wei; Zhu, Jianyun; Huang, Cong; Zhu, Mingming; Wu, Rui; Zhong, Caiyun

2016-04-01

The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice. Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF-MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis. Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK. Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

Using deuterated PAH amendments to validate chemical extraction methods to predict PAH bioavailability in soils

International Nuclear Information System (INIS)

Gomez-Eyles, Jose L.; Collins, Chris D.; Hodson, Mark E.

2011-01-01

Validating chemical methods to predict bioavailable fractions of polycyclic aromatic hydrocarbons (PAHs) by comparison with accumulation bioassays is problematic. Concentrations accumulated in soil organisms not only depend on the bioavailable fraction but also on contaminant properties. A historically contaminated soil was freshly spiked with deuterated PAHs (dPAHs). dPAHs have a similar fate to their respective undeuterated analogues, so chemical methods that give good indications of bioavailability should extract the fresh more readily available dPAHs and historic more recalcitrant PAHs in similar proportions to those in which they are accumulated in the tissues of test organisms. Cyclodextrin and butanol extractions predicted the bioavailable fraction for earthworms (Eisenia fetida) and plants (Lolium multiflorum) better than the exhaustive extraction. The PAHs accumulated by earthworms had a larger dPAH:PAH ratio than that predicted by chemical methods. The isotope ratio method described here provides an effective way of evaluating other chemical methods to predict bioavailability. - Research highlights: → Isotope ratios can be used to evaluate chemical methods to predict bioavailability. → Chemical methods predicted bioavailability better than exhaustive extractions. → Bioavailability to earthworms was still far from that predicted by chemical methods. - A novel method using isotope ratios to assess the ability of chemical methods to predict PAH bioavailability to soil biota.

Using deuterated PAH amendments to validate chemical extraction methods to predict PAH bioavailability in soils

Energy Technology Data Exchange (ETDEWEB)

Gomez-Eyles, Jose L., E-mail: j.l.gomezeyles@reading.ac.uk [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom); Collins, Chris D.; Hodson, Mark E. [University of Reading, School of Human and Environmental Sciences, Soil Research Centre, Reading, RG6 6DW Berkshire (United Kingdom)

2011-04-15

Validating chemical methods to predict bioavailable fractions of polycyclic aromatic hydrocarbons (PAHs) by comparison with accumulation bioassays is problematic. Concentrations accumulated in soil organisms not only depend on the bioavailable fraction but also on contaminant properties. A historically contaminated soil was freshly spiked with deuterated PAHs (dPAHs). dPAHs have a similar fate to their respective undeuterated analogues, so chemical methods that give good indications of bioavailability should extract the fresh more readily available dPAHs and historic more recalcitrant PAHs in similar proportions to those in which they are accumulated in the tissues of test organisms. Cyclodextrin and butanol extractions predicted the bioavailable fraction for earthworms (Eisenia fetida) and plants (Lolium multiflorum) better than the exhaustive extraction. The PAHs accumulated by earthworms had a larger dPAH:PAH ratio than that predicted by chemical methods. The isotope ratio method described here provides an effective way of evaluating other chemical methods to predict bioavailability. - Research highlights: > Isotope ratios can be used to evaluate chemical methods to predict bioavailability. > Chemical methods predicted bioavailability better than exhaustive extractions. > Bioavailability to earthworms was still far from that predicted by chemical methods. - A novel method using isotope ratios to assess the ability of chemical methods to predict PAH bioavailability to soil biota.

Migration of polycyclic aromatic hydrocarbons (PAHs) in urban treatment sludge to the air during PAH removal applications.

Science.gov (United States)

Karaca, Gizem; Cindoruk, S Siddik; Tasdemir, Yücel

2014-05-01

In the present study, the amounts of polycylic aromatic hydrocarbons (PAHs) penetrating into air during PAH removal applications from the urban treatment sludge were investigated. The effects of the temperature, photocatalyst type, and dose on the PAH removal efficiencies and PAH evaporation were explained. The sludge samples were taken from an urban wastewater treatment plant located in the city of Bursa, with 585,000 equivalent population. The ultraviolet C (UV-C) light of 254 nm wavelength was used within the UV applications performed on a specially designed setup. Internal air of the setup was vacuumed through polyurethane foam (PUF) columns in order to collect the evaporated PAHs from the sludge during the PAH removal applications. All experiments were performed with three repetitions. The PAH concentrations were measured by gas chromatography-mass spectrometry (GC-MS). It was observed that the amounts of PAHs penetrating into the air were increased with increase of temperature, and more than 80% of PAHs migrated to the air consisted of 3-ring compounds during the UV and UV-diethylamine (DEA) experiments at 38 and 53 degrees C. It was determined that 40% decrease was ensured in sigma12 (total of 12) PAH amounts with UV application and 13% of PAHs in sludge penetrated into the air. In the UV-TiO2 applications, a maximum 80% of sigma12 PAH removal was obtained by adding 0.5% TiO2 of dry weight of sludge. The quantity of PAH penetrating into air did not exceed 15%. UV-TiO2 applications ensured high levels of PAH removal in the sludge and also reduced the quantity of PAH penetrating into the air. Within the scope of the samples added with DEA, there was no increase in PAH removal efficiencies and the penetration of PAHs into air was not decreased. In light of these data, it was concluded that UV-TiO2 application is the most suitable PAH removal alternative that restricts the convection of PAH pollution.

Interstellar dehydrogenated PAH anions: vibrational spectra

Science.gov (United States)

Buragohain, Mridusmita; Pathak, Amit; Sarre, Peter; Gour, Nand Kishor

2018-03-01

Interstellar polycyclic aromatic hydrocarbon (PAH) molecules exist in diverse forms depending on the local physical environment. Formation of ionized PAHs (anions and cations) is favourable in the extreme conditions of the interstellar medium (ISM). Besides in their pure form, PAHs are also likely to exist in substituted forms; for example, PAHs with functional groups, dehydrogenated PAHs etc. A dehydrogenated PAH molecule might subsequently form fullerenes in the ISM as a result of ongoing chemical processes. This work presents a density functional theory (DFT) calculation on dehydrogenated PAH anions to explore the infrared emission spectra of these molecules and discuss any possible contribution towards observed IR features in the ISM. The results suggest that dehydrogenated PAH anions might be significantly contributing to the 3.3 μm region. Spectroscopic features unique to dehydrogenated PAH anions are highlighted that may be used for their possible identification in the ISM. A comparison has also been made to see the size effect on spectra of these PAHs.

Butyrate activates the monocarboxylate transporter MCT4 expression in breast cancer cells and enhances the antitumor activity of 3-bromopyruvate.

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Queirós, Odília; Preto, Ana; Pacheco, António; Pinheiro, Céline; Azevedo-Silva, João; Moreira, Roxana; Pedro, Madalena; Ko, Young H; Pedersen, Peter L; Baltazar, Fátima; Casal, Margarida

2012-02-01

Most malignant tumors exhibit the Warburg effect, which consists in increased glycolysis rates with production of lactate, even in the presence of oxygen. Monocarboxylate transporters (MCTs), maintain these glycolytic rates, by mediating the influx and/or efflux of lactate and are overexpressed in several cancer cell types. The lactate and pyruvate analogue 3-bromopyruvate (3-BP) is an inhibitor of the energy metabolism, which has been proposed as a specific antitumor agent. In the present study, we aimed at determining the effect of 3-BP in breast cancer cells and evaluated the putative role of MCTs on this effect. Our results showed that the three breast cancer cell lines used presented different sensitivities to 3-BP: ZR-75-1 ER (+)>MCF-7 ER (+)>SK-BR-3 ER (-). We also demonstrated that 3-BP reduced lactate production, induced cell morphological alterations and increased apoptosis. The effect of 3-BP appears to be cytotoxic rather than cytostatic, as a continued decrease in cell viability was observed after removal of 3-BP. We showed that pre-incubation with butyrate enhanced significantly 3-BP cytotoxicity, especially in the most resistant breast cancer cell line, SK-BR-3. We observed that butyrate treatment induced localization of MCT1 in the plasma membrane as well as overexpression of MCT4 and its chaperone CD147. Our results thus indicate that butyrate pre-treatment potentiates the effect of 3-BP, most probably by increasing the rates of 3-BP transport through MCT1/4. This study supports the potential use of butyrate as adjuvant of 3-BP in the treatment of breast cancer resistant cells, namely ER (-).

Phosphorylation of MCT-1 by p44/42 MAPK is required for its stabilization in response to DNA damage

DEFF Research Database (Denmark)

Nandi, S; Reinert, Line; Hachem, A

2007-01-01

We discovered a novel oncogene in a T-cell lymphoma cell line, multiple copies in T-cell lymphoma-1 (MCT-1), that has been shown to decrease cell-doubling time, shorten the duration of G(1) transit time and/or G(1)-S transition, and transform NIH3T3 fibroblasts. We subsequently demonstrated...... that there were significantly increased levels of MCT-1 protein in a subset of primary diffuse large B-cell lymphomas. Levels of MCT-1 protein were shown to be increased after exposure to DNA damaging agents. This increase did not require new protein synthesis, suggesting that post-translational mechanisms were...... growth and proliferation through phosphorylation-dependent regulation of several substrates. The MCT-1 protein is predicted to have numerous putative phosphorylation sites. Using a combination of genetic and pharmacological approaches, we established that phosphorylation of MCT-1 protein by p44/p42...

Influence of PAHs among other coastal environmental variables on total and PAH-degrading bacterial communities.

Science.gov (United States)

Sauret, Caroline; Tedetti, Marc; Guigue, Catherine; Dumas, Chloé; Lami, Raphaël; Pujo-Pay, Mireille; Conan, Pascal; Goutx, Madeleine; Ghiglione, Jean-François

2016-03-01

We evaluated the relative impact of anthropogenic polycyclic aromatic hydrocarbons (PAHs) among biogeochemical variables on total, metabolically active, and PAH bacterial communities in summer and winter in surface microlayer (SML) and subsurface seawaters (SSW) across short transects along the NW Mediterranean coast from three harbors, one wastewater effluent, and one nearshore observatory reference site. At both seasons, significant correlations were found between dissolved total PAH concentrations and PAH-degrading bacteria that formed a gradient from the shore to nearshore waters. Accumulation of PAH degraders was particularly high in the SML, where PAHs accumulated. Harbors and wastewater outfalls influenced drastically and in a different way the total and active bacterial community structure, but they only impacted the communities from the nearshore zone (PAH concentrations on the spatial and temporal dynamic of total and active communities in this area, but this effect was putted in perspective by the importance of other biogeochemical variables.

Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation.

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Christine M Armour

Full Text Available Mutations in the thyroid hormone (TH transporter MCT8 have been identified as the cause for Allan-Herndon-Dudley Syndrome (AHDS, characterized by severe psychomotor retardation and altered TH serum levels. Here we report a novel MCT8 mutation identified in 4 generations of one family, and its functional characterization.Proband and family members were screened for 60 genes involved in X-linked cognitive impairment and the MCT8 mutation was confirmed. Functional consequences of MCT8 mutations were studied by analysis of [125I]TH transport in fibroblasts and transiently transfected JEG3 and COS1 cells, and by subcellular localization of the transporter.The proband and a male cousin demonstrated clinical findings characteristic of AHDS. Serum analysis showed high T3, low rT3, and normal T4 and TSH levels in the proband. A MCT8 mutation (c.869C>T; p.S290F was identified in the proband, his cousin, and several female carriers. Functional analysis of the S290F mutant showed decreased TH transport, metabolism and protein expression in the three cell types, whereas the S290A mutation had no effect. Interestingly, both uptake and efflux of T3 and T4 was impaired in fibroblasts of the proband, compared to his healthy brother. However, no effect of the S290F mutation was observed on TH efflux from COS1 and JEG3 cells. Immunocytochemistry showed plasma membrane localization of wild-type MCT8 and the S290A and S290F mutants in JEG3 cells.We describe a novel MCT8 mutation (S290F in 4 generations of a family with Allan-Herndon-Dudley Syndrome. Functional analysis demonstrates loss-of-function of the MCT8 transporter. Furthermore, our results indicate that the function of the S290F mutant is dependent on cell context. Comparison of the S290F and S290A mutants indicates that it is not the loss of Ser but its substitution with Phe, which leads to S290F dysfunction.

Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation.

Science.gov (United States)

Armour, Christine M; Kersseboom, Simone; Yoon, Grace; Visser, Theo J

2015-01-01

Mutations in the thyroid hormone (TH) transporter MCT8 have been identified as the cause for Allan-Herndon-Dudley Syndrome (AHDS), characterized by severe psychomotor retardation and altered TH serum levels. Here we report a novel MCT8 mutation identified in 4 generations of one family, and its functional characterization. Proband and family members were screened for 60 genes involved in X-linked cognitive impairment and the MCT8 mutation was confirmed. Functional consequences of MCT8 mutations were studied by analysis of [125I]TH transport in fibroblasts and transiently transfected JEG3 and COS1 cells, and by subcellular localization of the transporter. The proband and a male cousin demonstrated clinical findings characteristic of AHDS. Serum analysis showed high T3, low rT3, and normal T4 and TSH levels in the proband. A MCT8 mutation (c.869C>T; p.S290F) was identified in the proband, his cousin, and several female carriers. Functional analysis of the S290F mutant showed decreased TH transport, metabolism and protein expression in the three cell types, whereas the S290A mutation had no effect. Interestingly, both uptake and efflux of T3 and T4 was impaired in fibroblasts of the proband, compared to his healthy brother. However, no effect of the S290F mutation was observed on TH efflux from COS1 and JEG3 cells. Immunocytochemistry showed plasma membrane localization of wild-type MCT8 and the S290A and S290F mutants in JEG3 cells. We describe a novel MCT8 mutation (S290F) in 4 generations of a family with Allan-Herndon-Dudley Syndrome. Functional analysis demonstrates loss-of-function of the MCT8 transporter. Furthermore, our results indicate that the function of the S290F mutant is dependent on cell context. Comparison of the S290F and S290A mutants indicates that it is not the loss of Ser but its substitution with Phe, which leads to S290F dysfunction.

Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity.

Science.gov (United States)

Eichner, Ruth; Heider, Michael; Fernández-Sáiz, Vanesa; van Bebber, Frauke; Garz, Anne-Kathrin; Lemeer, Simone; Rudelius, Martina; Targosz, Bianca-Sabrina; Jacobs, Laura; Knorn, Anna-Maria; Slawska, Jolanta; Platzbecker, Uwe; Germing, Ulrich; Langer, Christian; Knop, Stefan; Einsele, Herrmann; Peschel, Christian; Haass, Christian; Keller, Ulrich; Schmid, Bettina; Götze, Katharina S; Kuster, Bernhard; Bassermann, Florian

2016-07-01

Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin ligase complex, is the primary target by which IMiDs mediate anticancer and teratogenic effects. Here we identify a ubiquitin-independent physiological chaperone-like function of CRBN that promotes maturation of the basigin (BSG; also known as CD147) and solute carrier family 16 member 1 (SLC16A1; also known as MCT1) proteins. This process allows for the formation and activation of the CD147-MCT1 transmembrane complex, which promotes various biological functions, including angiogenesis, proliferation, invasion and lactate export. We found that IMiDs outcompete CRBN for binding to CD147 and MCT1, leading to destabilization of the CD147-MCT1 complex. Accordingly, IMiD-sensitive MM cells lose CD147 and MCT1 expression after being exposed to IMiDs, whereas IMiD-resistant cells retain their expression. Furthermore, del(5q) MDS cells have elevated CD147 expression, which is attenuated after IMiD treatment. Finally, we show that BSG (CD147) knockdown phenocopies the teratogenic effects of thalidomide exposure in zebrafish. These findings provide a common mechanistic framework to explain both the teratogenic and pleiotropic antitumor effects of IMiDs.

Peptide-micelle hybrids containing fasudil for targeted delivery to the pulmonary arteries and arterioles to treat pulmonary arterial hypertension.

Science.gov (United States)

Gupta, Nilesh; Ibrahim, Hany M; Ahsan, Fakhrul

2014-11-01

This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell-penetrating and lung-homing peptide, conjugated polyethylene glycol-distearoyl-phosphoethanolamine micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline-induced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14 nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7-fold and extended the drug half-life by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Ca2+ promoted the low transformation efficiency of plasmid DNA exposed to PAH contaminants.

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Fuxing Kang

Full Text Available The effects of interactions between genetic materials and polycyclic aromatic hydrocarbons (PAHs on gene expression in the extracellular environment remain to be elucidated and little information is currently available on the effect of ionic strength on the transformation of plasmid DNA exposed to PAHs. Phenanthrene and pyrene were used as representative PAHs to evaluate the transformation of plasmid DNA after PAH exposure and to determine the role of Ca(2+ during the transformation. Plasmid DNA exposed to the test PAHs demonstrated low transformation efficiency. In the absence of PAHs, the transformation efficiency was 4.7 log units; however, the efficiency decreased to 3.72-3.14 log units with phenanthrene/pyrene exposures of 50 µg · L(-1. The addition of Ca(2+ enhanced the low transformation efficiency of DNA exposed to PAHs. Based on the co-sorption of Ca(2+ and phenanthrene/pyrene by DNA, we employed Fourier-transform infrared spectroscopy (FTIR, X-ray photoelectron spectroscopy (XPS, and mass spectrometry (MS to determine the mechanisms involved in PAH-induced DNA transformation. The observed low transformation efficiency of DNA exposed to either phenanthrene or pyrene can be attributed to a broken hydrogen bond in the double helix caused by planar PAHs. Added Ca(2+ formed strong electrovalent bonds with "-POO(--" groups in the DNA, weakening the interaction between PAHs and DNA based on weak molecular forces. This decreased the damage of PAHs to hydrogen bonds in double-stranded DNA by isolating DNA molecules from PAHs and consequently enhanced the transformation efficiency of DNA exposed to PAH contaminants. The findings provide insight into the effects of anthropogenic trace PAHs on DNA transfer in natural environments.

Reliability studies of high operating temperature MCT photoconductor detectors

Science.gov (United States)

Wang, Wei; Xu, Jintong; Zhang, Yan; Li, Xiangyang

2010-10-01

This paper concerns HgCdTe (MCT) infrared photoconductor detectors with high operating temperature. The near room temperature operation of detectors have advantages of light weight, less cost and convenient usage. Their performances are modest and they suffer from reliable problems. These detectors face with stability of the package, chip bonding area and passivation layers. It's important to evaluate and improve the reliability of such detectors. Defective detectors were studied with SEM(Scanning electron microscope) and microscopy. Statistically significant differences were observed between the influence of operating temperature and the influence of humidity. It was also found that humility has statistically significant influence upon the stability of the chip bonding and passivation layers, and the amount of humility isn't strongly correlated to the damage on the surface. Considering about the commonly found failures modes in detectors, special test structures were designed to improve the reliability of detectors. An accelerated life test was also implemented to estimate the lifetime of the high operating temperature MCT photoconductor detectors.

Development and performance of a new version of the OASIS coupler, OASIS3-MCT_3.0

Science.gov (United States)

Craig, Anthony; Valcke, Sophie; Coquart, Laure

2017-09-01

OASIS is coupling software developed primarily for use in the climate community. It provides the ability to couple different models with low implementation and performance overhead. OASIS3-MCT is the latest version of OASIS. It includes several improvements compared to OASIS3, including elimination of a separate hub coupler process, parallelization of the coupling communication and run-time grid interpolation, and the ability to easily reuse mapping weight files. OASIS3-MCT_3.0 is the latest release and includes the ability to couple between components running sequentially on the same set of tasks as well as to couple within a single component between different grids or decompositions such as physics, dynamics, and I/O. OASIS3-MCT has been tested with different configurations on up to 32 000 processes, with components running on high-resolution grids with up to 1.5 million grid cells, and with over 10 000 2-D coupling fields. Several new features will be available in OASIS3-MCT_4.0, and some of those are also described.

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

Science.gov (United States)

Birsoy, Kivanc; Wang, Tim; Possemato, Richard; Yilmaz, Omer H.; Koch, Catherine E.; Chen, Walter W.; Hutchins, Amanda W.; Gultekin, Yetis; Peterson, Tim R.; Carette, Jan E.; Brummelkamp, Thijn R.; Clish, Clary B.; Sabatini, David M.

2012-01-01

SUMMARY There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anti-cancer therapy are underway. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, MCT1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Lastly, forced MCT1 expression in 3-BrPA resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors. PMID:23202129

Development and performance of a new version of the OASIS coupler, OASIS3-MCT_3.0

Directory of Open Access Journals (Sweden)

A. Craig

2017-09-01

Full Text Available OASIS is coupling software developed primarily for use in the climate community. It provides the ability to couple different models with low implementation and performance overhead. OASIS3-MCT is the latest version of OASIS. It includes several improvements compared to OASIS3, including elimination of a separate hub coupler process, parallelization of the coupling communication and run-time grid interpolation, and the ability to easily reuse mapping weight files. OASIS3-MCT_3.0 is the latest release and includes the ability to couple between components running sequentially on the same set of tasks as well as to couple within a single component between different grids or decompositions such as physics, dynamics, and I/O. OASIS3-MCT has been tested with different configurations on up to 32 000 processes, with components running on high-resolution grids with up to 1.5 million grid cells, and with over 10 000 2-D coupling fields. Several new features will be available in OASIS3-MCT_4.0, and some of those are also described.

Molecular dynamics simulation and TDDFT study of the structures and UV-vis absorption spectra of MCT-β-CD and its inclusion complexes.

Science.gov (United States)

Lu, Huijuan; Wang, Yujiao; Xie, Xiaomei; Chen, Feifei; Li, Wei

2015-01-01

In this research, the inclusion ratios and inclusion constants of MCT-β-CD/PERM and MCT-β-CD/CYPERM inclusion complexes were measured by UV-vis and fluorescence spectroscopy. The inclusion ratios are both 1:1, and the inclusion constants are 60 and 342.5 for MCT-β-CD/PERM and MCT-β-CD/CYPERM, respectively. The stabilities of inclusion complexes were investigated by MD simulation. MD shows that VDW energy plays a vital role in the stability of inclusion complex, and the destruction of inclusion complex is due to the increasing temperature. The UV-vis absorption spectra of MCT-β-CD and its inclusion complexes were studied by time-dependent density functional theory (TDDFT) method employing BLYP-D3, B3LYP-D3 and M06-2X-D3 functionals. BLYP-D3 well reproduces the UV-vis absorption spectrum and reveals that the absorption bands of MCT-β-CD mainly arise from n→π(∗) and n→σ(∗) transition, and those of inclusion complexes mainly arise from intramolecular charge transfer (ICT). ICT results in the shift of main absorption bands of MCT-β-CD. Copyright © 2015 Elsevier B.V. All rights reserved.

Kandungan Senyawa Polisiklik Aromatik Hidrokarbon (PAH di Teluk Jakarta (Polycyclic Aromatic Compounds Hydrocarbons (PAH Content in Jakarta Bay

Directory of Open Access Journals (Sweden)

Fasmi Ahmad

2013-07-01

Full Text Available Perairan Teluk Jakarta menerima limbah yang berasal dari darat maupun perairan itu sendiri. Salah satu limbah tersebut adalah senyawa organik Polisiklik Aromatik Hidrokarbon (PAH yang merupakan senyawa organik bersifat toksik terhadap biota laut. Penelitian dilakukan untuk mengetahui kandungan PAH air laut dan sedimen dalam kaitannya dengan kehidupan biota laut serta mengetahui sumber senyawa tersebut. Pengukuran dilakukan bulan Maret 2011. Contoh air laut diambil dengan water sampler dan contoh sedimen dengan grab pada 15 stasiun. Kadar PAH dianalisa dengan Gas Chromatography-Flame Ionization Detector. Hasil penelitian menunjukkan kadar PAH air laut di Teluk Jakarta Bagian Barat > Bagian Tengah > Bagian Timur. Kandungan PAH di Teluk Jakarta Bagian Barat berkisar 201,57-474,68 ppb dengan total PAH 1404,68 ppb, di Bagian Tengah 104,61-337,07 ppb dengan total 825,63 ppb, dan di Bagian Timur 112,91-370,79 ppb dengan total 806,73 ppb. Data ini menunjukkan Teluk Jakarta Bagian Barat lebih banyak menerima masukan limbah yang mengandung PAH. Sedangkan Kadar PAH sedimen di Teluk Jakarta Bagian Timur > Bagian Tengah > Bagian Barat. Kadar PAH di Teluk Jakarta Bagian Barat berkisar 1,92-64,241 ppm dengan total 107,931 ppm, di Bagian Tengah 16,14-77,71 ppm dengan total 170,61 ppm, dan di Bagian Timur 8,72-115,39 ppm dengan total 252,25 ppm. Data ini menunjukkan sedimen di Teluk Jakarta Bagian Timur lebih banyak mengakumulasi limbah yang mengandung PAH. Sumber PAH dalam air laut dan sedimen ini berasal dari berbagai sumber yakni pembakaran bahan organik, pembakaran minyak bumi, dan tumpahan minyak. Kadar PAH dalam air laut di Teluk Jakarta ini telah melebihi Nilai Ambang Batas yang ditetapkan oleh KMNLH untuk biota laut, dan Nilai Ambang Batas untuk sedimen yang ditetapkan oleh Handbook for Sediment Quality Assessment. Kata kunci: Teluk Jakarta, Polisiklik Aromatik Hidrokarbon, PAH, polusi Jakarta Bay receives various kinds of waste both from land and waters

Mitigation of PAH and nitro-PAH emissions from nonroad diesel engines.

Science.gov (United States)

Liu, Z Gerald; Wall, John C; Ottinger, Nathan A; McGuffin, Dana

2015-03-17

More stringent emission requirements for nonroad diesel engines introduced with U.S. Tier 4 Final and Euro Stage IV and V regulations have spurred the development of exhaust aftertreatment technologies. In this study, several aftertreatment configurations consisting of diesel oxidation catalysts (DOC), diesel particulate filters (DPF), Cu zeolite-, and vanadium-based selective catalytic reduction (SCR) catalysts, and ammonia oxidation (AMOX) catalysts are evaluated using both Nonroad Transient (NRTC) and Steady (8-mode NRSC) Cycles in order to understand both component and system-level effects of diesel aftertreatment on emissions of polycyclic aromatic hydrocarbons (PAH) and their nitrated derivatives (nitro-PAH). Emissions are reported for four configurations including engine-out, DOC+CuZ-SCR+AMOX, V-SCR+AMOX, and DOC+DPF+CuZ-SCR+AMOX. Mechanisms responsible for the reduction, and, in some cases, the formation of PAH and nitro-PAH compounds are discussed in detail, and suggestions are provided to minimize the formation of nitro-PAH compounds through aftertreatment design optimizations. Potency equivalency factors (PEFs) developed by the California Environmental Protection Agency are then applied to determine the impact of aftertreatment on PAH-derived exhaust toxicity. Finally, a comprehensive set of exhaust emissions including criteria pollutants, NO2, total hydrocarbons (THC), n-alkanes, branched alkanes, saturated cycloalkanes, aromatics, aldehydes, hopanes and steranes, and metals is provided, and the overall efficacy of the aftertreatment configurations is described. This detailed summary of emissions from a current nonroad diesel engine equipped with advanced aftertreatment can be used to more accurately model the impact of anthropogenic emissions on the atmosphere.

Hepatocellular integrity in patients requiring parenteral nutrition: comparison of structured MCT/LCT vs. a standard MCT/LCT emulsion and a LCT emulsion.

Science.gov (United States)

Piper, S N; Röhm, K D; Boldt, J; Odermatt, B; Maleck, W H; Suttner, S W

2008-07-01

The aetiology of parenteral nutrition-associated hepatic injury remains unresolved. The aim of the study was to evaluate the effects of structured triglycerides in parenteral nutrition compared either to a physical medium-chain triglycerides (MCT)/long-chain triglcerides (LCT) mixture or to a LCT emulsion on hepatic integrity. In a randomized, double-blinded trial, we studied 45 patients undergoing abdominal surgery, who were expected to receive parenteral nutrition for 5 days. Patients were allocated to one of three nutrition regimens: Group A (n = 15) received structured triglycerides, Group B (n = 15) a MCT/LCT and Group C (n = 15) a LCT lipid emulsion. Before the start of parenteral nutrition (T0), 24 h (T1), 48 h (T2), 72 h (T3) and 120 h (T4) after start of infusion the following parameters were measured: Alpha-glutathione S-transferase (alpha-GST), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose and serum triglycerides. At T3 and T4, alpha-GST levels were significantly higher in Group B (T3: 9.4 +/- 9.9; T4: 14.6 +/- 19.5 microg L-1) and Group C (T3: 14.2 +/- 20.8; T4: 22.4 +/- 39.3 microg L-1) compared with the patients receiving structured triglycerides (T3: 1.9 +/- 1.8; T4: 3.2 +/- 2.7 microg L-1). Whereas the mean alpha-GST-levels in structured triglycerides group always remained in the normal range, this was not the case in both other groups at T3 and T4. There were no significant differences concerning ALT, AST and glucose levels. At T3 and T4, triglyceride levels were significantly lower in Group A than in Groups B and C. Hepatic integrity was well retained with the administration of structured triglycerides, whereas both MCT/LCT emulsion and LCT emulsion caused subclinical hepatic injury.

Cerebral cortex hyperthyroidism of newborn Mct8-deficient mice transiently suppressed by Lat2 inactivation

OpenAIRE

Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M.; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during...

A study of DC-DC converters with MCT's for arcjet power supplies

Science.gov (United States)

Stuart, Thomas A.

1994-01-01

Many arcjet DC power supplies use PWM full bridge converters with large arrays of parallel FET's. This report investigates an alternative supply using a variable frequency series resonant converter with small arrays of parallel MCT's (metal oxide semiconductor controlled thyristors). The reasons for this approach are to: increase reliability by reducing the number of switching devices; and decrease the surface mounting area of the switching arrays. The variable frequency series resonant approach is used because the relatively slow switching speed of the MCT precludes the use of PWM. The 10 kW converter operated satisfactorily with an efficiency of over 91 percent. Test results indicate this efficiency could be increased further by additional optimization of the series resonant inductor.

Experimental increase in availability of a PAH complex organic contamination from an aged contaminated soil: Consequences on biodegradation

International Nuclear Information System (INIS)

Cébron, Aurélie; Faure, Pierre; Lorgeoux, Catherine; Ouvrard, Stéphanie; Leyval, Corinne

2013-01-01

Although high PAH content and detection of PAH-degraders, the PAH biodegradation is limited in aged-contaminated soils due to low PAH availability (i.e., 1%). Here, we tried to experimentally increase the soil PAH availability by keeping both soil properties and contamination composition. Organic extract was first removed and then re-incorporated in the raw soil as fresh contaminants. Though drastic, this procedure only allowed a 6-time increase in the PAH availability suggesting that the organic constituents more than ageing were responsible for low availability. In the re-contaminated soil, the mineralization rate was twice more important, the proportion of 5–6 cycles PAH was higher indicating a preferential degradation of lower molecular weight PAH. The extraction treatment induced bacterial and fungal community structures modifications, Pseudomonas and Fusarium solani species were favoured, and the relative quantity of fungi increased. In re-contaminated soil the percentage of PAH-dioxygenase gene increased, with 10 times more Gram negative representatives. -- Highlights: ► Re-incorporation of soil organic extract increased 6-times the PAH availability. ► Complexity of organic contamination is the main driver of PAH availability. ► Biodegradation of PAH with less than 5-cycles increased with increasing PAH availability. ► Pseudomonas and Fusarium species are favoured when PAH availability increased. -- More than ageing, the complexity of organic contamination is the main driver of PAH availability

THE INFRARED SPECTRA OF VERY LARGE IRREGULAR POLYCYCLIC AROMATIC HYDROCARBONS (PAHs): OBSERVATIONAL PROBES OF ASTRONOMICAL PAH GEOMETRY, SIZE, AND CHARGE

International Nuclear Information System (INIS)

Bauschlicher, Charles W.; Peeters, Els; Allamandola, Louis J.

2009-01-01

The mid-infrared (IR) spectra of six large, irregular polycyclic aromatic hydrocarbons (PAHs) with formulae (C 84 H 24 -C 120 H 36 ) have been computed using density functional theory (DFT). Trends in the dominant band positions and intensities are compared to those of large, compact PAHs as a function of geometry, size, and charge. Irregular edge moieties that are common in terrestrial PAHs, such as bay regions and rings with quartet hydrogens, are shown to be uncommon in astronomical PAHs. As for all PAHs comprised solely of C and H reported to date, mid-IR emission from irregular PAHs fails to produce a strong CC str band at 6.2 μm, the position characteristic of the important, class A astronomical PAH spectra. Earlier studies showed that inclusion of nitrogen within a PAH shifts this to 6.2 μm for PAH cations. Here we show that this band shifts to 6.3 μm in nitrogenated PAH anions, close to the position of the CC stretch in class B astronomical PAH spectra. Thus, nitrogenated PAHs may be important in all sources and the peak position of the CC stretch near 6.2 μm appears to directly reflect the PAH cation to anion ratio. Large irregular PAHs exhibit features at 7.8 μm but lack them near 8.6 μm. Hence, the 7.7 μm astronomical feature is produced by a mixture of small and large PAHs while the 8.6 μm band can only be produced by large compact PAHs. As with the CC str , the position and profile of these bands reflect the PAH cation to anion ratio.

Further insights into the allan-herndon-dudley syndrome: Clinical and functional characterization of a novel MCT8 mutation

NARCIS (Netherlands)

Armour, C.M. (Christine M.); S. Kersseboom (Simone); Yoon, G. (Grace); T.J. Visser (Theo)

2015-01-01

textabstractBackground. Mutations in the thyroid hormone (TH) transporter MCT8 have been identified as the cause for Allan-Herndon-Dudley Syndrome (AHDS), characterized by severe psychomotor retardation and altered TH serum levels. Here we report a novel MCT8 mutation identified in 4 generations of

Co-formation and co-release of genotoxic PAHs, alkyl-PAHs and soot nanoparticles from gasoline direct injection vehicles

Science.gov (United States)

Muñoz, Maria; Haag, Regula; Honegger, Peter; Zeyer, Kerstin; Mohn, Joachim; Comte, Pierre; Czerwinski, Jan; Heeb, Norbert V.

2018-04-01

describing the property of sub-200 nm particles being deposited in the alveoli transporting genotoxic compounds into the lung. These nanoparticles are persistent and may eventually penetrate the alveolar membrane reaching the blood circulation system. We showed that all GDI vehicles tested released large numbers of nanoparticles carrying substantial loads of genotoxic PAHs. If non-treated diesel exhaust is considered as class-1 carcinogen by the WHO inducing lung cancer in humans, these GDI vehicle exhausts may be a major health risk too for those exposed to them corroborating the progress achieved with current diesel vehicles, now equipped with efficient particle filters.

MR imaging of the pediatric spine: Comparison of myelography, MCT, and surgery

International Nuclear Information System (INIS)

Davis, P.C.; Hoffman, J.C.; Ball, T.I.; Wyly, J.B.; Braun, I.F.; Fry, S.M.

1986-01-01

Results of MR imaging of 53 pediatric patients with suspected spinal abnormalities were compared findings on metrizamide myelography, MCT, and surgery. Prototype surface coil studies with multisection multiplanar imaging (0.5 and 1.5 T) using T1-weighted sequences were optimum for anatomic definition, while T2-weighted sequences were utilized for intramedullary pathology. Diseases studied included neoplasia, infection, trauma, scoliosis, and dysrhaphsium. Surface coils were essential for imaging the thoracic and lumbar spine. MR imaging yielded approximately equivalent information to that obtained on myelography or MCT in 25 of 31 patients. Limitations to MR imaging included bony spurs, small eccentric lesions, tumor seeding, metal artifacts, postoperative scarring, and motion. With further refinements, MR imaging may replace more invasive techniques for pediatric spinal imaging

Distribution of polycyclic aromatic hydrocarbons (PAHs) in rivers and estuaries in Malaysia: a widespread input of petrogenic PAHs.

Science.gov (United States)

Zakaria, Mohamad Pauzi; Takada, Hideshige; Tsutsumi, Shinobu; Ohno, Kei; Yamada, Junya; Kouno, Eriko; Kumata, Hidetoshi

2002-05-01

This is the first publication on the distribution and sources of polycyclic aromatic hydrocarbons (PAHs) in riverine and coastal sediments in South East Asia where the rapid transfer of land-based pollutants into aquatic environments by heavy rainfall and runoff waters is of great concern. Twenty-nine Malaysian riverine and coastal sediments were analyzed for PAHs (3-7 rings) by gas chromatography mass spectrometry. Total PAHs concentrations in the sediment ranged from 4 to 924 ng/g. Alkylated homologues were abundant for all sediment samples. The ratio of the sum of methylphenanthrenes to phenanthrene (MP/P), an index of petrogenic PAHs contribution, was more than unity for 26 sediment samples and more than 3 for seven samples for urban rivers covering a broad range of locations. The MP/P ratio showed a strong correlation with the total PAHs concentrations, with an r2 value of 0.74. This ratio and all other compositional features indicated that Malaysian urban sediments are heavily impacted by petrogenic PAHs. This finding is in contrast to other studies reported in many industrialized countries where PAHs are mostly of pyrogenic origin. The MP/P ratio was also significantly correlated with higher molecular weight PAHs such as benzo[a]pyrene, suggesting unique PAHs source in Malaysia which contains both petrogenic PAHs and pyrogenic PAHs. PAHs and hopanes fingerprints indicated that used crankcase oil is one of the major contributors of the sedimentary PAHs. Two major routes of inputs to aquatic environments have been identified: (1) spillage and dumping of waste crankcase oil and (2) leakage of crankcase oils from vehicles onto road surfaces, with the subsequent washout by street runoff. N-Cyclohexyl-2-benzothiazolamine (NCBA), a molecular marker of street dust, was detected in the polluted sediments. NCBA and other biomarker profiles confirmed our hypothesis of the input from street dust contained the leaked crankcase oil. The fingerprints excluded crude oil

Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension

NARCIS (Netherlands)

Fowler, Ewan D.; Benoist, David; Drinkhill, Mark J.; Stones, Rachel; Helmes, Michiel; Wüst, Rob C. I.; Stienen, Ger J. M.; Steele, Derek S.; White, Ed

2015-01-01

Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control

Polycyclic Aromatic Hydrocarbon (PAH) and Oxygenated PAH (OPAH) Air–Water Exchange during the Deepwater Horizon Oil Spill

Science.gov (United States)

2015-01-01

Passive sampling devices were used to measure air vapor and water dissolved phase concentrations of 33 polycyclic aromatic hydrocarbons (PAHs) and 22 oxygenated PAHs (OPAHs) at four Gulf of Mexico coastal sites prior to, during, and after shoreline oiling from the Deepwater Horizon oil spill (DWH). Measurements were taken at each site over a 13 month period, and flux across the water–air boundary was determined. This is the first report of vapor phase and flux of both PAHs and OPAHs during the DWH. Vapor phase sum PAH and OPAH concentrations ranged between 1 and 24 ng/m3 and 0.3 and 27 ng/m3, respectively. PAH and OPAH concentrations in air exhibited different spatial and temporal trends than in water, and air–water flux of 13 individual PAHs were strongly associated with the DWH incident. The largest PAH volatilizations occurred at the sites in Alabama and Mississippi in the summer, each nominally 10 000 ng/m2/day. Acenaphthene was the PAH with the highest observed volatilization rate of 6800 ng/m2/day in September 2010. This work represents additional evidence of the DWH incident contributing to air contamination, and provides one of the first quantitative air–water chemical flux determinations with passive sampling technology. PMID:25412353

Polycyclic aromatic hydrocarbon (PAH) and oxygenated PAH (OPAH) air-water exchange during the deepwater horizon oil spill.

Science.gov (United States)

Tidwell, Lane G; Allan, Sarah E; O'Connell, Steven G; Hobbie, Kevin A; Smith, Brian W; Anderson, Kim A

2015-01-06

Passive sampling devices were used to measure air vapor and water dissolved phase concentrations of 33 polycyclic aromatic hydrocarbons (PAHs) and 22 oxygenated PAHs (OPAHs) at four Gulf of Mexico coastal sites prior to, during, and after shoreline oiling from the Deepwater Horizon oil spill (DWH). Measurements were taken at each site over a 13 month period, and flux across the water-air boundary was determined. This is the first report of vapor phase and flux of both PAHs and OPAHs during the DWH. Vapor phase sum PAH and OPAH concentrations ranged between 1 and 24 ng/m(3) and 0.3 and 27 ng/m(3), respectively. PAH and OPAH concentrations in air exhibited different spatial and temporal trends than in water, and air-water flux of 13 individual PAHs were strongly associated with the DWH incident. The largest PAH volatilizations occurred at the sites in Alabama and Mississippi in the summer, each nominally 10,000 ng/m(2)/day. Acenaphthene was the PAH with the highest observed volatilization rate of 6800 ng/m(2)/day in September 2010. This work represents additional evidence of the DWH incident contributing to air contamination, and provides one of the first quantitative air-water chemical flux determinations with passive sampling technology.

Occupational PAH Exposures during Prescribed Pile Burns

Science.gov (United States)

Robinson, M. S.; Anthony, T. R.; Littau, S. R.; Herckes, P.; Nelson, X.; Poplin, G. S.; Burgess, J. L.

2008-01-01

Wildland firefighters are exposed to particulate matter and gases containing polycyclic aromatic hydrocarbons (PAHs), many of which are known carcinogens. Our objective was to evaluate the extent of firefighter exposure to particulate and PAHs during prescribed pile burns of mainly ponderosa pine slash and determine whether these exposures were correlated with changes in urinary 1-hydroxypyrene (1-HP), a PAH metabolite. Personal and area sampling for particulate and PAH exposures were conducted on the White Mountain Apache Tribe reservation, working with 21 Bureau of Indian Affairs/Fort Apache Agency wildland firefighters during the fall of 2006. Urine samples were collected pre- and post-exposure and pulmonary function was measured. Personal PAH exposures were detectable for only 3 of 16 PAHs analyzed: naphthalene, phenanthrene, and fluorene, all of which were identified only in vapor-phase samples. Condensed-phase PAHs were detected in PM2.5 area samples (20 of 21 PAHs analyzed were detected, all but naphthalene) at concentrations below 1 μg m−3. The total PAH/PM2.5 mass fractions were roughly a factor of two higher during smoldering (1.06 ± 0.15) than ignition (0.55 ± 0.04 μg mg−1). There were no significant changes in urinary 1-HP or pulmonary function following exposure to pile burning. In summary, PAH exposures were low in pile burns, and urinary testing for a PAH metabolite failed to show a significant difference between baseline and post-exposure measurements. PMID:18515848

Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

Science.gov (United States)

Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

2014-12-01

In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

PAH effects on meio- and microbial benthic communities strongly depend on bioavailability.

Science.gov (United States)

Lindgren, J Fredrik; Hassellöv, Ida-Maja; Dahllöf, Ingela

2014-01-01

The effects of anthropogenic pollutants in dissimilar habitats can vary depending on differences in bioavailability. The factors determining bioavailability are not yet fully understood. This study was performed to evaluate whether analysis of total PAH concentrations in sediments is a satisfactory measurement to indicate environmental effects or if bioavailability is needed to be taken into account. We have here performed a 60-day experiment, where nominal PAH concentrations of 1,300 μg/kg sediment were added to three different marine sediments. Meiofaunal and microbial communities were analyzed for alterations in community response at 30 and 60 days. Results showed that bioavailability of PAHs varied between the three different sediments. Nonetheless, the petroleum addition gave rise to significant negative effects on all three sediments at both time points. The two direct measurements of toxicity on the microbial community, potential nitrification and denitrification, displayed a lower effect of the PAH addition in the muddy sediment at both time points, compared to the other two sediment types. No effects were seen in the analysis of meiofaunal community structure. Measurements of PAH bioavailability in the three sediment types concurred with the results from the microbial community, revealing a lower bioavailability in the muddy sediment compared to the other two sediment types, 34% compared to sandy and 18% compared to organic at day 0. At day 60 it was 61% lower compared to sandy and 20% lower compared to organic. The negative effects of the PAH addition on the microbial nitrogen cycle were in six out of eight cases best correlated to the amount of alkylated bioavailable PAH in the sediments, and thus microbial nitrogen cycle is a possible good indicator for assessing PAH-induced stress. The results presented here have implications for risk analysis studies of petroleum-contaminated marine sediments; consequently, sediment characteristics and its effects on

PAHs in Translucent Interstellar Clouds

Science.gov (United States)

Salama, Farid; Galazutdinov, G.; Krelowski, J.; Biennier, L.; Beletsky, Y.; Song, I.

2011-05-01

We discuss the proposal of relating the origin of some of the diffuse interstellar bands (DIBs) to neutral polycyclic aromatic hydrocarbons (PAHs) present in translucent interstellar clouds. The spectra of several cold, isolated gas-phase PAHs have been measured in the laboratory under experimental conditions that mimic the interstellar conditions and are compared with an extensive set of astronomical spectra of reddened, early type stars. This comparison provides - for the first time - accurate upper limits for the abundances of specific PAH molecules along specific lines-of-sight. Something that is not attainable from IR observations alone. The comparison of these unique laboratory data with high resolution, high S/N ratio astronomical observations leads to two major findings: (1) a finding specific to the individual molecules that were probed in this study and, which leads to the clear and unambiguous conclusion that the abundance of these specific neutral PAHs must be very low in the individual translucent interstellar clouds that were probed in this survey (PAH features remain below the level of detection) and, (2) a general finding that neutral PAHs exhibit intrinsic band profiles that are similar to the profile of the narrow DIBs indicating that the carriers of the narrow DIBs must have close molecular structure and characteristics. This study is the first quantitative survey of neutral PAHs in the optical range and it opens the way for unambiguous quantitative searches of PAHs in a variety of interstellar and circumstellar environments. // Reference: F. Salama et al. (2011) ApJ. 728 (1), 154 // Acknowledgements: F.S. acknowledges the support of the NASA's Space Mission Directorate APRA Program. J.K. acknowledges the financial support of the Polish State (grant N203 012 32/1550). The authors are deeply grateful to the ESO archive as well as to the ESO staff members for their active support.

Quantification of PAHs and oxy-PAHs on airborne particulate matter in Chiang Mai, Thailand, using gas chromatography high resolution mass spectrometry

Science.gov (United States)

Walgraeve, Christophe; Chantara, Somporn; Sopajaree, Khajornsak; De Wispelaere, Patrick; Demeestere, Kristof; Van Langenhove, Herman

2015-04-01

An analytical method using gas chromatography high resolution mass spectrometry was developed for the determination of 16 polycyclic aromatic hydrocarbons (PAHs) and 12 oxygenated PAHs (of which 4 diketones, 3 ketones, 4 aldehydes and one anhydride) on atmospheric particulate matter with an aerodynamic diameter less than 10 μm (PM10). The magnetic sector mass spectrometer was run in multiple ion detection mode (MID) with a mass resolution above 10 000 (10% valley definition) and allows for a selective accurate mass detection of the characteristic ions of the target analytes. Instrumental detection limits between 0.04 pg and 1.34 pg were obtained for the PAHs, whereas for the oxy-PAHs they ranged between 0.08 pg and 2.13 pg. Pressurized liquid extraction using dichloromethane was evaluated and excellent recoveries ranging between 87% and 98% for the PAHs and between 74% and 110% for 10 oxy-PAHs were obtained, when the optimum extraction temperature of 150 °C was applied. The developed method was finally used to determine PAHs and oxy-PAHs concentration levels from particulate matter samples collected in the wet season at 4 different locations in Chiang Mai, Thailand (n = 72). This study brings forward the first concentration levels of oxy-PAHs in Thailand. The median of the sum of the PAHs and oxy-PAHs concentrations was 3.4 ng/m3 and 1.1 ng/m3 respectively, which shows the importance of the group of the oxy-PAHs as PM10 constituents. High molecular weight PAHs contributed the most to the ∑PAHs. For example, benzo[ghi]perylene was responsible for 30-44% of the ∑PAHs. The highest contribution to ∑oxy-PAHs came from 1,8-napthalic anhydride (26-78%), followed by anthracene-9,10-dione (4-27%) and 7H-benzo[de]anthracene-7-one (6-26%). Indications of the degradation of PAHs and/or formation of oxy-PAHs were observed.

Resistance to diet-induced obesity and associated metabolic perturbations in haploinsufficient monocarboxylate transporter 1 mice.

OpenAIRE

Lengacher Sylvain; Nehiri-Sitayeb Touria; Steiner Nadia; Carneiro Lionel; Favrod Céline; Preitner Frédéric; Thorens Bernard; Stehle Jean-Christophe; Dix Laure; Pralong François; Magistretti Pierre J; Pellerin Luc

2013-01-01

The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1(+/-) mice developed normally. However, when fed high fat diet (HFD), MCT1(+/-) mice displayed resistance to development of diet-induced obesity ...

Destruction of PAHs by X-Rays in circumnuclear regions of AGNs

Science.gov (United States)

Monfredini, T.; Wolff, W.; Boechat-Roberty, H. M.; Sales, D. A.; Pastoriza, M. G.

2017-07-01

Emission bands associated with PAH molecules are observed in the direction of some classes of AGNs like Seyfert 2, LINERs and obscured quasars (e.g. Kaneda et al., 2008, Sansigre et al., 2008 and Sales et al. 2013). The molecular stability in these environments suggest the presence of very dense gas (˜ 1023-24 cm-2) to shield the cloud of PAHs against X-ray radiation (Voit, 1992, Tielens, 2011, Sales et al., 2013). We examined the photochemistry of simple PAHs: naphtalene (C10H8), anthracene (C14H10), methyl-anthracene (C15H12) and pyrene (C16H10) at the photon energies of 275 eV, 310 eV, 1900 eV and 2500 eV in order to apply the findings at the AGN scenario. The absolute single and double photoionization and photodissociation cross sections were determined for each molecule at each energy. Their ionization and destruction induced by X-rays were examined in the conditions of the circumnuclear region of NGC 1808, a Seyfert 2 galaxy, where PAH emission was detected at 26 pc from the central object (Sales et al., 2013). It was verified the higher photostability of PAHs without functional groups attached. At higher photon energies, the results suggest a higher production yield of double charged PAHs in comparision with the single charged ones (e.g., 2 × higher for double ionized naphtalene at 2500 eV). The production of double charged molecules increase with the size of the molecules. We also discuss a minimum formation rate of PAH to balance the photodestruction rate and maintain a minimum density for their detection (e.g. 4,0× 10-7 M⊙ year-1 for a column density NH of 1023 cm-2 at 26 pc).

Strong Impact on the Polycyclic Aromatic Hydrocarbon (PAH)-Degrading Community of a PAH-Polluted Soil but Marginal Effect on PAH Degradation when Priming with Bioremediated Soil Dominated by Mycobacteria

DEFF Research Database (Denmark)

Johnsen, Anders R.; Schmidt, Stine; Hybholdt, Trine K.

2007-01-01

Bioaugmentation of soil polluted with polycyclic aromatic hydrocarbons (PAHs) is often disappointing because of the low survival rate and low activity of the introduced degrader bacteria. We therefore investigated the possibility of priming PAH degradation in soil by adding 2% of bioremediated soil...... with a high capacity for PAH degradation. The culturable PAH-degrading community of the bioremediated primer soil was dominated by Mycobacterium spp. A microcosm containing pristine soil artificially polluted with PAHs and primed with bioremediated soil showed a fast, 100- to 1,000-fold increase in numbers...... of culturable phenanthrene-, pyrene-, and fluoranthene degraders and a 160-fold increase in copy numbers of the mycobacterial PAH dioxygenase gene pdo1. A nonpolluted microcosm primed with bioremediated soil showed a high rate of survival of the introduced degrader community during the 112 days of incubation...

Urban sprawl leaves its PAH signature

Science.gov (United States)

Van Metre, P.C.; Mahler, B.J.; Furlong, E.T.

2000-01-01

The increasing vehicle traffic associated with urban sprawl in the United States is frequently linked to degradation of air quality, but its effect on aquatic sediment is less well-recognized. This study evaluates trends in PAHs, a group of contaminants with multiple urban sources, in sediment cores from 10 reservoirs and lakes in six U.S. metropolitan areas. The watersheds chosen represent a range in degree and age of urbanization. Concentrations of PAHs in all 10 reservoirs and lakes increased during the past 20-40 years. PAH contamination of the most recently deposited sediment at all sites exceeded sediment-quality guidelines established by Environment Canada, in some cases by several orders of magnitude. These results add a new chapter to the story told by previous coring studies that reported decreasing concentrations of PAHs after reaching highs in the 1950s. Concurrent with the increase in concentrations is a change in the assemblage of PAHs that indicates the increasing trends are driven by combustion sources. The increase in PAH concentrations tracks closely with increases in automobile use, even in watersheds that have not undergone substantial changes in urban land-use levels since the 1970s.The increasing vehicle traffic associated with urban sprawl in the United States is frequently linked to degradation of air quality, but its effect on aquatic sediment is less well-recognized. This study evaluates trends in PAHs, a group of contaminants with multiple urban sources, in sediment cores from 10 reservoirs and lakes in six U.S. metropolitan areas. The watersheds chosen represent a range in degree and age of urbanization. Concentrations of PAHs in all 10 reservoirs and lakes increased during the past 20-40 years. PAH contamination of the most recently deposited sediment at all sites exceeded sediment-quality guidelines established by Environment Canada, in some cases by several orders of magnitude. These results add a new chapter to the story told by

Expression of CYP1C1 and CYP1A in Fundulus heteroclitus during PAH-induced carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Wang Lu [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States); Camus, Alvin C. [Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA (United States); Dong, Wu; Thornton, Cammi [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States); Willett, Kristine L., E-mail: kwillett@olemiss.edu [Pharmacology and Environmental Toxicology, University of Mississippi, University, MS (United States)

2010-09-15

CYP1C1 is a relatively newly identified member of the cytochrome P450 family 1 in teleost fish. However, CYP1C1's expression and physiological roles relative to the more recognized CYP1A in polycyclic aromatic hydrocarbons (PAHs) induced toxicities are unclear. Fundulus heteroclitus fry were exposed at 6-8 days post-hatch (dph) and again at 13-15 dph for 6 h to dimethyl sulfoxide (DMSO) control, 5 mg/L benzo[a]pyrene (BaP), or 5 mg/L dimethylbenzanthracene (DMBA). Fry were euthanized at 0, 6, 18, 24 and 30 h after the second exposure. In these groups, both CYP1A and CYP1C1 protein expression were induced within 6 h after the second exposure. Immunohistochemistry (IHC) results from fry revealed strongest CYP1C1 expression in renal tubular and intestinal epithelial cells. Additional fish were examined for liver lesions 8 months after initial exposure. Gross lesions were observed in 20% of the BaP and 35% of the DMBA-treated fish livers. Histopathologic findings included foci of cellular alteration and neoplasms, including hepatocellular adenoma, hepatocellular carcinoma and cholangioma. Strong CYP1A immunostaining was detected diffusely in altered cell foci and on the invading margin of hepatocelluar carcinomas. Lower CYP1A expression was seen in central regions of the neoplasms. In contrast, CYP1C1 was only detectable and highly expressed in proliferated bile duct epithelial cells. Our CYP1C1 results suggest the potential for tissue specific CYP1C1-mediated PAH metabolism but not a more chronic role in progression to liver hepatocellular carcinoma.

Do 16 Polycyclic Aromatic Hydrocarbons Represent PAH Air Toxicity?

Science.gov (United States)

Samburova, Vera; Zielinska, Barbara; Khlystov, Andrey

2017-08-15

Estimation of carcinogenic potency based on analysis of 16 polycyclic aromatic hydrocarbons (PAHs) ranked by U.S. Environmental Protection Agency (EPA) is the most popular approach within scientific and environmental air quality management communities. The majority of PAH monitoring projects have been focused on particle-bound PAHs, ignoring the contribution of gas-phase PAHs to the toxicity of PAH mixtures in air samples. In this study, we analyzed the results of 13 projects in which 88 PAHs in both gas and particle phases were collected from different sources (biomass burning, mining operation, and vehicle emissions), as well as in urban air. The aim was to investigate whether 16 particle-bound U.S. EPA priority PAHs adequately represented health risks of inhalation exposure to atmospheric PAH mixtures. PAH concentrations were converted to benzo(a)pyrene-equivalent (BaPeq) toxicity using the toxic equivalency factor (TEF) approach. TEFs of PAH compounds for which such data is not available were estimated using TEFs of close isomers. Total BaPeq toxicities (∑ 88 BaPeq) of gas- and particle-phase PAHs were compared with BaPeq toxicities calculated for the 16 particle-phase EPA PAH (∑ 16EPA BaPeq). The results showed that 16 EPA particle-bound PAHs underrepresented the carcinogenic potency on average by 85.6% relative to the total (gas and particle) BaPeq toxicity of 88 PAHs. Gas-phase PAHs, like methylnaphthalenes, may contribute up to 30% of ∑ 88 BaPeq. Accounting for other individual non-EPA PAHs (i.e., benzo(e)pyrene) and gas-phase PAHs (i.e., naphthalene, 1- and 2-methylnaphthalene) will make the risk assessment of PAH-containing air samples significantly more accurate.

Enhanced Accessibility of Polycyclic Aromatic Hydrocarbons (PAHs) and Heterocyclic PAHs in Industrially Contaminated Soil after Passive Dosing of a Competitive Sorbate

DEFF Research Database (Denmark)

Humel, Stefan; Nørgaard Schmidt, Stine; Sumetzberger-Hasinger, Marion

2017-01-01

To assess the exposure to polycyclic aromatic hydrocarbons (PAHs) it is important to understand the binding mechanisms between specific soil constituents and the organic pollutant. In this study, sorptive bioaccessibility extraction (SBE) was applied to quantify the accessible PAH fraction...... in industrially contaminated soil with and without passive dosing of a competitive sorbate. SBE experiments revealed an accessible PAH fraction of 41 ± 1% (∑16 US EPA PAHs + 5 further PAHs). The passive dosing of toluene below its saturation level revealed competitive binding and resulted in an average increase.......4% PAH. We explain increased PAH desorption after addition of toluene by competitive adsorption to high-affinity sorption sites while acknowledging that toluene could additionally have increased PAH mobility within the soil matrix. Findings suggest that the presence of copollutants at contaminated sites...

PAH Spectroscopy: Past, Present and Future

Science.gov (United States)

Mattioda, Andrew

2016-01-01

Since their discovery in the 1970's, astronomers, astrophysicists and astrochemists have been intrigued by the nearly ubiquitous unidentified infrared emission (UIR) bands. In the 1980's, investigators determined the most probably source of these emissions was a family of molecules known as Polycyclic Aromatic Hydrocarbons or simply PAHs. In order to better understand these interstellar IR features and utilize them as chemical probes of the cosmos, laboratory spectroscopists have spent the last three decades investigating the spectroscopy of PAHs under astrophysically relevant conditions. This presentation will discuss the similarities and differences in the spectroscopic properties of PAHs as one goes from the Far to Mid to Near infrared wavelength regions and probe the changes observed in PAH spectra as they go from neutral to ionized molecules suspended in an inert gas matrix, to PAHs in a water ice matrix and as a thin film. In selected instances, the experimental results will be compared to theoretical values. The presentation will conclude with a discussion on the future directions of PAH spectroscopy.

Comparison of CFD Simulations of Moderator Circulation Phenomena for a CANDU-6 Reactor and MCT Facility

International Nuclear Information System (INIS)

Kim, Hyoung Tae; Cha, Jae Eun Cha; Seo, Han

2013-01-01

The Korea Atomic Energy Research Institute is constructing a Moderator Circulation Test (MCT) facility to simulate thermal-hydraulic phenomena in a 1/4 scale-down moderator tank similar to that in a prototype power plant during steady state operation and accident conditions. In the present study, two numerical CFD simulations for the prototype and scaled-down moderator tanks were carried out to check whether the moderator flow and temperature patterns of both the prototype reactor and scaled-down facility are identical. Two different sets of simulations of the moderator circulation phenomena were performed for a CANDU-6 reactor and MCT facility. The results of both simulations were compared to study the effects of scaling on the moderator flow and temperature patterns. There is no significant difference in the results between the prototype and scaled-down model. It was concluded that the present scaling method is properly employed to model the real reactor in the MCT facility

Comparison of CFD Simulations of Moderator Circulation Phenomena for a CANDU-6 Reactor and MCT Facility

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyoung Tae; Cha, Jae Eun Cha; Seo, Han [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-10-15

The Korea Atomic Energy Research Institute is constructing a Moderator Circulation Test (MCT) facility to simulate thermal-hydraulic phenomena in a 1/4 scale-down moderator tank similar to that in a prototype power plant during steady state operation and accident conditions. In the present study, two numerical CFD simulations for the prototype and scaled-down moderator tanks were carried out to check whether the moderator flow and temperature patterns of both the prototype reactor and scaled-down facility are identical. Two different sets of simulations of the moderator circulation phenomena were performed for a CANDU-6 reactor and MCT facility. The results of both simulations were compared to study the effects of scaling on the moderator flow and temperature patterns. There is no significant difference in the results between the prototype and scaled-down model. It was concluded that the present scaling method is properly employed to model the real reactor in the MCT facility.

Administration of structured lipid composed of MCT and fish oil reduces net protein catabolism in enterally fed burned rats.

Science.gov (United States)

Teo, T C; DeMichele, S J; Selleck, K M; Babayan, V K; Blackburn, G L; Bistrian, B R

1989-01-01

The effects of enteral feeding with safflower oil or a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil (MCT/fish oil) on protein and energy metabolism were compared in gastrostomy-fed burned rats (30% body surface area) by measuring oxygen consumption, carbon dioxide production, nitrogen balance, total liver protein, whole-body leucine kinetics, and rectus muscle and liver protein fractional synthetic rates (FSR, %/day). Male Sprague-Dawley rats (195 +/- 5g) received 50 ml/day of an enteral regimen containing 50 kcal, 2 g amino acids, and 40% nonprotein calories as lipid for three days. Protein kinetics were estimated by using a continuous L-[1-14C] leucine infusion technique on day 2. Thermally injured rats enterally fed MCT/fish oil yielded significantly higher daily and cumulative nitrogen balances (p less than or equal to 0.025) and rectus muscle (39%) FSR (p less than or equal to 0.05) when compared with safflower oil. MCT/fish oil showed a 22% decrease (p less than or equal to 0.005) in per cent flux oxidized and a 7% (p less than or equal to 0.05) decrease in total energy expenditure (TEE) versus safflower oil. A 15% increase in liver FSR was accompanied by a significant elevation (p less than or equal to 0.025) in total liver protein with MCT/fish oil. This novel SL shares the properties of other structured lipids in that it reduces the net protein catabolic effects of burn injury, in part, by influencing tissue protein synthetic rates. The reduction in TEE is unique to MCT/fish oil and may relate to the ability of fish oil to diminish the injury response. PMID:2500898

Identifying carcinogenic activity of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) through electronic and topological indices

CERN Document Server

Braga, R S; Barone, P M V B

2000-01-01

Polycyclic aromatic hydrocarbons (PAHs) are a class of planar molecules, abundant in urban environment, which can induce chemical carcinogenesis. Their carcinogenic power varies in a large range, from very strong carcinogens to inactive ones. In a previous study, we proposed a methodology to identify the PAHs carcinogenic activity exploring electronic and topological indices. In the present work, we show that it is possible to simplify that methodology and expand its applicability to include methylated PAHs compounds. Using very simple rules, we can predict their carcinogenic activity with high accuracy (approx 89%).

Polysykliske aromatiske hydrokarboner (PAH) i fisk

OpenAIRE

Knutzen, J.

1987-01-01

Det er sammenstilt litteraturdata om polysykliske aromatiske hydrokarboner (PAH, tjærestoffer) i fisk fra et lite påvirkede og fra forurensede områder og sammenlignet med utvalgte data for PAH i røkt fisk. På grunn av sparsomt og delvis tvilsomt materiale, har det bare latt seg gjøre å antyde øvre grense for et "diffust bakgrunnsnivå" av benzo(a)pyren i fiskefilet: 1 µg/kg frisk vekt. Ofte har ikke total-PAH eller utvalgte PAH-forbindelser latt seg påvise, selv i områder som vites å være mark...

PAH in Some Brands of Tea and Coffee

DEFF Research Database (Denmark)

Duedahl-Olesen, Lene; Navaratnam, Marin Arosha; Jewula, J.

2015-01-01

The presence of 25 polycyclic aromatic hydrocarbons (PAHs) in tea and coffee were investigated with focus on four PAHs (PAH4), classified by the European Food Safety Authority (EFSA) as suitable indicators; benz[a]anthracene (BaA), chrysene (CHR), benzo[b]fluoranthene (BbF) and benzo[a]pyrene (Ba......P). PAH4 from samples of 18 brands of tea leaves and 13 brands of coffee were extracted by pressurized liquid extraction (PLE) followed by highly automated clean up steps for gel permeation chromatography (SX-3) and solid phase extraction (500mg silica). GC-MS were applied for detection of PAH4. The limit...... of detection (LOD) ranged from 0.1–0.3 μg/kg with recoveries from 94–106% for PAH4. Concentrations of PAH4 followed the pattern of the total sum of 25 PAHs with higher concentrations with a maximum of 115 μg/kg in tea leaves compared to 5.1 μg/kg in coffee. The highest PAH4 levels were found in black tea...

Distribution of PAHs and the PAH-degrading bacteria in the deep-sea sediments of the high-latitude Arctic Ocean

Science.gov (United States)

Dong, C.; Bai, X.; Sheng, H.; Jiao, L.; Zhou, H.; Shao, Z.

2015-04-01

Polycyclic aromatic hydrocarbons (PAHs) are common organic pollutants that can be transferred long distances and tend to accumulate in marine sediments. However, less is known regarding the distribution of PAHs and their natural bioattenuation in the open sea, especially the Arctic Ocean. In this report, sediment samples were collected at four sites from the Chukchi Plateau to the Makarov Basin in the summer of 2010. PAH compositions and total concentrations were examined with GC-MS. The concentrations of 16 EPA-priority PAHs varied from 2.0 to 41.6 ng g-1 dry weight and decreased with sediment depth and movement from the southern to the northern sites. Among the targeted PAHs, phenanthrene was relatively abundant in all sediments. The 16S rRNA gene of the total environmental DNA was analyzed with Illumina high-throughput sequencing (IHTS) to determine the diversity of bacteria involved in PAH degradation in situ. The potential degraders including Cycloclasticus, Pseudomonas, Halomonas, Pseudoalteromonas, Marinomonas, Bacillus, Dietzia, Colwellia, Acinetobacter, Alcanivorax, Salinisphaera and Shewanella, with Dietzia as the most abundant, occurred in all sediment samples. Meanwhile, enrichment with PAHs was initiated onboard and transferred to the laboratory for further enrichment and to obtain the degrading consortia. Most of the abovementioned bacteria in addition to Hahella, Oleispira, Oceanobacter and Hyphomonas occurred alternately as predominant members in the enrichment cultures from different sediments based on IHTS and PCR-DGGE analysis. To reconfirm their role in PAH degradation, 40 different bacteria were isolated and characterized, among which Cycloclasticus Pseudomonas showed the best degradation capability under low temperatures. Taken together, PAHs and PAH-degrading bacteria were widespread in the deep-sea sediments of the Arctic Ocean. We propose that bacteria of Cycloclasticus, Pseudomonas, Pseudoalteromonas, Halomonas, Marinomonas and Dietzia may

Downregulation of MicroRNA-126 Contributes to the Failing Right Ventricle in Pulmonary Arterial Hypertension.

Science.gov (United States)

Potus, François; Ruffenach, Grégoire; Dahou, Abdellaziz; Thebault, Christophe; Breuils-Bonnet, Sandra; Tremblay, Ève; Nadeau, Valérie; Paradis, Renée; Graydon, Colin; Wong, Ryan; Johnson, Ian; Paulin, Roxane; Lajoie, Annie C; Perron, Jean; Charbonneau, Eric; Joubert, Philippe; Pibarot, Philippe; Michelakis, Evangelos D; Provencher, Steeve; Bonnet, Sébastien

2015-09-08

Right ventricular (RV) failure is the most important factor of both morbidity and mortality in pulmonary arterial hypertension (PAH). However, the underlying mechanisms resulting in the failed RV in PAH remain unknown. There is growing evidence that angiogenesis and microRNAs are involved in PAH-associated RV failure. We hypothesized that microRNA-126 (miR-126) downregulation decreases microvessel density and promotes the transition from a compensated to a decompensated RV in PAH. We studied RV free wall tissues from humans with normal RV (n=17), those with compensated RV hypertrophy (n=8), and patients with PAH with decompensated RV failure (n=14). Compared with RV tissues from patients with compensated RV hypertrophy, patients with decompensated RV failure had decreased miR-126 expression (quantitative reverse transcription-polymerase chain reaction; P<0.01) and capillary density (CD31(+) immunofluorescence; P<0.001), whereas left ventricular tissues were not affected. miR-126 downregulation was associated with increased Sprouty-related EVH1 domain-containing protein 1 (SPRED-1), leading to decreased activation of RAF (phosphorylated RAF/RAF) and mitogen-activated protein kinase (MAPK); (phosphorylated MAPK/MAPK), thus inhibiting the vascular endothelial growth factor pathway. In vitro, Matrigel assay showed that miR-126 upregulation increased angiogenesis of primary cultured endothelial cells from patients with decompensated RV failure. Furthermore, in vivo miR-126 upregulation (mimic intravenous injection) improved cardiac vascular density and function of monocrotaline-induced PAH animals. RV failure in PAH is associated with a specific molecular signature within the RV, contributing to a decrease in RV vascular density and promoting the progression to RV failure. More importantly, miR-126 upregulation in the RV improves microvessel density and RV function in experimental PAH. © 2015 American Heart Association, Inc.

Formation of nitro-PAHs from the heterogeneous reaction of ambient particle-bound PAHs with NO3/N2O5

Science.gov (United States)

Zimmermann, K.; Jariyasopit, N.; Simonich, S. L.; Atkinson, R.; Arey, J.

2012-12-01

Polycyclic aromatic hydrocarbons (PAHs) and their nitrated derivatives (nitro-PAHs) have been shown to be mutagenic in bacterial and mammalian assays and are classified as probable human carcinogens. Semi-volatile PAHs partition between the gas and particulate phases, depending on their liquid-phase vapor pressures and ambient temperatures. These PAHs have been extensively measured in ambient particulate matter and can ultimately undergo long-range transport from source regions (e.g., China to the western USA) (1). During transport these particle-bound PAHs may undergo reaction with NO3/N2O5 to form nitro-PAH derivatives. Previous studies of heterogeneous nitration of PAHs have used particles composed of graphite, diesel soot, and wood smoke (2-4). This study investigates the heterogeneous formation of nitro-PAHs from ambient particle-bound PAHs from Beijing, China and sites located within the Los Angeles air basin. These ambient particle samples, along with filters coated with isotopically labeled PAHs, were exposed to a mix of NO2/NO3/N2O5 in a 7000 L Teflon chamber, with analysis focused on the heterogeneous formation of molecular weight 247 and 273 nitro-PAHs. The heterogeneous formation of certain nitro-PAHs (including1-nitropyrene and 1- and 2-nitrotriphenylene) was observed for some, but not all, ambient samples. Formation of nitro-PAHs typically formed through gas-phase reactions (2-nitrofluoranthene and 2-nitropyrene) was not observed. The effect of particle age and local photochemical conditions during sampling on the degree of nitration in environmental chamber reactions, as well as ambient implications, will be presented. 1. Primbs, T.; Simonich, S.; Schmedding, D.; Wilson, G.; Jaffe, D.; Takami, A.; Kato, S.; Hatakeyama, S.; Kajii, Y. Environ. Sci. Technol. 2007, 41, 3551-3558. 2. Esteve, W.; Budzinski, H.; Villenave, E. Atmospheric Environment 2004, 38, 6063-6072. 3. Nguyen, M.; Bedjanian, Y.; Guilloteau, A. Journal of Atmospheric Chemistry 2009, 62

Distributions and Concentrations of PAHs in Hong Kong Soils

International Nuclear Information System (INIS)

Zhang, H.B.; Luo, Y.M.; Wong, M.H.; Zhao, Q.G.; Zhang, G.L.

2006-01-01

Surface soil (0-10 cm) samples from 53 sampling sites including rural and urban areas of Hong Kong were collected and analyzed for 16 EPA priority polycyclic aromatic hydrocarbons (PAHs). Total PAH concentrations were in the range of 7.0-410 μg kg -1 (dry wt), with higher concentrations in urban soils than that in rural soils. The three predominant PAHs were Fluoranthene, Naphthalene and Pyrene in rural soils, while Fluoranthene, Naphthalene and Benzo(b + k)fluoranthene dominated the PAHs of urban soils. The values of PAHs isomer indicated that biomass burning might be the major origin of PAHs in rural soils, but vehicular emission around the heavy traffic roads might contribute to the soil PAHs in urban areas. A cluster analysis was performed and grouped the detectable PAHs under 4 clusters, which could be indicative of the PAHs with different origins and PAHs affected by soil organic carbon contents respectively. - Baseline information is provided on levels, distributions and possible sources of PAHs in Hong Kong soils

Developing the Infrared PAH Emission Bands Into Calibrated Probes of Astrophysical Conditions with The NASA Ames PAH IR Spectroscopic Database

Science.gov (United States)

Boersma, Christiaan

We propose to quantitatively calibrate the PAH band strength ratios that have been traditionally used as qualitative proxies of PAH properties and linking PAH observables with local astrophysical conditions, thus developing PAHs into quantitative probes of astronomical environments. This will culminate in a toolbox (calibration charts) that can be used by PAH experts and non-PAH experts alike to unlock the information hidden in PAH emission sources that are part of the Spitzer and ISO archives. Furthermore, the proposed work is critical to mine the treasure trove of information JWST will return as it will capture, for the first time, the complete mid-infrared (IR) PAH spectrum with fully resolved features, through a single aperture, and along single lines-of-sight; making it possible to fully extract the information contained in the PAH spectra. In short, the work proposed here represents a major step in enabling the astronomical PAH model to reach its full potential as a diagnostic of the physical and chemical conditions in objects spanning the Universe. Polycyclic aromatic hydrocarbons (PAHs), a common and important reservoir of accessible carbon across the Universe, play an intrinsic part in the formation of stars, planets and possibly even life itself. While most PAH spectra appear quite similar, they differ in detail and contain a wealth of untapped information. Thanks to recent advances in laboratory studies and computer-based calculations of PAH spectra, the majority of which have been made at NASA Ames, coupled with the astronomical modeling tools we have developed, we can interpret the spectral details at levels never before possible. This enables us to extract local physical conditions and track subtle changes in these conditions at levels previously impossible. Building upon the tools and paradigms developed as part of the publicly available NASA Ames PAH IR Spectroscopic Database (PAHdb; www.astrochem.org/pahdb/), the purpose of our proposed research is

Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs metabolites.

Directory of Open Access Journals (Sweden)

Jian Ye

Full Text Available Exposure to polycyclic aromatic hydrocarbons (PAHs is associated with reduced heart rate variability (HRV, a strong predictor of cardiovascular diseases, but the mechanism is not well understood.We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6 and heat shock protein 70 (Hsp70 were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs were measured by gas chromatography-mass spectrometry.We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05; and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP and low frequency (LF (Ptrend = 0.014 and 0.006, respectively. In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05, but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN, TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05. We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.

Photolysis of polycyclic aromatic hydrocarbons (PAHs) on Fe3+-montmorillonite surface under visible light: Degradation kinetics, mechanism, and toxicity assessments.

Science.gov (United States)

Zhao, Song; Jia, Hanzhong; Nulaji, Gulimire; Gao, Hongwei; Wang, Fu; Wang, Chuanyi

2017-10-01

Photochemical behavior of various polycyclic aromatic hydrocarbons (PAHs) on Fe 3+ -modified montmorillonite was explored to determine their potential kinetics, pathways, and mechanism under visible light. Depending on the type of PAH molecules, the transformation rate follows the order of benzo[a]pyrene ≈ anthracene > benzo[a]anthracene > phenanthrene. Quantum simulation results confirm the crucial role of "cation-π" interaction between Fe 3+ and PAHs on their transformation kinetics. Primary intermediates, including quinones, ring-opening products and benzene derivatives, were identified by gas chromatography-mass spectrometer (GC-MS), and the possible photodegradation pathway of benzo[a]pyrene was proposed. Meanwhile, radical intermediates, such as reactive oxygen species (ROS) and free organic radicals, were detected by electron paramagnetic resonance (EPR) technique. The photolysis of selected PAHs, such as anthracene and benzo[a]pyrene, on clay surface firstly occurs by electron transfer from PAHs to Fe 3+ -montmorillonite, followed by degradation involving photo-induced ROS such as ·OH and ·O 2 - . To investigate the acute toxicity of photolysis products, the Microtox ® toxicity test was performed during the photodegradation processes of various PAHs. As a result, the photo-irradiation initially induces increased toxicity by generating reactive intermediates, such as free organic radicals, and then the toxicity gradually decreases with increasing of reaction time. Overall, the present study provides useful information to understand the fate and photo-transformation of PAHs in contaminated soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improved source apportionment of PAHs and Pb by integrating Pb stable isotopes and positive matrix factorization application (PAHs): A historical record case study from the northern South China Sea.

Science.gov (United States)

Cai, Minggang; Lin, Yan; Chen, Meng; Yang, Weifeng; Du, Huihong; Xu, Ye; Cheng, Shayen; Xu, Fangjian; Hong, Jiajun; Chen, Mian; Ke, Hongwei

2017-12-31

To obtain the historical changes of pyrogenic sources, integrated source apportionment methods, which include PAH compositions, diagnostic ratios (DRs), Pb isotopic ratios, and positive matrix factorization (PMF) model, were developed and applied in sediments of the northern South China Sea. These methods provided a gradually clear picture of energy structural change. Spatially, Σ 15 PAH (11.3 to 95.5ng/g) and Pb (10.2 to 74.6μg/g) generally exhibited decreasing concentration gradient offshore; while the highest levels of PAHs and Pb were observed near the southern Taiwan Strait, which may be induced by accumulation of different fluvial input. Historical records of pollutants followed closely with the economic development of China, with fast growth of Σ 15 PAH and Pb occurring since the 1980s and 1990s, respectively. The phasing-out of leaded gasoline in China was captured with a sharp decrease of Pb after the mid-1990s. PAHs and Pb correlated well with TOC and clay content for core sediments, which was not observed for surface sediments. There was an up-core increase of high molecular PAH proportions. Coal and biomass burning were then qualitatively identified as the major sources of PAHs with DRs. Furthermore, shift toward less radiogenic signatures of Pb isotopic ratios after 1900 revealed the start and growing importance of industrial sources. Finally, a greater separation and quantification of various input was achieved by a three-factor PMF model, which made it clear that biomass burning, coal combustion, and vehicle emissions accounted for 40±20%, 41±13%, and 19±12% of PAHs through the core. Biomass and coal combustion acted as major sources before 2000, while contributions from vehicle emission soared thereafter. The integrated multi-methodologies here improved the source apportionment by reducing biases with a step-down and cross-validation perspective, which could be similarly applied to other aquatic systems. Copyright © 2017 Elsevier B.V. All

Infrared spectra of interstellar deuteronated PAHs

Science.gov (United States)

Buragohain, Mridusmita; Pathak, Amit; Sarre, Peter

2015-08-01

Polycyclic Aromatic Hydrocarbon (PAH) molecules have emerged as a potential constituent of the ISM that emit strong features at 3.3, 6.2, 7.7, 8.6, 11.2 and 12.7 μm with weaker and blended features in the 3-20μm region. These features are proposed to arise from the vibrational relaxation of PAH molecules on absorption of background UV photons (Tielens 2008). These IR features have been observed towards almost all types of astronomical objects; say H II regions, photodissociation regions, reflection nebulae, planetary nebulae, young star forming regions, external galaxies, etc. A recent observation has proposed that interstellar PAHs are major reservoir for interstellar deuterium (D) (Peeters et al. 2004). According to the `deuterium depletion model' as suggested by Draine (2006), some of the Ds formed in the big bang are depleted in PAHs, which can account for the present value of D/H in the ISM. Hence, study of deuterated PAHs (PADs) is essential in order to measure D/H in the ISM.In this work, we consider another probable category of the large PAH family, i.e. Deuteronated PAHs (DPAH+). Onaka et al. have proposed a D/H ratio which is an order of magnitude smaller than the proposed value of D/H by Draine suggesting that if Ds are depleted in PAHs, they might be accommodated in large PAHs (Onaka et al. 2014). This work reports a `Density Functional Theory' calculation of large deuteronated PAHs (coronene, ovalene, circumcoronene and circumcircumcoronene) to determine the expected region of emission features and to find a D/H ratio that is comparable to the observational results. We present a detailed analysis of the IR spectra of these molecules and discuss the possible astrophysical implications.ReferencesDraine B. T. 2006, in ASP Conf. Ser. 348, Proc. Astrophysics in the Far Ultraviolet: Five Years of Discovery with FUSE, ed. G. Sonneborn, H. Moos, B-G Andersson (San Francisco, CA:ASP) 58Onaka T., Mori T. I., Sakon I., Ohsawa R., Kaneda H., Okada Y., Tanaka M

PAH in tea and coffee

DEFF Research Database (Denmark)

Duedahl-Olesen, Lene; Navarantem, Marin; Adamska, Joanna

For food regulation in the European Union maximum limits on other foods than tea and coffee includes benzo[a]pyrene and the sum of PAH4 (sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene). This study includes analysis of the above mentioned PAH in both, tea leaves, coffee...... beans and ready-to-drink preparations. Compared to other food matrices (e.g. fish), the analytical methods were challenged by the hot water extracts. Preparation of tea includes roasting and drying of the tea leaves using combustion gases from burning wood, oil, or coal. These are responsible...... for accumulation of PAH in tea leaves. Different varieties of tea leaves were analyzed and highest concentrations were found in leaves from mate and black tea with maximum concentrations of 32 μg/kg for benzo[a]pyrene and 115 μg/kg for the sum of PAH4. Also, coffee beans are roasted during processing. However...

Kidney in potassium depletion. I. Na+-K+-ATPase activity and [3H]ouabain binding in MCT

International Nuclear Information System (INIS)

Hayashi, M.; Katz, A.I.

1987-01-01

The effect of potassium depletion on renal Na + K + -ATPase was studied in rats. K depletion produced a striking, time-dependent increase in Na + -K + -ATPase activity of the outer medullary collecting tubules (inner stripe; MCT/sub is/). After 3 wk on the K-free diet, when the urine was almost potassium-free, Na + -K + -ATPase activity in MCT/sub is/ was over fourfold higher than in control animals. Repletion of potassium restored enzyme activity to base line within 7 days which corresponds to the catabolic rate of the renal enzyme, suggesting the cessation of enhanced synthesis that took place during K deprivation. Changes in Na + -K + -ATPase activity and aldosterone levels during both K depletion and repletion occurred in opposite directions and were therefore independent of each other. [ 3 H]Ouabain binding to intact MCT/sub is/, reflecting the number of pump sites on the basolateral membrane, was similar in K-depleted and control animals; in contrast, tubule permeabilization that exposes additional pump units to the ligand, unmasked a nearly fourfold increase in [ 3 H]ouabain binding in K-depleted rats, comparable to the increment in Na + -K + -ATPase activity. These results show that K depletion leads to a marked increase in Na + -K + -ATPase activity of MCT/sub is/, and suggest that the new enzyme units are located at a ouabain-inaccessible site in the intact tubule, i.e., either in an intracellular compartment or at the luminal membrane, where they may be involved in potassium reabsorption

PAH related effects on fish in sedimentation ponds for road runoff and potential transfer of PAHs from sediment to biota.

Science.gov (United States)

Grung, Merete; Petersen, Karina; Fjeld, Eirik; Allan, Ian; Christensen, Jan H; Malmqvist, Linus M V; Meland, Sondre; Ranneklev, Sissel

2016-10-01

Road runoff is an important source of pollution to the aquatic environment, and sedimentation ponds have been installed to mitigate effects on the aquatic environment. The purpose of this study was to investigate if a) fish from sedimentation ponds were affected by road pollution and; b) the transfer of PAHs from road runoff material to aquatic organisms was substantial. Minnow from a sedimentation pond (Skullerud) near Oslo (Norway) had higher levels of CYP1A enzyme and DNA stand breaks than minnow from the nearby river, but high concentrations of PAH-metabolites in bile revealed that both populations were highly exposed. Principal component analysis revealed that CYP1A and age of fish were correlated, while levels of PAH-metabolites were not correlated to CYP1A or DNA damage. Minnow from a lake un-affected by traffic had much lower levels of PAH-metabolites than the exposed fish, and also an improved condition. The latter results indicate that fish health was affected by road runoff. A closer investigation of PAH levels of the ecosystems of two sedimentation ponds (Skullerud and Vassum) and nearby environments were conducted. The concentration of the 16 EPA PAHs in sediments of the sedimentation ponds were high (1900-4200ngg(-1)), and even higher levels were observed in plants. Principal component analysis of selected ion chromatograms of PAHs showed a clear separation of plants vs. sediments. The plants preferentially accumulated the high molecular PAHs, both from sedimentation ponds with a petrogenic PAH isomer ratio in sediments; and from a lake with pyrogenic PAH isomer ratio in sediments. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8).

Science.gov (United States)

Rodrigues, Tiago B; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8.

Directory of Open Access Journals (Sweden)

Tiago B Rodrigues

Full Text Available Mutations of the monocarboxylate transporter 8 (MCT8 cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3 transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13C glucose and brain extracts prepared and analyzed by (13C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

Variations of emission characterization of PAHs emitted from different utility boilers of coal-fired power plants and risk assessment related to atmospheric PAHs

International Nuclear Information System (INIS)

Wang, Ruwei; Liu, Guijian; Zhang, Jiamei

2015-01-01

Coal-fired power plants (CFPPs) represent important source of atmospheric PAHs, however, their emission characterization are still largely unknown. In this work, the concentration, distribution and gas-particle partitioning of PM_1_0- and gas-phase PAHs in flue gas emitted from different coal-fired utility boilers were investigated. Moreover, concentration and distribution in airborne PAHs from different functional areas of power plants were studied. People's inhalatory and dermal exposures to airborne PAHs at these sites were estimated and their resultant lung cancer and skin cancer risks were assessed. Results indicated that the boiler capacity and operation conditions have significant effect on PAH concentrations in both PM_1_0 and gas phases due to the variation of combustion efficiency, whereas they take neglected effect on PAH distributions. The wet flue gas desulphurization (WFGD) takes significant effect on the scavenging of PAH in both PM_1_0 and gas phases, higher scavenging efficiency were found for less volatile PAHs. PAH partitioning is dominated by absorption into organic matter and accompanied by adsorption onto PM_1_0 surface. In addition, different partitioning mechanism is observed for individual PAHs, which is assumed arising from their chemical affinity and vapor pressure. Risk assessment indicates that both inhalation and dermal contact greatly contribute to the cancer risk for CFPP workers and nearby residents. People working in workshop are exposed to greater inhalation and dermal exposure risk than people living in nearby vicinity and working office. - Highlights: • PAH distribution in PM_1_0 and gas phases primarily depend on the vapor pressure. • Combustion conditions and WFGD show typical effects on PAH level and profile. • PAH partitioning is dominated by absorption and also accompanied by adsorption. • Individual PAHs show different partitioning mechanisms in PM_1_0- and gas-phases. • People in workshop suffer greater cancer

Genetic variations in the MCT1 (SLC16A1) gene in the Chinese population of Singapore.

Science.gov (United States)

Lean, Choo Bee; Lee, Edmund Jon Deoon

2009-01-01

MCT1(SLC16A1) is the first member of the monocarboxylate transporter (MCT) and its family is involved in the transportation of metabolically important monocarboxylates such as lactate, pyruvate, acetate and ketone bodies. This study identifies genetic variations in SLC16A1 in the ethnic Chinese group of the Singaporean population (n=95). The promoter, coding region and exon-intron junctions of the SLC16A1 gene encoding the MCT1 transporter were screened for genetic variation in the study population by DNA sequencing. Seven genetic variations of SLC16A1, including 4 novel ones, were found: 2 in the promoter region, 2 in the coding exons (both nonsynonymous variations), 2 in the 3' untranslated region (3'UTR) and 1 in the intron. Of the two mutations detected in the promoter region, the -363-855T>C is a novel mutation. The 1282G>A (Val(428)Ile) is a novel SNP and was found as heterozygotic in 4 subjects. The 1470T>A (Asp(490)Glu) was found to be a common polymorphism in this study. Lastly, IVS3-17A>C in intron 3 and 2258 (755)A>G in 3'UTR are novel mutations found to be common polymorphisms in the local Chinese population. To our knowledge, this is the first report of a comprehensive analysis on the MCT1 gene in any population.

Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome.

Science.gov (United States)

Wirth, Eva K; Roth, Stephan; Blechschmidt, Cristiane; Hölter, Sabine M; Becker, Lore; Racz, Ildiko; Zimmer, Andreas; Klopstock, Thomas; Gailus-Durner, Valerie; Fuchs, Helmut; Wurst, Wolfgang; Naumann, Thomas; Bräuer, Anja; de Angelis, Martin Hrabé; Köhrle, Josef; Grüters, Annette; Schweizer, Ulrich

2009-07-29

Thyroid hormone transport into cells requires plasma membrane transport proteins. Mutations in one of these, monocarboxylate transporter 8 (MCT8), have been identified as underlying cause for the Allan-Herndon-Dudley syndrome, an X-linked mental retardation in which the patients also present with abnormally high 3',3,5-triiodothyronine (T(3)) plasma levels. Mice deficient in Mct8 replicate the thyroid hormone abnormalities observed in the human condition. However, no neurological deficits have been described in mice lacking Mct8. Therefore, we subjected Mct8-deficient mice to a comprehensive immunohistochemical, neurological, and behavioral screen. Several behavioral abnormalities were found in the mutants. Interestingly, some of these behavioral changes are compatible with hypothyroidism, whereas others rather indicate hyperthyroidism. We thus hypothesized that neurons exclusively dependent on Mct8 are in a hypothyroid state, whereas neurons expressing other T(3) transporters become hyperthyroid, if they are exposed directly to the high plasma T(3). The majority of T(3) uptake in primary cortical neurons is mediated by Mct8, but pharmacological inhibition suggested functional expression of additional T(3) transporter classes. mRNAs encoding six T(3) transporters, including L-type amino acid transporters (LATs), were coexpressed with Mct8 in isolated neurons. We then demonstrated Lat2 expression in cultured neurons and throughout murine brain development. In contrast, LAT2 is expressed in microglia in the developing human brain during gestation, but not in neurons. We suggest that lack of functional complementation by alternative thyroid hormone transporters in developing human neurons precipitates the devastating neurodevelopmental phenotype in MCT8-deficient patients, whereas Mct8-deficient mouse neurons are functionally complemented by other transporters, for possibly Lat2.

Emission characterization and δ{sup 13}C values of parent PAHs and nitro-PAHs in size-segregated particulate matters from coal-fired power plants

Energy Technology Data Exchange (ETDEWEB)

Wang, Ruwei [CAS Key Laboratory of Crust-Mantle Materials and the Environments, School of Earth and Space Sciences, University of Science and Technology of China, Hefei 230026 (China); State Key Laboratory of Loess and Quaternary Geology, Institute of Earth Environment, The Chinese Academy of Sciences, Xi’an 710075 Shaanxi (China); Yousaf, Balal; Sun, Ruoyu [CAS Key Laboratory of Crust-Mantle Materials and the Environments, School of Earth and Space Sciences, University of Science and Technology of China, Hefei 230026 (China); Zhang, Hong [Anhui Department of Environmental Protection, Anhui Academy of Environmental Science, Hefei 230071 (China); Zhang, Jiamei [CAS Key Laboratory of Crust-Mantle Materials and the Environments, School of Earth and Space Sciences, University of Science and Technology of China, Hefei 230026 (China); Liu, Guijian, E-mail: lgj@ustc.edu.cn [CAS Key Laboratory of Crust-Mantle Materials and the Environments, School of Earth and Space Sciences, University of Science and Technology of China, Hefei 230026 (China); State Key Laboratory of Loess and Quaternary Geology, Institute of Earth Environment, The Chinese Academy of Sciences, Xi’an 710075 Shaanxi (China)

2016-11-15

Highlights: • pPAHs and NPAHs were strongly associated with PM{sub 1–2.5} and PM{sub 1} compared with PM{sub 2.5–10}. • Combustion conditions and WFGD showed typical effects on PAH level and profile. • Diagnostic ratio of PAH was to indicative of emission sources to a certain degree. • δ{sup 13}C values of PAHs were useful for differentiating coal combustion source. • δ{sup 13}C values of PAHs were unable to differentiate coal-processing sources. - Abstract: The objective of this study was to characterize parent polycyclic aromatic hydrocarbons (pPAHs) and their nitrated derivatives (NPAHs) in coarse (PM{sub 2.5–10}), intermediate (PM{sub 1–2.5}) and fine (PM{sub 1}) particulate matters emitted from coal-fired power plants (CFPPs) in Huainan, China. The diagnostic ratios and the stable carbon isotopic approaches to characterize individual PAHs were applied in order to develop robust tools for tracing the origins of PAHs in different size-segregated particular matters (PMs) emitted CFPP coal combustion. The concentrations of PAH compounds in flue gas emissions varied greatly, depending on boiler types, operation and air pollution control device (APCD) conditions. Both pPAHs and NPAHs were strongly enriched in PM{sub 1–2.5} and PM{sub 1}. In contrary to low molecular weight (LMW) PAHs, high molecular weight (HMW) PAHs were more enriched in finer PMs. The PAH diagnostic ratios in size-segregated PMs are small at most cases, highlighting their potential application in tracing CFPP emitted PAHs attached to different sizes of PMs. Yet, substantial uncertainty still exists to directly apply PAH diagnostic ratios as emission tracers. Although the stable carbon isotopic composition of PAH molecular was useful in differentiating coal combustion emissions from other sources such as biomass combustion and vehicular exhausts, it was not feasible to differentiate isotopic fractionation processes such as low-temperature carbonization, high

Emission characterization and δ"1"3C values of parent PAHs and nitro-PAHs in size-segregated particulate matters from coal-fired power plants

International Nuclear Information System (INIS)

Wang, Ruwei; Yousaf, Balal; Sun, Ruoyu; Zhang, Hong; Zhang, Jiamei; Liu, Guijian

2016-01-01

Highlights: • pPAHs and NPAHs were strongly associated with PM_1_–_2_._5 and PM_1 compared with PM_2_._5_–_1_0. • Combustion conditions and WFGD showed typical effects on PAH level and profile. • Diagnostic ratio of PAH was to indicative of emission sources to a certain degree. • δ"1"3C values of PAHs were useful for differentiating coal combustion source. • δ"1"3C values of PAHs were unable to differentiate coal-processing sources. - Abstract: The objective of this study was to characterize parent polycyclic aromatic hydrocarbons (pPAHs) and their nitrated derivatives (NPAHs) in coarse (PM_2_._5_–_1_0), intermediate (PM_1_–_2_._5) and fine (PM_1) particulate matters emitted from coal-fired power plants (CFPPs) in Huainan, China. The diagnostic ratios and the stable carbon isotopic approaches to characterize individual PAHs were applied in order to develop robust tools for tracing the origins of PAHs in different size-segregated particular matters (PMs) emitted CFPP coal combustion. The concentrations of PAH compounds in flue gas emissions varied greatly, depending on boiler types, operation and air pollution control device (APCD) conditions. Both pPAHs and NPAHs were strongly enriched in PM_1_–_2_._5 and PM_1. In contrary to low molecular weight (LMW) PAHs, high molecular weight (HMW) PAHs were more enriched in finer PMs. The PAH diagnostic ratios in size-segregated PMs are small at most cases, highlighting their potential application in tracing CFPP emitted PAHs attached to different sizes of PMs. Yet, substantial uncertainty still exists to directly apply PAH diagnostic ratios as emission tracers. Although the stable carbon isotopic composition of PAH molecular was useful in differentiating coal combustion emissions from other sources such as biomass combustion and vehicular exhausts, it was not feasible to differentiate isotopic fractionation processes such as low-temperature carbonization, high-temperature carbonization, gasification and

PAH related effects on fish in sedimentation ponds for road runoff and potential transfer of PAHs from sediment to biota

DEFF Research Database (Denmark)

Grung, Merete; Petersen, Karina; Fjeld, Eirik

2016-01-01

of the sedimentation ponds were high (1900-4200ngg(-1)), and even higher levels were observed in plants. Principal component analysis of selected ion chromatograms of PAHs showed a clear separation of plants vs. sediments. The plants preferentially accumulated the high molecular PAHs, both from sedimentation ponds......) the transfer of PAHs from road runoff material to aquatic organisms was substantial. Minnow from a sedimentation pond (Skullerud) near Oslo (Norway) had higher levels of CYP1A enzyme and DNA stand breaks than minnow from the nearby river, but high concentrations of PAH-metabolites in bile revealed that both...... populations were highly exposed. Principal component analysis revealed that CYP1A and age of fish were correlated, while levels of PAH-metabolites were not correlated to CYP1A or DNA damage. Minnow from a lake un-affected by traffic had much lower levels of PAH-metabolites than the exposed fish, and also...

Effects of group metacognitive training (MCT on mental capacity and functioning in patients with psychosis in a secure forensic psychiatric hospital: a prospective-cohort waiting list controlled study

Directory of Open Access Journals (Sweden)

Naughton Marie

2012-06-01

Full Text Available Abstract Background Metacognitive Training (MCT is a manualised cognitive intervention for psychosis aimed at transferring knowledge of cognitive biases and providing corrective experiences. The aim of MCT is to facilitate symptom reduction and protect against relapse. In a naturalistic audit of clinical effectiveness we examined what effect group MCT has on mental capacity, symptoms of psychosis and global function in patients with a psychotic illness, when compared with a waiting list comparison group. Methods Of 93 patients detained in a forensic mental health hospital under both forensic and civil mental health legislation, 19 were assessed as suitable for MCT and 11 commenced. These were compared with 8 waiting list patients also deemed suitable for group MCT who did not receive it in the study timeframe. The PANSS, GAF, MacArthur Competence Assessment Tool- Treatment (MacCAT-T and MacArthur Competence Assessment Tool-Fitness to Plead (MacCAT-FP were recorded at baseline and repeated after group MCT or following treatment as usual in the waiting list group. Results When baseline functioning was accounted for, patients that attended MCT improved in capacity to consent to treatment as assessed by the MacCAT-T (p = 0.019. The more sessions attended, the greater the improvements in capacity to consent to treatment, mainly due to improvement in MacCAT-T understanding (p = 0.014 and reasoning . The GAF score improved in patients who attended the MCT group when compared to the waiting list group (p = 0.038 but there were no changes in PANSS scores. Conclusion Measures of functional mental capacity and global function can be used as outcome measures for MCT. MCT can be used successfully even in psychotic patients detained in a forensic setting. The restoration of elements of decision making capacity such as understanding and reasoning may be a hither-to unrecognised advantage of such treatment. Because pharmacotherapy can be optimised

Effects of group metacognitive training (MCT) on mental capacity and functioning in patients with psychosis in a secure forensic psychiatric hospital: a prospective-cohort waiting list controlled study.

Science.gov (United States)

Naughton, Marie; Nulty, Andrea; Abidin, Zareena; Davoren, Mary; O'Dwyer, Sarah; Kennedy, Harry G

2012-06-18

Metacognitive Training (MCT) is a manualised cognitive intervention for psychosis aimed at transferring knowledge of cognitive biases and providing corrective experiences. The aim of MCT is to facilitate symptom reduction and protect against relapse. In a naturalistic audit of clinical effectiveness we examined what effect group MCT has on mental capacity, symptoms of psychosis and global function in patients with a psychotic illness, when compared with a waiting list comparison group. Of 93 patients detained in a forensic mental health hospital under both forensic and civil mental health legislation, 19 were assessed as suitable for MCT and 11 commenced. These were compared with 8 waiting list patients also deemed suitable for group MCT who did not receive it in the study timeframe. The PANSS, GAF, MacArthur Competence Assessment Tool- Treatment (MacCAT-T) and MacArthur Competence Assessment Tool-Fitness to Plead (MacCAT-FP) were recorded at baseline and repeated after group MCT or following treatment as usual in the waiting list group. When baseline functioning was accounted for, patients that attended MCT improved in capacity to consent to treatment as assessed by the MacCAT-T (p = 0.019). The more sessions attended, the greater the improvements in capacity to consent to treatment, mainly due to improvement in MacCAT-T understanding (p = 0.014) and reasoning . The GAF score improved in patients who attended the MCT group when compared to the waiting list group (p = 0.038) but there were no changes in PANSS scores. Measures of functional mental capacity and global function can be used as outcome measures for MCT. MCT can be used successfully even in psychotic patients detained in a forensic setting. The restoration of elements of decision making capacity such as understanding and reasoning may be a hither-to unrecognised advantage of such treatment. Because pharmacotherapy can be optimised and there is likely to be enough time to complete the course

Using slow-release permanganate candles to remediate PAH-contaminated water

International Nuclear Information System (INIS)

Rauscher, Lindy; Sakulthaew, Chainarong; Comfort, Steve

2012-01-01

Highlights: ► We quantified the efficacy of slow-release permanganate-paraffin candles to degrade and mineralize PAHs. ► 14 C-labeled PAHs were used to quantify both adsorption and transformation. ► Permanganate-treated PAHs were more biodegradable in soil microcosms. ► A flow-through candle system was used to quantify PAH removal in urban runoff. - Abstract: Surface waters impacted by urban runoff in metropolitan areas are becoming increasingly contaminated with polycyclic aromatic hydrocarbons (PAHs). Slow-release oxidant candles (paraffin–KMnO 4 ) are a relatively new technology being used to treat contaminated groundwater and could potentially be used to treat urban runoff. Given that these candles only release permanganate when submerged, the ephemeral nature of runoff events would influence when the permanganate is released for treating PAHs. Our objective was to determine if slow-release permanganate candles could be used to degrade and mineralize PAHs. Batch experiments quantified PAH degradation rates in the presence of the oxidant candles. Results showed most of the 16 PAHs tested were degraded within 2–4 h. Using 14 C-labled phenanthrene and benzo(a)pyrene, we demonstrated that the wax matrix of the candle initially adsorbs the PAH, but then releases the PAH back into solution as transformed, more water soluble products. While permanganate was unable to mineralize the PAHs (i.e., convert to CO 2 ), we found that the permanganate-treated PAHs were much more biodegradable in soil microcosms. To test the concept of using candles to treat PAHs in multiple runoff events, we used a flow-through system where urban runoff water was pumped over a miniature candle in repetitive wet–dry, 24-h cycles. Results showed that the candle was robust in removing PAHs by repeatedly releasing permanganate and degrading the PAHs. These results provide proof-of-concept that permanganate candles could potentially provide a low-cost, low-maintenance approach to

Using slow-release permanganate candles to remediate PAH-contaminated water

Energy Technology Data Exchange (ETDEWEB)

Rauscher, Lindy, E-mail: purplerauscher@neb.rr.com [School of Natural Resources, University of Nebraska, Lincoln, NE 68583-0915 (United States); Sakulthaew, Chainarong, E-mail: chainarong@huskers.unl.edu [School of Natural Resources, University of Nebraska, Lincoln, NE 68583-0915 (United States); Department of Veterinary Technology, Kasetsart University, Bangkok 10900 (Thailand); Comfort, Steve, E-mail: scomfort1@unl.edu [School of Natural Resources, University of Nebraska, Lincoln, NE 68583-0915 (United States)

2012-11-30

Highlights: Black-Right-Pointing-Pointer We quantified the efficacy of slow-release permanganate-paraffin candles to degrade and mineralize PAHs. Black-Right-Pointing-Pointer {sup 14}C-labeled PAHs were used to quantify both adsorption and transformation. Black-Right-Pointing-Pointer Permanganate-treated PAHs were more biodegradable in soil microcosms. Black-Right-Pointing-Pointer A flow-through candle system was used to quantify PAH removal in urban runoff. - Abstract: Surface waters impacted by urban runoff in metropolitan areas are becoming increasingly contaminated with polycyclic aromatic hydrocarbons (PAHs). Slow-release oxidant candles (paraffin-KMnO{sub 4}) are a relatively new technology being used to treat contaminated groundwater and could potentially be used to treat urban runoff. Given that these candles only release permanganate when submerged, the ephemeral nature of runoff events would influence when the permanganate is released for treating PAHs. Our objective was to determine if slow-release permanganate candles could be used to degrade and mineralize PAHs. Batch experiments quantified PAH degradation rates in the presence of the oxidant candles. Results showed most of the 16 PAHs tested were degraded within 2-4 h. Using {sup 14}C-labled phenanthrene and benzo(a)pyrene, we demonstrated that the wax matrix of the candle initially adsorbs the PAH, but then releases the PAH back into solution as transformed, more water soluble products. While permanganate was unable to mineralize the PAHs (i.e., convert to CO{sub 2}), we found that the permanganate-treated PAHs were much more biodegradable in soil microcosms. To test the concept of using candles to treat PAHs in multiple runoff events, we used a flow-through system where urban runoff water was pumped over a miniature candle in repetitive wet-dry, 24-h cycles. Results showed that the candle was robust in removing PAHs by repeatedly releasing permanganate and degrading the PAHs. These results provide

Variations of emission characterization of PAHs emitted from different utility boilers of coal-fired power plants and risk assessment related to atmospheric PAHs

Energy Technology Data Exchange (ETDEWEB)

Wang, Ruwei [CAS Key Laboratory of Crust-Mantle and the Environment, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, Anhui (China); State Key Laboratory of Loess and Quaternary Geology, Institute of Earth Environment, The Chinese Academy of Sciences, Xi' an 710075, Shanxi (China); Liu, Guijian, E-mail: lgj@ustc.edu.cn [CAS Key Laboratory of Crust-Mantle and the Environment, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, Anhui (China); State Key Laboratory of Loess and Quaternary Geology, Institute of Earth Environment, The Chinese Academy of Sciences, Xi' an 710075, Shanxi (China); Zhang, Jiamei [CAS Key Laboratory of Crust-Mantle and the Environment, School of Earth and Space Sciences, University of Science and Technology of China, Hefei, Anhui (China)

2015-12-15

Coal-fired power plants (CFPPs) represent important source of atmospheric PAHs, however, their emission characterization are still largely unknown. In this work, the concentration, distribution and gas-particle partitioning of PM{sub 10}- and gas-phase PAHs in flue gas emitted from different coal-fired utility boilers were investigated. Moreover, concentration and distribution in airborne PAHs from different functional areas of power plants were studied. People's inhalatory and dermal exposures to airborne PAHs at these sites were estimated and their resultant lung cancer and skin cancer risks were assessed. Results indicated that the boiler capacity and operation conditions have significant effect on PAH concentrations in both PM{sub 10} and gas phases due to the variation of combustion efficiency, whereas they take neglected effect on PAH distributions. The wet flue gas desulphurization (WFGD) takes significant effect on the scavenging of PAH in both PM{sub 10} and gas phases, higher scavenging efficiency were found for less volatile PAHs. PAH partitioning is dominated by absorption into organic matter and accompanied by adsorption onto PM{sub 10} surface. In addition, different partitioning mechanism is observed for individual PAHs, which is assumed arising from their chemical affinity and vapor pressure. Risk assessment indicates that both inhalation and dermal contact greatly contribute to the cancer risk for CFPP workers and nearby residents. People working in workshop are exposed to greater inhalation and dermal exposure risk than people living in nearby vicinity and working office. - Highlights: • PAH distribution in PM{sub 10} and gas phases primarily depend on the vapor pressure. • Combustion conditions and WFGD show typical effects on PAH level and profile. • PAH partitioning is dominated by absorption and also accompanied by adsorption. • Individual PAHs show different partitioning mechanisms in PM{sub 10}- and gas-phases. • People in

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

International Nuclear Information System (INIS)

Jarvis, Ian W.H.; Bergvall, Christoffer; Bottai, Matteo; Westerholm, Roger; Stenius, Ulla; Dreij, Kristian

2013-01-01

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

Energy Technology Data Exchange (ETDEWEB)

Jarvis, Ian W.H., E-mail: Ian.Jarvis@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Bergvall, Christoffer, E-mail: Christoffer.Bergvall@anchem.su.se [Department of Analytical Chemistry, Stockholm University, Svante Arrhenius väg 16, SE-106 91 Stockholm (Sweden); Bottai, Matteo, E-mail: Matteo.Bottai@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Westerholm, Roger, E-mail: Roger.Westerholm@anchem.su.se [Department of Analytical Chemistry, Stockholm University, Svante Arrhenius väg 16, SE-106 91 Stockholm (Sweden); Stenius, Ulla, E-mail: Ulla.Stenius@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden); Dreij, Kristian, E-mail: Kristian.Dreij@ki.se [Institute of Environmental Medicine, Karolinska Institutet, Box 210, SE-171 77 Stockholm (Sweden)

2013-02-01

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNA damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.

The adsorption of allergoids and 3-O-desacyl-4'-monophosphoryl lipid A (MPL®) to microcrystalline tyrosine (MCT) in formulations for use in allergy immunotherapy.

Science.gov (United States)

Bell, A J; Heath, M D; Hewings, S J; Skinner, M A

2015-11-01

Infectious disease vaccine potency is affected by antigen adjuvant adsorption. WHO and EMA guidelines recommend limits and experimental monitoring of adsorption in vaccines and allergy immunotherapies. Adsorbed allergoids and MPL® in MATA-MPL allergy immunotherapy formulations effectively treat IgE mitigated allergy. Understanding vaccine antigen adjuvant adsorption allows optimisation of potency and should be seen as good practice; however current understanding is seldom applied to allergy immunotherapies. The allergoid and MPL® adsorption to MCT in MATA-MPL allergy immunotherapy formulations was experimental determination using specific allergen IgE allerginicity and MPL® content methods. Binding forces between MPL® and MCT were investigated by competition binding experiments. MATA-MPL samples with different allergoids gave results within 100-104% of the theoretical 50μg/mL MPL® content. Unmodified drug substance samples showed significant desirable IgE antigenicity, 1040-170 QAU/mL. MATA-MPL supernatant samples with different allergoids gave results of ≤2 μg/mL MPL® and ≤0.1-1.4 QAU/mL IgE antigenicity, demonstrating approximately ≥96 & 99% adsorption respectively. Allergoid and MPL® adsorption in different MATA-MPL allergy immunotherapy formulations is consistent and meets guideline recommendations. MCT formulations treated to disrupt electrostatic, hydrophobic and ligand exchange interactions, gave an MPL® content of ≤2 μg/mL in supernatant samples. MCT formulations treated to disrupt aromatic interactions, gave an MPL® content of 73-92 μg/mL in supernatant samples. MPL® adsorption to l-tyrosine in MCT formulations is based on interactions between the 2-deoxy-2-aminoglucose backbone on MPL® and aromatic ring of l-tyrosine in MCT, such as C-H⋯π interaction. MCT could be an alternative adjuvant depot for some infectious disease antigens. Copyright © 2015. Published by Elsevier Inc.

Development of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT®) questionnaire: a new patient-reported outcome instrument for PAH.

Science.gov (United States)

McCollister, Deborah; Shaffer, Shannon; Badesch, David B; Filusch, Arthur; Hunsche, Elke; Schüler, René; Wiklund, Ingela; Peacock, Andrew

2016-06-14

Regulators and clinical experts increasingly recognize the importance of incorporating patient-reported outcomes (PROs) in clinical studies of therapies for pulmonary arterial hypertension (PAH). No PAH-specific instruments have been developed to date in accordance with the 2009 FDA guidance for the development of PROs as endpoints in clinical trials. A qualitative research study was conducted to develop a new instrument assessing PAH symptoms and their impacts following the FDA PRO guidance. A cross-sectional study was conducted at 5 centers in the US in symptomatic PAH patients aged 18-80 years. Concept elicitation was based on 5 focus group discussions, after which saturation of emergent concepts was reached. A PRO instrument for PAH symptoms and their impacts was drafted. To assess the appropriateness of items, instructions, response options, and recall periods, 2 rounds of one-on-one cognitive interviews were conducted, with instrument revisions following each round. Additional interviews tested the usability of an electronic version (ePRO). PRO development considered input from an international Steering Committee, and translatability and lexibility assessments. Focus groups comprised 25 patients (5 per group); 20 additional patients participated in cognitive interviews (10 per round); and 10 participated in usability interviews. Participants had a mean ± SD age of 53.1 ± 15.8 years, were predominantly female (93 %), and were diverse in race/ethnicity, WHO functional class (FC I/II: 56 %, III/IV: 44 %), and PAH etiology (idiopathic: 56 %, familial: 2 %, associated: 42 %). The draft PRO instrument (PAH-SYMPACT®) was found to be clear, comprehensive, and relevant to PAH patients in cognitive interviews. Items were organized in a draft conceptual framework with 16 symptom items in 4 domains (respiratory symptoms, tiredness, cardiovascular symptoms, other symptoms) and 25 impact items in 5 domains (physical activities, daily activities, social

Differences in MCT1 A1470T polymorphism prevalence between runners and swimmers.

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Ben-Zaken, S; Eliakim, A; Nemet, D; Rabinovich, M; Kassem, E; Meckel, Y

2015-06-01

Skeletal muscle is the major producer and user of lactate in the body. Therefore, transport of lactate across cells' membrane is of considerable importance. Lactate transport is mediated by proton-linked monocarboxylate transporter (MCT1). The A1470T polymorphism (rs1049434) in MCT1 gene influences lactate transport, with T allele associated with reduction of lactate transport rate and elevation in blood lactate levels. The aim of the current study was to compare allelic and genotype frequencies of MCT1 A1470T polymorphism among Israeli track-and-field athletes, swimmers, and non-athletes. Genomic DNA was extracted from 173 track-and-field athletes (age 17-50), 80 swimmers (age 16-49), and 128 non-athletes (age 19-29). Track-and-field athletes were assigned to three subgroups: long-distance runners, middle-distance runners, and power event athletes. Swimmers were assigned to two subgroups: long-distance swimmers and short-distance swimmers. Genotyping was performed using polymerase chain reaction. T-allele frequency was significantly higher among long-distance swimmers (45%) compared with long- and middle-distance runners (27% and 30%, respectively; P < 0.01). In addition, T-allele frequency was significantly higher among short-distance swimmers (40%) compared with power event athletes (25%, P < 0.01). Overall, T-allele frequency was significantly higher among swimmers (42%) compared with runners (27%, P < 0.001). More research is needed to clarify whether this polymorphism displays advantage for swimming performance. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Source characterisation and distribution of selected PCBs, PAHs and alkyl PAHs in sediments from the Klip and Jukskei Rivers, South Africa.

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Rimayi, Cornelius; Chimuka, Luke; Odusanya, David; de Boer, Jacob; Weiss, Jana M

2017-07-01

A study of the distribution of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) utilising 16 priority PAHs, benzo(e)pyrene, perylene, 19 alkylated PAHs and 31 ortho substituted PCBs in South Africa is presented. It was aimed to (a) deduce characteristic contamination patterns for both PCBs and PAHs and (b) provide the first comprehensive dataset for establishment of source characterisation of PCBs and PAHs. This is in line with new South African legislation on mandatory monitoring of PCB and PAH emissions. Bar charts, principal component analysis (PCA) and biplots were utilised to identify signature contamination patterns and distribution of PCBs and PAHs within the Jukskei and Klip Rivers. Sediments from the Jukskei and Klip River catchments both showed distinct contamination signatures for hexa to nonachlorinated PCBs, characteristic of contamination by Aroclor 1254 and 1260 technical mixtures. PCB signature patterns in order of abundance were 138 > 180 > 206 > 153 > 187 > 149 and 138 > 153 > 180 > 149 > 187 > 110 > 170 for the Jukskei and Klip River sediments, respectively. The upstream Alberton point had the highest Σ31 PCB and Σ (parent+alkyl) PAH concentrations in the Klip River of 61 and 6000 μg kg -1 dry weight (dw), respectively. In the Jukskei River, the upstream Marlboro point had the highest Σ31 PCB concentration of 19 μg kg -1 dw and the N14 site recorded the highest Σ (parent+alkyl) PAH concentration of 2750 μg kg -1 dw. PAH concentrations in both the Jukskei and Klip Rivers were significantly higher than the PCB concentrations. Fluoranthene, phenanthrene and pyrene were found in the highest concentrations in both the Jukskei and Klip River sediments. Both the Jukskei and Klip River sediments showed trends of a mixed pyrogenic-petrogenic PAH source contamination.

The Role of Human Aldo-Keto Reductases in the Metabolic Activation and Detoxication of Polycyclic Aromatic Hydrocarbons: Interconversion of PAH Catechols and PAH o-Quinones

Science.gov (United States)

Zhang, Li; Jin, Yi; Huang, Meng; Penning, Trevor M.

2012-01-01

Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants. They are procarcinogens requiring metabolic activation to elicit their deleterious effects. Aldo-keto reductases (AKR) catalyze the oxidation of proximate carcinogenic PAH trans-dihydrodiols to yield electrophilic and redox-active PAH o-quinones. AKRs are also found to be capable of reducing PAH o-quinones to form PAH catechols. The interconversion of o-quinones and catechols results in the redox-cycling of PAH o-quinones to give rise to the generation of reactive oxygen species and subsequent oxidative DNA damage. On the other hand, PAH catechols can be intercepted through phase II metabolism by which PAH o-quinones could be detoxified and eliminated. The aim of the present review is to summarize the role of human AKRs in the metabolic activation/detoxication of PAH and the relevance of phase II conjugation reactions to human lung carcinogenesis. PMID:23162467

Characteristics of PAHs from deep-frying and frying cooking fumes.

Science.gov (United States)

Yao, Zhiliang; Li, Jing; Wu, Bobo; Hao, Xuewei; Yin, Yong; Jiang, Xi

2015-10-01

Cooking fumes are an important indoor source of polycyclic aromatic hydrocarbons (PAHs). Because indoor pollution has a more substantial impact on human health than outdoor pollution, PAHs from cooking fumes have drawn considerable attention. In this study, 16 PAHs emitted through deep-frying and frying methods using rapeseed, soybean, peanut, and olive oil were examined under a laboratory fume hood. Controlled experiments were conducted to collect gas- and particulate-phase PAHs emitted from the cooking oil fumes, and PAH concentrations were quantified via high-performance liquid chromatography (HPLC). The results show that deep-frying methods generate more PAHs and benzo[a]pyrene (B[a]P) (1.3 and 10.9 times, respectively) because they consume greater volumes of edible oil and involve higher oil temperatures relative to those of frying methods. In addition, the total B[a]Peq concentration of deep-frying is 2.2-fold larger than that of frying. Regarding the four types of edible oils studied, rapeseed oil produced more PAH emission than the other three oil varieties. For all of the cooking tests, three- and four-ringed PAHs were the main PAH components regardless of the food and oil used. Concerning the PAH partition between gas and particulate phase, the gaseous compounds accounted for 59-96 % of the total. Meanwhile, the particulate fraction was richer of high molecular weight PAHs (five-six rings). Deep-frying and frying were confirmed as important sources of PAH pollution in internal environments. The results of this study provide additional insights into the polluting features of PAHs produced via cooking activities in indoor environments.

The hydrogen coverage of interstellar PAHs [Polycyclic Aromatic Hydrocarbons

International Nuclear Information System (INIS)

Tielens, A.G.G.M.; Allamandola, L.J.; Barker, J.R.; Cohen, M.

1986-02-01

The rate at which the CH bond in interstellar Polycyclic Aromatic Hydrocarbons (PAHs) rupture due to the absorption of a uv photon has been calculated. The results show that small PAHs (less than or equal to 25 carbon atoms) are expected to be partially dehydrogenated in regions with intense uv fields, while large PAHs (greater than or equal to 25 atoms) are expected to be completely hydrogenated in those regions. Because estimate of the carbon content of interstellar PAHs lie in the range of 20 to 25 carbon atoms, dehydrogenation is probably not very important. Because of the absence of other emission features besides the 11.3 micrometer feature in ground-based 8 to 13 micrometer spectra, it has been suggested that interstellar PAHs are partially dehydrogenated. However, IRAS 8 to 22 micrometer spectra of most sources that show strong 7.7 and 11.2 micrometer emission features also show a plateau of emission extending from about 11.3 to 14 micrometer. Like the 11.3 micrometer feature, this new feature is attributed to the CH out of plane bending mode in PAHs. This new feature shows that interstellar PAHs are not as dehydrogenated as estimated from ground-based 8 to 13 micrometer spectra. It also constrains the molecular structure of interstellar PAHs. In particular, it seems that very condensed PAHs, such as coronene and circumcoronene, dominate the interstellar PAH mixture as expected from stability arguments

Fungal Community Successions in Rhizosphere Sediment of Seagrasses Enhalus acoroides under PAHs Stress

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Juan Ling

2015-06-01

Full Text Available Seagrass meadows represent one of the highest productive marine ecosystems and are of great ecological and economic values. Recently, they have been confronted with worldwide decline. Fungi play important roles in sustaining the ecosystem health as degraders of polycyclic aromatic hydrocarbons (PAHs, but fewer studies have been conducted in seagrass ecosystems. Hence, we investigated the dynamic variations of the fungal community succession under PAH stress in rhizosphere sediment of seagrasses Enhalus acoroides in this study. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE, quantitative PCR (qPCR and a clone library have been employed to analyze the fungal community’s shifts. Sequencing results of DGGE and the clone library showed that the predominant species belong to phyla Ascomycota and Basidiomycota. The abundance of three groups decreased sharply over the incubation period, whereas they demonstrated different fungal diversity patterns. Both the exposure time and the PAH concentrations affected the microbial diversity as assessed by PCR-DGGE analysis. Redundancy analysis (RDA indicated that significant factors driving community shifts were ammonium and pH (p < 0.05. Significant amounts of the variations (31.1% were explained by pH and ammonium, illustrating that those two parameters were the most likely ones to influence or be influenced by the fungal communities’ changes. Investigation results also indicated that fungal communities in seagrass meadow were very sensitive to PAH-induced stress and may be used as potential indicators for the PAH contamination.

Global time trends in PAH emissions from motor vehicles

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Shen, Huizhong; Tao, Shu; Wang, Rong; Wang, Bin; Shen, Guofeng; Li, Wei; Su, Shenshen; Huang, Ye; Wang, Xilong; Liu, Wenxin; Li, Bengang; Sun, Kang

2011-04-01

Emission from motor vehicles is the most important source of polycyclic aromatic hydrocarbons (PAHs) in urban areas. Emission factors of individual PAHs for motor vehicles reported in the literature varied 4 to 5 orders of magnitude, leading to high uncertainty in emission inventory. In this study, key factors affecting emission factors of PAHs (EF PAH) for motor vehicles were evaluated quantitatively based on thousands of EF PAH measured in 16 countries for over 50 years. The result was used to develop a global emission inventory of PAHs from motor vehicles. It was found that country and vehicle model year are the most important factors affecting EF PAH, which can be quantified using a monovariate regression model with per capita gross domestic production (purchasing power parity) as a sole independent variable. On average, 29% of variation in log-transformed EF PAH could be explained by the model, which was equivalent to 90% reduction in overall uncertainty on arithmetic scale. The model was used to predict EF PAH and subsequently PAH emissions from motor vehicles for various countries in the world during a period from 1971 to 2030. It was estimated that the global emission reached its peak value of approximate 101 Gg in 1978 and decreased afterwards due to emission control in developed countries. The annual emission picked up again since 1990 owing to accelerated energy consumption in China and other developing countries. With more and more rigid control measures taken in the developing world, global emission of PAHs is currently passing its second peak. It was predicted that the emission would decrease from 77 Gg in 2010 to 42 Gg in 2030.

Specific long non-coding RNAs response to occupational PAHs exposure in coke oven workers.

Science.gov (United States)

Gao, Chen; He, Zhini; Li, Jie; Li, Xiao; Bai, Qing; Zhang, Zhengbao; Zhang, Xiao; Wang, Shan; Xiao, Xinhua; Wang, Fangping; Yan, Yan; Li, Daochuan; Chen, Liping; Zeng, Xiaowen; Xiao, Yongmei; Dong, Guanghui; Zheng, Yuxin; Wang, Qing; Chen, Wen

2016-01-01

To explore whether the alteration of lncRNA expression is correlated with polycyclic aromatic hydrocarbons (PAHs) exposure and DNA damage, we examined PAHs external and internal exposure, DNA damage and lncRNAs (HOTAIR, MALAT1, TUG1 and GAS5) expression in peripheral blood lymphocytes (PBLCs) of 150 male coke oven workers and 60 non-PAHs exposure workers. We found the expression of HOTAIR, MALAT1, and TUG1 were enhanced in PBLCs of coke oven workers and positively correlated with the levels of external PAHs exposure (adjusted P trend  TUG1). However, only HOTAIR and MALAT1 were significantly associated with the level of internal PAHs exposure (urinary 1-hydroxypyrene) with adjusted β  = 0.298, P  = 0.024 for HOTAIR and β  = 0.090, P  = 0.034 for MALAT1. In addition, the degree of DNA damage was positively associated with MALAT1 and HOTAIR expression in PBLCs of all subjects (adjusted β  = 0.024, P  = 0.002 for HOTAIR and β  = 0.007, P  = 0.003 for MALAT1). Moreover, we revealed that the global histone 3 lysine 27 trimethylation (H3K27me3) modification was positively associated with the degree of genetic damage ( β  = 0.061, P  < 0.001) and the increase of HOTAIR expression ( β  = 0.385, P  = 0.018). Taken together, our findings suggest that altered HOTAIR and MALAT1 expression might be involved in response to PAHs-induced DNA damage.

Variations of emission characterization of PAHs emitted from different utility boilers of coal-fired power plants and risk assessment related to atmospheric PAHs.

Science.gov (United States)

Wang, Ruwei; Liu, Guijian; Zhang, Jiamei

2015-12-15

Coal-fired power plants (CFPPs) represent important source of atmospheric PAHs, however, their emission characterization are still largely unknown. In this work, the concentration, distribution and gas-particle partitioning of PM10- and gas-phase PAHs in flue gas emitted from different coal-fired utility boilers were investigated. Moreover, concentration and distribution in airborne PAHs from different functional areas of power plants were studied. People's inhalatory and dermal exposures to airborne PAHs at these sites were estimated and their resultant lung cancer and skin cancer risks were assessed. Results indicated that the boiler capacity and operation conditions have significant effect on PAH concentrations in both PM10 and gas phases due to the variation of combustion efficiency, whereas they take neglected effect on PAH distributions. The wet flue gas desulphurization (WFGD) takes significant effect on the scavenging of PAH in both PM10 and gas phases, higher scavenging efficiency were found for less volatile PAHs. PAH partitioning is dominated by absorption into organic matter and accompanied by adsorption onto PM10 surface. In addition, different partitioning mechanism is observed for individual PAHs, which is assumed arising from their chemical affinity and vapor pressure. Risk assessment indicates that both inhalation and dermal contact greatly contribute to the cancer risk for CFPP workers and nearby residents. People working in workshop are exposed to greater inhalation and dermal exposure risk than people living in nearby vicinity and working office. Copyright © 2015. Published by Elsevier B.V.

The cataract and glucosuria associated monocarboxylate transporter MCT12 is a new creatine transporter

Science.gov (United States)

Abplanalp, Jeannette; Laczko, Endre; Philp, Nancy J.; Neidhardt, John; Zuercher, Jurian; Braun, Philipp; Schorderet, Daniel F.; Munier, Francis L.; Verrey, François; Berger, Wolfgang; Camargo, Simone M.R.; Kloeckener-Gruissem, Barbara

2013-01-01

Creatine transport has been assigned to creatine transporter 1 (CRT1), encoded by mental retardation associated SLC6A8. Here, we identified a second creatine transporter (CRT2) known as monocarboxylate transporter 12 (MCT12), encoded by the cataract and glucosuria associated gene SLC16A12. A non-synonymous alteration in MCT12 (p.G407S) found in a patient with age-related cataract (ARC) leads to a significant reduction of creatine transport. Furthermore, Slc16a12 knockout (KO) rats have elevated creatine levels in urine. Transport activity and expression characteristics of the two creatine transporters are distinct. CRT2 (MCT12)-mediated uptake of creatine was not sensitive to sodium and chloride ions or creatine biosynthesis precursors, breakdown product creatinine or creatine phosphate. Increasing pH correlated with increased creatine uptake. Michaelis–Menten kinetics yielded a Vmax of 838.8 pmol/h/oocyte and a Km of 567.4 µm. Relative expression in various human tissues supports the distinct mutation-associated phenotypes of the two transporters. SLC6A8 was predominantly found in brain, heart and muscle, while SLC16A12 was more abundant in kidney and retina. In the lens, the two transcripts were found at comparable levels. We discuss the distinct, but possibly synergistic functions of the two creatine transporters. Our findings infer potential preventive power of creatine supplementation against the most prominent age-related vision impaired condition. PMID:23578822

Using slow-release permanganate candles to remediate PAH-contaminated water.

Science.gov (United States)

Rauscher, Lindy; Sakulthaew, Chainarong; Comfort, Steve

2012-11-30

Surface waters impacted by urban runoff in metropolitan areas are becoming increasingly contaminated with polycyclic aromatic hydrocarbons (PAHs). Slow-release oxidant candles (paraffin-KMnO(4)) are a relatively new technology being used to treat contaminated groundwater and could potentially be used to treat urban runoff. Given that these candles only release permanganate when submerged, the ephemeral nature of runoff events would influence when the permanganate is released for treating PAHs. Our objective was to determine if slow-release permanganate candles could be used to degrade and mineralize PAHs. Batch experiments quantified PAH degradation rates in the presence of the oxidant candles. Results showed most of the 16 PAHs tested were degraded within 2-4 h. Using (14)C-labled phenanthrene and benzo(a)pyrene, we demonstrated that the wax matrix of the candle initially adsorbs the PAH, but then releases the PAH back into solution as transformed, more water soluble products. While permanganate was unable to mineralize the PAHs (i.e., convert to CO(2)), we found that the permanganate-treated PAHs were much more biodegradable in soil microcosms. To test the concept of using candles to treat PAHs in multiple runoff events, we used a flow-through system where urban runoff water was pumped over a miniature candle in repetitive wet-dry, 24-h cycles. Results showed that the candle was robust in removing PAHs by repeatedly releasing permanganate and degrading the PAHs. These results provide proof-of-concept that permanganate candles could potentially provide a low-cost, low-maintenance approach to remediating PAH-contaminated water. Copyright © 2012 Elsevier B.V. All rights reserved.

Valsartan attenuates pulmonary hypertension via suppression of mitogen activated protein kinase signaling and matrix metalloproteinase expression in rodents.

Science.gov (United States)

Lu, Yuyan; Guo, Haipeng; Sun, Yuxi; Pan, Xin; Dong, Jia; Gao, Di; Chen, Wei; Xu, Yawei; Xu, Dachun

2017-08-01

It has previously been demonstrated that the renin-angiotensin system is involved in the pathogenesis and development of pulmonary hypertension (PH). However, the efficacy of angiotensin II type I (AT1) receptor blockers in the treatment of PH is variable. The present study examined the effects of the AT1 receptor blocker valsartan on monocrotaline (MCT)‑induced PH in rats and chronic hypoxia‑induced PH in mice. The results demonstrated that valsartan markedly attenuated development of PH in rats and mice, as indicated by reduced right ventricular systolic pressure, diminished lung vascular remodeling and decreased right ventricular hypertrophy, compared with vehicle treated animals. Immunohistochemical analyses of proliferating cell nuclear antigen expression revealed that valsartan suppressed smooth muscle cell proliferation. Western blot analysis demonstrated that valsartan limited activation of p38, c‑Jun N‑terminal kinase 1/2 and extracellular signal‑regulated kinase 1/2 signaling pathways and significantly reduced MCT‑induced upregulation of pulmonary matrix metalloproteinases‑2 and ‑9, and transforming growth factor‑β1 expression. The results suggested that valsartan attenuates development of PH in rodents by reducing expression of extracellular matrix remodeling factors and limiting smooth muscle cell proliferation to decrease pathological vascular remodeling. Therefore, valsartan may be a valuable future therapeutic approach for the treatment of PH.

Coal-tar pavement sealants might substantially increase children's PAH exposures

Science.gov (United States)

Williams, E. Spencer; Mahler, Barbara J.; Van Metre, Peter C.

2012-01-01

Dietary ingestion has been identified repeatedly as the primary route of human exposure to polycyclic aromatic hydrocarbons (PAHs), seven of which are classified as probable human carcinogens (B2 PAHs) by the U.S. EPA. Humans are exposed to PAHs through ingestion of cooked and uncooked foods, incidental ingestion of soil and dust, inhalation of ambient air, and absorption through skin. Although PAH sources are ubiquitous in the environment, one recently identified PAH source stands out: Coal-tar-based pavement sealant—a product applied to many parking lots, driveways, and even playgrounds primarily in the central, southern, and eastern U.S.—has PAH concentrations 100–1000 times greater than most other PAH sources. It was reported recently that PAH concentrations in house dust in residences adjacent to parking lots with coal-tar-based sealant were 25 times higher than in residences adjacent to unsealed asphalt parking lots.

THE FAR-INFRARED EMISSION FROM THE Mg+-PAH SPECIES

International Nuclear Information System (INIS)

Bauschlicher, Charles W. Jr.; Ricca, Alessandra

2009-01-01

The far-infrared (FIR) spectra of several Mg + -PAH species are studied using density functional theory. The Mg + -PAH stretching mode, regardless of the polycyclic aromatic hydrocarbon (PAH) species, carries a reasonable intensity and tends to fall in a narrow range near 40 μm. Because the bands tend to fall at very similar frequencies, the average spectra of several Mg + -PAH species produce a broadband with an intensity that is about 20% of the well known C-H out-of-plane bending mode. In contrast, an average of seven large compact pure PAHs has no FIR bands that carry any significant intensity.

Sources of polyaromatic hydrocarbons (PAH); Kildebestemmelse af polyaromatiske kulbrinter (PAH)

Energy Technology Data Exchange (ETDEWEB)

Egsgaard, H. [Forskningscenetr Risoe, Ald. for Plantebiologi og Biokemi (DK); Larsen, E. [Forskningscenter Risoe, Ald. for Optic og Fluid Dynamik (Denmark)

2000-03-01

Aromatic hydrocarbons including PAH compounds are thermally and chemically very stable compounds and are formed by gasification/pyrolysis of biomass. With reference to the tar compounds present in the produced gas from updraft gasifiers the sources responsible for the formation of naphthalene and poly-aromatic hydrocarbons have been investigated. The focus has been on thermal and oxidative conversions of compounds related to the lignin building blocks. Thus, phenols, 2-methoxy-phenols and 4-substituted-2-methoxy-phenols were investigated by introducing water solutions of the compounds into a continuos flow system operating in the temperature range 600-850 deg. C. The pyrolysis products were identified by GC/MS. The tar compounds reveal a well-defined and characteristic thermal transformation. Phenol is a strong source to naphthalene and indenes while 2-methoxyphenols are sources to aromatic oxo-compounds such as cinnamaldehyde. More complex systems are sources to higer PAH compounds. Thus, oligomers of phenol and 2-methoxyphenol give dibenzofuran and oligomers of isoeugenol are important sources to acenaphthylene. It is characteristic that the simple tar compounds investigated undergo loss of CO and hereby loss of the aromatic structure. The intermediary compounds are very reactive cyclo-pentadienes entering Diels-Alder reactions. The later products are transformed to aromatic compounds. The results may facilitate the determination of optimum conditions for updraft gasifiers and hence a reduction of PAH formation. (au)

Fast analysis of 29 polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs with ultra-high performance liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometry

Science.gov (United States)

Lung, Shih-Chun Candice; Liu, Chun-Hu

2015-01-01

Polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs are ubiquitous in the environment. Some of them are probable carcinogens and some are source markers. This work presents an ultra-high performance liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometry (UHPLC-APPI-MS/MS) method for simultaneous analysis of 20 PAHs and nine nitro-PAHs. These compounds are separated in 15 minutes in the positive mode and 11 minutes in the negative mode, one half of GC/MS analysis time. Two pairs of precursor/product ions are offered, which is essential for confirmation. This method separates and quantifies benzo[a]pyrene (the most toxic PAHs) and non-priority benzo[e]pyrene (isomers, little toxicity) to avoid overestimation of toxin levels, demonstrating its importance for health-related researches. With 0.5% 2,4-difluoroanisole in chlorobenzene as the dopant, limits of detection of PAHs except acenaphthylene and those of nitro-PAHs except 2-nitrofluoranthene are below 10 pg and 3 pg, respectively, mostly lower than or comparable to those reported using LC-related systems. The responses were linear over two orders of magnitude with fairly good accuracy and precision. Certified reference materials and real aerosol samples were analyzed to demonstrate its applicability. This fast, sensitive, and reliable method is the first UHPLC-APPI-MS/MS method capable of simultaneously analyzing 29 environmentally and toxicologically important PAHs and nitro-PAHs. PMID:26265155

The Role of Human Aldo-Keto Reductases (AKRs in the Metabolic Activation and Detoxication of Polycyclic Aromatic Hydrocarbons: Interconversion of PAH-catechols and PAH o-Quinones

Directory of Open Access Journals (Sweden)

Li eZhang

2012-11-01

Full Text Available Polycyclic aromatic hydrocarbons (PAH are ubiquitous environmental pollutants. They are procarcinogens requiring metabolic activation to elicit their deleterious effects. Aldo-keto reductases (AKR catalyze the oxidation of proximate carcinogenic PAH trans-dihydrodiols to yield electrophilic and redox-active PAH o-quiniones. AKRs are also found to be capable of reducing PAH o-quinones to form PAH catechols. The interconversion of o-quinones and catechols results in the redox cycling of PAH o-quinones to give rise to the generation of reactive oxygen species and subsequent oxidative DNA damage. On the other hand, PAH catechols can be intercepted through phase II metabolism by which PAH o-quinones could be detoxified and eliminated. The aim of the present review is to summarize the role of human AKRs in the metabolic activation/detoxication of PAH and the relevance of phase II conjugation reactions to human lung carcinogenesis.

Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish

International Nuclear Information System (INIS)

Goodale, Britton C.; Tilton, Susan C.; Corvi, Margaret M.; Wilson, Glenn R.; Janszen, Derek B.; Anderson, Kim A.; Waters, Katrina M.; Tanguay, Robert L.

2013-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the aryl hydrocarbon receptor (AHR) in a structurally dependent manner, and induce toxicity via both AHR-dependent and -independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at concentrations that induced developmental malformations by 120 h post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burdens were analyzed at both time points using GC–MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the least number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure, and may provide a path for unraveling the toxicity of complex PAH mixtures. - Highlights: • Defined global mRNA expression

Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension

International Nuclear Information System (INIS)

Lim, Jisun; Kim, YongHwan; Heo, Jinbeom; Kim, Kang-Hyun; Lee, Seungun; Lee, Sei Won; Kim, Kyunggon; Kim, In-Gyu; Shin, Dong-Myung

2016-01-01

Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called “priming” factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 μM C1P showed improved migration activity in Transwell assays compared with non-primed MSCs and concomitantly activated MAPK p42/44 and AKT signaling cascades. Although C1P priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit-fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with C1P significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of α-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that C1P priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti-inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients. - Highlights: • Human BM-derived MSCs primed with C1P have enhanced migratory activity. • C1P primed MSCs increase proliferation, self-renewal, and anti-inflammatory capacity. • C1P priming enhances the therapeutic capacity of MSCs in a PAH animal model.

Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension

Energy Technology Data Exchange (ETDEWEB)

Lim, Jisun [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Physiology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul 05505 (Korea, Republic of); Kim, YongHwan; Heo, Jinbeom; Kim, Kang-Hyun; Lee, Seungun [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Physiology, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Lee, Sei Won [Department of Pulmonary and Critical Care Medicine and Clinical Research Center for Chronic Obstructive Airway Diseases, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, Kyunggon [Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Clinical Proteomics Core Lab, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Kim, In-Gyu, E-mail: igkim@plaza.snu.ac.kr [Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 88 Olympic-ro 43 gil, Songpa-gu, Seoul 05505 (Korea, Republic of); Shin, Dong-Myung, E-mail: d0shin03@amc.seoul.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Department of Physiology, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2016-04-22

Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called “priming” factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 μM C1P showed improved migration activity in Transwell assays compared with non-primed MSCs and concomitantly activated MAPK{sup p42/44} and AKT signaling cascades. Although C1P priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit-fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with C1P significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of α-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that C1P priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti-inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients. - Highlights: • Human BM-derived MSCs primed with C1P have enhanced migratory activity. • C1P primed MSCs increase proliferation, self-renewal, and anti-inflammatory capacity. • C1P priming enhances the therapeutic capacity of MSCs in a PAH animal model.

Effect of rhamnolipids on the uptake of PAHs by ryegrass

International Nuclear Information System (INIS)

Zhu Lizhong; Zhang Ming

2008-01-01

A hydroponic experiment was conducted to investigate the effect of rhamnolipids, a biosurfactant, on the uptake of polycyclic aromatic hydrocarbons (PAHs) by ryegrass. Results showed that rhamnolipids could enhance the uptake of PAHs by ryegrass roots. With increasing concentration of rhamnolipids, the PAH content in ryegrass roots initially increased and then decreased, while the PAH content in ryegrass shoots did not change. Batch studies also showed that the sorption of phenanthrene by fresh ryegrass roots was dependent on rhamnolipid concentration and showed the same trends as the uptake experiment. The increase of permeability of ryegrass root cells with the increase of rhamnolipid concentration may lead to the initial enhancement of PAH content in ryegrass roots, and the decrease of PAH adsorption onto the root surface with further increase of rhamnolipids led to the decrease of PAH content in ryegrass roots. - Rhamnolipids, a biosurfactant, can promote the uptake of PAHs by ryegrass, which indicates a potential application of surfactant-enhanced phytoremediation

Effect of rhamnolipids on the uptake of PAHs by ryegrass

Energy Technology Data Exchange (ETDEWEB)

Zhu Lizhong [Department of Environmental Science, Zhejiang University, Hangzhou, Zhejiang 310028 (China); Ministry of Education Key Laboratory of Environmental Remediation and Ecological Health, Zhejiang University, Hangzhou, Zhejiang 310029 (China)], E-mail: zlz@zju.edu.cn; Zhang Ming [Department of Environmental Science, Zhejiang University, Hangzhou, Zhejiang 310028 (China)], E-mail: zhangming@zju.edu.cn

2008-11-15

A hydroponic experiment was conducted to investigate the effect of rhamnolipids, a biosurfactant, on the uptake of polycyclic aromatic hydrocarbons (PAHs) by ryegrass. Results showed that rhamnolipids could enhance the uptake of PAHs by ryegrass roots. With increasing concentration of rhamnolipids, the PAH content in ryegrass roots initially increased and then decreased, while the PAH content in ryegrass shoots did not change. Batch studies also showed that the sorption of phenanthrene by fresh ryegrass roots was dependent on rhamnolipid concentration and showed the same trends as the uptake experiment. The increase of permeability of ryegrass root cells with the increase of rhamnolipid concentration may lead to the initial enhancement of PAH content in ryegrass roots, and the decrease of PAH adsorption onto the root surface with further increase of rhamnolipids led to the decrease of PAH content in ryegrass roots. - Rhamnolipids, a biosurfactant, can promote the uptake of PAHs by ryegrass, which indicates a potential application of surfactant-enhanced phytoremediation.

PAH volatilization following application of coal-tar-based pavement sealant

Science.gov (United States)

Van Metre, Peter C.; Majewski, Michael S.; Mahler, Barbara J.; Foreman, William T.; Braun, Christopher L.; Wilson, Jennifer T.; Burbank, Teresa L.

2012-01-01

Coal-tar-based pavement sealants, a major source of PAHs to urban water bodies, have recently been identified as a source of volatile PAHs to the atmosphere. We tracked the volatilization of PAHs for 1 year after application of a coal-tar-based pavement sealant by measuring gas-phase PAH concentrations above the pavement surface and solid-phase PAH concentrations in sealant scraped from the surface. Gas-phase concentrations at two heights (0.03 and 1.28 m) and wind speed were used to estimate volatilization flux. The sum of the concentrations of eight frequently detected PAHs (ΣPAH8) in the 0.03-m sample 1.6 h after application (297,000 ng m-3) was about 5000 times greater than that previously reported for the same height above unsealed parking lots (66 ng m-3). Flux at 1.6 h after application was estimated at 45,000 μg m-2 h-1 and decreased rapidly during the 45 days after application to 160 μg m-2 h-1. Loss of PAHs from the adhered sealant also was rapid, with about a 50% decrease in solid-phase ΣPAH8 concentration over the 45 days after application. There was general agreement, given the uncertainties, in the estimated mass of ΣPAH8 lost to the atmosphere on the basis of air sampling (2–3 g m-2) and adhered sealant sampling (6 g m-2) during the first 16 days after application, translating to a loss to the atmosphere of one-quarter to one-half of the PAHs in the sealcoat product. Combining the estimated mass of ΣPAH8 released to the atmosphere with a national-use estimate of coal-tar-based sealant suggests that PAH emissions from new coal-tar-based sealcoat applications each year (~1000 Mg) are larger than annual vehicle emissions of PAHs for the United States.

Decontamination of soils containing PAHs by electroremediation: a review.

Science.gov (United States)

Pazos, M; Rosales, E; Alcántara, T; Gómez, J; Sanromán, M A

2010-05-15

During the last years, the anthropogenic sources have contributed to organic compound penetration into the environment. One large group of persistent and toxic contaminants is the hydrophobic organic contaminants. Among them, polycyclic aromatic hydrocarbons (PAHs) have been recognized as a representative group of these pollutants with low solubility. In this paper, it is showed the electroremediation of soil contaminated with PAHs as an alternative, to organic compound removal. This technique, mainly used for heavy metal extraction, applies the electric current to promote the movement of contaminants. Nowadays the application of this technique alone or combined with other techniques as for example Fenton or bioremediation is taking fine results to PAHs removal. Although the PAHs soil decontamination by means of the electric field is in an initial stage, many researchers have demonstrated the treatment effectiveness. This paper describes the foremost principles to carry out the electroremediation of soils contaminated with PAHs, just like the different alternatives to improve the electroremediation of PAHs and also the new methodologies of PAHs removal by using hybrid technologies. Copyright (c) 2009 Elsevier B.V. All rights reserved.

PAH emissions from coal combustion and waste incineration.

Science.gov (United States)

Hsu, Wei Ting; Liu, Mei Chen; Hung, Pao Chen; Chang, Shu Hao; Chang, Moo Been

2016-11-15

The characteristics of PAHs that are emitted by a municipal waste incinerator (MWI) and coal-fired power plant are examined via intensive sampling. Results of flue gas sampling reveal the potential for PAH formation within the selective catalytic reduction (SCR) system of a coal-fired power plant. In the large-scale MWI, the removal efficiency of PAHs achieved with the pilot-scaled catalytic filter (CF) exceeds that achieved by activated carbon injection with a bag filter (ACI+BF) owing to the effective destruction of gas-phase contaminants by a catalyst. A significantly lower PAH concentration (1640ng/g) was measured in fly ash from a CF module than from an ACI+BF system (5650ng/g). Replacing the ACI+BF system with CF technology would significantly reduce the discharge factor (including emission and fly ash) of PAHs from 251.6 to 77.8mg/ton-waste. The emission factors of PAHs that are obtained using ACI+BF and the CF system in the MWI are 8.05 and 7.13mg/ton, respectively. However, the emission factor of MWI is significantly higher than that of coal-fired power plant (1.56mg/ton). From the perspective of total environmental management to reduce PAH emissions, replacing the original ACI+BF process with a CF system is expected to reduce environmental impact thereof. Copyright © 2016 Elsevier B.V. All rights reserved.

Relief from Back Pain Through Postural Adjustment: a Controlled Clinical Trial of the Immediate Effects of Muscular Chains Therapy (MCT).

Science.gov (United States)

Rosario, Jose L

2014-09-01

Back pain can be one of the most common health problems, causing suffering, disabilities, and financial losses. Postural models for pain treatment state that poor posture alters the joint position and causes pain, such as back pain. Muscular Chain Therapy (MCT) is a technique that is used to treat posture pathologies, among others. The aim of the present study was to assess the efficiency of a single session of Muscular Chain Therapy (MCT) on complaints of undiagnosed musculoskeletal spinal pain. Physical therapy clinic of the University of Center-West (Guarapuava, Brazil). 100 subjects, aged between 20 and 39 years, with complaints of spinal musculoskeletal pain. Randomized controlled trial. The participants were randomly assigned by a non-care provider into two groups: The MCT Group that received Muscular Chain Treatment and the Control Group that received a placebo treatment of 15 minutes turned off ultrasound therapy. All volunteers were assessed before and after treatment using an analog pain scale. A score of 0 indicated no pain and 10 was the maximum degree of pain on the scale. Degree of pain measured by analog scale. The chi-square goodness of fit test was used to compare gender distribution among groups displayed a p value = .25. Subject age had differences analyzed using the unpaired t test (p = .44). Pain assessment for treatment and placebo control groups was analyzed using a paired t test and unpaired t test. The paired t test was used for intragroup before/after treatment comparison (MCT p = .00001; Control Group p = .0001). The unpaired t test was used for comparing the difference of the pain level before and after treatment between groups (p = .0001). A priori statistical significance was set a p = .05. It is possible to conclude that one MCT session is an effective treatment of undiagnosed spinal musculoskeletal pain.

Effects of group metacognitive training (MCT) on mental capacity and functioning in patients with psychosis in a secure forensic psychiatric hospital: a prospective-cohort waiting list controlled study.

LENUS (Irish Health Repository)

Naughton, Marie

2012-06-01

Metacognitive Training (MCT) is a manualised cognitive intervention for psychosis aimed at transferring knowledge of cognitive biases and providing corrective experiences. The aim of MCT is to facilitate symptom reduction and protect against relapse. In a naturalistic audit of clinical effectiveness we examined what effect group MCT has on mental capacity, symptoms of psychosis and global function in patients with a psychotic illness, when compared with a waiting list comparison group.

Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks.

Science.gov (United States)

Borm, Paul J A; Cakmak, Gonca; Jermann, Erich; Weishaupt, Christel; Kempers, Pascal; van Schooten, Frederik Jan; Oberdörster, Günter; Schins, Roel P F

2005-06-01

The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m(3)). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 microM) and a mixture of 16 PAHs (0.1 microM) were used. No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 microg/cm(2)) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely.

Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks

International Nuclear Information System (INIS)

Borm, Paul J.A.; Cakmak, Gonca; Jermann, Erich; Weishaupt, Christel; Kempers, Pascal; Schooten, Frederik Jan van; Oberdoerster, Guenter; Schins, Roel P.F.

2005-01-01

Objective: The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. Methods: In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m 3 ). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 μM) and a mixture of 16 PAHs (0.1 μM) were used. Results: No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 μg/cm 2 ) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. Conclusion: The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely

Developmental exposure to a complex PAH mixture causes persistent behavioral effects in naive Fundulus heteroclitus (killifish) but not in a population of PAH-adapted killifish.

Science.gov (United States)

Brown, D R; Bailey, J M; Oliveri, A N; Levin, E D; Di Giulio, R T

2016-01-01

Acute exposures to some individual polycyclic aromatic hydrocarbons (PAHs) and complex PAH mixtures are known to cause cardiac malformations and edema in the developing fish embryo. However, the heart is not the only organ impacted by developmental PAH exposure. The developing brain is also affected, resulting in lasting behavioral dysfunction. While acute exposures to some PAHs are teratogenically lethal in fish, little is known about the later life consequences of early life, lower dose subteratogenic PAH exposures. We sought to determine and characterize the long-term behavioral consequences of subteratogenic developmental PAH mixture exposure in both naive killifish and PAH-adapted killifish using sediment pore water derived from the Atlantic Wood Industries Superfund Site. Killifish offspring were embryonically treated with two low-level PAH mixture dilutions of Elizabeth River sediment extract (ERSE) (TPAH 5.04 μg/L and 50.4 μg/L) at 24h post fertilization. Following exposure, killifish were raised to larval, juvenile, and adult life stages and subjected to a series of behavioral tests including: a locomotor activity test (4 days post-hatch), a sensorimotor response tap/habituation test (3 months post hatch), and a novel tank diving and exploration test (3months post hatch). Killifish were also monitored for survival at 1, 2, and 5 months over 5-month rearing period. Developmental PAH exposure caused short-term as well as persistent behavioral impairments in naive killifish. In contrast, the PAH-adapted killifish did not show behavioral alterations following PAH exposure. PAH mixture exposure caused increased mortality in reference killifish over time; yet, the PAH-adapted killifish, while demonstrating long-term rearing mortality, had no significant changes in mortality associated with ERSE exposure. This study demonstrated that early embryonic exposure to PAH-contaminated sediment pore water caused long-term locomotor and behavioral alterations in

UV-Visible Spectra of PAHs and Derivatives Seeded in Supersonic Jet. Astrophysical Implications

Science.gov (United States)

Salma, Bejaoui; Salama, Farid

2018-06-01

Laboratory absorption spectra of Polycyclic Aromatic Hydrocarbons (PAHs) and PAH derivatives measured under astrophysical relevant conditions are crucial to test the PAHs-DIBs hypothesis as well as the PAH model for the IR emission bands. Our dedicated experimental setup on the COsmic SImulation Chamber (COSmIC) provides an excellent platform to study neutral and ionized PAHs under the low temperature and pressure conditions that are representative of interstellar environments [1]. In this work, we study the effect of the substitution of CH bond(s) by a nitrogen atom(s) on the electronic spectra of phenanthrene. The electronic transitions associated with the lower excited states of neutral phenanthrene (C14H10) and phenanthridine (C13H9N) are measured in gas phase in the 315-345 nm region. Molecules are seeded in a supersonic expansion of argon gas and the absorption spectra are measured using the Cavity Ring Down Spectroscopy (CRDS) technique. Additional measurements of the absorption spectra of phenanthrene, phenantridine and 1,10-phenanthroline (C12H8N2) isolated in 10 K argon matrices are also performed. The comparison between the CRDS spectra with the absorption of the matrix-isolated molecules highlight the matrix-induced perturbations in band position, profiles and broadening and illustrates the need of gas phase measurements for more accurate comparisons with astronomical spectra.[1] Salama, F., Galazutdinov, G., Krelowski, et al. ApJ 728, 154[FS1] (2011).[2] A. Tielens, ApJ 526 Pt 1265–273 (2008),Acknowledgements: This research is supported by the APRA Program of NASA SMD

Phototoxic effects of PAH and UVA exposure on molecular responses and developmental success in coral larvae

KAUST Repository

Overmans, Sebastian; Nordborg, Mikaela; Rua, Ruben Diaz; Brinkman, Diane L.; Negri, Andrew P.; Agusti, Susana

2018-01-01

Exposure to polycyclic aromatic carbons (PAHs) poses a growing risk to coral reefs due to increasing shipping and petroleum extraction in tropical waters. Damaging effects of specific PAHs can be further enhanced by the presence of ultraviolet radiation, known as phototoxicity. We tested phototoxic effects of the PAHs anthracene and phenanthrene on larvae of the scleractinian coral Acropora tenuis in the presence and absence of UVA (320–400 nm). Activity of superoxide dismutase (SOD) enzyme was reduced by anthracene while phenanthrene and UVA exposure did not have any effect. Gene expression of MnSod remained constant across all treatments. The genes Catalase, Hsp70 and Hsp90 showed increased expression levels in larvae exposed to anthracene, but not phenanthrene. Gene expression of p53 was upregulated in the presence of UVA, but downregulated when exposed to PAHs. The influence on stress-related biochemical pathways and gene expresson in A. tenuis larvae was considerably greater for anthracene than phenanthrene, and UVA-induced phototoxicity was only evident for anthracene. The combined effects of UVA and PAH exposure on larval survival and metamorphosis paralleled the sub-lethal stress responses, clearly highlighting the interaction of UVA on anthracene toxicity and ultimately the coral’s development.

Phototoxic effects of PAH and UVA exposure on molecular responses and developmental success in coral larvae

KAUST Repository

Overmans, Sebastian

2018-03-09

Exposure to polycyclic aromatic carbons (PAHs) poses a growing risk to coral reefs due to increasing shipping and petroleum extraction in tropical waters. Damaging effects of specific PAHs can be further enhanced by the presence of ultraviolet radiation, known as phototoxicity. We tested phototoxic effects of the PAHs anthracene and phenanthrene on larvae of the scleractinian coral Acropora tenuis in the presence and absence of UVA (320–400 nm). Activity of superoxide dismutase (SOD) enzyme was reduced by anthracene while phenanthrene and UVA exposure did not have any effect. Gene expression of MnSod remained constant across all treatments. The genes Catalase, Hsp70 and Hsp90 showed increased expression levels in larvae exposed to anthracene, but not phenanthrene. Gene expression of p53 was upregulated in the presence of UVA, but downregulated when exposed to PAHs. The influence on stress-related biochemical pathways and gene expresson in A. tenuis larvae was considerably greater for anthracene than phenanthrene, and UVA-induced phototoxicity was only evident for anthracene. The combined effects of UVA and PAH exposure on larval survival and metamorphosis paralleled the sub-lethal stress responses, clearly highlighting the interaction of UVA on anthracene toxicity and ultimately the coral’s development.

Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

Directory of Open Access Journals (Sweden)

Xu Xue-Feng

2013-02-01

Full Text Available Abstract Background Accumulating evidence reveals that intrauterine growth retardation (IUGR can cause varying degrees of pulmonary arterial hypertension (PAH later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR. Methods The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC were isolated from the rat lungs by magnetic-activated cell sorting (MACS. We investigated epigenetic regulation of the endothelin-1 (ET-1 gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia. Results The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling. Conclusions These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.

Biodegradation aspects of Polycyclic Aromatic Hydrocarbons (PAHs): A review

Energy Technology Data Exchange (ETDEWEB)

Haritash, A.K., E-mail: akharitash@gmail.com [Department of Environmental Science and Engineering, Guru Jambheshwar University of Science and Technology, Hisar, Haryana (India); Kaushik, C.P. [Department of Environmental Science and Engineering, Guru Jambheshwar University of Science and Technology, Hisar, Haryana (India)

2009-09-30

PAHs are aromatic hydrocarbons with two or more fused benzene rings with natural as well as anthropogenic sources. They are widely distributed environmental contaminants that have detrimental biological effects, toxicity, mutagenecity and carcinogenicity. Due to their ubiquitous occurrence, recalcitrance, bioaccumulation potential and carcinogenic activity, the PAHs have gathered significant environmental concern. Although PAH may undergo adsorption, volatilization, photolysis, and chemical degradation, microbial degradation is the major degradation process. PAH degradation depends on the environmental conditions, number and type of the microorganisms, nature and chemical structure of the chemical compound being degraded. They are biodegraded/biotransformed into less complex metabolites, and through mineralization into inorganic minerals, H{sub 2}O, CO{sub 2} (aerobic) or CH{sub 4} (anaerobic) and rate of biodegradation depends on pH, temperature, oxygen, microbial population, degree of acclimation, accessibility of nutrients, chemical structure of the compound, cellular transport properties, and chemical partitioning in growth medium. A number of bacterial species are known to degrade PAHs and most of them are isolated from contaminated soil or sediments. Pseudomonas aeruginosa, Pseudomons fluoresens, Mycobacterium spp., Haemophilus spp., Rhodococcus spp., Paenibacillus spp. are some of the commonly studied PAH-degrading bacteria. Lignolytic fungi too have the property of PAH degradation. Phanerochaete chrysosporium, Bjerkandera adusta, and Pleurotus ostreatus are the common PAH-degrading fungi. Enzymes involved in the degradation of PAHs are oxygenase, dehydrogenase and lignolytic enzymes. Fungal lignolytic enzymes are lignin peroxidase, laccase, and manganese peroxidase. They are extracellular and catalyze radical formation by oxidation to destabilize bonds in a molecule. The biodegradation of PAHs has been observed under both aerobic and anaerobic conditions

Biodegradation aspects of Polycyclic Aromatic Hydrocarbons (PAHs): A review

International Nuclear Information System (INIS)

Haritash, A.K.; Kaushik, C.P.

2009-01-01

PAHs are aromatic hydrocarbons with two or more fused benzene rings with natural as well as anthropogenic sources. They are widely distributed environmental contaminants that have detrimental biological effects, toxicity, mutagenecity and carcinogenicity. Due to their ubiquitous occurrence, recalcitrance, bioaccumulation potential and carcinogenic activity, the PAHs have gathered significant environmental concern. Although PAH may undergo adsorption, volatilization, photolysis, and chemical degradation, microbial degradation is the major degradation process. PAH degradation depends on the environmental conditions, number and type of the microorganisms, nature and chemical structure of the chemical compound being degraded. They are biodegraded/biotransformed into less complex metabolites, and through mineralization into inorganic minerals, H 2 O, CO 2 (aerobic) or CH 4 (anaerobic) and rate of biodegradation depends on pH, temperature, oxygen, microbial population, degree of acclimation, accessibility of nutrients, chemical structure of the compound, cellular transport properties, and chemical partitioning in growth medium. A number of bacterial species are known to degrade PAHs and most of them are isolated from contaminated soil or sediments. Pseudomonas aeruginosa, Pseudomons fluoresens, Mycobacterium spp., Haemophilus spp., Rhodococcus spp., Paenibacillus spp. are some of the commonly studied PAH-degrading bacteria. Lignolytic fungi too have the property of PAH degradation. Phanerochaete chrysosporium, Bjerkandera adusta, and Pleurotus ostreatus are the common PAH-degrading fungi. Enzymes involved in the degradation of PAHs are oxygenase, dehydrogenase and lignolytic enzymes. Fungal lignolytic enzymes are lignin peroxidase, laccase, and manganese peroxidase. They are extracellular and catalyze radical formation by oxidation to destabilize bonds in a molecule. The biodegradation of PAHs has been observed under both aerobic and anaerobic conditions and the rate can

Pristine Arctic: Background mapping of PAHs, PAH metabolites and inorganic trace elements in the North-Atlantic Arctic and sub-Arctic coastal environment

Energy Technology Data Exchange (ETDEWEB)

Jörundsdóttir, Hrönn Ólína, E-mail: hronn.o.jorundsdottir@matis.is [Matis Ltd., Icelandic Food and Biotech R and D, Vinlandsleid 12, 113 Reykjavik (Iceland); Jensen, Sophie [Matis Ltd., Icelandic Food and Biotech R and D, Vinlandsleid 12, 113 Reykjavik (Iceland); Hylland, Ketil; Holth, Tor Fredrik [Department of Biosciences, University of Oslo, P.O. Box 1066 Blindern, N-0316 Oslo (Norway); Gunnlaugsdóttir, Helga [Matis Ltd., Icelandic Food and Biotech R and D, Vinlandsleid 12, 113 Reykjavik (Iceland); Svavarsson, Jörundur [University of Iceland, Department of Life and Environmental Sciences, Askja - Natural Science Building, Sturlugata 7, 101 Reykjavík (Iceland); Ólafsdóttir, Ásdís [The University of Iceland´s Research Centre in Sudurnes, Gardvegi 1, 245 Sandgerdi (Iceland); El-Taliawy, Haitham [Matis Ltd., Icelandic Food and Biotech R and D, Vinlandsleid 12, 113 Reykjavik (Iceland); Rigét, Frank; Strand, Jakob [Department of Bioscience, Arctic Research Centre, Aarhus University, Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde (Denmark); Nyberg, Elisabeth; Bignert, Anders [Swedish Museum of Natural History, P.O. Box 50007, 104 05 Stockholm (Sweden); Hoydal, Katrin S. [The Faroese Environment Agency, Traðagøta 38, P.O. Box 2048, FO-165 Argir, the Faroe Islands (Faroe Islands); Halldórsson, Halldór Pálmar [The University of Iceland´s Research Centre in Sudurnes, Gardvegi 1, 245 Sandgerdi (Iceland)

2014-09-15

As the ice cap of the Arctic diminishes due to global warming, the polar sailing route will be open larger parts of the year. These changes are likely to increase the pollution load on the pristine Arctic due to large vessel traffic from specific contaminant groups, such as polycyclic aromatic hydrocarbons (PAHs). A well-documented baseline for PAH concentrations in the biota in the remote regions of the Nordic Seas and the sub-Arctic is currently limited, but will be vital in order to assess future changes in PAH contamination in the region. Blue mussels (Mytilus edulis) were collected from remote sites in Greenland, Iceland, the Faroe Islands, Norway and Sweden as well as from urban sites in the same countries for comparison. Cod (Gadus morhua) was caught north of Iceland and along the Norwegian coast. Sixteen priority PAH congeners and the inorganic trace elements arsenic, cadmium, mercury and lead were analysed in the blue mussel samples as well as PAH metabolites in cod bile. Σ{sub 16}PAHs ranged from 28 ng/g dry weight (d.w.) (Álftafjörður, NW Iceland) to 480 ng/g d.w. (Ísafjörður, NW Iceland). Mussel samples from Mjóifjörður, East Iceland and Maarmorilik, West Greenland, contained elevated levels of Σ{sub 16}PAHs, 370 and 280 ng/g d.w., respectively. Levels of inorganic trace elements varied with highest levels of arsenic in mussels from Ísafjörður, Iceland (79 ng/g d.w.), cadmium in mussels from Mjóifjörður, Iceland (4.3 ng/g d.w.), mercury in mussels from Sørenfjorden, Norway (0.23 ng/g d.w.) and lead in mussels from Maarmorilik, Greenland (21 ng/g d.w.). 1-OH-pyrene was only found above limits of quantification (0.5 ng/mL) in samples from the Norwegian coast, ranging between 44 and 140 ng/ml bile. Generally, PAH levels were low in mussels from the remote sites investigated in the study, which indicates limited current effect on the environment. - Highlights: • Low levels of PAHs in blue mussels from remote areas of the Arctic. • Low

[Comparison of polycyclic aromatic hydrocarbons (PAHS) contents in bakery products].

Science.gov (United States)

Ciemniak, Artur; Witczak, Agata

2010-01-01

Polycyclic aromatic hydrocarbons are a group of well-known chemical carcinogens with a wide distribution in the environment and formed by the incomplete combustion of organic substances. PAHs have attracted most attention because of their carcinogenic potential. PAHs have been found as contaminants in different food categories such as dairy products, smoked and barbecued meat, vegetables, fruits, oils, coffee, tea, and cereals. Processing of food at high temperatures increases the amount of PAHs in the food Diet is the major source of human exposure to PAHs. The major dietary source of PAH are oils and fats, cereals products and vegetables. The aims of this study were to determine the content levels of 23 PAHs in various sorts of bread. The analytical procedure was based Soxhlet extraction with n--hexane and cleaned up in aflorisil cartridge. Chromatographic separation was performed using gas chromatography (HP 6890) coupled to mass spectrometry (HP 5973). The total concentration of PAHs was low end varied between 2.61 microg/kg to 43.4 microg/kg. Furthermore, the results revealed differences in concentrations of PAHs between rind and bread-crumb.

Cloud deposition of PAHs at Mount Lushan in southern China

Energy Technology Data Exchange (ETDEWEB)

Wang, Ruixia [School of Environmental Science and Engineering, Shandong University, Jinan, 250100 (China); Wang, Yan, E-mail: wangyan405@gmail.com [School of Environmental Science and Engineering, Shandong University, Jinan, 250100 (China); Li, Hongli, E-mail: lihongli1225@163.com [Environmental Monitoring Central Station of Shandong Province, Jinan, 250101 (China); Yang, Minmin; Sun, Lei [School of Environmental Science and Engineering, Shandong University, Jinan, 250100 (China); Wang, Tao [Department of Civil and Structural Engineering, The Hong Kong Polytechnic University, Hong Kong (China); Wang, Wenxing [Environment Research Institute, Shandong University, Jinan, 250100 (China)

2015-09-01

Cloud water samples were collected from Mount Lushan, a high alpine area of southern China, and analyzed using GC–MS to investigate the concentration levels, seasonal variations, particle-dissolved phase partitioning, ecological risk of PAHs and its relationship to the atmosphere and rainwater. The average concentration of total (dissolved + particle) PAHs in cloud water was 819.90 ng/L, which ranged from 2.30 ng/L for DbA to 295.38 ng/L for PhA. PhA (33.11%) contributed the most individual PAHs, followed by Flu (28.24%). Distinct seasonal variations in the total PAHs measured in this research had a higher concentration during the spring and a lower concentration during the summer. When cloud events occurred, the concentration of the atmospheric PAHs of the two phases decreased. The contribution from the gaseous phase of total PAHs in the air to the dissolved phase in cloud water was up to 60.43%, but the particulate phase in the air only contributed 39.57% to the total scavenging. The contribution of total PAHs from the atmosphere to clouds is higher in the gaseous phase than in the particulate phase. A comparative study of the concentrations of cloud water and the closest rain water revealed that the PAH concentration in rainwater was 1.80 times less than that of cloud water and that the dominant individual compounds in cloud water and rainwater were PhA and Flu. A total of 81.27% of the PAHs in cloud samples and 72.21% of the PAHs in rain samples remained in the dissolved phase. Ecological risk assessment indicated that PAHs in cloud water in spring and summer caused a certain degree of ecosystem risk and the mean ecosystem risk in spring was higher than that in summer. - Highlights: • The site is in the high pollution emission area, having many sources of PAHs around. • Mount Lushan is a unique site for cloud chemistry monitoring. • Atmospheric PAHs mostly deposited and transferred into cloud water. • Special case showed PAHs are more concentrated in

Cloud deposition of PAHs at Mount Lushan in southern China

International Nuclear Information System (INIS)

Wang, Ruixia; Wang, Yan; Li, Hongli; Yang, Minmin; Sun, Lei; Wang, Tao; Wang, Wenxing

2015-01-01

Cloud water samples were collected from Mount Lushan, a high alpine area of southern China, and analyzed using GC–MS to investigate the concentration levels, seasonal variations, particle-dissolved phase partitioning, ecological risk of PAHs and its relationship to the atmosphere and rainwater. The average concentration of total (dissolved + particle) PAHs in cloud water was 819.90 ng/L, which ranged from 2.30 ng/L for DbA to 295.38 ng/L for PhA. PhA (33.11%) contributed the most individual PAHs, followed by Flu (28.24%). Distinct seasonal variations in the total PAHs measured in this research had a higher concentration during the spring and a lower concentration during the summer. When cloud events occurred, the concentration of the atmospheric PAHs of the two phases decreased. The contribution from the gaseous phase of total PAHs in the air to the dissolved phase in cloud water was up to 60.43%, but the particulate phase in the air only contributed 39.57% to the total scavenging. The contribution of total PAHs from the atmosphere to clouds is higher in the gaseous phase than in the particulate phase. A comparative study of the concentrations of cloud water and the closest rain water revealed that the PAH concentration in rainwater was 1.80 times less than that of cloud water and that the dominant individual compounds in cloud water and rainwater were PhA and Flu. A total of 81.27% of the PAHs in cloud samples and 72.21% of the PAHs in rain samples remained in the dissolved phase. Ecological risk assessment indicated that PAHs in cloud water in spring and summer caused a certain degree of ecosystem risk and the mean ecosystem risk in spring was higher than that in summer. - Highlights: • The site is in the high pollution emission area, having many sources of PAHs around. • Mount Lushan is a unique site for cloud chemistry monitoring. • Atmospheric PAHs mostly deposited and transferred into cloud water. • Special case showed PAHs are more concentrated in

The flavonoid quercetin reverses pulmonary hypertension in rats.

Directory of Open Access Journals (Sweden)

Daniel Morales-Cano

Full Text Available Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH.

Phyto remediation of PAH contaminated soil

International Nuclear Information System (INIS)

Petruzzelli, G.; Pedron, F.; Barbafieri, M.; Cervelli, St.; Vigna Guidi, G.

2005-01-01

Phyto-remediation may enhance degradation of organic compounds promoting an adequate substrate for microbial growth. The aim of this work was to evaluate the efficiency of two plant species, Lupinus albus and Zea mais, in the bio-remediation of a PAH contaminated soil. This soil has been collected in a contaminated industrial area in Italy characterized by PAH concentrations up to 16000 mg/Kg. Microcosms experiments were carried out by planting Lupinus albus and Zea mais in the polluted soil; controls without plants were run separately. Growing period lasted by three months. Plants favoured PAH biodegradation by percentages of 32% with Lupinus albus and 22% with Zea mais, with respect to non vegetated microcosms. (authors)

Bulky PAH-DNA induced by exposure of a co-culture model of human alveolar macrophages and embryonic epithelial cells to atmospheric particulate pollution

International Nuclear Information System (INIS)

Abbas, Imane; Garcon, Guillaume; Billet, Sylvain; Shirali, Pirouz; Andre, Veronique; Le Goff, Jeremie; Sichel, Francois; Roy Saint-Georges, Francoise; Mulliez, Philippe

2012-01-01

Because of their deep penetration in human lungs, fine airborne particulate matter were described as mainly responsible for the deleterious effects of exposure to air pollution on health. Organic constituents are adsorbed on particles surface and, after inhalation, some (polycyclic aromatic hydrocarbons, PAHs) can be activated into reactive metabolites and can bind to DNA. The formation of bulky DNA adducts has been researched after exposure of mono-and co-cultures of alveolar macrophages (AM) and human embryonic human lung epithelial (L132), to fine air pollution particulate matter Air samples have been collected with cascade impactor and characterized: size distribution (92.15% 2 /g), inorganic (Fe, AI, Ca, Na, K, Mg, Pb, etc.) and organic compounds (PAHs, etc.). 32 P post-labeling method was applied to detect bulky DNA adducts in AM and L132, in mono-and co-cultures, 72 h after their exposure to atmospheric particles at their Lethals and Effects concentrations or (LC or CE) to 50% (i.e. MA: EC 50 = 74.63 μg/mL and L132: LC-5-0 = 75.36 μg/mL). Exposure to desorbed particles (MA: C1= 61.11 μg/mL and L132 : C2 = 61.71 μg/mL) and B[a]P (1 μM) were included. Bulky PAH-DNA adducts were detected in AM in mono-culture after exposure to total particles (Pt), to B[a]P and desorbed particles (Pd). Whatever the exposure, no DNA adduct was detected in L132 in mono-culture. These results are coherent with the enzymatic activities of cytochrome P450 l Al in AM and L132. Exposure of co-culture to Pt, or Pd induced bulky adducts to DNA in AM but not in L132. Exposure to B[a]P alone has altered the DNA of AM and L132, in co-culture. Exposure to Pt is closer to the environmental conditions, but conferred an exposure to amounts of genotoxic agents compared to studies using organic extracts. The formation of bulky DNA adducts was nevertheless observed in AM exposed to Pt, in mono- or co-culture, indicating that they were competent in terms of metabolic activation of PAHs. The

The PAH Emission Characteristics of the Reflection Nebula NGC 2023

International Nuclear Information System (INIS)

Peeters, Els; Bauschlicher, Charles W. Jr.; Allamandola, Louis J.; Tielens, Alexander G. G. M.; Ricca, Alessandra; Wolfire, Mark G.

2017-01-01

We present 5–20 μ m spectral maps of the reflection nebula NGC 2023 obtained with the Infrared Spectrograph SL and SH modes on board the Spitzer Space Telescope, which reveal emission from polycyclic aromatic hydrocarbons (PAHs), C 60 , and H 2 superposed on a dust continuum. We show that several PAH emission bands correlate with each other and exhibit distinct spatial distributions that reveal a spatial sequence with distance from the illuminating star. We explore the distinct morphology of the 6.2, 7.7, and 8.6 μ m PAH bands and find that at least two spatially distinct components contribute to the 7–9 μ m PAH emission in NGC 2023. We report that the PAH features behave independently of the underlying plateaus. We present spectra of compact, oval PAHs ranging in size from C 66 to C 210 , determined computationally using density functional theory, and we investigate trends in the band positions and relative intensities as a function of PAH size, charge, and geometry. Based on the NASA Ames PAH database, we discuss the 7–9 μ m components in terms of band assignments and relative intensities. We assign the plateau emission to very small grains with possible contributions from PAH clusters and identify components in the 7–9 μ m emission that likely originate in these structures. Based on the assignments and the observed spatial sequence, we discuss the photochemical evolution of the interstellar PAH family as the PAHs are more and more exposed to the radiation field of the central star in the evaporative flows associated with the Photo-Dissociation Regions in NGC 2023.

The PAH Emission Characteristics of the Reflection Nebula NGC 2023

Energy Technology Data Exchange (ETDEWEB)

Peeters, Els [Department of Physics and Astronomy, University of Western Ontario, London, ON N6A 3K7 (Canada); Bauschlicher, Charles W. Jr. [Entry Systems and Technology Division, Mail Stop 230-3, NASA Ames Research Center, Moffett Field, CA 94035 (United States); Allamandola, Louis J. [NASA Ames Research Center, Space Science Division, Mail Stop 245-6, Moffett Field, CA 94035 (United States); Tielens, Alexander G. G. M. [Leiden Observatory, P.O. Box 9513, 2300 RA Leiden (Netherlands); Ricca, Alessandra [Carl Sagan Center, SETI Institute, 189 N. Bernardo Avenue, Suite 100, Mountain View, CA 94043 (United States); Wolfire, Mark G., E-mail: epeeters@uwo.ca [Astronomy Department, University of Maryland, College Park, MD 20742 (United States)

2017-02-20

We present 5–20 μ m spectral maps of the reflection nebula NGC 2023 obtained with the Infrared Spectrograph SL and SH modes on board the Spitzer Space Telescope, which reveal emission from polycyclic aromatic hydrocarbons (PAHs), C{sub 60}, and H{sub 2} superposed on a dust continuum. We show that several PAH emission bands correlate with each other and exhibit distinct spatial distributions that reveal a spatial sequence with distance from the illuminating star. We explore the distinct morphology of the 6.2, 7.7, and 8.6 μ m PAH bands and find that at least two spatially distinct components contribute to the 7–9 μ m PAH emission in NGC 2023. We report that the PAH features behave independently of the underlying plateaus. We present spectra of compact, oval PAHs ranging in size from C{sub 66} to C{sub 210}, determined computationally using density functional theory, and we investigate trends in the band positions and relative intensities as a function of PAH size, charge, and geometry. Based on the NASA Ames PAH database, we discuss the 7–9 μ m components in terms of band assignments and relative intensities. We assign the plateau emission to very small grains with possible contributions from PAH clusters and identify components in the 7–9 μ m emission that likely originate in these structures. Based on the assignments and the observed spatial sequence, we discuss the photochemical evolution of the interstellar PAH family as the PAHs are more and more exposed to the radiation field of the central star in the evaporative flows associated with the Photo-Dissociation Regions in NGC 2023.

Senyawa polisiklik aromatik hidrokarbon (PAH dalam air laut di Teluk Jakarta

Directory of Open Access Journals (Sweden)

Edward .

2014-01-01

Full Text Available Research on polycyclic aromatic hydrocarbons (pahs compound at Jakarta Bay seawater were carried out on July 2011. The objectives of this research were to measure the concentration of total polycyclic aromatic hydrocarbons (PAH compound, concentration of individual PAH compound, and to identify sources of PAH compound in seawater. PAH compound concentration was measured by Gas Chromatography (Gas Chromatography-Flame Ionization Detector and sources of polycyclic aromatic hydrocarbons compound were identified by diagnostic ratio analysis. The results show that the concentration of PAH compound in the middle of Jakarta Bay was higher compared to the west and the east. In the west and middle of Jakarta Bay, it is found that 11 PAH types, and 10 types in the east. Individual PAH compound dominated by high moleculer weight of PAH Benzo(aAnthracene, Chrysene, Benzo(bFluoranthene, Benzo(aPyrene, dan Indeno(123-cd Pyrene. The results of PAH compound ratio individual analysis showed that polycyclic aromatic hydrocarbons compound at Jakarta Bay seawater came from oil spill and incomplete combustion mixture of organic material such as wood, grass, fuel oil, and fuel industry combustion activity.

PAH biomarkers in common eelpout (Zoarces viviparus) from Danish waters

DEFF Research Database (Denmark)

Tairova, Zhanna; Strand, Jakob; Chevalier, Julie

2012-01-01

Eelpouts (Zoarces viviparus) sampled at surveillance stations during the fall of 2007 and spring 2008 in different Danish coastal areas, were studied for biomarkers of polycyclic aromatic hydrocarbons (PAHs) exposure and effects. Two analytical techniques, synchronous fluorescence spectrometry (SFS......) and high-performance liquid chromatography with fluorescence detection (HPLC/F), were applied for detecting PAH metabolites in bile and urine. CYP1A activity, in this study regarded as potential biomarker of effect, was measured as 7-ethoxyresorufin-O-deethylase (EROD) activity in liver of eelpouts from...... different stations. Biliary PAH metabolite measurements were used for monitoring the environmental PAH load at the surveillance stations. There was found significant difference in biliary PAH metabolite content between sexes with male fish containing higher concentrations of PAH metabolites than females...

Vegetative cover and PAHs accumulation in soils of urban green space

International Nuclear Information System (INIS)

Peng Chi; Ouyang Zhiyun; Wang Meie; Chen Weiping; Jiao Wentao

2012-01-01

We investigated how urban land uses influence soil accumulation of polycyclic aromatic hydrocarbons (PAHs) in the urban green spaces composed of different vegetative cover. How did soil properties, urbanization history, and population density affect the outcomes were also considered. Soils examined were obtained at 97 green spaces inside the Beijing metropolis. PAH contents of the soils were influenced most significantly by their proximity to point source of industries such as the coal combustion installations. Beyond the influence circle of industrial emissions, land use classifications had no significant effect on the extent of PAH accumulation in soils. Instead, the nature of vegetative covers affected PAH contents of the soils. Tree–shrub–herb and woodland settings trapped more airborne PAH and soils under these vegetative patterns accumulated more PAHs than those of the grassland. Urbanization history, population density and soil properties had no apparent impact on PAHs accumulations in soils of urban green space. - Highlights: ► Land use did not affect PAHs in soils except for areas adjacent to industrial sources. ► Tree–shrub–herb and woodland cover amass more PAHs in soils than grassland cover. ► Urban development and soil property factors had little effect on PAHs in soils. - Industrial emissions aside, vegetative cover is the dominant factor controlling accumulation of PAHs in urban green space soils.

Characteristics of particulate PAHs during a typical haze episode in Guangzhou, China

Science.gov (United States)

Tan, Jihua; Guo, Songjun; Ma, Yongliang; Duan, Jingchun; Cheng, Yuan; He, Kebin; Yang, Fumo

2011-10-01

The concentrations of polycyclic aromatic hydrocarbons (PAHs) in PM 2.5 and TSP were measured in Guangzhou during a typical haze episode. This episode included NH (non-haze, 3 days), HFN (haze when air masses from north and northeast, 6 days) and HFS (haze when air masses from south, 4 days). The air quality in HFN was much worse than that in NH and HFS. The total average concentrations of PAHs in PM 2.5 were 13.25 ng m -3, 59.82 ng m -3 and 13.09 ng m -3 in NH, HFN and HFS, respectively. It indicated PAH pollution had been substantially aggravated by HFN. PAHs(5 + 6) were the most abundant compounds in HFN and HFS, which accounted for 55-75% of total concentration of PAHs, while PAHs(3 + 4) were the most abundant compounds in NH, which accounted for 54-67% of total concentration of PAHs. TEF (Toxic Equivalency Factors)-adjusted concentrations of 13 particulate PAHs were very high in HFN, indicating high health risks to humans for PAH exposure in HFN. The characteristic ratios of PAHs indicated coal combustion and traffic emission were the major contributors to PAHs in HFN and HFS. The concentrations of particulate PAHs in haze episode were strongly affected by wind speed and wind direction. PAHs in NH could be from long-range transport with high north wind speed, while local emission could be the main contributor of particle-associated PAHs in HFN. The transport speed of air masses was found to play an important role on PAH concentrations.

Novel mechanisms of sildenafil in pulmonary hypertension involving cytokines/chemokines, MAP kinases and Akt.

Directory of Open Access Journals (Sweden)

Tamas Kiss

Full Text Available Pulmonary arterial hypertension (PH is associated with high mortality due to right ventricular failure and hypoxia, therefore to understand the mechanism by which pulmonary vascular remodeling initiates these processes is very important. We used a well-characterized monocrotaline (MCT-induced rat PH model, and analyzed lung morphology, expression of cytokines, mitogen-activated protein kinase (MAPK phosphorylation, and phosphatidylinositol 3-kinase-Akt (PI-3k-Akt pathway and nuclear factor (NF-κB activation in order to elucidate the mechanisms by which sildenafil's protective effect in PH is exerted. Besides its protective effect on lung morphology, sildenafil suppressed multiple cytokines involved in neutrophil and mononuclear cells recruitment including cytokine-induced neutrophil chemoattractant (CINC-1, CINC-2α/β, tissue inhibitor of metalloproteinase (TIMP-1, interleukin (IL-1α, lipopolysaccharide induced CXC chemokine (LIX, monokine induced by gamma interferon (MIG, macrophage inflammatory protein (MIP-1α, and MIP-3α. NF-κB activation and phosphorylation were also attenuated by sildenafil. Furthermore, sildenafil reduced extracellular signal-regulated kinase (ERK1/2 and p38 MAPK activation while enhanced activation of the cytoprotective Akt pathway in PH. These data suggest a beneficial effect of sildenafil on inflammatory and kinase signaling mechanisms that substantially contribute to its protective effects, and may have potential implications in designing future therapeutic strategies in the treatment of pulmonary hypertension.

Water-Sediment Partition of Polycyclic Aromatic Hydrocarbons (PAHs) in Nansi Lake

Science.gov (United States)

Zhang, Guizhai; Diao, Youjiang

2018-06-01

Based on field data of polycyclic aromatic hydrocarbons (PAHs) in water and sediment in Nansi Lake. The concentrations and the partitioning characteristic of PAHs in the water and sediment were studied. The lgKd of high molecular weight PAHs were higher than the low molecular weight PAHs. The most of PAHs Kd values were negligible correlated with TOC, soluble salt, clay and pH of the sediment in Nansi Lake.

Specific long non-coding RNAs response to occupational PAHs exposure in coke oven workers

Directory of Open Access Journals (Sweden)

Chen Gao

Full Text Available To explore whether the alteration of lncRNA expression is correlated with polycyclic aromatic hydrocarbons (PAHs exposure and DNA damage, we examined PAHs external and internal exposure, DNA damage and lncRNAs (HOTAIR, MALAT1, TUG1 and GAS5 expression in peripheral blood lymphocytes (PBLCs of 150 male coke oven workers and 60 non-PAHs exposure workers. We found the expression of HOTAIR, MALAT1, and TUG1 were enhanced in PBLCs of coke oven workers and positively correlated with the levels of external PAHs exposure (adjusted Ptrend < 0.001 for HOTAIR and MALAT1, adjusted Ptrend = 0.006 for TUG1. However, only HOTAIR and MALAT1 were significantly associated with the level of internal PAHs exposure (urinary 1-hydroxypyrene with adjusted β = 0.298, P = 0.024 for HOTAIR and β = 0.090, P = 0.034 for MALAT1. In addition, the degree of DNA damage was positively associated with MALAT1 and HOTAIR expression in PBLCs of all subjects (adjusted β = 0.024, P = 0.002 for HOTAIR and β = 0.007, P = 0.003 for MALAT1. Moreover, we revealed that the global histone 3 lysine 27 trimethylation (H3K27me3 modification was positively associated with the degree of genetic damage (β = 0.061, P < 0.001 and the increase of HOTAIR expression (β = 0.385, P = 0.018. Taken together, our findings suggest that altered HOTAIR and MALAT1 expression might be involved in response to PAHs-induced DNA damage. Keywords: Polycyclic aromatic hydrocarbons, Long non-coding RNA, Peripheral blood lymphocytes, DNA damage response, HOTAIR, MALAT

Cloud deposition of PAHs at Mount Lushan in southern China.

Science.gov (United States)

Wang, Ruixia; Wang, Yan; Li, Hongli; Yang, Minmin; Sun, Lei; Wang, Tao; Wang, Wenxing

2015-09-01

Cloud water samples were collected from Mount Lushan, a high alpine area of southern China, and analyzed using GC-MS to investigate the concentration levels, seasonal variations, particle-dissolved phase partitioning, ecological risk of PAHs and its relationship to the atmosphere and rainwater. The average concentration of total (dissolved+particle) PAHs in cloud water was 819.90 ng/L, which ranged from 2.30 ng/L for DbA to 295.38 ng/L for PhA. PhA (33.11%) contributed the most individual PAHs, followed by Flu (28.24%). Distinct seasonal variations in the total PAHs measured in this research had a higher concentration during the spring and a lower concentration during the summer. When cloud events occurred, the concentration of the atmospheric PAHs of the two phases decreased. The contribution from the gaseous phase of total PAHs in the air to the dissolved phase in cloud water was up to 60.43%, but the particulate phase in the air only contributed 39.57% to the total scavenging. The contribution of total PAHs from the atmosphere to clouds is higher in the gaseous phase than in the particulate phase. A comparative study of the concentrations of cloud water and the closest rain water revealed that the PAH concentration in rainwater was 1.80 times less than that of cloud water and that the dominant individual compounds in cloud water and rainwater were PhA and Flu. A total of 81.27% of the PAHs in cloud samples and 72.21% of the PAHs in rain samples remained in the dissolved phase. Ecological risk assessment indicated that PAHs in cloud water in spring and summer caused a certain degree of ecosystem risk and the mean ecosystem risk in spring was higher than that in summer. Copyright © 2015 Elsevier B.V. All rights reserved.

Grafted cellulose for PAHs removal present in industrial discharge waters

Science.gov (United States)

Euvrard, Elise; Druart, Coline; Poupeney, Amandine; Crini, Nadia; Vismara, Elena; Lanza, Tommaso; Torri, Giangiacomo; Gavoille, Sophie; Crini, Gregorio

2014-05-01

Keywords: cellulose; biosorbent; PAHs; polycontaminated wastewaters; trace levels. Polycyclic aromatic hydrocarbons (PAHs), chemicals essentially formed during incomplete combustion of organic materials from anthropogenic activities, were present in all compartments of the ecosystem, air, water and soil. Notably, a part of PAHs found in aquatic system was introduced through industrial discharge waters. Since the Water Framework Directive has classified certain PAHs as priority hazardous substances, industrials are called to take account this kind of organic pollutants in their global environmental concern. Conventional materials such as activated carbons definitively proved their worth as finishing treatment systems but remained costly. In this study, we proposed to use cellulose grafted with glycidyl methacrylate [1] for the removal of PAHs present in discharge waters of surface treatment industries. Firstly, to develop the device, we worked with synthetic solutions containing 16 PAHs at 500 ng/L. Two types of grafted cellulose were tested over a closed-loop column with a concentration of 4g cellulose/L: cellulose C2 with a hydroxide group and cellulose C4 with an amine group. No PAH was retained by the raw cellulose whereas abatement percentages of PAHs were similar between C2 and C4 (94% and 98%, respectively, for the sum of the 16 PAHs) with an experiment duration of 400 min (corresponding to about 20 cycles through grafted cellulose). Secondly, to determine the shorter time to abate the amount maximum of PAHs through the system, a kinetic was realized from 20 min (one cycle) to 400 min with C4. The steady state (corresponding to about 95% of abatement of the total PAHs) was reached at 160 min. Finally, the system was then tested with real industrial discharge waters containing both mineral and organic compounds. The results indicated that the abatement percentage of PAHs was similar between C2 and C4, corroborating the tests with synthetic solution. In return

Phototransformation rate constants of PAHs associated with soot particles

International Nuclear Information System (INIS)

Kim, Daekyun; Young, Thomas M.; Anastasio, Cort

2013-01-01

Photodegradation is a key process governing the residence time and fate of polycyclic aromatic hydrocarbons (PAHs) in particles, both in the atmosphere and after deposition. We have measured photodegradation rate constants of PAHs in bulk deposits of soot particles illuminated with simulated sunlight. The photodegradation rate constants at the surface (k p 0 ), the effective diffusion coefficients (D eff ), and the light penetration depths (z 0.5 ) for PAHs on soot layers of variable thickness were determined by fitting experimental data with a model of coupled photolysis and diffusion. The overall disappearance rates of irradiated low molecular weight PAHs (with 2–3 rings) on soot particles were influenced by fast photodegradation and fast diffusion kinetics, while those of high molecular weight PAHs (with 4 or more rings) were apparently controlled by either the combination of slow photodegradation and slow diffusion kinetics or by very slow diffusion kinetics alone. The value of z 0.5 is more sensitive to the soot layer thickness than the k p 0 value. As the thickness of the soot layer increases, the z 0.5 values increase, but the k p 0 values are almost constant. The effective diffusion coefficients calculated from dark experiments are generally higher than those from the model fitting method for illumination experiments. Due to the correlation between k p 0 and z 0.5 in thinner layers, D eff should be estimated by an independent method for better accuracy. Despite some limitations of the model used in this study, the fitted parameters were useful for describing empirical results of photodegradation of soot-associated PAHs. - Highlights: ► PAHs on soot were evaluated by a model of coupled photolysis and diffusion. ► Photodegradation rate at the surface, diffusion coefficient, and light penetration path were determined. ► Low MW PAHs were influenced by fast photodegradation and fast diffusion. ► High MW PAHs were controlled either by slow

Kidney in potassium depletion. I. Na/sup +/-K/sup +/-ATPase activity and (/sup 3/H)ouabain binding in MCT

Energy Technology Data Exchange (ETDEWEB)

Hayashi, M.; Katz, A.I.

1987-03-01

The effect of potassium depletion on renal Na/sup +/K/sup +/-ATPase was studied in rats. K depletion produced a striking, time-dependent increase in Na/sup +/-K/sup +/-ATPase activity of the outer medullary collecting tubules (inner stripe; MCT/sub is/). After 3 wk on the K-free diet, when the urine was almost potassium-free, Na/sup +/-K/sup +/-ATPase activity in MCT/sub is/ was over fourfold higher than in control animals. Repletion of potassium restored enzyme activity to base line within 7 days which corresponds to the catabolic rate of the renal enzyme, suggesting the cessation of enhanced synthesis that took place during K deprivation. Changes in Na/sup +/-K/sup +/-ATPase activity and aldosterone levels during both K depletion and repletion occurred in opposite directions and were therefore independent of each other. (/sup 3/H)Ouabain binding to intact MCT/sub is/, reflecting the number of pump sites on the basolateral membrane, was similar in K-depleted and control animals; in contrast, tubule permeabilization that exposes additional pump units to the ligand, unmasked a nearly fourfold increase in (/sup 3/H)ouabain binding in K-depleted rats, comparable to the increment in Na/sup +/-K/sup +/-ATPase activity. These results show that K depletion leads to a marked increase in Na/sup +/-K/sup +/-ATPase activity of MCT/sub is/, and suggest that the new enzyme units are located at a ouabain-inaccessible site in the intact tubule, i.e., either in an intracellular compartment or at the luminal membrane, where they may be involved in potassium reabsorption.

3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells.

Science.gov (United States)

Liu, Zhe; Sun, Yiming; Hong, Haiyu; Zhao, Surong; Zou, Xue; Ma, Renqiang; Jiang, Chenchen; Wang, Zhiwei; Li, Huabin; Liu, Hao

2015-01-01

Increasing evidence demonstrates that the hexokinase inhibitor 3-bromopyruvate (3-BrPA) induces the cell apoptotic death by inhibiting ATP generation in human cancer cells. Interestingly, some tumor cell lines are less sensitive to 3-BrPA-induced apoptosis than others. Moreover, the molecular mechanism of 3-BrPA-trigged apoptosis is unclear. In the present study, we examined the effects of 3-BrPA on the viability of the breast cancer cell lines MDA-MB-231 and MCF-7. We further investigated the potential roles of monocarboxylate transporter 1 (MCT1) in drug accumulation and efflux of breast cancer cells. Finally, we explored whether 3-BrPA enhanced daunorubicin (DNR)-induced cytotoxicity through regulation of MCT1 in breast cancer cells. MTT and colony formation assays were used to measure cell viability. Western blot analysis, flow cytometric analysis and fluorescent microscopy were used to determine the molecular mechanism of actions of MCT1 in different breast cancer cell lines. Whole-body bioluminescence imaging was used to investigate the effect of 3-BrPA in vivo. We found that 3-BrPA significantly inhibited cell growth and induced apoptosis in MCF-7 cell line, but not in MDA-MB-231 cells. Moreover, we observed that 3-BrPA efficiently enhanced DNR-induced cytotoxicity in MCF-7 cells by inhibiting the activity of ATP-dependent efflux pumps. We also found that MCT1 overexpression increased the efficacy of 3-BrPA in MDA-MB-231 cells. 3-BrPA markedly suppressed subcutaneous tumor growth in combination with DNR in nude mice implanted with MCF-7 cells. Lastly, our whole-body bioluminescence imaging data indicated that 3-BrPA promoted DNR accumulation in tumors. These findings collectively suggest that 3-BrPA enhanced DNR antitumor activity in breast cancer cells involved MCT-1, suggesting that inhibition of glycolysis could be an effective therapeutic approach for breast cancer treatment.

Phosphaturic mesenchymal tumor of the brain without tumor-induced osteomalacia in an 8-year-old girl: case report.

Science.gov (United States)

Ellis, Mark B; Gridley, Daniel; Lal, Suresh; Nair, Geetha R; Feiz-Erfan, Iman

2016-05-01

Phosphaturic mesenchymal tumor (mixed connective tissue variant) (PMT-MCT) are tumors that may cause tumor-induced osteomalacia and rarely appear intracranially. The authors describe the case of an 8-year-old girl who was found to have PMT-MCT with involvement of the cerebellar hemisphere and a small tumor pedicle breaching the dura mater and involving the skull. This was removed surgically in gross-total fashion without further complication. Histologically the tumor was confirmed to be a PMT-MCT. There was no evidence of tumor-induced osteomalacia. At the 42-month follow-up, the patient is doing well, has no abnormalities, and is free of recurrence. PMT-MCTs are rare tumors that may involve the brain parenchyma. A gross-total resection may be effective to cure these lesions.

Ability of natural attenuation and phytoremediation using maize (Zea mays L.) to decrease soil contents of polycyclic aromatic hydrocarbons (PAHs) derived from biomass fly ash in comparison with PAHs-spiked soil.

Science.gov (United States)

Košnář, Zdeněk; Mercl, Filip; Tlustoš, Pavel

2018-05-30

A 120-day pot experiment was conducted to compare the ability of natural attenuation and phytoremediation approaches to remove polycyclic aromatic hydrocarbons (PAHs) from soil amended with PAHs-contaminated biomass fly ash. The PAH removal from ash-treated soil was compared with PAHs-spiked soil. The removal of 16 individual PAHs from soil ranged between 4.8% and 87.8% within the experiment. The natural attenuation approach led to a negligible total PAH removal. The phytoremediation was the most efficient approach for PAH removal, while the highest removal was observed in the case of ash-treated soil. The content of low molecular weight (LMW) PAHs and the total PAHs in this treatment significantly decreased (P <.05) over the whole experiment by 47.6% and 29.4%, respectively. The tested level of PAH soil contamination (~1600 µg PAH/kg soil dry weight) had no adverse effects on maize growth as well on the biomass yield. In addition, the PAHs were detected only in maize roots and their bioaccumulation factors were significantly lower than 1 suggesting negligible PAH uptake from soil by maize roots. The results showed that PAHs of ash origin were similarly susceptible to removal as spiked PAHs. The presence of maize significantly boosted the PAH removal from soil and its aboveground biomass did not represent any environmental risk. Copyright © 2018 Elsevier Inc. All rights reserved.

PAH exposure through soil ingestion: Combining digestion models and bioassays

Energy Technology Data Exchange (ETDEWEB)

Wiele, T.R. van de; Verstraete, W. [Ghent University (BE).Laboratory Microbial Ecology and Technology (LabMET); Siciliano, S.D. [University of Saskatchewan (Canada). Department of Soil Science

2003-07-01

Exposure to environmental contaminants through soil ingestion is an important issue in current health risk assessment. Polycyclic aromatic hydrocarbons (PAH) or their metabolites pose risks to humans due to their toxic, mutagenic, carcinogenic or even (anti)estrogenic properties. PAH mobilization from a soil matrix (49.1{+-}1.5 mg PAH/kg DW) was assessed using a Simulator of the Human Intestinal Microbial Ecosystem (SHIME). PAH GC-MS analysis was performed on the pellet and supernatant of SHIME digests and gave 101, 92, 89 and 97% recovery for water, stomach, duodenal and colon digests, respectively. PAH release was highest for the water extract (0.51%) and the stomach digestion (0.44%). Lower mobilized fractions in the duodenum (0.13%) and colon (0.30%) digests could be attributed to PAH complexation with bile salts, dissolved organic matter or colon microbiota. The digestion model provides us with relevant information to what extent soil bound PAHs are mobilized in the gastrointestinal tract and thus reach the gut wall, prior to absorption. (orig.)

Generation of polycyclic aromatic hydrocarbons (PAH during woodworking operations

Directory of Open Access Journals (Sweden)

Evin Danisman Bruschweiler

2012-10-01

Full Text Available Occupational exposures to wood dust have been associated with an elevated risk of sinonasal cancer (SNC. Wood dust is recognized as a human carcinogen but the specific cancer causative agent remains unknown. One possible explanation is a co-exposure to; wood dust and polycyclic aromatic hydrocarbons (PAHs. PAHs could be generated during incomplete combustion of wood due to heat created by use of power tools.To determine if PAHs are generated from wood during common woodworking operations, PAHs concentrations in wood dust samples collected in an experimental chamber operated under controlled conditions were analyzed. In addition, personal air samples from workers exposed to wood dust (n=30 were collected.Wood dust was generated using tree different power tools: vibrating sander, belt sander, and saw; and six wood materials: fir, Medium Density Fiberboard (MDF, beech, mahogany, oak and wood melamine. Monitoring of wood workers was carried out by means of personnel sampler device during wood working operations. We measured 21 PAHs concentrations in wood dust samples by capillary gas chromatographic-ion trap mass spectrometric analysis (GC-MS.Total PAH concentrations in wood dust varied greatly (0.24 – 7.95 ppm with the lowest being in MDF dust and the highest in wood melamine dust. Personal exposures to PAHs observed were between 37.5-119.8 ng m-3 among workers during wood working operations.Our results suggest that PAH exposures during woodworking operation are present and hence could play a role in the mechanism of cancer induction related to wood dust exposure.

Analysis of PAH in soil samples

International Nuclear Information System (INIS)

Haeufel, J.; Weisweiler, W.

1994-01-01

The supercritical fluid extraction of polycyclic aromatic hydrocarbons (PAH) from soil samples is described. Carbon dioxide mixed with a small amount of methanol is used for solvent. The results are compared with those obtained by a classical extraction method (that means with the use of organic liquids). The extracted PAH from both procedures can be separated by HPLC and analyzed with UV- and fluorescence detection. (orig.) [de

Polynuclear aromatic hydrocarbons (PAHs) mediate cadmium toxicity to an emergent wetland species

International Nuclear Information System (INIS)

Zhang, Zhenhua; Rengel, Zed; Meney, Kathy; Pantelic, Ljiljana; Tomanovic, Radmila

2011-01-01

Growth and pollutant removal by emergent wetland plants may be influenced by interactions among mixed pollutants in constructed wetlands. A glasshouse experiment was conducted to investigate interactive effects of cadmium (Cd) x polynuclear aromatic hydrocarbons (PAHs) x plant treatments on growth of Juncus subsecundus, Cd and PAH removal from soil and the total number of microorganisms in soil. Growth and biomass of J. subsecundus were significantly influenced by interaction of Cd and PAHs, significantly decreasing with either Cd or PAH additions, but with the effect of Cd on plant growth being stronger than that of PAHs. The mixture of low Cd and low PAH lessened Cd toxicity to plants, resulting in improved plant growth and increased Cd accumulation in plant tissues, thus enhancing Cd removal by plants. The dissipation of PAHs in soils was significantly influenced by interactions of Cd, PAH and plant presence or absence. The total number of microorganisms in soils was significantly increased by the PAH additions. The interactive effect of Cd and PAHs on plant growth may be linked to the changes in the abundance of microorganisms in the rhizosphere, probably via a positive effect of PAH metabolites and/or phytohormones produced by microorganisms on plant growth.

Coal-tar-based sealcoated pavement: A major PAH source to urban stream sediments

International Nuclear Information System (INIS)

Witter, Amy E.; Nguyen, Minh H.; Baidar, Sunil; Sak, Peter B.

2014-01-01

We used land-use analysis, PAH concentrations and assemblages, and multivariate statistics to identify sediment PAH sources in a small (∼1303 km 2 ) urbanizing watershed located in South-Central, Pennsylvania, USA. A geographic information system (GIS) was employed to quantify land-use features that may serve as PAH sources. Urban PAH concentrations were three times higher than rural levels, and were significantly and highly correlated with combined residential/commercial/industrial land use. Principal components analysis (PCA) was used to group sediments with similar PAH assemblages, and correlation analysis compared PAH sediment assemblages to common PAH sources. The strongest correlations were observed between rural sediments (n = 7) and coke-oven emissions sources (r = 0.69–0.78, n = 5), and between urban sediments (n = 22) and coal-tar-based sealcoat dust (r = 0.94, n = 47) suggesting that coal-tar-based sealcoat is an important urban PAH source in this watershed linked to residential and commercial/industrial land use. -- Highlights: • Total PAH concentrations were measured at 35 sites along an urbanizing land-use gradient. • PAH concentrations increased with increasing urban land-use. • Urban land-use metrics were measured at three spatial scales using GIS. • PAH assemblages indicate coal-tar-based sealcoat is a major urban PAH source. • PAH assemblages indicate coke-oven emissions are an important rural PAH source. -- Coal-tar-based sealcoated pavement is a major PAH source to urban freshwater stream sediments in south-central Pennsylvania, USA

Single photon infrared emission spectroscopy: a study of IR emission from UV laser excited PAHs between 3 and 15 micrometers

Science.gov (United States)

Cook, D. J.; Schlemmer, S.; Balucani, N.; Wagner, D. R.; Harrison, J. A.; Steiner, B.; Saykally, R. J.

1998-01-01

Single-photon infrared emission spectroscopy (SPIRES) has been used to measure emission spectra from polycyclic aromatic hydrocarbons (PAHs). A supersonic free-jet expansion has been used to provide emission spectra of rotationally cold and vibrationally excited naphthalene and benzene. Under these conditions, the observed width of the 3.3-micrometers (C-H stretch) band resembles the bandwidths observed in experiments in which emission is observed from naphthalene with higher rotational energy. To obtain complete coverage of IR wavelengths relevant to the unidentified infrared bands (UIRs), UV laser-induced desorption was used to generate gas-phase highly excited PAHs. Lorentzian band shapes were convoluted with the monochromator-slit function in order to determine the widths of PAH emission bands under astrophysically relevant conditions. Bandwidths were also extracted from bands consisting of multiple normal modes blended together. These parameters are grouped according to the functional groups mostly involved in the vibration, and mean bandwidths are obtained. These bandwidths are larger than the widths of the corresponding UIR bands. However, when the comparison is limited to the largest PAHs studied, the bandwidths are slightly smaller than the corresponding UIR bands. These parameters can be used to model emission spectra from PAH cations and cations of larger PAHs, which are better candidate carriers of the UIRs.

Drug-induced pulmonary arterial hypertension: a recent outbreak

Directory of Open Access Journals (Sweden)

Gérald Simonneau

2013-09-01

Full Text Available Pulmonary arterial hypertension (PAH is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH.

Comparing PAH availability from manufactured gas plant soils and sediments with chemical and biological tests. 1. PAH release during water desorption and supercritical carbon dioxide extraction.

Science.gov (United States)

Hawthorne, Steven B; Poppendieck, Dustin G; Grabanski, Carol B; Loehr, Raymond C

2002-11-15

Soil and sediment samples from oil gas (OG) and coal gas (CG) manufactured gas plant (MGP) sites were selected to represent a range of PAH concentrations (150-40,000 mg/kg) and sample matrix compositions. Samples varied from vegetated soils to lampblack soot and had carbon contents from 3 to 87 wt %. SFE desorption (120 min) and water/XAD2 desorption (120 days) curves were determined and fit with a simple two-site model to determine the rapid-released fraction (F) for PAHs ranging from naphthalene to benzo[ghi]perylene. F values varied greatly among the samples, from ca. 10% to >90% for the two- and three-ring PAHs and from <1% to ca. 50% for the five- and six-ring PAHs. Release rates did not correlate with sample matrix characteristics including PAH concentrations, elemental composition (C, H, N, S), or "hard" and "softs" organic carbon, indicating that PAH release cannot easily be estimated on the basis of sample matrix composition. Fvalues for CG site samples obtained with SFE and water desorption agreed well (linear correlation coefficient, r2 = 0.87, slope = 0.93), but SFE yielded higher F values for the OG samples. These behaviors were attributed to the stronger ability of carbon dioxide than water to desorb PAHs from the highly aromatic (hard) carbon of the OG matrixes, while carbon dioxide and water showed similar abilities to desorb PAHs from the more polar (soft) carbon of the CG samples. The combined SFE and water desorption approaches should improve the understanding of PAH sequestration and release from contaminated soils and sediments and provide the basis for subsequent studies using the same samples to compare PAH release with PAH availability to earthworms.

Identification of PAH Isomeric Structure in Cosmic Dust Analogs: The AROMA Setup

Energy Technology Data Exchange (ETDEWEB)

Sabbah, Hassan; Bonnamy, Anthony; Joblin, Christine [Université de Toulouse, UPS-OMP, Institut de Recherche en Astrophysique et Planétologie, 9 avenue du Colonel Roche, 31028 Toulouse Cedex 4 (France); Papanastasiou, Dimitris [Fasmatech Science + Technology, Athens, GR (Greece); Cernicharo, Jose; Martín-Gago, Jose-Angel, E-mail: christine.joblin@irap.omp.eu [Instituto de Ciencia de Materiales de Madrid, Sor Juana Inés de la Cruz, 3, Cantoblanco, E-28049 Madrid (Spain)

2017-07-01

We developed a new analytical experimental setup called AROMA (Astrochemistry Research of Organics with Molecular Analyzer) that combines laser desorption/ionization techniques with ion trap mass spectrometry. We report here on the ability of the apparatus to detect aromatic species in complex materials of astrophysical interest and characterize their structures. A limit of detection of 100 femto-grams has been achieved using pure polycyclic aromatic hydrocarbon (PAH) samples, which corresponds to 2 × 10{sup 8} molecules in the case of coronene (C{sub 24}H{sub 12}). We detected the PAH distribution in the Murchison meteorite, which is made of a complex mixture of extraterrestrial organic compounds. In addition, collision induced dissociation experiments were performed on selected species detected in Murchison, which led to the first firm identification of pyrene and its methylated derivatives in this sample.

Growth of nano hexagon-like flake arrays cerium carbonate created with PAH as the substrate

Energy Technology Data Exchange (ETDEWEB)

Li, M., E-mail: limei@imust.cn [School of Materials Science and Engineering, Beijing University of Chemical Engineering, Department of Materials, Beijing 100029 (China); School of Materials and Metallurgy, Inner Mongolia University of Science and Technology, Department of Inorganic and Metalloid Materials, Key Laboratory of New Technologies of Modern Metallurgy and Application of Rare Materials, Baotou 014010 (China); Hu, Y.H., E-mail: bthyh@163.com [School of Materials Science and Engineering, Beijing University of Chemical Engineering, Department of Materials, Beijing 100029 (China); School of Materials and Metallurgy, Inner Mongolia University of Science and Technology, Department of Inorganic and Metalloid Materials, Key Laboratory of New Technologies of Modern Metallurgy and Application of Rare Materials, Baotou 014010 (China); Liu, Z.G.; Wang, X.F.; Wang, M.T. [School of Materials and Metallurgy, Inner Mongolia University of Science and Technology, Department of Inorganic and Metalloid Materials, Key Laboratory of New Technologies of Modern Metallurgy and Application of Rare Materials, Baotou 014010 (China)

2015-01-15

Petals-like Ce{sub 2}(CO{sub 3}){sub 3} on Ce{sub 2}(CO{sub 3}){sub 3} nano hexagon-like flake arrays have been precipitatingly fabricated using PAH substrates. By changing the way of feeding, PAH concentration and aging time, petals-like Ce{sub 2}(CO{sub 3}){sub 3} was created best when adding PAH into the Ce(NO{sub 3}){sub 3} solution, joined (NH{sub 4}){sub 2}CO{sub 3} solution along with mixing, PAH concentration is 0.9 g/L, aging time is 4 h. A growth mechanism was proposed to account for the growth of the petals-like Ce{sub 2}(CO{sub 3}){sub 3} with PAH as the substrate. Poly allylamine hydrochloride (PAH) is as template agent which forms π-allyl complex with Ce{sup 3+} and controls the morphology of Ce{sub 2}(CO{sub 3}){sub 3} particle. PAH and Ce{sup 3+} form π-allyl complex, and then induce the formation of Ce{sub 2}(CO{sub 3}){sub 3} crystal nucleus. And infrared spectrum analysis verified. XRD show that after adding PAH which is adsorbed on the crystal plane, the growth of Ce{sub 2}(CO{sub 3}){sub 3} crystal is inhibited on (2 4 2), the growth is promoted on (2 0 2) which is differentiated into the new (1 5 1), (2 2 2) is unchanged, Ce{sub 2}(CO{sub 3}){sub 3} crystal is accumulated petals shape by hexagon-like flake. UV absorption spectra show that CeO{sub 2} as prepared precursor Ce{sub 2}(CO{sub 3}){sub 3} after calcinations in air at high temperatures, the petal-like CeO{sub 2} has strong UV absorption and reflection effects, and absorption interval changed significantly by the move to UVA from UVB. - Graphical abstract: Each Ce-atom connects three Cl-atoms and three allyls in three dimensional spaces. To take the plane as a reference plane which is arrayed with three Ce-atom as equilateral triangle. The triangular each vertex is Ce-atom, the triangular center place is Cl-atom, the equilateral triangle which is mutually perpendicular with Ce-triangle surface and the inclined angle is 60° is made up with three Cl-atoms. - Highlights: • Petals

Intestinal metabolism of PAH: in vitro demonstration and study of its impact on PAH transfer through the intestinal epithelium

International Nuclear Information System (INIS)

Cavret, Severine; Feidt, Cyril

2005-01-01

Food would seem to be one of the main ways of animal and human contamination with polycyclic aromatic hydrocarbons (PAHs). In vivo studies suggest a transfer in intestinal epithelium by diffusion, which appears extensively governed by the physicochemical properties of PAHs, particularly lipophilicity. However, other mechanisms, such as metabolism, are considered to intervene. Our work aimed at testing in vitro intestinal metabolism and defining its impact on transepithelial transport of PAHs. Caco-2 cells were cultivated on permeable filters and incubated with 14 C-labeled benzo[a]pyrene (BaP), pyrene (Pyr), and phenanthrene (Phe), which differ in their physicochemical properties. The results showed that the cells were able to metabolize the compounds. In basal media, Phe appeared to be the least hydroxylated molecule (45% after a 6-h exposure), followed by Pyr (65%) and finally BaP (96%). Inhibition of PAH metabolism showed a determinant effect on kinetics profiles. Transfer in the basal compartment of BaP, Pyr, and Phe radioactivities was, respectively, 26, 4, and 2 times lower with inhibitors, corroborating that intestinal metabolism of PAHs would have a positive impact on their transfer, an impact that increased with their lipophilicity. Furthermore, after a 6-h incubation, metabolites were also detected in apical medium. These findings suggested that intestinal metabolism might play a key role in intestinal barrier permeability and thus in the bioavailability of tested micropollutants

Distribution of polycyclic aromatic hydrocarbons (PAHs) in surface sediments of Pulau Tinggi, Johor

Science.gov (United States)

Razak, Ezzati Sulhi Abdul; Halim, Izzyan Syazwani Abdul; Ali, Masni Mohd

2016-11-01

Surface sediments samples were collected at 11 stations around the Pulau Tinggi, Johor in September 2015. A total of 15 PAHs were determined and quantified by gas chromatography coupled with mass spectrometry (GC-MS). The total PAH concentrations of surface sediments from Pulau Tinggi ranged from 39.61 ng/g to 149.2 ng/g and they were classified as being in low to moderate pollution range. Individual PAH analysis showed that two and three rings PAHs were the most frequently detected isomers and accounted for 22 - 46% of the total PAH concentrations. The sources of PAHs were evaluated by employing diagnostic ratiosof specific PAH compounds.PAH ratios analysis showed a prevalence of pyrogenic PAH origin at most of the stations with exception of only a few stations.

The abundance of health-associated bacteria is altered in PAH polluted soils-Implications for health in urban areas?

Directory of Open Access Journals (Sweden)

Anirudra Parajuli

Full Text Available Long-term exposure to polyaromatic hydrocarbons (PAHs has been connected to chronic human health disorders. It is also well-known that i PAH contamination alters soil bacterial communities, ii human microbiome is associated with environmental microbiome, and iii alteration in the abundance of members in several bacterial phyla is associated with adverse or beneficial human health effects. We hypothesized that soil pollution by PAHs altered soil bacterial communities that had known associations with human health. The rationale behind our study was to increase understanding and potentially facilitate reconsidering factors that lead to health disorders in areas characterized by PAH contamination. Large containers filled with either spruce forest soil, pine forest soil, peat, or glacial sand were left to incubate or contaminated with creosote. Biological degradation of PAHs was monitored using GC-MS, and the bacterial community composition was analyzed using 454 pyrosequencing. Proteobacteria had higher and Actinobacteria and Bacteroidetes had lower relative abundance in creosote contaminated soils than in non-contaminated soils. Earlier studies have demonstrated that an increase in the abundance of Proteobacteria and decreased abundance of the phyla Actinobacteria and Bacteroidetes are particularly associated with adverse health outcomes and immunological disorders. Therefore, we propose that pollution-induced shifts in natural soil bacterial community, like in PAH-polluted areas, can contribute to the prevalence of chronic diseases. We encourage studies that simultaneously address the classic "adverse toxin effect" paradigm and our novel "altered environmental microbiome" hypothesis.

Treatment of PAH-contaminated soil using cement-activated persulfate.

Science.gov (United States)

Ma, Fujun; Zhang, Qian; Wu, Bin; Peng, Changsheng; Li, Ning; Li, Fasheng; Gu, Qingbao

2018-01-01

In this study, a novel method for the treatment of polycyclic aromatic hydrocarbon -contaminated soil using cement-activated persulfate was developed. The removal of PAHs in soil rose with increasing initial persulfate concentration, initial Portland cement (PC) concentration, and oxidation reaction time. At an initial persulfate and PC concentration of 19.20 mmol/kg and 10% of soil weight and a reaction time of 2 h, the removal rate of PAHs reached 57.3%. Residual PAHs were mainly adsorbed within the soil granules and thus became less available. The mechanism of PC facilitating the oxidation reaction was that PC addition can increase the pH and temperature of the system. When the soil was stabilized/solidified by 10% of PC, the leaching concentration of PAHs and TOC was significantly higher than that leached from untreated soil. Persulfate oxidation decreased the leaching concentration of PAHs but increased the leaching concentration of TOC in solidification/stabilization products. The addition of activated carbon can decrease the leaching concentrations of both PAHs and TOC. Freeze-thaw durability tests revealed that the leachability of PAHs was not affected by freeze-thaw cycles. The unconfined compressive strength (UCS) of treated soil samples after 12 freeze-thaw cycles was only 49.0% of that curing for 52 days, but the UCS was still > 1 MPa. The treated soil samples can resist disintegration during the process of freeze-thaw cycles.

Rapid collection, detection, and assessment of environmental polycyclic aromatic hydrocarbons (PAHs)

International Nuclear Information System (INIS)

Johnson, T.; Huckins, J.; Petty, J.; Butorin, A.

1995-01-01

PAHs, an important class of environmental chemical contaminants found primarily in petroleum and coal products, frequently are the most numerous and ubiquitous organic pollutants recovered in sediment residues. PAHs are considered hazardous in water and soil because many are acutely toxic and have the potential for genotoxic activity. Selected EPA priority pollutants (2, 3, 4, and 5-ring PAHs) and complex PAH mixtures (crude oil, gasoline, and recycled motor oil) were collected and concentrated from water and sediment with semipermeable polymeric membrane devices (SPMDs) that contain a thin film of triolein. Analytes were extracted from the SPMDs by dialysis in hexane or directly by rinsing with acetone DMSO, concentrated in the carrier solvent DMSO, and detected with the luminescent bacterial assays Microtox reg-sign and Mutatox reg-sign. High SPMD-water concentration factors of PAHs appeared to correspond closely to the occurrence of PAHs in sediments previously reported in the literature; for example, pyrene had the highest SPMD concentration factor and was the most commonly found PAH in sediment residues. Mutatox reg-sign with rat hepatic S9 activation detected all PAHs tested. The PAH's molecular weight and number of rings appeared to directly influence acute toxicity (EC50, microg/mL); for example, two-ring naphthalene had an EC50 value of 0.78 whereas five-ring benzo(a)pyrene had an EC50 value of 15.0, about a twenty-fold difference, Microtox reg-sign and Mutatox reg-sign, in combination with SPMDs were able to rapidly (< 24h) assess the bioavailability, toxicity, and genotoxicity of these environmental PAHs

Ecotoxicological and Health Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) in Short-Neck Clam (Paphia undulata) and Contaminated Sediments in Malacca Strait, Malaysia.

Science.gov (United States)

Keshavarzifard, Mehrzad; Zakaria, Mohamad Pauzi; Sharifi, Reza

2017-10-01

The distribution, sources, and human health risk assessment of polycyclic aromatic hydrocarbons (PAHs) in surface sediment and the edible tissue of short-neck clam (Paphia undulata) from mudflat ecosystem in the west coast of Malaysia were investigated. The concentrations of ∑ 16 PAHs varied from 347.05 to 6207.5 and 179.32 to 1657.5 ng g -1 in sediment and short-neck clam samples, respectively. The calculations of mean PEL quotients (mean-PELQs) showed that the ecological risk of PAHs in the sediment samples was low to moderate-high level, whereas the total health risk through ingestion and dermal contact was considerably high. The PAHs biota sediment accumulation factors data for short-neck clam were obtained in this study, indicating a preferential accumulation of lower molecular weight PAHs. The source apportionment of PAHs in sediment using positive matrix factorization model indicated that the highest contribution to the PAHs was from diesel emissions (30.38%) followed by oil and oil derivate and incomplete coal combustion (23.06%), vehicular emissions (16.43%), wood combustion (15.93%), and natural gas combustion (14.2%). A preliminary evaluation of human health risk using chronic daily intake, hazard index, benzo[a]pyrene-equivalent (BaP eq ) concentration, and the incremental lifetime cancer risk indicated that PAHs in short-neck clam would induce potential carcinogenic effects in the consumers.

Enrichment behavior and transport mechanism of soil-bound PAHs during rainfall-runoff events

International Nuclear Information System (INIS)

Zheng Yi; Luo Xiaolin; Zhang Wei; Wu Bin; Han Feng; Lin Zhongrong; Wang Xuejun

2012-01-01

Polycyclic Aromatic Hydrocarbons (PAHs) transported by surface runoff result in nonpoint source pollution and jeopardize aquatic ecosystems. The transport mechanism of PAHs during rainfall-runoff events has been rarely studied regarding pervious areas. An experimental system was setup to simulate the runoff pollution process on PAHs-contaminated soil. The enrichment behavior of soil-bound PAHs was investigated. The results show that soil organic matters (SOM), rather than clay particles, seem to be the main carrier of PAHs. The enrichment is highly conditioned on runoff and erosion processes, and its magnitude varies among PAH compounds. It is not feasible to build a simple and universal relationship between enrichment ratio and sediment discharge following the traditional enrichment theory. To estimate the flux of PAHs from pervious areas, soil erosion process has to be clearly understood, and both organic carbon content and composition of SOM should be factored into the calculation. - Highlights: ► Significant enrichment of particle-bound PAHs during rainfall-runoff events. ► Organic matters as the direct carrier of PAHs in runoff from contaminated soil. ► The traditional enrichment theory is not fully valid for PAHs. - The traditional enrichment theory is not fully valid for PAHs, and soil organic matters have a significant impact on the transport of PAHs during rainfall-runoff events.

Response of PAH-degrading genes to PAH bioavailability in the overlying water, suspended sediment, and deposited sediment of the Yangtze River.

Science.gov (United States)

Xia, Xinghui; Xia, Na; Lai, Yunjia; Dong, Jianwei; Zhao, Pujun; Zhu, Baotong; Li, Zhihuang; Ye, Wan; Yuan, Yue; Huang, Junxiong

2015-06-01

The degrading genes of hydrophobic organic compounds (HOCs) serve as indicators of in situ HOC degradation potential, and the existing forms and bioavailability of HOCs might influence the distribution of HOC-degrading genes in natural waters. However, little research has been conducted to study the relationship between them. In the present study, nahAc and nidA genes, which act as biomarkers for naphthalene- and pyrene-degrading bacteria, were selected as model genotypes to investigate the response of polycyclic aromatic hydrocarbon (PAH)-degrading genes to PAH bioavailability in the overlying water, suspended sediment (SPS), and deposited sediment of the Yangtze River. The freely dissolved concentration, typically used to reflect HOC bioavailability, and total dissolved, as well as sorbed concentrations of PAHs were determined. Phylogenetic analysis showed that all the PAH-ring hydroxylating dioxygenase gene sequences of Gram-negative bacteria (PAH-RHD[GN]) were closely related to nahAc, nagAc, nidA, and uncultured PAH-RHD genes. The PAH-RHD[GN] gene diversity as well as nahAc and nidA gene copy numbers decreased in the following order: deposited sediment>SPS>overlying water. The nahAc and nidA gene abundance was not significantly correlated with environmental parameters but was significantly correlated with the bioavailable existing forms of naphthalene and pyrene in the three phases. The nahAc gene copy numbers in the overlying water and deposited sediment were positively correlated with freely dissolved naphthalene concentrations in the overlying and pore water phases, respectively, and so were nidA gene copy numbers. This study suggests that the distribution and abundance of HOC-degrading bacterial population depend on the HOC bioavailability in aquatic environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanism-Based Classification of PAH Mixtures to Predict Carcinogenic Potential.

Science.gov (United States)

Tilton, Susan C; Siddens, Lisbeth K; Krueger, Sharon K; Larkin, Andrew J; Löhr, Christiane V; Williams, David E; Baird, William M; Waters, Katrina M

2015-07-01

We have previously shown that relative potency factors and DNA adduct measurements are inadequate for predicting carcinogenicity of certain polycyclic aromatic hydrocarbons (PAHs) and PAH mixtures, particularly those that function through alternate pathways or exhibit greater promotional activity compared to benzo[a]pyrene (BaP). Therefore, we developed a pathway-based approach for classification of tumor outcome after dermal exposure to PAH/mixtures. FVB/N mice were exposed to dibenzo[def,p]chrysene (DBC), BaP, or environmental PAH mixtures (Mix 1-3) following a 2-stage initiation/promotion skin tumor protocol. Resulting tumor incidence could be categorized by carcinogenic potency as DBC > BaP = Mix2 = Mix3 > Mix1 = Control, based on statistical significance. Gene expression profiles measured in skin of mice collected 12 h post-initiation were compared with tumor outcome for identification of short-term bioactivity profiles. A Bayesian integration model was utilized to identify biological pathways predictive of PAH carcinogenic potential during initiation. Integration of probability matrices from four enriched pathways (P PAH mixtures. These data further provide a 'source-to-outcome' model that could be used to predict PAH interactions during tumorigenesis and provide an example of how mode-of-action-based risk assessment could be employed for environmental PAH mixtures. © 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.

Increased zooplankton PAH concentrations across hydrographic fronts in the East China Sea.

Science.gov (United States)

Hung, Chin-Chang; Ko, Fung-Chi; Gong, Gwo-Ching; Chen, Kuo-Shu; Wu, Jian-Ming; Chiang, Hsin-Lun; Peng, Sen-Chueh; Santschi, Peter H

2014-06-15

The Changjiang has transported large quantities of polycyclic aromatic hydrocarbons (PAHs) to the East China Sea (ECS), but information of these pollutants in zooplankton is limited. To understand PAHs pollution in zooplankton in the ECS, total concentrations of PAHs in zooplankton from surface waters were measured. Values of PAHs ranged from 2 to 3500 ng m(-3) in the ECS, with highest PAHs levels located at the salinity front between the Changjiang Diluted Water (CDW) and the mid-shelf waters. In contrast, concentrations of zooplankton PAHs in the mid-shelf and outer-shelf waters were significantly lower (2-23 ng m(-3)) than those in the CDW. These results demonstrate that PAHs are conspicuously accumulated in zooplankton at the salinity front between the CDW and the mid-shelf waters. These higher levels of PAHs in zooplankton at the salinity front may be further biomagnified in marine organisms of higher trophic levels through their feeding activities. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

PAH diagnostic ratios for the identification of pollution emission sources

International Nuclear Information System (INIS)

Tobiszewski, Marek; Namieśnik, Jacek

2012-01-01

Polycyclic aromatic hydrocarbon (PAH) diagnostic ratios have recently come into common use as a tool for identifying and assessing pollution emission sources. Some diagnostic ratios are based on parent PAHs, others on the proportions of alkyl-substituted to non-substituted molecules. The ratios are applicable to PAHs determined in different environmental media: air (gas + particle phase), water, sediment, soil, as well as biomonitor organisms such as leaves or coniferous needles, and mussels. These ratios distinguish PAH pollution originating from petroleum products, petroleum combustion and biomass or coal burning. The compounds involved in each ratio have the same molar mass, so it is assumed they have similar physicochemical properties. Numerous studies show that diagnostic ratios change in value to different extents during phase transfers and environmental degradation. The paper reviews applications of diagnostic ratios, comments on their use and specifies their limitations. - Highlights: ► PAH diagnostic ratios may identify pollution coming from petroleum spills, fuel combustion and coal or biomass burning. ► They are sensitive to changes during PAHs environmental fate processes. ► Some diagnostic ratios are of limited value due to fast photodegradation of one of the compounds. - The paper reviews PAH diagnostic ratios that are applied to identify pollution emission originating from petroleum products, fuel combustion or coal and biomass burning.

The North Cape oil spill assessment: PAHs in oil

International Nuclear Information System (INIS)

Brown, J.; Boehm, P. D.; Hardestine, J. H.; Douglas, G. S.

1997-01-01

The North Cape oil spill in January 1996 resulted in the release of an estimated 827,000 gallons of No. 2 home heating oil into the nearshore turbulent waters of coastal Rhode Island. The oil was mixed into the water column and was transported on the surface as well as below the surface. Some of the spilled oil entered the coastal ponds behind the beaches. Sampling and chemical analysis for detailed suites of petroleum saturated and polycyclic aromatic hydrocarbons (PAHs) was undertaken as part of the assessment of the fate of the oil spill and of the exposure to the marine environment. The ponds were found to contain significant quantities of background petroleum hydrocarbons, including petrogenic PAHs and combustion PAHs. Initial assessment pointed (incorrectly as it turned out) to widespread contamination due only to the North Cape spill. Application of advanced chemical fingerprinting approaches, and geochemical biomarker data illustrated that many of the PAHs consisted of combustion-related 4- and 5-ringed PAHs, attributable to diesel fuel used routinely by boats in the area. The analysis demonstrated that the use of non-specific total PAH data and insufficient fingerprinting and allocation of petrogenic residues has the potential to overestimate contamination and hence injury to the environment in similar oil spill situations

Development of methods for determination of PAH based on measured CO-content; Metodutveckling foer indirekt bestaemning av PAH-halt utgaaende fraan maett momentan CO-halt

Energy Technology Data Exchange (ETDEWEB)

Ingman, Rolf; Schuster, Robert [AaF Energikonsult Stockholm AB, Stockholm (Sweden)

2001-02-01

The aim of the project 'Development of methods for determination of PAH based on measured CO-content' is to investigate the possibility to develop a method for continuous optimisation of NO{sub x}-emissions by decreased air ratio, without significant increase of polyaromatic hydrocarbons such as PAH. The general idea has been to find a indirect online method to predict the emissions of heavier hydrocarbons by: - creating a correlation between the content of CO and PAH, - controlling the air ratio by the CO-content, and - integrating the calculated PAH-content from CO-content. Today many boilers are operated with a low air ratio to minimise the NO{sub x} content and the NO{sub x}-fee. A low ratio increases the risk of high CO contents in the flue gas as well as increased contents of VOC and PAH. Other boilers are operated with high air ratios in order to minimise the CO content, which in some cases will result in unnecessary high NO{sub x} emissions. One of the main difficulties in optimising the air ratio to the most environmental friendly level is the lack of a suitable and well proven PAH instrument. There are today no available instruments for instantaneous and continuous measurement of PAH. PAH is normally measured as an average value during a period of at least one hour. It is not possible to detect short peaks. The development of the CO-method has been based on data from a CFB-boiler in Korsta in Sundsvall (Vaermeforskrapport 541). The data shows a clear correlation between THC and CO. The correlation seems to be mostly dependent of moisture content and load. The development presented in the report shows that it is possible to find a method to predict the PAH content from the CO-content in the flue gas. The next phase aims to improve and implement the method, by measurements and adaptation in a plant. The practical use of the method is as a tool to optimise the emission of CO, NO{sub x}, THC and PAH and/or to predict the PAH-emission during

Polycyclic aromatic hydrocarbons (PAHs), their transfer into and dislocation within soil; Eintraege von polyzyklischen aromatischen Kohlenwasserstoffen (PAH) und ihre Verlagerung im Boden

Energy Technology Data Exchange (ETDEWEB)

Duerbeck, H W; Niehaus, R; Mueller, U; Bueker, I [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Angewandte Physikalische Chemie

1998-12-31

In order to assess the terrestrial hazard potential of polycyclic aromatic hydrocarbons (PAHs), it is vital to investigate their nuisance concentrations and deposition to soil and plants as well as their dislocation in soil. This was the object of the first part of the research programme ``Locational evaluation of chemical soil pollution``, conducted by the national research institutions. It was headed ``Analysis of exposure`` and comprised the following individual contributions: 1. Integrated long-term measurements of polycyclic aromatic hydrocarbons in soil air at ground level (FZJ), 2. Determination of PAH nuisance concentrations at the Scheyern experimental station as well as at the motorway by-passing Munich to the east (A 99), near Kirchheim (GSF), 3. Investigations regarding PAH exposure via the air pathway and inclusion of acquired data in substance flows made up for the east-German dry zone (Bad Lauchstaedt), (UFZ), 4. Simulation of PAH concentration and deposition in south-western Germany (FZK). (orig./SR) [Deutsch] Zur Abschaetzung des Gefaehrdungspotentials von Polycyclischen Aromatischen Kohlenwasserstoffen (PAK) im terrestrischen Bereich sind daher Untersuchungen ueber die Immissionskonzentrationen und die Deposition auf Boeden und Pflanzen sowie ueber ihre Verlagerung im Boden von essentieller Bedeutung. Die Bearbeitung dieser Thematik erfolgte im Teilbereich I `Eintragsanalyse` des AGF-Programms `Standortgerechte Bewertung chemischer Bodenbelastungen` mit folgenden Einzelbeitraegen: 1. Integrierende Langzeitmessung von Polycyclischen Aromatischen Kohlenwasserstoffen in bodennaher Luft, (FZJ) 2. Bestimmung der PAH-Immissionskonzentrationen am Versuchsgut Scheyern sowie an der oestlichen Autobahnumgehung von Muenchen (A 99) bei Kirchheim, (GSF) 3. Untersuchungen zum Eintrag von PAH ueber den Luftpfad und Einbeziehung der Daten in Stoffkreislaeufe im Mitteldeutschen Trockengebiet (Bad Lauchstaedt), (UFZ) 4. Simulation der PAH-Konzentration und

Polycyclic aromatic hydrocarbons (PAHs), their transfer into and dislocation within soil; Eintraege von polyzyklischen aromatischen Kohlenwasserstoffen (PAH) und ihre Verlagerung im Boden

Energy Technology Data Exchange (ETDEWEB)

Duerbeck, H.W.; Niehaus, R.; Mueller, U.; Bueker, I. [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Angewandte Physikalische Chemie

1997-12-31

In order to assess the terrestrial hazard potential of polycyclic aromatic hydrocarbons (PAHs), it is vital to investigate their nuisance concentrations and deposition to soil and plants as well as their dislocation in soil. This was the object of the first part of the research programme ``Locational evaluation of chemical soil pollution``, conducted by the national research institutions. It was headed ``Analysis of exposure`` and comprised the following individual contributions: 1. Integrated long-term measurements of polycyclic aromatic hydrocarbons in soil air at ground level (FZJ), 2. Determination of PAH nuisance concentrations at the Scheyern experimental station as well as at the motorway by-passing Munich to the east (A 99), near Kirchheim (GSF), 3. Investigations regarding PAH exposure via the air pathway and inclusion of acquired data in substance flows made up for the east-German dry zone (Bad Lauchstaedt), (UFZ), 4. Simulation of PAH concentration and deposition in south-western Germany (FZK). (orig./SR) [Deutsch] Zur Abschaetzung des Gefaehrdungspotentials von Polycyclischen Aromatischen Kohlenwasserstoffen (PAK) im terrestrischen Bereich sind daher Untersuchungen ueber die Immissionskonzentrationen und die Deposition auf Boeden und Pflanzen sowie ueber ihre Verlagerung im Boden von essentieller Bedeutung. Die Bearbeitung dieser Thematik erfolgte im Teilbereich I `Eintragsanalyse` des AGF-Programms `Standortgerechte Bewertung chemischer Bodenbelastungen` mit folgenden Einzelbeitraegen: 1. Integrierende Langzeitmessung von Polycyclischen Aromatischen Kohlenwasserstoffen in bodennaher Luft, (FZJ) 2. Bestimmung der PAH-Immissionskonzentrationen am Versuchsgut Scheyern sowie an der oestlichen Autobahnumgehung von Muenchen (A 99) bei Kirchheim, (GSF) 3. Untersuchungen zum Eintrag von PAH ueber den Luftpfad und Einbeziehung der Daten in Stoffkreislaeufe im Mitteldeutschen Trockengebiet (Bad Lauchstaedt), (UFZ) 4. Simulation der PAH-Konzentration und

Comparing PAH availability from manufactured gas plant soils and sediments with chemical and biological tests. 1. PAH release during water desorption and supercritical carbon dioxide extraction

Energy Technology Data Exchange (ETDEWEB)

Hawthorne, S.B.; Poppendieck, D.G.; Grabanski, C.B.; Loehr, R.C. [University of North Dakota, Grand Forks, ND (US). Energy and Environmental Research Center

2002-11-15

Soil and sediment samples from OG (oil gas) and CG (coal gas) manufactured gas plant (MGP) sites in the United States that had been closed for about 50 years were selected to represent a range of PAH concentrations and sample matrix compositions. Samples varied from vegetated soils to lampblack soot and had carbon contents from 3 to 87 wt%. Supercritical carbon dioxide, SFE desorption and water/XAD{sub 2} desorption curves were determined and fit with a simple two-site model to determine the rapid-released fraction (F) for PAHs ranging from naphthalene to benzo-(ghi)perylene. F values varied greatly among the samples. Release rates did not correlate with sample matrix characteristics including PAH concentrations, elemental composition or 'hard' and 'soft' organic carbon, indicating that PAH release cannot easily be estimated on the basis of sample matrix composition. F values for CG site samples obtained with SFE and water desorption agreed well but SFE yielded higher F values for the OG samples. These behaviors were attributed to the stronger ability of carbon dioxide than water to desorb PAHs from the highly aromatic (hard) carbon of the OG matrixes, while carbon dioxide and water showed similar abilities to desorb PAHs from the more polar (soft) carbon of the CG samples. The combined SFE and water desorption approaches should improve the understanding of PAH sequestration and release from contaminated soils and sediments and provide the basis for subsequent studies, using the same samples to compare PAH release with PAH availability to earthworms. 46 refs., 4 figs., 4 tabs.

Temporal variability in sediment PAHs accumulation in the northern Gulf of Mexico Shelf

Science.gov (United States)

Bam, W.; Maiti, K.; Adhikari, P. L.

2017-12-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous group of organic pollutants, some of which are known to be toxic, and/or carcinogenic to humans. The major source of these PAHs into the northern Gulf of Mexico (NGOM) are Mississippi River discharge, coastal erosion, atmospheric deposition, and numerous natural oil seeps and spills. In addition to these background source of PAHs, the Deepwater Horizon (DWH) oil spill in 2010 added 21,000 tons of PAHs into the NGOM water. In this study, we measured PAHs distribution and accumulation rates in coastal sediments near the Mississippi River mouth in 2011 and 2015 to understand the effect of DWH oil spill in PAHs accumulation in coastal sediments. Sediment cores were collected and sliced at 1 cm interval to measure PAHs concentration, and to estimate 210Pb-based sedimentation and the PAHs' accumulation rates. The results showed that the sediment deposition rates in this region varied between 0.5 to 0.9 cm/yr. The results also showed that the concentration of total PAHs (ΣPAH43) and their accumulation rates vary between 68 - 100 ng g-1 and 7 - 160 ng cm-2 yr-1, respectively. While the PAHs accumulation rate in coastal sediment varied over the years, there is no significant variation in PAHs accumulation rate before and after the DWH oil spill.

Prediction of target genes for miR-140-5p in pulmonary arterial hypertension using bioinformatics methods.

Science.gov (United States)

Li, Fangwei; Shi, Wenhua; Wan, Yixin; Wang, Qingting; Feng, Wei; Yan, Xin; Wang, Jian; Chai, Limin; Zhang, Qianqian; Li, Manxiang

2017-12-01

The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat. Identification of target genes for miR-140-5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR-140-5p to provide theoretical evidences for further researches on role of miR-140-5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR-140-5p were predicted in the analysis. Gene ontology (GO) enrichment analysis indicated that downstream target genes of miR-140-5p were enriched in many biological processes, such as biological regulation, signal transduction, response to chemical stimulus, stem cell proliferation, cell surface receptor signaling pathways. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis found that downstream target genes were mainly located in Notch, TGF-beta, PI3K/Akt, and Hippo signaling pathway. According to TF-miRNA-mRNA network, the important downstream target genes of miR-140-5p were PPI, TGF-betaR1, smad4, JAG1, ADAM10, FGF9, PDGFRA, VEGFA, LAMC1, TLR4, and CREB. After thoroughly reviewing published literature, we found that 23 target genes and seven signaling pathways were truly inhibited by miR-140-5p in various tissues or cells; most of these verified targets were in accordance with our present prediction. Other predicted targets still need further verification in vivo and in vitro .

Mutação nova do gene MCT8 em menino Brasileiro com resistência ao hormônio tireioidiano e neuropatia grave

OpenAIRE

MENEZES FILHO, Hamilton Cabral de; MARUI, Suemi; MANNA, Thais Della; BRUST, Ester Saraiva; RADONSKY, Vanessa; KUPERMAN, Hilton; DICHTCHEKENIAN, Vaê; SETIAN, Nuvarte; DAMIANI, Durval

2011-01-01

MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation dis...

Review of PAH contamination in food products and their health hazards.

Science.gov (United States)

Bansal, Vasudha; Kim, Ki-Hyun

2015-11-01

Public concern over the deleterious effects of polycyclic aromatic hydrocarbons (PAHs) has grown rapidly due to recognition of their toxicity, carcinogenicity, and teratogenicity. The aim of this review is to describe the status of PAH pollution among different food types, the route of dietary intake, measures for its reduction, and legislative approaches to control PAH. To this end, a comprehensive review is outlined to evaluate the status of PAH contamination in many important food categories along with dietary recommendations. Our discussion is also extended to describe preventive measures to reduce PAH in food products to help reduce the risks associated with human intake. Copyright © 2015 Elsevier Ltd. All rights reserved.

Polyaromatic hydrocarbons (PAHs) levels from two industrial zones ...

African Journals Online (AJOL)

Polyaromatic hydrocarbons (PAHs) levels from two industrial zones (Sihwa and Banwal) located in An-san city ... PROMOTING ACCESS TO AFRICAN RESEARCH ... method (HVAS-Sibata) was employed to collect airborne PAHs in both the particulate and gas phases. ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

PAH (Polycyclic Aromatic Hydrocarbon) bioaccumulation and PAHs/shell weight index in Ruditapes philippinarum (Adams & Reeve, 1850) from the Vallona lagoon (northern Adriatic Sea, NE Italy).

Science.gov (United States)

Cacciatore, Federica; Bernarello, Valentina; Boscolo Brusà, Rossella; Sesta, Giulio; Franceschini, Gianluca; Maggi, Chiara; Gabellini, Massimo; Lamberti, Clauda Virno

2018-02-01

The Vallona lagoon is a transitional area located in the Po River delta (NE, ITALY) traditionally exploited for Manila clam (Ruditapes philippinarum) farming. During 2007-2008, a pipeline was buried in the middle of the lagoon to connect an off-shore structure to facilities on land. PAH levels were monitored in Manila clams and sediments before, during and after the pipeline construction to assess the impact of the activities through the pattern of distribution of the PAH compounds. PAH bioaccumulation in clams displayed seasonal fluctuations with higher levels in autumnal and wintry surveys than in spring-summer. Principal component analysis applied to PAHs in clams highlighted a petrogenic input during ante operam period and a pyrolytic origin during the burying activities. On the contrary, sediment PAH concentrations resulted quite similar both among sites and periods. Biota-Sediment-Accumulation-Factor values also confirmed that sediments were not the major source of PAH pollution for clams in this study. The welfare of clams was examined through two physiological indices (condition index and survival in air) to check the effects of the activities on a commercial resource. Both physiological indices exhibited seasonal variations connected to natural endogenous and exogenous factors; however survival in air was the most sensitive index in highlighting the effects of the pipeline burying activities. Finally, to ensure that PAH bioavailability assessment was not affected by seasonal variation of soft tissues of molluscs, PAHs/shell weight index was applied. Higher levels of this index were observed before and during the burying activities, whilst, after that, values significantly lowered. Moreover, the normalization enabled us to highlight the PAH uptake from clams in some particular periods and to compare different populations in a long-term biomonitoring program with data obtained from different periods of the year. Copyright © 2017 Elsevier Inc. All rights

Effect of a cationic surfactant on the volatilization of PAHs from soil.

Science.gov (United States)

Lu, Li; Zhu, Lizhong

2012-06-01

Cationic surfactants are common in soils because of their use in daily cosmetic and cleaning products, and their use as a soil amendment for the mitigation and remediation of organic contaminated soils has been proposed. Such surfactant may affect the transfer and fate of organic contaminants in the environment. This study investigated the effect of a cationic surfactant, dodecylpyridinium bromide (DDPB), on the volatilization of polycyclic aromatic hydrocarbons (PAHs) from a paddy soil. The volatilization of PAHs from moist soil amended with different concentrations of DDPB was tested in an open system. The specific effects of DDPB on the liquid-vapor and solid-vapor equilibriums of PAHs were separately investigated in closed systems by headspace analysis. DDPB affects both liquid-vapor and solid-vapor processes of PAHs in soil. At DDPB concentrations below the critical micelle concentration (CMC), movement of PAHs from the bulk solution to the gas-liquid interface appeared to be facilitated by interaction between PAHs and the surfactant monomers adsorbed at the gas-liquid interface, promoting the volatilization of PAHs from solution. However, when DDPB was greater than the CMC, volatilization was inhibited due to the solubilization of PAHs by micelles. On the other hand, the formation of sorbed surfactant significantly inhibited the solid-vapor volatilization of PAHs. The overall effect of the two simultaneous effects of DDPB on liquid-vapor and solid-vapor processes was a decreased volatilization loss of PAHs from soil. Inhibition of PAH volatilization was more significant for the soil with a lower moisture content.

Splicing of phenylalanine hydroxylase (PAH) exon 11 is vulnerable - Molecular pathology of mutations in PAH exon 11

DEFF Research Database (Denmark)

Heintz, Caroline; Dobrowolski, Steven F.; Andersen, Henriette Skovgaard

2012-01-01

as a vulnerable exon and used patient derived lymphoblast cell lines and PAH minigenes to study the molecular defect that impacted pre-mRNA processing. We showed that the c.1144T>C and c.1066-3C>T mutations cause exon 11 skipping, while the c.1139C>T mutation is neutral or slightly beneficial. The c.1144T......In about 20-30% of phenylketonuria (PKU) patients, phenylalanine (Phe) levels can be controlled by cofactor 6R-tetrahydrobiopterin (BH(4)) administration. The phenylalanine hydroxylase (PAH) genotype has a predictive value concerning BH(4)-response and therefore a correct assessment of the mutation...... molecular pathology is important. Mutations that disturb the splicing of exons (e.g. interplay between splice site strength and regulatory sequences like exon splicing enhancers (ESEs)/exon splicing silencers (ESSs)) may cause different severity of PKU. In this study, we identified PAH exon 11...

Dissipation of polycyclic aromatic hydrocarbons (PAHs) in the rhizosphere: Synthesis through meta-analysis

International Nuclear Information System (INIS)

Ma Bin; He Yan; Chen Huaihai; Xu Jianming; Rengel, Zed

2010-01-01

Polycyclic aromatic hydrocarbons (PAHs) are widespread and persistent organic pollutants with high carcinogenic effect and toxicity; their behavior and fate in the soil-plant system have been widely investigated. In the present paper, meta-analysis was used to explore the interaction between plant growth and dissipation of PAHs in soil based on the large body of published literature. Plants have a promoting effect on PAH dissipation in soils. There was no difference in PAH dissipation between soils contaminated with single and mixed PAHs. However, plants had a more obvious effect on PAH dissipation in freshly-spiked soils than in long-term field-polluted soils. Additionally, a positive effect of the number of microbial populations capable of degrading PAHs was observed in the rhizosphere compared with the bulk soil. Our meta-analysis established the importance of the rhizosphere effect on PAH dissipation in variety of the soil-plant systems. - The meta-analysis provides the first quantitative evidence of the positive effect of rhizosphere processes on PAH dissipation.

Ambient water quality criteria for polycyclic aromatic hydrocarbons (PAHs)

Energy Technology Data Exchange (ETDEWEB)

Nagpal, N.K.

1993-08-13

Ambient water quality criteria are established for polyaromatic hydrocarbons (PAH) in British Columbia. Major sources of PAH in the atmosphere and aquatic environments include, for the atmosphere, forest and prairie fires, agricultural burning, refuse burning, enclosed incineration, and heating and power, and for the aquatic environment, petroleum spillage, atmospheric deposition, wastewaters, surface land runoff, and biosynthesis. Details are presented of PAH and their characteristics, forms and transformations, occurrence in the environment, drinking water concerns, aquatic life concerns, wildlife concerns, livestock water supply concerns, and irrigation concerns. Application of criteria for aquatic life is discussed including phototoxic vs long term criteria, assessment of existing water quality, setting water quality objectives, and PAH levels in smoked fish. 221 refs., 5 figs., 30 tabs.

Watershed-scale modeling on the fate and transport of polycyclic aromatic hydrocarbons (PAHs)

International Nuclear Information System (INIS)

Ligaray, Mayzonee; Baek, Sang Soo; Kwon, Hye-Ok; Choi, Sung-Deuk; Cho, Kyung Hwa

2016-01-01

PAHs are potentially carcinogenic substances that are persistent in the environment. Increasing concentrations of PAHs were observed due to rapid urbanization, thus; monitoring PAHs concentrations is necessary. However, it is expensive to conduct intensive monitoring activities of a large number of PAHs. This study addressed this issue by developing a multimedia model coupled with a hydrological model (i.e., Soil and Water Assessment Tool (SWAT)) for Taehwa River (TR) watershed in Ulsan, the industrial capital of South Korea. The hydrologic module of the SWAT was calibrated, and further used to simulate the fate and transport of PAHs in soil and waterbody. The model demonstrated that the temporal or seasonal variation of PAHs in soil and waterbody can be well reproduced. Meanwhile, the spatial distribution of PAHs showed that urban areas in TR watershed have the highest PAH loadings compared to rural areas. Sensitivity analyses of the PAH soil and PAH water parameters were also able to determine the critical processes in TR watershed: degradation, deposition, volatilization, and wash off mechanism. We hope that this model will be able to aid the stakeholders in: regulating PAH concentrations emitted by various sources; and also apply the model to other Persistent Organic Pollutants (POPs).

Watershed-scale modeling on the fate and transport of polycyclic aromatic hydrocarbons (PAHs)

Energy Technology Data Exchange (ETDEWEB)

Ligaray, Mayzonee; Baek, Sang Soo [School of Urban and Environmental Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 44919 (Korea, Republic of); Kwon, Hye-Ok [Disaster Scientific Investigation Division, National Disaster Management Research Institute, 365 Jongga-ro Jung-gu, Ulsan 44538 (Korea, Republic of); Choi, Sung-Deuk, E-mail: sdchoi@unist.ac.kr [School of Urban and Environmental Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 44919 (Korea, Republic of); Cho, Kyung Hwa, E-mail: khcho@unist.ac.kr [School of Urban and Environmental Engineering, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 44919 (Korea, Republic of)

2016-12-15

PAHs are potentially carcinogenic substances that are persistent in the environment. Increasing concentrations of PAHs were observed due to rapid urbanization, thus; monitoring PAHs concentrations is necessary. However, it is expensive to conduct intensive monitoring activities of a large number of PAHs. This study addressed this issue by developing a multimedia model coupled with a hydrological model (i.e., Soil and Water Assessment Tool (SWAT)) for Taehwa River (TR) watershed in Ulsan, the industrial capital of South Korea. The hydrologic module of the SWAT was calibrated, and further used to simulate the fate and transport of PAHs in soil and waterbody. The model demonstrated that the temporal or seasonal variation of PAHs in soil and waterbody can be well reproduced. Meanwhile, the spatial distribution of PAHs showed that urban areas in TR watershed have the highest PAH loadings compared to rural areas. Sensitivity analyses of the PAH soil and PAH water parameters were also able to determine the critical processes in TR watershed: degradation, deposition, volatilization, and wash off mechanism. We hope that this model will be able to aid the stakeholders in: regulating PAH concentrations emitted by various sources; and also apply the model to other Persistent Organic Pollutants (POPs).

Electrochemical Oxidation of PAHs in Water from Harbor Sediment Purification

DEFF Research Database (Denmark)

Muff, Jens; Søgaard, Erik Gydesen

2010-01-01

generated oxidant solution with a free chlorine concentration of 2 gL-1. Both strategies resulted in a successful degradation of 5 PAHs to fulfil the discharge limit on 0.010 µgL-1. The intermixing-with-oxidant approach can also be applied as a method to address the actual sediment matrix....... of the discharge water addressing primarily polycyclic aromatic hydrocarbons (PAHs). PAHs are by-products of incomplete combustion of organic materials with recalcitrant and strong mutagenic/carcinogenic properties, due to their benzene analogue structures. PAHs are hydrophobic compounds and their persistence...... evidence for the importance of the indirect oxidation mechanism in the degradation of the PAHs. The proof-of-concept study was conducted both by a direct treatment approach and an intermixing-with-oxidant approach, where the contaminated water was intermixed in different ratios with an electrochemically...

Study of PAH emission from the solid fuels combustion in residential furnaces

International Nuclear Information System (INIS)

Kakareka, Sergey V.; Kukharchyk, Tamara I.; Khomich, Valery S.

2005-01-01

The procedure for and results of a test study of polycyclic aromatic hydrocarbon (PAH) emission from a few types of solid fuels combustion in residential furnaces of various designs typical for Belarus are discussed. Greatest levels of PAH emission were detected from domestic wastes and wood waste combustion. Lowest levels of PAH emission are from peat briquette combustion. It was found that PAH concentration in off-gases from firewood combustion also varies significantly depending on the type of wood: the highest values of PAH are typical for waste gases from birch firewood combustion in comparison with pine firewood combustion. Draft PAH emission factors are proposed with intended application for emission inventory of such installations

Generation and distribution of PAHs in the process of medical waste incineration

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying, E-mail: echochen327@163.com [School of Environment, Tsinghua University, Beijing 100084 (China); National Center of Solid Waste Management, Ministry of Environmental Protection, Beijing 100029 (China); Zhao, Rongzhi [Civil and Environmental Engineering School, University of Science and Technology Beijing, Beijing 100083 (China); Xue, Jun [National Center of Solid Waste Management, Ministry of Environmental Protection, Beijing 100029 (China); Li, Jinhui, E-mail: jinhui@tsinghua.edu.cn [State Key Joint Laboratory of Environment Simulation and Pollution Control, School of Environment, Tsinghua University, Beijing 100084 (China)

2013-05-15

Highlights: ► PAHs generation and distribution features of medical waste incineration are studied. ► More PAHs were found in fly ash than that in bottom ash. ► The highest proportion of PAHs consisted of the seven most carcinogenic ones. ► Increase of free oxygen molecule and burning temperature promote PAHs degradation. ► There is a moderate positive correlation between total PCDD/Fs and total PAHs. - Abstract: After the deadly earthquake on May 12, 2008 in Wenchuan county of China, several different incineration approaches were used for medical waste disposal. This paper investigates the generation properties of polycyclic aromatic hydrocarbons (PAHs) during the incineration. Samples were collected from the bottom ash in an open burning slash site, surface soil at the open burning site, bottom ash from a simple incinerator, bottom ash generated from the municipal solid waste (MSW) incinerator used for medical waste disposal, and bottom ash and fly ash from an incinerator exclusively used for medical waste. The species of PAHs were analyzed, and the toxicity equivalency quantities (TEQs) of samples calculated. Analysis results indicate that the content of total PAHs in fly ash was 1.8 × 10{sup 3} times higher than that in bottom ash, and that the strongly carcinogenic PAHs with four or more rings accumulated sensitively in fly ash. The test results of samples gathered from open burning site demonstrate that Acenaphthylene (ACY), Acenaphthene (ACE), Fluorene (FLU), Phenanthrene (PHE), Anthracene (ANT) and other PAHs were inclined to migrate into surrounding environment along air and surface watershed corridors, while 4- to 6-ring PAHs accumulated more likely in soil. Being consistent with other studies, it has also been confirmed that increases in both free oxygen molecules and combustion temperatures could promote the decomposition of polycyclic PAHs. In addition, without the influence of combustion conditions, there is a positive correlation between

Generation and distribution of PAHs in the process of medical waste incineration

International Nuclear Information System (INIS)

Chen, Ying; Zhao, Rongzhi; Xue, Jun; Li, Jinhui

2013-01-01

Highlights: ► PAHs generation and distribution features of medical waste incineration are studied. ► More PAHs were found in fly ash than that in bottom ash. ► The highest proportion of PAHs consisted of the seven most carcinogenic ones. ► Increase of free oxygen molecule and burning temperature promote PAHs degradation. ► There is a moderate positive correlation between total PCDD/Fs and total PAHs. - Abstract: After the deadly earthquake on May 12, 2008 in Wenchuan county of China, several different incineration approaches were used for medical waste disposal. This paper investigates the generation properties of polycyclic aromatic hydrocarbons (PAHs) during the incineration. Samples were collected from the bottom ash in an open burning slash site, surface soil at the open burning site, bottom ash from a simple incinerator, bottom ash generated from the municipal solid waste (MSW) incinerator used for medical waste disposal, and bottom ash and fly ash from an incinerator exclusively used for medical waste. The species of PAHs were analyzed, and the toxicity equivalency quantities (TEQs) of samples calculated. Analysis results indicate that the content of total PAHs in fly ash was 1.8 × 10 3 times higher than that in bottom ash, and that the strongly carcinogenic PAHs with four or more rings accumulated sensitively in fly ash. The test results of samples gathered from open burning site demonstrate that Acenaphthylene (ACY), Acenaphthene (ACE), Fluorene (FLU), Phenanthrene (PHE), Anthracene (ANT) and other PAHs were inclined to migrate into surrounding environment along air and surface watershed corridors, while 4- to 6-ring PAHs accumulated more likely in soil. Being consistent with other studies, it has also been confirmed that increases in both free oxygen molecules and combustion temperatures could promote the decomposition of polycyclic PAHs. In addition, without the influence of combustion conditions, there is a positive correlation between total

Enhanced PM10 bounded PAHs from shipping emissions

Science.gov (United States)

Pongpiachan, S.; Hattayanone, M.; Choochuay, C.; Mekmok, R.; Wuttijak, N.; Ketratanakul, A.

2015-05-01

Earlier studies have highlighted the importance of maritime transport as a main contributor of air pollutants in port area. The authors intended to investigate the effects of shipping emissions on the enhancement of PM10 bounded polycyclic aromatic hydrocarbons (PAHs) and mutagenic substances in an industrial area of Rayong province, Thailand. Daily PM10 speciation data across two air quality observatory sites in Thailand during 2010-2013 were collected. Diagnostic binary ratios of PAH congeners, analysis of variances (ANOVA), and principal component analysis (PCA) were employed to evaluate the enhanced genotoxicity of PM10 during the docking period. Significant increase of PAHs and mutagenic index (MI) of PM10 were observed during the docking period in both sampling sites. Although stationary sources like coal combustions from power plants and vehicular exhausts from motorway can play a great role in enhancing PAH concentrations, regulating shipping emissions from diesel engine in the port area like Rayong is predominantly crucial.

An Optimised Method to Determine PAHs in a Contaminated Soil; Metodo Optimizado para la Determinacion de PAHs en un Suelo Contaminado

Energy Technology Data Exchange (ETDEWEB)

Garcia Alonso, S.; Perez Pastor, R. M.; Sevillano castano, M. L.; Escolano Segovia, O.; Garcia Frutos, F. J.

2007-07-20

An analytical study is presented based on an optimised method to determine selected polycyclic aromatic hydrocarbons (PAHs) by High Performance Liquid Chromatography (HPLC) with fluorescence detection. The work was focused to obtain reliable measurements of PAH in a gas work contaminated soil and was performed in the frame of the project 'Assessment of natural remediation technologies for PAHs in contaminated soils' (Spanish Plan Nacional l+D+i, CTM 2004-05832-CO2-01): First assays were focused to evaluate an initial proposed procedure by sonication extraction in the contaminated soil. Afterwards to extend the efficiency and reduce solvent and time consuming of extraction procedures, the more relevant parameters that affect the extraction step were investigated. A comparison between sonication and microwave procedures was done, and the influence of sample grinding was studied. In general, both extraction techniques led on comparable results, although sonication procedure needs to be more carefully optimised. Finally, as a final application of the optimised method, the effect of particle size on relative distribution of selected PAHs in the contaminated soil was investigated. Relative abundance of more volatile PAHs showed a decreasing according to lower grain size, while relative abundance of less volatile compounds indicated an increasing of concentration levels for lower grain size. (Author) 10 refs.

Reductions of PAH and Soot by Center Air Injection

Directory of Open Access Journals (Sweden)

Kazuhiro Yamamoto

2014-07-01

Full Text Available In this study, to reduce the amount of pollutant PAH and soot in the flame, we examined the burner system equipped with a center air injection. For this purpose, by using PAH-LIF and soot LII, we evaluated relative PAH and soot amounts in both the triple port burner and the conventional co-axial burner (double port burner to discuss effects of center air injection on the formation of PAH and soot. The fuel was propane. In the triple port burner, two different blue flames are observed near the burner rim, followed by bright luminous flames with soot. The flame length is longer when the fuel flow velocity is increased. On the other hand, the flame length is shorter with an increase in internal air flow velocity. As for PAH and soot, these amounts of the triple port burner are much smaller than those of the double port burner. For the triple port burner, due to the center air injection, the fuel consumption occurs in both inner and outer flames. On the other hand, for the double port burner, the oxygen is supplied from one side air, and as a result, the fuel consumption rate is relatively lower. Hence, by the center air injection, the fuel consumption is largely accelerated, resulting in the reduction of PAH and soot.

Alkyl PAH in crude oil cause chronic toxicity to early life stages of fish

Energy Technology Data Exchange (ETDEWEB)

Hodson, P.V.; Khan, C.W.; Saravanabhavan, G.; Clarke, L.; Brown, R.S. [Queen' s Univ., Kingston, ON (Canada). School of Environmental Studies; Hollebone, B.; Wang, Z. [Environment Canada, Ottawa, ON (Canada). ; Short, J. [National Oceanic and Atmospheric Administration, Juneau, AK (United States). Auke Bay Lab; Lee, K.; King, T. [Fisheries and Oceans Canada, Dartmouth, NS (Canada). Centre for Offshore Oil and Gas Environmental Research

2007-07-01

In order to mitigate the risk to fisheries following an offshore oil spill, it is necessary to know the components of crude oil that are toxic. Chronic exposure of early life stages of fish to crude oil causes Blue Sac Disease, a syndrome characterized by induction of the cytochrome P450 (CYP1A) enzyme. In this study, effects-driven fractionation of Alaska North Slope Crude was used to identify the classes of compounds that cause CYP1A induction in juvenile rainbow trout and chronic toxicity to developing stages of Japanese medaka. Four fractions of compounds were created by low temperature vacuum distillation. This separated the constituents of oil according to their volatility within defined temperature ranges. The fractions were separated according to their boiling points. With a temperature range of 287-481 degrees C, fraction F3 was the only fraction as toxic as whole oil and induced CYPP1A enzymes of fish. Fractions containing specific classes of alkyl PAH were also collected. For all separations, the performance of the method was evaluated by the extent to which PAH were separated from aliphatics, resins and waxes, as well as by the quantitative recovery of mass in fractions and subfractions. The induction of CYP1A enzymes showed that PAH was present in all fractions that were highly toxic, but the toxicity tests indicated that not all fractions containing PAH were toxic. This research provided a scientific basis for comparing the risks of different crude oils based on chemical analyses that show the different proportions or amounts of PAH present. The results indicate which compounds of concern should be used to determine the extent and success of oil spill remediation, and provide a biological interpretation of chemical fingerprinting used to discriminate the sources of oil pollution. 15 refs., 1 tab.

Spatial Distribution of Polycyclic Aromatic Hydrocarbon (PAH) Concentrations in Soils from Bursa, Turkey.

Science.gov (United States)

Karaca, Gizem

2016-02-01

The objectives of this study were to identify regional variations in soil polycyclic aromatic hydrocarbon (PAH) contamination in Bursa, Turkey, and to determine the distributions and sources of various PAH species and their possible sources. Surface soil samples were collected from 20 different locations. The PAH concentrations in soil samples were analyzed using gas chromatography-mass spectrometry (GC-MS). The total PAH concentrations (∑12 PAH) varied spatially between 8 and 4970 ng/g dry matter (DM). The highest concentrations were measured in soils taken from traffic+barbecue+ residential areas (4970 ng/g DM) and areas with cement (4382 ng/g DM) and iron-steel (4000 ng/g DM) factories. In addition, the amounts of ∑7 carcinogenic PAH ranged from 1 to 3684 ng/g DM, and between 5 and 74 % of the total PAHs consisted of such compounds. Overall, 4-ring PAH compounds (Fl, Pyr, BaA and Chr) were dominant in the soil samples, with 29-82 % of the ∑12 PAH consisting of 4-ring PAH compounds. The ∑12 BaPeq values ranged from 0.1 to 381.8 ng/g DM. Following an evaluation of the molecular diagnostic ratios, it was concluded that the PAH pollution in Bursa soil was related to pyrolytic sources; however, the impact of petrogenic sources should not be ignored.

Growth and Destruction of PAH Molecules in Reactions with Carbon Atoms

Energy Technology Data Exchange (ETDEWEB)

Krasnokutski, Serge A.; Huisken, Friedrich; Jäger, Cornelia; Henning, Thomas [Laboratory Astrophysics Group of the Max Planck Institute for Astronomy at the Friedrich Schiller University Jena, Helmholtzweg 3, D-07743 Jena (Germany)

2017-02-10

A very high abundance of atomic carbon in the interstellar medium (ISM), and the high reactivity of these species toward different hydrocarbon molecules including benzene, raise questions regarding the stability of polycyclic aromatic hydrocarbon (PAH) molecules in space. To test the efficiency of destruction of PAH molecules via reactions with atomic carbon, we performed a set of laboratory and computational studies of the reactions of naphthalene, anthracene, and coronene molecules with carbon atoms in the ground state. The reactions were investigated in liquid helium droplets at T = 0.37 K and by quantum chemical computations. Our studies suggest that all small and all large catacondensed PAHs react barrierlessly with atomic carbon, and therefore should be efficiently destroyed by such reactions in a broad temperature range. At the same time, large compact pericondensed PAHs should be more inert toward such a reaction. In addition, taking into account their higher photostability, much higher abundances of pericondensed PAHs should be expected in various astrophysical environments. The barrierless reactions between carbon atoms and small PAHs also suggest that, in the ISM, these reactions could lead to the bottom-up formation of PAH molecules.

EZH2 Inhibition Ameliorates Transverse Aortic Constriction-Induced Pulmonary Arterial Hypertension in Mice

Directory of Open Access Journals (Sweden)

Zhan-Li Shi

2018-01-01

Full Text Available Background. EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice. Methods. We assigned 15 (6–8 weeks old male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg−1, once a week for 4 weeks. On day 28 following TAC operation, the right ventricular systolic blood pressure (RVSBP was measured, and lung tissues were collected for laboratory examinations (DHE, Western blot, real-time PCR, and ChIP. Results. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner. Conclusion. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

Incidence of real-world automotive parent and halogenated PAH in urban atmosphere.

Science.gov (United States)

Gao, Pan-Pan; Zhao, Yi-Bo; Ni, Hong-Gang

2018-06-01

This study reports results from a tunnel experiment impact of real-world traffic-related particle and gas parent and halogenated polycyclic aromatic hydrocarbons (PAHs and HPAHs) on urban air. The traffic related emission characteristics and subsequent environmental behavior of these compounds were investigated. To understand the significance of real-world transport emissions to the urban air, traffic-related mass emissions of PAHs and HPAHs were estimated based on measured emission factors. According to our results, PAHs and HPAHs emissions via particulate phase were greater than those via gaseous phase; particles in 2.1-3.3 μm size fraction, have the major contribution to particulate PAHs and HPAHs emissions. Over all, contribution of traffic-related emission of PAHs (only ∼3% of the total PAHs emission in China) is an overstated source of PAHs pollution in China. Actually, exhaust pipe emission contributed much less than the total traffic-related emission of pollutants. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of Smoking on Polycyclic Aromatic Hydrocarbons (PAHS ...

African Journals Online (AJOL)

ADOWIE PERE

Manage. Vol. 22 (2) 293 - 297. February 2018. Full-text Available Online at ... aromatic hydrocarbons (PAHs) were studied in raw and smoked samples of catfish (Clarias ... inferred that the smoking process generally increased the mean total PAH levels in the fish .... with 5 g of anhydrous sodium sulphate in a laboratory.

APPLICATION OF PSEUDOMONAS PUTIDA AND RHODOCOCCUS SP. BY BIODEGRADATION OF PAH(S, PCB(S AND NEL SOIL SAMPLES FROM THE HAZARDOUS WASTE DUMP IN POZĎÁTKY (CZECH REPUBLIC

Directory of Open Access Journals (Sweden)

Radmila Kucerova

2006-12-01

Full Text Available The objective of the project was a laboratory check of biodegradation of soil samples contaminated by PAH(s, PCB(s and NEL from the hazardous waste dump in the Pozďátky locality. For the laboratory check, pure bacterial cultures of Rhodococcus sp. and Pseudomonas putida have been used. It is apparent from the laboratory experiments results that after one-month bacterial leaching, applying the bacterium of Rhodococcus sp. there is a 83 % removal of NEL, a 79 % removal of PAH(s and a 14 % removal of PCB(s. Applying a pure culture of Pseudomonas putida there is a 87 % removal of NEL, a 81 % removal of PAH(s and a 14 % removal of PCB(s.

THE CHARGE STATE OF POLYCYCLIC AROMATIC HYDROCARBONS ACROSS REFLECTION NEBULAE: PAH CHARGE BALANCE AND CALIBRATION

International Nuclear Information System (INIS)

Boersma, C.; Bregman, J.; Allamandola, L. J.

2016-01-01

Low-resolution Spitzer spectral map data (>1700 spectra) of ten reflection nebulae (RNe) fields are analyzed using the data and tools available through the NASA Ames PAH IR Spectroscopic Database. The PAH emission is broken down into PAH charge state using a database fitting approach. Here, the physics of the PAH emission process is taken into account and uses target appropriate parameters, e.g., a stellar radiation model for the exciting star. The breakdown results are combined with results derived using the traditional PAH band strength approach, which interprets particular PAH band strength ratios as proxies for the PAH charge state, e.g., the 6.2/11.2 μ m PAH band strength ratio. These are successfully calibrated against their database equivalent; the PAH ionized fraction ( f i ). The PAH ionized fraction is converted into the PAH ionization parameter, which relates the PAH ionized fraction to the strength of the radiation field, gas temperature and electron density. The behavior of the 12.7 μ m PAH band is evaluated as a tracer for PAH ionization and erosion. The plot of the 8.6 versus 11.2 μ m PAH band strength for the northwest photo-dominated region (PDR) in NGC 7023 is shown to be a robust diagnostic template for the PAH ionized fraction. Remarkably, most of the other RNe fall within the limits set by NGC 7023. Finally, PAH spectroscopic templates are constructed and verified as principal components. Template spectra derived from NGC 7023 and NGC 2023 compare extremely well with each other, with those derived for NGC 7023 successfully reproducing the PAH emission observed from NGC 2023.

THE CHARGE STATE OF POLYCYCLIC AROMATIC HYDROCARBONS ACROSS REFLECTION NEBULAE: PAH CHARGE BALANCE AND CALIBRATION

Energy Technology Data Exchange (ETDEWEB)

Boersma, C.; Bregman, J.; Allamandola, L. J., E-mail: Christiaan.Boersma@nasa.gov [NASA Ames Research Center, MS 245-6, Moffett Field, CA 94035-0001 (United States)

2016-11-20

Low-resolution Spitzer spectral map data (>1700 spectra) of ten reflection nebulae (RNe) fields are analyzed using the data and tools available through the NASA Ames PAH IR Spectroscopic Database. The PAH emission is broken down into PAH charge state using a database fitting approach. Here, the physics of the PAH emission process is taken into account and uses target appropriate parameters, e.g., a stellar radiation model for the exciting star. The breakdown results are combined with results derived using the traditional PAH band strength approach, which interprets particular PAH band strength ratios as proxies for the PAH charge state, e.g., the 6.2/11.2 μ m PAH band strength ratio. These are successfully calibrated against their database equivalent; the PAH ionized fraction ( f {sub i} ). The PAH ionized fraction is converted into the PAH ionization parameter, which relates the PAH ionized fraction to the strength of the radiation field, gas temperature and electron density. The behavior of the 12.7 μ m PAH band is evaluated as a tracer for PAH ionization and erosion. The plot of the 8.6 versus 11.2 μ m PAH band strength for the northwest photo-dominated region (PDR) in NGC 7023 is shown to be a robust diagnostic template for the PAH ionized fraction. Remarkably, most of the other RNe fall within the limits set by NGC 7023. Finally, PAH spectroscopic templates are constructed and verified as principal components. Template spectra derived from NGC 7023 and NGC 2023 compare extremely well with each other, with those derived for NGC 7023 successfully reproducing the PAH emission observed from NGC 2023.

Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

Science.gov (United States)

Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

2015-12-22

Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

Effects of profession on urinary PAH metabolite levels in the US population.

Science.gov (United States)

Liu, Bian; Jia, Chunrong

2016-01-01

Although exposure to polycyclic aromatic hydrocarbons (PAHs) is common in both environmental and occupational settings, few studies have compared PAH exposure among people with different professions. The purpose of this study was to investigate the variations in recent PAH exposure among different occupational groups over time using national representative samples. The study population consisted of 4162 participants from the 2001 to 2008 National Health and Nutrition Examination Survey, who had both urinary PAH metabolites and occupational information. Four corresponding monohydroxy-PAH urine metabolites: naphthalene (NAP), fluorene (FLUO), phenanthrene (PHEN), and pyrene (PYR) among seven broad occupational groups were analyzed using weighted linear regression models, adjusting for creatinine levels, sociodemographic factors, smoking status, and sampling season. The overall geometric mean concentrations of NAP, FLUO, PHEN, and PYR were 6927, 477, 335, and 87 ng/L, respectively. All four PAH metabolites were elevated in the "extractive, construction, and repair (ECR)" group, with 21-42 % higher concentrations than those in the reference group of "management." Similar trends were seen in the "operators, fabricators, and laborers (OFL)" group for FLUO, PHEN, and PYR. In addition, both "service" and "support" groups had elevated FLUO. Significant (p PAH exposure. Heterogeneous distributions of urinary PAH metabolites among people with different job categories exist at the population level. The upward temporal trends in NAP and PYR warrant reduction in PAH exposure, especially among those with OFL and ECR occupations.

Characteristics of PAHs in farmland soil and rainfall runoff in Tianjin, China.

Science.gov (United States)

Shi, Rongguang; Xu, Mengmeng; Liu, Aifeng; Tian, Yong; Zhao, Zongshan

2017-10-14

Rainfall runoff can remove certain amounts of pollutants from contaminated farmland soil and result in a decline in water quality. However, the leaching behaviors of polycyclic aromatic hydrocarbons (PAHs) with rainfall have been rarely reported due to wide variations in the soil compositions, rainfall conditions, and sources of soil PAHs in complex farmland ecosystems. In this paper, the levels, spatial distributions, and composition profiles of PAHs in 30 farmland soil samples and 49 rainfall-runoff samples from the Tianjin region in 2012 were studied to investigate their leaching behaviors caused by rainfall runoff. The contents of the Σ 16 PAHs ranged from 58.53 to 3137.90 μg/kg in the soil and 146.58 to 3636.59 μg/L in the runoff. In total, most of the soil sampling sites (23 of 30) were contaminated, and biomass and petroleum combustion were proposed as the main sources of the soil PAHs. Both the spatial distributions of the soil and the runoff PAHs show a decreasing trend moving away from the downtown, which suggested that the leaching behaviors of PAHs in a larger region during rainfall may be mainly affected by the compounds themselves. In addition, 4- and 5-ring PAHs are the dominant components in farmland soil and 3- and 4-ring PAHs dominate the runoff. Comparisons of the PAH pairs and enrichment ratios showed that acenaphthylene, acenaphthene, benzo[a]anthracene, chrysene, and fluoranthene were more easily transferred into water systems from soil than benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[ghi]perylene, and indeno[123-cd]pyrene, which indicated that PAHs with low molecular weight are preferentially dissolved due to their higher solubility compared to those with high molecular weight.

Coal-tar-based sealcoated pavement: a major PAH source to urban stream sediments.

Science.gov (United States)

Witter, Amy E; Nguyen, Minh H; Baidar, Sunil; Sak, Peter B

2014-02-01

We used land-use analysis, PAH concentrations and assemblages, and multivariate statistics to identify sediment PAH sources in a small (~1303 km(2)) urbanizing watershed located in South-Central, Pennsylvania, USA. A geographic information system (GIS) was employed to quantify land-use features that may serve as PAH sources. Urban PAH concentrations were three times higher than rural levels, and were significantly and highly correlated with combined residential/commercial/industrial land use. Principal components analysis (PCA) was used to group sediments with similar PAH assemblages, and correlation analysis compared PAH sediment assemblages to common PAH sources. The strongest correlations were observed between rural sediments (n = 7) and coke-oven emissions sources (r = 0.69-0.78, n = 5), and between urban sediments (n = 22) and coal-tar-based sealcoat dust (r = 0.94, n = 47) suggesting that coal-tar-based sealcoat is an important urban PAH source in this watershed linked to residential and commercial/industrial land use. Copyright © 2013 Elsevier Ltd. All rights reserved.

Observational Evidence Linking Interstellar UV Absorption to PAH Molecules

Energy Technology Data Exchange (ETDEWEB)

Blasberger, Avi; Behar, Ehud; Perets, Hagai B. [Department of Physics, Technion (Israel); Brosch, Noah [The Wise Observatory and School of Physics and Astronomy, Tel Aviv University (Israel); Tielens, Alexander G. G. M. [Leiden Observatory, Leiden University (Netherlands)

2017-02-20

The 2175 Å UV extinction feature was discovered in the mid-1960s, yet its physical origin remains poorly understood. One suggestion is absorption by polycyclic aromatic hydrocarbon (PAH) molecules, which is supported by theoretical molecular structure computations and by laboratory experiments. PAHs are positively detected by their 3.3, 6.2, 7.7, 8.6, 11.3, and 12.7 μ m IR emission bands, which are specified by their modes of vibration. A definitive empirical link between the 2175 Å UV extinction and the IR PAH emission bands, however, is still missing. We present a new sample of hot stars that have both 2175 Å absorption and IR PAH emission. We find significant shifts of the central wavelength of the UV absorption feature, up to 2350 Å, but predominantly in stars that also have IR PAH emission. These UV shifts depend on stellar temperature in a fashion that is similar to the shifts of the 6.2 and 7.7 μ m IR PAH bands, that is, the features are increasingly more redshifted as the stellar temperature decreases, but only below ∼15 kK. Above 15 kK both UV and IR features retain their nominal values. Moreover, we find a suggestive correlation between the UV and IR shifts. We hypothesize that these similar dependences of both the UV and IR features on stellar temperature hint at a common origin of the two in PAH molecules and may establish the missing link between the UV and IR observations. We further suggest that the shifts depend on molecular size, and that the critical temperature of ∼15 kK above which no shifts are observed is related to the onset of UV-driven hot-star winds and their associated shocks.

Observational Evidence Linking Interstellar UV Absorption to PAH Molecules

International Nuclear Information System (INIS)

Blasberger, Avi; Behar, Ehud; Perets, Hagai B.; Brosch, Noah; Tielens, Alexander G. G. M.

2017-01-01

The 2175 Å UV extinction feature was discovered in the mid-1960s, yet its physical origin remains poorly understood. One suggestion is absorption by polycyclic aromatic hydrocarbon (PAH) molecules, which is supported by theoretical molecular structure computations and by laboratory experiments. PAHs are positively detected by their 3.3, 6.2, 7.7, 8.6, 11.3, and 12.7 μ m IR emission bands, which are specified by their modes of vibration. A definitive empirical link between the 2175 Å UV extinction and the IR PAH emission bands, however, is still missing. We present a new sample of hot stars that have both 2175 Å absorption and IR PAH emission. We find significant shifts of the central wavelength of the UV absorption feature, up to 2350 Å, but predominantly in stars that also have IR PAH emission. These UV shifts depend on stellar temperature in a fashion that is similar to the shifts of the 6.2 and 7.7 μ m IR PAH bands, that is, the features are increasingly more redshifted as the stellar temperature decreases, but only below ∼15 kK. Above 15 kK both UV and IR features retain their nominal values. Moreover, we find a suggestive correlation between the UV and IR shifts. We hypothesize that these similar dependences of both the UV and IR features on stellar temperature hint at a common origin of the two in PAH molecules and may establish the missing link between the UV and IR observations. We further suggest that the shifts depend on molecular size, and that the critical temperature of ∼15 kK above which no shifts are observed is related to the onset of UV-driven hot-star winds and their associated shocks.

Mobility and availability of PAH in soil-sewage sludges systems; Mobilite et disponibilite des HAP dans des systemes terre-boue de station d'epuration

Energy Technology Data Exchange (ETDEWEB)

Bryselbout, C

2002-07-15

This work deals with the increase of the availability of polycyclic aromatic hydrocarbons (PAH) induced by the supply of organic matter to a soil in the framework of the agricultural valorization of organic wastes. The sharing of PAH with the organic matter of a model of soil and sewage sludge mixture has been studied first, using extractions and adsorption kinetics (Kd methanol). Then, the evolution of the PAH availability in a sludge-earth mixture has ben studied over a period of 185 days. Finally, the plants PAH availability in the presence of residual sludge has been studied at the laboratory and in-situ. Results show that Kd methanol and PAH extractability in a earth-sludge mixture are proportional to the total organic carbon ratio and to the incubation time. The presence of sludges leads to the immobilization of a smaller amount of PAH. The PAH availability from a sludge-earth mixture is limited by the presence of sludge and cations, such as mercuric mercury. It seems that the organic matter of sludges is more washable than the one of the soil leading to an increased risk of migration of micro-pollutants in the environment. The agricultural valorization of organic wastes, as it is already implemented in France, does not indicate any direct effect on the mobility and availability of PAH in soils. However, a long-term effect on water and soil quality is to be feared. The limitation of PAH fluxes towards agricultural areas would be a societal answer. (J.S.)

The formation of aromatics and PAH's in laminar flames

International Nuclear Information System (INIS)

Marinov, N M; Pitz, W J; Westbrook, C K

1999-01-01

The formation of aromatics and PAH's is an important problem in combustion. These compounds are believed to contribute to the formation of soot whose emission from diesel engines is regulated widely throughout the industrial world. Additionally, the United States Environmental Protection Agency regulates the emission of many aromatics and PAH species from stationary industrial burners, under the 1990 Clean Air Act Amendments. The above emission regulations have created much interest in understanding how these species are formed in combustion systems. Much previous work has been done on aromatics and PAH's. The work is too extensive to review here, but is reviewed in Reference 1. A few recent developments are highlighted here. McEnally, Pfefferle and coworkers have studied aromatic, PAH and soot formation in a variety of non-premixed flames with hydrocarbon additives[2-4]. They found additives that contain a C5 ring increase the concentration of aromatics and soot[4]. Howard and coworkers have studied the formation of aromatic and PAH's in low pressure, premixed, laminar hydrocarbon flames. They found the cyclopentadienyl radical to be a key species in naphthalene formation in a fuel-rich, benzene/Ar/O2 flame[5

PAHs sensitivity of picophytoplankton populations in the Red Sea

KAUST Repository

Kottuparambil, Sreejith

2018-04-25

In this study, we investigated the in situ responses of Red Sea picophytoplankton, the dominant phytoplankton group in the oligotrophic ocean, to two toxic polycyclic aromatic hydrocarbons (PAHs), phenanthrene and pyrene. The experiments were conducted across a latitudinal gradient of the Saudi Arabian Red Sea, an area sensitive to oil pollution. We observed significant adverse effects on the growth and abundance of the picocyanobacteria Synechococcus and picoeukaryotes, at all stations sampled. Prochlorococcus, which was abundant only at one of the stations, also appeared to be affected. Pyrene was found to be more toxic to phytoplankton at all stations. In general, picoeukaryotes exhibited higher sensitivity to PAHs than Synechococcus. Populations in the highly oligotrophic Northern region of the Red Sea were more tolerant to PAHs, presumably influenced by the natural selection of more resistant strains of phytoplankton due to the prolonged exposure to PAHs. Toxicity threshold values estimated here are higher than those reported for picophytoplankton from other oligotrophic marine waters and exceed by far the natural levels of PAHs in many oceans. Our findings reveal a possible adaptation of picophytoplankton populations to oil-related contaminants, which may clearly influence their spatial distribution patterns in the Red Sea.

Enhanced bioremediation of PAH contaminated soils from coal processing sites

International Nuclear Information System (INIS)

Joshi, M.M.; Lee, S.

1995-01-01

The polycyclic aromatic hydrocarbons (PAH) are a potential hazard to health due to their carcinogenic, mutagenic nature and acute toxicity and there is an imminent need for remediation of PAH contaminated soils abounding the several coke oven and town gas sites. Aerobic biological degradation of PAHs is an innovative technology and has shown high decontamination efficiencies, complete mineralization of contaminants, and is environmentally safe. The present study investigates the remediation of PAH contaminated soils achieved using Acinetobacter species and fungal strain Phanerochaete Chrysosporium. The soil used for the experiments was an industrially contaminated soil obtained from Alberta Research Council (ARC) primary cleanup facility, Alberta, Canada. Soil characterization was done using High Performance Liquid Chromatography (HPLC) to qualitatively and quantitatively determine the contaminants in the soil. Artificially contaminated soil was also used for some experiments. All the experiments were conducted under completely mixed conditions with suitable oxygen and nutrient amendments. The removal efficiency obtained for various PAHs using the two microorganisms was compared

Biomonitoring seasonal variation of urban air polycyclic aromatic hydrocarbons (PAHs) using Ficus benghalensis leaves

International Nuclear Information System (INIS)

Prajapati, Santosh Kumar; Tripathi, B.D.

2008-01-01

Temporal and seasonal variations of polycyclic aromatic hydrocarbons (PAHs) concentrations in leaves of Ficus benghalensis were investigated in Varanasi city (India). Leaf samples were collected from six sites from urban area of Varanasi and from a control site. PAH extraction was done by sonication in dichloromethane-acetone and quantification by GC-MS. In January total leaf PAHs concentrations at all the urban sites were twice higher as compared to other season's viz. summer and rainy. In contrast, at the control site leaf PAHs concentrations showed lower values than urban sites. The maximum concentrations of total PAHs in winter were due to the medium molecular weight PAHs which increases with respect to both low and high molecular weight PAHs. The temporal variation of medium molecular weight PAHs was similar both at the urban and remote sites. These results support biomonitoring ability of Ficus benghalensis leaves to temporal variations in PAHs contamination. - Biomonitoring PAHs in atmosphere using F. benghalensis leaves for its temporal and seasonal variation is cost effective as well as easier

Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

Science.gov (United States)

Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

2016-02-01

Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

Heterogeneous ozonation reactions of PAHs and fatty acid methyl esters in biodiesel particulate matter

Science.gov (United States)

Kasumba, John; Holmén, Britt A.

2018-02-01

Numerous studies have examined the oxidation of PAHs found in diesel particulate matter (PM) by ozone, but no studies have investigated the ozone oxidation of biodiesel exhaust PM. Fatty acid methyl esters (FAMEs), found in high abundance in biodiesel PM, can potentially alter the kinetics of the reactions between atmospheric oxidants such as ozone and particle-phase PAHs. In this study, the heterogeneous reactivity of 16 EPA PAHs upon 24 h exposure to 0.4 ppm ozone in the presence (PAH + FAMES) and absence (PAH-only) of FAMEs was investigated at room temperature and 50% relative humidity. The ozone-reactivity of the PAHs detected in 20% biodiesel (B20) exhaust PM was also investigated. In the absence of FAMEs, the pseudo-first order ozone reaction rate constant, kO 3 , of PAHs varied from 0.086 ± 0.030 hr-1 (chrysene) to 0.184 ± 0.078 hr-1 (anthracene). In the presence of FAMEs, kO 3 of the PAHs varied between 0.013 ± 0.012 hr-1 (benzo[b]fluoranthene) and 0.168 ± 0.028 hr-1 (benzo[a]pyrene), and with the exception of benzo[a]pyrene, the kO 3 of PAHs were 1.2-8 times lower compared to those obtained during the PAH-only ozone exposure. Only one PAH, benzo[a]pyrene (BaP), did not show a significant change in kO3 with addition of FAMEs. Phenanthrene, fluoranthene, and pyrene, the only PAHs detected in the B20 PM, had kO 3 values about 4 times lower in B20 PM than those obtained when spiked PAHs-only were exposed to ozone. The kO 3 values of phenanthrene and fluoranthene in the B20 PM were 2 times higher than rates obtained when the PAH mix was exposed to ozone in the presence of the FAMEs. In contrast, pyrene's kO 3 in the B20 PM was about 2 times lower than that obtained for the PAH + FAMEs exposure. Observed differences in PAH behavior demonstrate individual PAH heterogeneous reactivity with gas-phase ozone is sensitive to PAH (vapor pressure, solubility/sorption to matrix components, chemical reactivity) as well as substrate properties (PAH and O3 diffusivity

Polycyclic aromatic hydrocarbons (PAH) formation from the pyrolysis of different municipal solid waste fractions

International Nuclear Information System (INIS)

Zhou, Hui; Wu, Chunfei; Onwudili, Jude A.; Meng, Aihong; Zhang, Yanguo; Williams, Paul T.

2015-01-01

Highlights: • PAH from pyrolysis of 9 MSW fractions was investigated. • Pyrolysis of plastics released more PAH than that of biomass. • Naphthalene was the most abundant PAH in the tar. • The mechanism of PAH release from biomass and plastics was proposed. - Abstract: The formation of 2–4 ring polycyclic aromatic hydrocarbons (PAH) from the pyrolysis of nine different municipal solid waste fractions (xylan, cellulose, lignin, pectin, starch, polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), and polyethylene terephthalate (PET)) were investigated in a fixed bed furnace at 800 °C. The mass distribution of pyrolysis was also reported. The results showed that PS generated the most total PAH, followed by PVC, PET, and lignin. More PAH were detected from the pyrolysis of plastics than the pyrolysis of biomass. In the biomass group, lignin generated more PAH than others. Naphthalene was the most abundant PAH, and the amount of 1-methynaphthalene and 2-methynaphthalene was also notable. Phenanthrene and fluorene were the most abundant 3-ring PAH, while benzo[a]anthracene and chrysene were notable in the tar of PS, PVC, and PET. 2-ring PAH dominated all tar samples, and varied from 40 wt.% to 70 wt.%. For PS, PET and lignin, PAH may be generated directly from the aromatic structure of the feedstock

Relation between PAH and black carbon contents in size fractions of Norwegian harbor sediments

International Nuclear Information System (INIS)

Oen, Amy M.P.; Cornelissen, Gerard; Breedveld, Gijs D.

2006-01-01

Distributions of total organic carbon (TOC), black carbon (BC), and polycyclic aromatic hydrocarbons (PAH) were investigated in different particle size fractions for four Norwegian harbor sediments. The total PAH (16-EPA) concentrations ranged from 2 to 113 mg/kg dry weight with the greatest fraction of PAH mass in the sand fraction for three of the four sediments. TOC contents ranged from 0.84% to 14.2% and BC contents from 0.085% to 1.7%. This corresponds to organic carbon (OC = TOC - BC) contents in the range of 0.81-14% and BC:TOC ratios of 1.3-18.1%. PAH isomer ratios suggested that the PAH in all four sediments were of pyrogenic origin. Furthermore, stronger correlations between PAH versus BC (r 2 = 0.85) than versus OC (r 2 = 0.15) were found. For all size fractions and bulk sediments, the PAH-to-BC ratios for the total PAHs were on average 6 ± 3 mg PAH/g BC. These results suggest that PAH distributions were dominated by the presence of BC, rather than OC. As sorption to BC is much stronger than sorption to OC, this may result in significantly lower dissolved concentrations of PAH than expected on the basis of organic carbon partitioning alone. - PAH contents correlated better with black carbon than organic carbon for four Norwegian harbor sediments

Polycyclic aromatic hydrocarbons (PAH) formation from the pyrolysis of different municipal solid waste fractions

Energy Technology Data Exchange (ETDEWEB)

Zhou, Hui [Key Laboratory for Thermal Science and Power Engineering of Ministry of Education, Department of Thermal Engineering, Tsinghua University, Beijing 100084 (China); Energy Research Institute, University of Leeds, Leeds LS2 9JT (United Kingdom); Wu, Chunfei, E-mail: c.wu@leeds.ac.uk [Energy Research Institute, University of Leeds, Leeds LS2 9JT (United Kingdom); Onwudili, Jude A. [Energy Research Institute, University of Leeds, Leeds LS2 9JT (United Kingdom); Meng, Aihong [Key Laboratory for Thermal Science and Power Engineering of Ministry of Education, Department of Thermal Engineering, Tsinghua University, Beijing 100084 (China); Zhang, Yanguo, E-mail: zhangyg@tsinghua.edu.cn [Key Laboratory for Thermal Science and Power Engineering of Ministry of Education, Department of Thermal Engineering, Tsinghua University, Beijing 100084 (China); Williams, Paul T., E-mail: p.t.williams@leeds.ac.uk [Energy Research Institute, University of Leeds, Leeds LS2 9JT (United Kingdom)

2015-02-15

Highlights: • PAH from pyrolysis of 9 MSW fractions was investigated. • Pyrolysis of plastics released more PAH than that of biomass. • Naphthalene was the most abundant PAH in the tar. • The mechanism of PAH release from biomass and plastics was proposed. - Abstract: The formation of 2–4 ring polycyclic aromatic hydrocarbons (PAH) from the pyrolysis of nine different municipal solid waste fractions (xylan, cellulose, lignin, pectin, starch, polyethylene (PE), polystyrene (PS), polyvinyl chloride (PVC), and polyethylene terephthalate (PET)) were investigated in a fixed bed furnace at 800 °C. The mass distribution of pyrolysis was also reported. The results showed that PS generated the most total PAH, followed by PVC, PET, and lignin. More PAH were detected from the pyrolysis of plastics than the pyrolysis of biomass. In the biomass group, lignin generated more PAH than others. Naphthalene was the most abundant PAH, and the amount of 1-methynaphthalene and 2-methynaphthalene was also notable. Phenanthrene and fluorene were the most abundant 3-ring PAH, while benzo[a]anthracene and chrysene were notable in the tar of PS, PVC, and PET. 2-ring PAH dominated all tar samples, and varied from 40 wt.% to 70 wt.%. For PS, PET and lignin, PAH may be generated directly from the aromatic structure of the feedstock.

Infrared absorption and emission characteristics of interstellar PAHs [Polycyclic Aromatic Hydrocarbon

International Nuclear Information System (INIS)

Allamandola, L.J.; Tielens, A.G.G.M.; Barker, J.R.

1986-01-01

The mid-infrared interstellar emission spectrum with features at 3050, 1610, 1300, 1150, and 885 cm -1 (3.28, 6.2, 7.7, 8.7 and 11.3 microns) is discussed in terms of the Polycyclic Aromatic Hydrocarbon (PAH) hypothesis. This hypothesis is based on the suggestive, but inconclusive comparison between the interstellar emission spectrum with the infrared absorption and Raman spectra of a few PAHs. The fundamental vibrations of PAHs and PAH-like species which determine the ir and Raman properties are discussed. Interstellar ir band emission is due to relaxation from highly vibrationally excited PAHs which have been excited by ultraviolet photons. The excitation/emission process is described in general and the ir fluorescence from one PAH, chrysene, is traced in detail. Generally, there is sufficient energy to populate several vibrational levels in each mode. Molecular vibrational potentials are anharmonic and emission from these higher levels will fall at lower frequencies and produce weak features to the red of the stronger fundamentals. This process is also described and can account for some spectroscopic details of the interstellar emission spectra previously unexplained. Analysis of the interstellar spectrum shows that PAHs containing between 20 and 30 carbon atoms are responsible for the emission. 43 refs., 11 figs

Infrared absorption and emission characteristics of interstellar PAHs (Polycyclic Aromatic Hydrocarbon)

Energy Technology Data Exchange (ETDEWEB)

Allamandola, L.J.; Tielens, A.G.G.M.; Barker, J.R.

1986-01-01

The mid-infrared interstellar emission spectrum with features at 3050, 1610, 1300, 1150, and 885 cm/sup -1/ (3.28, 6.2, 7.7, 8.7 and 11.3 microns) is discussed in terms of the Polycyclic Aromatic Hydrocarbon (PAH) hypothesis. This hypothesis is based on the suggestive, but inconclusive comparison between the interstellar emission spectrum with the infrared absorption and Raman spectra of a few PAHs. The fundamental vibrations of PAHs and PAH-like species which determine the ir and Raman properties are discussed. Interstellar ir band emission is due to relaxation from highly vibrationally excited PAHs which have been excited by ultraviolet photons. The excitation/emission process is described in general and the ir fluorescence from one PAH, chrysene, is traced in detail. Generally, there is sufficient energy to populate several vibrational levels in each mode. Molecular vibrational potentials are anharmonic and emission from these higher levels will fall at lower frequencies and produce weak features to the red of the stronger fundamentals. This process is also described and can account for some spectroscopic details of the interstellar emission spectra previously unexplained. Analysis of the interstellar spectrum shows that PAHs containing between 20 and 30 carbon atoms are responsible for the emission. 43 refs., 11 figs.

Impact of natural gas extraction on PAH levels in ambient air.

Science.gov (United States)

Paulik, L Blair; Donald, Carey E; Smith, Brian W; Tidwell, Lane G; Hobbie, Kevin A; Kincl, Laurel; Haynes, Erin N; Anderson, Kim A

2015-04-21

Natural gas extraction, often referred to as "fracking," has increased rapidly in the U.S. in recent years. To address potential health impacts, passive air samplers were deployed in a rural community heavily affected by the natural gas boom. Samplers were analyzed for 62 polycyclic aromatic hydrocarbons (PAHs). Results were grouped based on distance from each sampler to the nearest active well. PAH levels were highest when samplers were closest to active wells. Additionally, PAH levels closest to natural gas activity were an order of magnitude higher than levels previously reported in rural areas. Sourcing ratios indicate that PAHs were predominantly petrogenic, suggesting that elevated PAH levels were influenced by direct releases from the earth. Quantitative human health risk assessment estimated the excess lifetime cancer risks associated with exposure to the measured PAHs. Closest to active wells, the risk estimated for maximum residential exposure was 2.9 in 10 000, which is above the U.S. EPA's acceptable risk level. Overall, risk estimates decreased 30% when comparing results from samplers closest to active wells to those farthest. This work suggests that natural gas extraction may be contributing significantly to PAHs in air, at levels that are relevant to human health.

Impact of natural gas extraction on Pah levels in ambient air

Science.gov (United States)

Paulik, L. Blair; Donald, Carey E.; Smith, Brian W.; Tidwell, Lane G.; Hobbie, Kevin A.; Kincl, Laurel; Haynes, Erin N.; Anderson, Kim A.

2015-01-01

Natural gas extraction, often referred to as “fracking,” has increased rapidly in the U.S. in recent years. To address potential health impacts, passive air samplers were deployed in a rural community heavily affected by the natural gas boom. Samplers were analyzed for 62 polycyclic aromatic hydrocarbons (PAHs). Results were grouped based on distance from each sampler to the nearest active well. PAH levels were highest when samplers were closest to active wells. Additionally, PAH levels closest to natural gas activity were an order of magnitude higher than levels previously reported in rural areas. Sourcing ratios indicate that PAHs were predominantly petrogenic, suggesting that elevated PAH levels were influenced by direct releases from the earth. Quantitative human health risk assessment estimated the excess lifetime cancer risks associated with exposure to the measured PAHs. Closest to active wells, the risk estimated for maximum residential exposure was 2.9 in 10,000, which is above the U.S. EPA's acceptable risk level. Overall, risk estimates decreased 30% when comparing results from samplers closest to active wells to those farthest. This work suggests that natural gas extraction may be contributing significantly to PAHs in air, at levels that are relevant to human health. PMID:25810398

Barns kjemiske lekemiljø: Nivå og kilder til PAH i barnehagejord i Trondheim

OpenAIRE

Frøland, Stine Lindset

2008-01-01

Innholdet av 16 PAH-forbindelser og sumPAH(16) ble bestemt i 107 prøver av overflatejord fordelt på 10 barnehager i Trondheim. Sammenlignet med tidligere undersøkelser av PAH i Trondheim viser barnehagene det laveste innholdet av PAH. I barnehagene antydes det at vedfyring og veitrafikk er viktige kilder til den diffuse forurensningen av PAH.

[The mutation analysis of PAH gene and prenatal diagnosis in classical phenylketonuria family].

Science.gov (United States)

Yan, Yousheng; Hao, Shengju; Yao, Fengxia; Sun, Qingmei; Zheng, Lei; Zhang, Qinghua; Zhang, Chuan; Yang, Tao; Huang, Shangzhi

2014-12-01

To characterize the mutation spectrum of phenylalanine hydroxylase (PAH) gene and perform prenatal diagnosis for families with classical phenylketonuria. By stratified sequencing, mutations were detected in the exons and flaking introns of PAH gene of 44 families with classical phenylketonuria. 47 fetuses were diagnosed by combined sequencing with linkage analysis of three common short tandem repeats (STR) (PAH-STR, PAH-26 and PAH-32) in the PAH gene. Thirty-one types of mutations were identified. A total of 84 mutations were identified in 88 alleles (95.45%), in which the most common mutation have been R243Q (21.59%), EX6-96A>G (6.82%), IVS4-1G>A (5.86%) and IVS7+2T>A (5.86%). Most mutations were found in exons 3, 5, 6, 7, 11 and 12. The polymorphism information content (PIC) of these three STR markers was 0.71 (PAH-STR), 0.48 (PAH-26) and 0.40 (PAH-32), respectively. Prenatal diagnosis was performed successfully with the combined method in 47 fetuses of 44 classical phenylketonuria families. Among them, 11 (23.4%) were diagnosed as affected, 24 (51.1%) as carriers, and 12 (25.5%) as unaffected. Prenatal diagnosis can be achieved efficiently and accurately by stratified sequencing of PAH gene and linkage analysis of STR for classical phenylketonuria families.

Steps Toward Identifying PAHs: A Child's Garden of Recent Results

Science.gov (United States)

Hudgins, Douglas M.

2005-01-01

Based on over two decades of experimental, observational and theoretical studies by scientists around the world. It is now widely accepted that the composite emission of mixtures of vibrationally-excited PAHs and PAH ions can accommodate the general pattern of band positions, intensities, and profiles observed in the discreet IR emission features of carbon-rich interstellar dust, as well as the variations in those characteristics. These variations provide insight into the detailed nature of the emitting PAH population and reflect conditions within the emitting regions giving the population enormous potential as probes of astrophysical environments. Moreover, the ubiquity and abundance of this material has impacts that extend well beyond the IR. In this presentation we will examine recent, combined experimental, theoretical, and observational studies that indicate that nitrogen-substituted PAHs represent an important component of the interstellar dust population, and we will go on to explore some of the ramifications of this result. We will also explore the results of recent experimental studies of the strong, low-lying electronic transitions of ionized PAH ions in the Near-IR (0.7 - 2.5 microns) and explore the role that these transitions might play in pumping the PAH IR emission in regions of low-excitation.

PAH Metabolites in Bile of European Eel (Anguilla anguilla) from Morocco.

Science.gov (United States)

Wariaghli, Fatima; Kammann, Ulrike; Hanel, Reinhold; Yahyaoui, Ahmed

2015-12-01

Environmental pollution of fish with organic contaminants is a topic of rising attention in Morocco. Polycyclic aromatic hydrocarbons (PAH) are prominent organic contaminants which are rapidly metabolized in fish. Their metabolites are accumulated in the bile fluid and can be used to assess PAH exposure. The two PAH metabolites 1-hydroxypyrene and 1-hydroxyphenanthrene were quantified in European eels (Anguilla anguilla) from two Moroccan river systems by high-performance liquid chromatography with fluorescence detection. Mean values ranged from 52 to 210 ng/mL 1-hydroxypyrene and from 61 to 73 ng/mL 1-hydroxyphenanthrene. The overall concentrations of PAH metabolites in eel from Morocco appeared moderate compared to eel from European rivers and coastal sites. The present study provides first information on concentrations of PAH metabolites in fish from Morocco.

Vertical distributions of PAHs in the sediments of four lakes in Japan

Energy Technology Data Exchange (ETDEWEB)

Fukushima, Takehiko; Watanabe, Seigo; Kamiya, Koichi [Tsukuba Univ., Ibaraki (Japan). Graduate School of Life and Environment; Ozaki, Noriatsu [Hiroshima Univ., Higashihiroshima (Japan). Graduate School of Engineering

2012-12-15

Purpose: The purpose of this study was to elucidate historical trends, spatial variations, and the sources of polycyclic aromatic hydrocarbons (PAHs) pollution in several Japanese lakes. Materials and methods: The vertical distributions of PAHs in the core samples of sediments taken at several points in lakes Kasumigaura, Suwa, Kizaki, and Shinji were determined using a gas chromatograph equipped with a mass selective detector and combined with chronological information and the physical/elemental properties of the sediment. Results and discussion: Seventeen related compounds (congeners) typically had concentration peaks at sediment depths corresponding to the 1960s to 1970s. In Lake Shinji and one bay of Lake Kasumigaura, there was a tendency for PAH concentrations to increase downstream; in contrast, another bay of Lake Kasumigaura showed the reverse trend. During big flood events, the fluxes of PAHs increased due to large inputs of particulate matter, although PAH concentrations were reduced. For the four study lakes and other similar lakes, PAH concentrations of surface sediments were approximately proportional to population densities in the respective watersheds, while the total input of PAHs to the lakes were correlated with their population and watershed area. The source apportionment analysis using isomer ratios for the congener profiles indicated that the principal sources of the PAHs in the lake sediments were gasoline and/or diesel engine exhausts and biomass burning. Conclusions: The observed concentration peaks showed a deterioration of the chemical quality of atmospheric conditions around 1960-1970 and a recent tendency for their amelioration. Between-lake differences suggest that the influence of human activity in the watersheds influences sediment PAH concentrations. The PAH sources were identified to be of pyrogenic origin. (orig.)

PAH emissions from old and new types of domestic hot water boilers.

Science.gov (United States)

Horak, Jiri; Kubonova, Lenka; Krpec, Kamil; Hopan, Frantisek; Kubesa, Petr; Motyka, Oldrich; Laciok, Vendula; Dej, Milan; Ochodek, Tadeas; Placha, Daniela

2017-06-01

Five different domestic heating boilers (automatic, over-fire, with down-draft combustion and gasification) and three types of fuel (lignite, wood and mixed fuel) were examined in 25 combustion tests and correlated with the emissions of particulate matter (PM), carbon monoxide (CO), total organic carbon (TOC) and 12 polycyclic aromatic hydrocarbons (PAHs with MW = 178-278 g/mol) focusing on particle phase. However, the distribution of 12 PAHs in gas phase was considered as well due to the presence mainly of lighter PAHs in gas phase. The PAHs, as well as the CO and TOC, are the indicators of incomplete combustion, and in this study PAH emission increased significantly with increasing emissions of CO and TOC. The PAHs were mainly detected on PM 2.5 , their contents were increasing linearly with increasing PM 2.5 emissions. The highest emission factors of PAHs were measured for boilers of old construction, such as over-fire boiler (5.8-929 mg/kg) and boiler with down-draft combustion (3.1-54.1 mg/kg). Modern types of boilers produced much lower emissions of PAHs, in particular, automatic boiler (0.3-3.3 mg/kg) and gasification boilers (0.2-6.7 mg/kg). In general, the inefficient combustion at reduced output of boilers generated 1.4-17.7 times more emissions of PAHs than the combustion at nominal output of boilers. It is recommended to operate boilers at nominal output with sufficient air supply and to use the proper fuel to minimise PAHs emissions from domestic heating appliances. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative survey of PAHs incidence in Portuguese traditional meat and blood sausages.

Science.gov (United States)

Roseiro, L C; Gomes, A; Patarata, L; Santos, C

2012-06-01

Sixteen polycyclic aromatic hydrocarbons (PAHs) in representative traditional sausages produced in "Trás-os-Montes" and "Alentejo", were determined. Light PAHs represented similar overall contents in both regions and showed close decreasing order patterns (ACY, PHE, FLR and NAP), irrespective of the product type considered. Amongst the carcinogenic/mutagenic PAHs analyzed (PAH8), both regions also had greater contents associated to BaA and CHR, with slightly higher values for the former compound in "Alentejo" and, oppositely, for the later in "Trás-os-Montes". However, their quantitative comparison showed that the general mean total PAH content found in "Trás-os-Montes" was almost 3-fold higher than in similar products from "Alentejo" and this factor was about 8-fold superior when the PAH8 and PAH4 indicators were compared, expressing benzo[a]pyrene toxic equivalencies (BaPE), 15 times (total mean toxicity), 34 times (PAH8) and 9 times (PAH4) higher. In general terms, the mean BaP content of all analyzed samples from "Alentejo" was 0.41 μg kg(-1). Differently that value in "Trás-os-Montes" reached 3.57 μg kg(-1), expressing concerning average contents of 5.35, 5.87 and 4.51 μg kg(-1) in Chouriço de Carne, Moura and Salpicão sausages, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Remarkably constant PAH concentrations in Swiss soils over the last 30 years.

Science.gov (United States)

Gubler, Andreas; Wächter, Daniel; Blum, Franziska; Bucheli, Thomas D

2015-10-01

Although polycyclic aromatic hydrocarbons (PAH) are of concern due to their carcinogenic, mutagenic, and teratogenic properties and their ubiquitous occurrence in environmental compartments, only few studies assessed the temporal evolutions of PAH contents of soils over extended time periods. The Swiss Soil Monitoring Network NABO runs long-term monitoring sites resampled every five years since the 1980s. In the present study, soil (0-20 cm) samples collected from 1985 through 2013 at 25 selected monitoring sites were analysed for the 16 priority PAH according to the U.S. EPA and five PAH marker substances. We observed divergent trends for light PAH, such as naphthalene and phenanthrene, compared with heavy PAH, such as benzo[a]pyrene and benzo[ghi]perylene. Whereas the former showed decreasing concentrations since the late 1980s, no significant trends were found for the latter. Furthermore, the analyses showed that naphthalene contents decreased most strongly at rural sites featuring low population densities, while phenanthrene contents generally decreased most strongly at semi-rural sites. The deviating evolutions of light and heavy PAH were mainly attributed to their differing physico-chemical properties. Temporal evolutions in soils contradict emission inventory data suggesting PAH emissions to decline since the 1980s.

Polycyclic Aromatic Hydrocarbon (PAH Exposure and DNA Adduct Semi-Quantitation in Archived Human Tissues

Directory of Open Access Journals (Sweden)

M. Margaret Pratt

2011-06-01

Full Text Available Polycyclic aromatic hydrocarbons (PAHs are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products, considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS. These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and vulva; glandular epithelium of the prostate; and cytotrophoblast cells and syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA adduct accumulation in specific, vulnerable, cell types. This semi-quantative method for PAH-DNA adduct measurement could potentially see widespread use in molecular epidemiology studies.

Preparation of silver nanoparticles from synthetic and natural sources: remediation model for PAHs

International Nuclear Information System (INIS)

Abbasi, M.; Saeed, F.; Rafique, U.

2013-01-01

The emergence of nanoscience and technology is gaining popularity with an increasing demand for metal nanoparticles applicability in various areas such as electronics, catalysis, chemistry, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. In this work, an attempt is made to compare the efficiency of two different synthesis methods and application of each for the remediation of poly aromatic hydrocarbons (PAHs). In this regard, silver nanoparticles are prepared by green and wet chemical method using plant extract of garlic (Allium sativum). The extract is known to reduce the metal during synthesis and acts as stabilizing ligand. These synthesized silver nanoparticles (Agp) and (AgW) were applied as adsorbents in synthetic batch mode experiments at varying parameters of pH and temperature. A concentration of 0.01mg/L of Phenanthrene, Anthracene, and Pyrene were induced at fixed dosage of 1mg/Kg of adsorbent. Residual concentration of each PAH was analyzed on UV-Visible spectrophotometer. The results indicated that both adsorbents follow the sequence of Phenanthrene>Pyrene>Anthracene with optimal removal of higher than 85 percentage in each case. A distinguishing privilege is attained by Agp adsorbent showing 3, 3 and 11 orders of magnitude higher efficiency than Agw. It may be attributed to more functional groups in the plant extract participating in binding of PAH to the surface. Each synthesized adsorbents was characterized by FTIR, SEM and EDX. The average particle size was determined to be of the order of 13-26 nm. The study concludes the use of alternate economical and green adsorbents for control of poly aromatic hydrocarbons (PAHs). (author)

Preparation of Silver Nanoparticles from Synthetic and Natural Sources: Remediation Model for PAHs

International Nuclear Information System (INIS)

Abbasi, Maryam; Saeed, Fatima; Rafique, Uzaira

2014-01-01

The emergence of nanoscience and technology is gaining popularity with an increasing demand for metal nanoparticles applicability in various areas such as electronics, catalysis, chemistry, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. In this work, an attempt is made to compare the efficiency of two different synthesis methods and application of each for the remediation of poly aromatic hydrocarbons (PAHs). In this regard, silver nanoparticles are prepared by green and wet chemical method using plant extract of garlic (Allium sativum). The extract is known to reduce the metal during synthesis and acts as stabilizing ligand. These synthesized silver nanoparticles (Agp) and (AgW) were applied as adsorbents in synthetic batch mode experiments at varying parameters of pH and temperature. A concentration of 0.01mg/L of Phenanthrene, Anthracene, and Pyrene were induced at fixed dosage of 1mg/Kg of adsorbent. Residual concentration of each PAH was analyzed on UV-Visible spectrophotometer. The results indicated that both adsorbents follow the sequence of Phenanthrene>Pyrene>Anthracene with optimal removal of higher than 85% in each case. A distinguishing privilege is attained by Agp adsorbent showing 3, 3 and 11 orders of magnitude higher efficiency than Agw. It may be attributed to more functional groups in the plant extract participating in binding of PAH to the surface. Each synthesized adsorbents was characterized by FTIR, SEM and EDX. The average particle size was determined to be of the order of 13-26 nm. The study concludes the use of alternate economical and green adsorbents for control of poly aromatic hydrocarbons (PAHs)

Preparation of Silver Nanoparticles from Synthetic and Natural Sources: Remediation Model for PAHs

Science.gov (United States)

Abbasi, Maryam; Saeed, Fatima; Rafique, Uzaira

2014-06-01

The emergence of nanoscience and technology is gaining popularity with an increasing demand for metal nanoparticles applicability in various areas such as electronics, catalysis, chemistry, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. In this work, an attempt is made to compare the efficiency of two different synthesis methods and application of each for the remediation of poly aromatic hydrocarbons (PAHs). In this regard, silver nanoparticles are prepared by green and wet chemical method using plant extract of garlic (Allium sativum). The extract is known to reduce the metal during synthesis and acts as stabilizing ligand. These synthesized silver nanoparticles (Agp) and (AgW) were applied as adsorbents in synthetic batch mode experiments at varying parameters of pH and temperature. A concentration of 0.01mg/L of Phenanthrene, Anthracene, and Pyrene were induced at fixed dosage of 1mg/Kg of adsorbent. Residual concentration of each PAH was analyzed on UV-Visible spectrophotometer. The results indicated that both adsorbents follow the sequence of Phenanthrene>Pyrene>Anthracene with optimal removal of higher than 85% in each case. A distinguishing privilege is attained by Agp adsorbent showing 3, 3 and 11 orders of magnitude higher efficiency than Agw. It may be attributed to more functional groups in the plant extract participating in binding of PAH to the surface. Each synthesized adsorbents was characterized by FTIR, SEM and EDX. The average particle size was determined to be of the order of 13-26 nm. The study concludes the use of alternate economical and green adsorbents for control of poly aromatic hydrocarbons (PAHs).

Microorganism selection and performance in bioslurry reactors treating PAH-contaminated soil.

Science.gov (United States)

Cassidy, D P; Hudak, A J

2002-09-01

A continuous-flow reactor (CSTR) and a soil slurry-sequencing batch reactor (SS-SBR) were operated in 81 vessels for 200 days to treat a soil contaminated with polycyclic aromatic hydrocarbons (PAH). Filtered slurry samples were used to quantify bulk biosurfactant concentrations and PAH emulsification. Concentrations of Corynebacterium aquaticum, Flavobacterium mizutaii, Mycobacterium gastri, Pseudomonas aeruginosa, and Pseudomonas putida were determined using fatty acid methyl ester (FAME) analysis. The CSTR and SS-SBR selected microbial consortia with markedly different surfactant-producing and PAH-degrading abilities. Biosurfactant levels in the SS-SBR reached 4 times the critical micelle concentration (CMC) that resulted in considerable emulsification of PAH. In contrast, CSTR operation resulted in nomeasurable biosurfactant production. Total PAH removal efficiency was 93% in the SS-SBR, compared with only 66% in the CSTR, and stripping of PAH was 3 times less in the SS-SBR. Reversing the mode of operation on day 100 caused a complete reversal in microbial consortia and in reactor performance by day 140. These results show that bioslurry reactor operation can be manipulated to control overall reactor performance.

Dry Deposition of Polycyclic Aromatic Hydrocarbons (PAHs) at a Suburban Site in Beijing, China

Science.gov (United States)

Zhang, Xincheng; Wang, Weiyu; Zhu, Xianlei

2017-04-01

A great amount of polycyclic aromatic hydrocarbons (PAHs) have been generated by industrial production, waste incineration and landfill, traffic and road dust etc. They are emitted into atmosphere and afterwards enter into water body and soil through deposition, resulting in wide distribution of PAHs in environment. However, the dry deposition of PAHs from atmosphere has not been well studied, especially in the aspects of its characteristics, environmental and health effects, sources and mechanism. This study measured PAHs dry deposition in the northwest suburban area of Beijing. Dry deposition samples (i.e. dustfall samples) were collected at the sampling site located in China University of Petroleum - Beijing in 2012-2016. And PAHs in the samples were determined by GC/MS. The dry deposition flux of 16 US EPA priority PAHs (ΣPAH16) was 2.58 μg/(m^2·d), which was lower than those in other regions of North China. Its seasonal variability was more significant than annual variability (p spring > autumn > summer. The amount of ΣPAH16 removed from the atmosphere by dry deposition process accounted for only 1.2% of their emissions, indicating that the atmosphere self-purification capacity was quite limited and emission reduction measures would play a key role in controlling PAHs air pollution. However, PAHs dry deposition would deteriorate soil quality since the content of ΣPAH16 in dustfall was 1-2 orders of magnitude higher than that in soil in the same area. Dermal exposure resulting from PAHs dry deposition was not the major route. The sources of PAHs dry deposition varied with seasons. The profile and specific ratios of PAHs showed that in winter, domestic coal combustion was the main source of PAHs with the contribution up to 77%; in spring and summer, the impact of coal combustion decreased and the contribution of vehicle exhaust increased to 30% - 45%; in fall, in addition to coal combustion and vehicle exhaust, the impact of biomass burning was observed

Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

International Nuclear Information System (INIS)

Satwiko, Muhammad Gahan; Ikeda, Koji; Nakayama, Kazuhiko; Yagi, Keiko; Hocher, Berthold; Hirata, Ken-ichi; Emoto, Noriaki

2015-01-01

Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension

Energy Technology Data Exchange (ETDEWEB)

Satwiko, Muhammad Gahan [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Ikeda, Koji [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Nakayama, Kazuhiko [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Yagi, Keiko [Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan); Hocher, Berthold [Institute for Nutritional Science, University of Potsdam, Potsdam (Germany); Hirata, Ken-ichi [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Emoto, Noriaki, E-mail: emoto@med.kobe-u.ac.jp [Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe (Japan); Department of Clinical Pharmacy, Kobe Pharmaceutical University, Kobe (Japan)

2015-09-25

Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. - Highlights: • Role of endothelin-1 in pulmonary arterial hypertension (PAH) was investigated. • The endothelin-1 transgenic (ETTG) and wild type (WT) mice were analyzed. • ETTG mice spontaneously developed PAH under normoxia conditions. • SU5416 further aggravated PAH in ETTG mice. • Enhanced endothelin system activity could be a causative factor in

Evaluation of bio-remediation technologies for PAHs contaminated soils

International Nuclear Information System (INIS)

Garcia Frutos, F.J.; Diaz, J.; Rodriguez, V.; Escolano, O.; Garcia, S.; Perez, R.; Martinez, R.; Oromendia, R.

2005-01-01

Natural attenuation is a new concept related to polluted soil remediation. Can be understood like an 'in situ' bio-remediation process with low technical intervention. This low intervention may be in order to follow the behaviour of pollutants 'monitored natural attenuation' or include an optimisation process to improve biological remediation. The use of this technology is a fact for light hydrocarbon polluted soil, but few is known about the behaviour of polycyclic aromatic hydrocarbons (PAHs) in this process. PAHs are more recalcitrant to bio-remediation due to their physic-chemical characteristics, mainly hydrophobicity and electrochemical stability. PAHs are a kind of pollutants widely distributed in the environment, not only in the proximity of the source. This linked to the characteristics of some of them related to toxicity and mutagenicity implies its inclusion as target compounds from an environmental point of view. Their low availability, solubility and the strong tendency to bind to soil particle, especially to the organic phase affect PAHs biological mineralisation. So, if the pollutant is not available to microorganisms it can not be bio-degraded. Bioavailability can be assessed form several but complementary points of view: physico-chemical and biological. First including the term availability and the second to point out the capacity of soil microorganisms to mineralize PAHs. Availability and Bio-degradability must be determined, as well as the presence and activity of specific degraders among the soil organisms, once settled these points is necessary to study the biological requirements to optimise biodegradation kinetics of these compounds. In this work we present a study carried out on a soil, contaminated by PAHs, the study includes three main topics: bioavailability assessment (both term availability and bio-degradability), bio-remediation assessment, once optimised conditions for natural attenuation and finally a simulation of the

Biomonitoring of PAHs by using Quercus ilex leaves: Source diagnostic and toxicity assessment

Science.gov (United States)

De Nicola, Flavia; Claudia, Lancellotti; MariaVittoria, Prati; Giulia, Maisto; Anna, Alfani

2011-03-01

Quercus ilex L. leaves were sampled at nineteen urban sites and two remote sites in order to evaluate PAH contamination degree. One-, two- and three-year-old leaves were collected and leaf lipid content was measured to investigate the influence of leaf age and lipids in PAH accumulation. Some PAH diagnostic ratios, such as Ant/Ant + Phen, Flt/Flt + Pyr, B[a]A/B[a]A + Crys and IP/IP + B[g,h,i]P, were calculated. The results suggest that Q. ilex leaves are effective biomonitors of PAH air contamination: in fact, a great PAH accumulation in leaves from the urban areas, until 30-time higher compared to those from the remote sites, has been observed. At each site, the similar total PAH concentrations in leaves of different age, probably due to a canopy effect, indicate an ability of all leaf age classes to monitor local PAH concentrations in air, remarking practical implications for air biomonitoring. The findings suggest that PAH adsorption in Q. ilex leaves does not result limited by leaf lipid content. Moreover, this study demonstrates the source-diagnostic potential of Q. ilex leaves, because, in particular, the Flt/Flt + Pyr and IP/IP + B[g,h,i]P ratios indicate vehicular traffic as the main source of PAHs in the urban areas and wood combustion in the remote areas. Moreover, to distinguish biomass combustion source, a promising tracer PAH as DB[a,h]A could be used. The high contribution of DB[a,h]A to total PAH concentrations at the remote sites determines a high carcinogenic potential in this area, similar to that calculated for the urban area where the carcinogenic PAH concentrations in absolute values are often higher.

Urinary 1-hydroxypyrene, a PAH biomarker in foundry workers

DEFF Research Database (Denmark)

Omland, Øyvind; Sherson, David; Hansen, Åse Marie

1996-01-01

Exposure to PAH in foundry workers has been studied by urinary 1-hydroxypyrene (HPU) levels, quantitatively measured by reversed phase HPLC. Seventy male foundry workers and 68 matched controls were investigated. Polycyclic aromatic hydrocarbon (PAH) exposure was defined by 17 breathing zone hygi...

Source apportionment of atmospheric polycyclic aromatic hydrocarbons (PAHs) in Palm Beach County, Florida.

Science.gov (United States)

Afshar-Mohajer, Nima; Wilson, Christina; Wu, Chang-Yu; Stormer, James E

2016-04-01

Due to concerns about adverse health effects associated with inhalation of atmospheric polycyclic aromatic hydrocarbons (PAHs), 30 ambient air samples were obtained at an air quality monitoring station in Palm Beach County, Florida, from March 2013 to March 2014. The ambient PAH concentration measurements and fractional emission rates of known sources were incorporated into a chemical mass balance model, CMB8.2, developed by EPA, to apportion contributions of three major PAH sources including preharvest sugarcane burning, mobile vehicles, and wildland fires. Strong association between the number of benzene rings and source contribution was found, and mobile vehicles were identified to be the prevailing source (contribution≥56%) for the observed PAHs concentration with lower molecular weights (four or fewer benzene rings) throughout the year. Preharvest sugarcane burning was the primary contributing source for PAHs with relatively higher molecular weights (five or more benzene rings) during the sugarcane burning season (from October to May of the next year). Source contribution of wildland fires varied among PAH compounds but was consistently lower than for sugarcane burning during the sugarcane harvest season. Determining the major sources responsible for ground-level PAHs serves as a tool to improving management strategies for PAH emitting sources and a step toward better protection of the health of residents in terms of exposure to PAHs. The results obtain insight into temporal dominance of PAH polluting sources for those residential areas located near sugarcane burning facilities and have implications beyond Palm Beach County, in areas with high concerns of PAHs and their linked sources. Source apportionment of atmospheric polycyclic hydrocarbons (PAHs) in Palm Beach County, Florida, meant to estimate contributions of major sources in PAH concentrations measured at Belle Glade City of Palm Beach County. Number of benzene rings was found to be the key parameter

Monitoring PAH contamination in water: Comparison of biological and physico-chemical tools

International Nuclear Information System (INIS)

Bourgeault, A.; Gourlay-Francé, C.

2013-01-01

The suitability of biological methods and chemical-based passive samplers to determine exposure to PAHs was tested by deploying zebra mussels and SPMDs along the Seine River over 11 months. The concentration of 13 PAHs was analyzed every month in both water and mussels. The sum of the PAH concentrations in mussels, initially at 299 ng g dry wt −1 , reached 2654, 3972 and 3727 ng g −1 at the end of exposure in the three sampling points taken through the river. The respective SPMD-available concentrations of TPAHs reached 9, 52 and 34 ng L −1 . Results showed seasonal variations of total PAH concentrations in the mussels, characterized by a decrease during spawning. The non-achievement of steady state concentration that was observed in mussels may be accounted for by the temporal variation of environmental concentrations. Thus, a bioaccumulation model based on kinetic rather than simple equilibrium partitioning was found to be more appropriate to describe PAH content in mussels. Moreover, biodynamic kinetic modeling proved useful to better understand the uptake and loss processes of pyrene. It clearly shows that these processes are markedly influenced by the biological state of the zebra mussels. The most realistic hypothesis is that the temporal variation of the biodynamic parameters may originate from a decrease of the mussels' metabolization of PAHs during spawning. Since SPMD passive samplers cannot integrate such biological factors, they are poor predictors of PAH bioavailability in mussels. - Highlights: • PAH contamination was monitored by deploying mussels and SPMDs over 11 months along the Seine River. • 5–6 ring PAHs which could not be quantified in spot samples, were measured in SPMDs. • PAH concentrations in the mussels decreased during spawning. • Temporal variation of bioaccumulated PAH may originate from a decrease of the mussels' metabolism during spawning. • Biodynamic model was allowed to explain the bioaccumulation

Monitoring PAH contamination in water: Comparison of biological and physico-chemical tools

Energy Technology Data Exchange (ETDEWEB)

Bourgeault, A., E-mail: bourgeault@ensil.unilim.fr; Gourlay-Francé, C.

2013-06-01

The suitability of biological methods and chemical-based passive samplers to determine exposure to PAHs was tested by deploying zebra mussels and SPMDs along the Seine River over 11 months. The concentration of 13 PAHs was analyzed every month in both water and mussels. The sum of the PAH concentrations in mussels, initially at 299 ng g{sub dry} {sub wt}{sup −1}, reached 2654, 3972 and 3727 ng g{sup −1} at the end of exposure in the three sampling points taken through the river. The respective SPMD-available concentrations of TPAHs reached 9, 52 and 34 ng L{sup −1}. Results showed seasonal variations of total PAH concentrations in the mussels, characterized by a decrease during spawning. The non-achievement of steady state concentration that was observed in mussels may be accounted for by the temporal variation of environmental concentrations. Thus, a bioaccumulation model based on kinetic rather than simple equilibrium partitioning was found to be more appropriate to describe PAH content in mussels. Moreover, biodynamic kinetic modeling proved useful to better understand the uptake and loss processes of pyrene. It clearly shows that these processes are markedly influenced by the biological state of the zebra mussels. The most realistic hypothesis is that the temporal variation of the biodynamic parameters may originate from a decrease of the mussels' metabolization of PAHs during spawning. Since SPMD passive samplers cannot integrate such biological factors, they are poor predictors of PAH bioavailability in mussels. - Highlights: • PAH contamination was monitored by deploying mussels and SPMDs over 11 months along the Seine River. • 5–6 ring PAHs which could not be quantified in spot samples, were measured in SPMDs. • PAH concentrations in the mussels decreased during spawning. • Temporal variation of bioaccumulated PAH may originate from a decrease of the mussels' metabolism during spawning. • Biodynamic model was allowed to explain

Mobility and availability of PAH in soil-sewage sludges systems; Mobilite et disponibilite des HAP dans des systemes terre-boue de station d'epuration

Energy Technology Data Exchange (ETDEWEB)

Bryselbout, C.

2002-07-15

This work deals with the increase of the availability of polycyclic aromatic hydrocarbons (PAH) induced by the supply of organic matter to a soil in the framework of the agricultural valorization of organic wastes. The sharing of PAH with the organic matter of a model of soil and sewage sludge mixture has been studied first, using extractions and adsorption kinetics (Kd methanol). Then, the evolution of the PAH availability in a sludge-earth mixture has ben studied over a period of 185 days. Finally, the plants PAH availability in the presence of residual sludge has been studied at the laboratory and in-situ. Results show that Kd methanol and PAH extractability in a earth-sludge mixture are proportional to the total organic carbon ratio and to the incubation time. The presence of sludges leads to the immobilization of a smaller amount of PAH. The PAH availability from a sludge-earth mixture is limited by the presence of sludge and cations, such as mercuric mercury. It seems that the organic matter of sludges is more washable than the one of the soil leading to an increased risk of migration of micro-pollutants in the environment. The agricultural valorization of organic wastes, as it is already implemented in France, does not indicate any direct effect on the mobility and availability of PAH in soils. However, a long-term effect on water and soil quality is to be feared. The limitation of PAH fluxes towards agricultural areas would be a societal answer. (J.S.)

PAHs sensitivity of picophytoplankton populations in the Red Sea.

Science.gov (United States)

Kottuparambil, Sreejith; Agusti, Susana

2018-04-25

In this study, we investigated the in situ responses of Red Sea picophytoplankton, the dominant phytoplankton group in the oligotrophic ocean, to two toxic polycyclic aromatic hydrocarbons (PAHs), phenanthrene and pyrene. The experiments were conducted across a latitudinal gradient of the Saudi Arabian Red Sea, an area sensitive to oil pollution. We observed significant adverse effects on the growth and abundance of the picocyanobacteria Synechococcus and picoeukaryotes, at all stations sampled. Prochlorococcus, which was abundant only at one of the stations, also appeared to be affected. Pyrene was found to be more toxic to phytoplankton at all stations. In general, picoeukaryotes exhibited higher sensitivity to PAHs than Synechococcus. Populations in the highly oligotrophic Northern region of the Red Sea were more tolerant to PAHs, presumably influenced by the natural selection of more resistant strains of phytoplankton due to the prolonged exposure to PAHs. Toxicity threshold values estimated here are higher than those reported for picophytoplankton from other oligotrophic marine waters and exceed by far the natural levels of PAHs in many oceans. Our findings reveal a possible adaptation of picophytoplankton populations to oil-related contaminants, which may clearly influence their spatial distribution patterns in the Red Sea. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tubule urate and PAH transport: sensitivity and specificity of serum protein inhibition

International Nuclear Information System (INIS)

Grantham, J.J.; Kennedy, J.; Cowley, B.

1987-01-01

Macromolecules in rabbit serum inhibit the cellular uptake and transepithelial secretion of [ 14 C]urate and p-[ 3 H]aminohippurate ([ 3 H]PAH) in rabbit S 2 proximal tubule segments. To understand better the potential role these inhibitors may have in the regulation of renal organic anion excretion, the authors examined the specificity and relative inhibitory effects on tubule urate and PAH transport of albumin and γ-globulin, the major inhibitory proteins in rabbit serum. Native rabbit serum markedly inhibited the cellular accumulation or urate and PAH by isolated nonperfused segments. Urate and PAH transport was also inhibited by bovine serum, human serum, Cohn-fractionated rabbit albumin, and rabbit γ-globulin, but not by Cohn-fractionated bovine serum albumin. α-Lactalbumin and β-lactoglobulin, derived from milk, also inhibited urate and PAH transport, but to a lesser extent than albumin and γ-globulin. The transport inhibitory effects of proteins were independent of their binding to urate and PAH. Unidirectional influx and the steady-state intracellular accumulation of urate and PAH in suspensions of proximal tubules were decreased by rabbit serum proteins, suggesting that these inhibitors act on the external face of the cells to diminish the uptake of the organic anions. These studies indicate that the principal plasma proteins (albumin and γ-globulin) significantly inhibit urate and PAH transporters in the basolateral membranes of S 2 proximal tubules. They suggest that circulating plasma proteins that can penetrate the basement membrane of proximal tubules may directly modulate the renal excretion of urate and PAH

PAHs soil decontamination in two steps: desorption and electrochemical treatment.

Science.gov (United States)

Alcántara, M Teresa; Gómez, Jose; Pazos, Marta; Sanromán, M Angeles

2009-07-15

The presence of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in soils poses a potential threat to human health if exposure levels are too high. Nevertheless, the removal of these contaminants presents a challenge to scientists and engineers. The high hydrophobic nature of PAHs enables their strong sorption onto soil or sediments. Thus, the use of surfactants could favour the release of sorbed hydrophobic organic compounds from contaminated soils. In this work, five surfactants, namely Brij 35, Tergitol NP10, Tween 20, Tween 80 and Tyloxapol, are evaluated on the desorption of PAHs [benzanthracene (BzA), fluoranthene (FLU), and pyrene (PYR), single and in mixture] from a model sample such as kaolin. In all cases, the best results were obtained when Tween 80 was employed. In order to obtain the global decontamination of PAHs, their electrochemical degradation is investigated. It is concluded that the order of increasing degradation for single compounds is BzA>FLU>PYR when they are subject to the same electrochemical treatment. In addition, there is a direct relationship between the ionization potential and the electrochemical degradation of PAH.

Biodegradation, bioaccessibility, and genotoxicity of diffuse polycyclic aromatic hydrocarbon (PAH) pollution at a motorway site

DEFF Research Database (Denmark)

Johnsen, A.R.; de Lipthay, J.R.; Reichenberg, F.

2006-01-01

Diffuse pollution of surface soil with polycyclic aromatic hydrocarbons (PAHs) is problematic in terms of the large areas and volumes of polluted soil. The levels and effects of diffuse PAH pollution at a motorway site were investigated. Surface soil was sampled with increasing distance from...... in the most polluted samples close to the pavement. Hydroxypropyl-beta-cyclodextrin extraction of soil PAHs, as a direct estimate of the bioaccessibility, indicated that only 1-5% of the PAHs were accessible to soil bacteria. This low bioaccessibility is suggested to be due to sorption to traffic soot...... the asphalt pavement and tested for total amounts of PAHs, amounts of bioaccessible PAHs, total bacterial populations, PAH degrader populations, the potential for mineralization of C-14-PAHs, and mutagenicity. Elevated PAH concentrations were found in the samples taken 1-8 m from the pavement. Soil sampled...

Surfactant-enhanced bioremediation of PAH- and PCB-contaminated soils

International Nuclear Information System (INIS)

Ghosh, M.M.; Yeom, I.T.; Shi, Z.; Cox, C.D.; Robinson, K.G.

1995-01-01

The role of surfactants in the desorption of soil-bound polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) was investigated. The solubilization of individual PAHs in an extract of a weathered, coal tar-contaminated soil containing a mixture of PAHs and other petroleum derivatives was found to be significantly less than that for pure compounds. Batch soil washing with Triton X-100 (a commercial, nonionic alkyl phenol ethoxylate) was found to increase the effective diffusion rate of PAHs from the contaminated soil by four orders of magnitude compared to that obtained by gas purging when the results were analyzed using a radial diffusion model. At concentrations of up to 24 times its critical micelle concentration (CMC), Triton X-100 did not seem to enhance hydrocarbon degradation in the coal tar-contaminated soil; however, the biosurfactant rhamnolipid R1, at a concentration of 50x CMC, increased the rate of mineralization of 4,4'-chlorinated biphenyl mobilized from a laboratory-contaminated soil by more than 60 times

Enrichment behavior and transport mechanism of soil-bound PAHs during rainfall-runoff events.

Science.gov (United States)

Zheng, Yi; Luo, Xiaolin; Zhang, Wei; Wu, Bin; Han, Feng; Lin, Zhongrong; Wang, Xuejun

2012-12-01

Polycyclic Aromatic Hydrocarbons (PAHs) transported by surface runoff result in nonpoint source pollution and jeopardize aquatic ecosystems. The transport mechanism of PAHs during rainfall-runoff events has been rarely studied regarding pervious areas. An experimental system was setup to simulate the runoff pollution process on PAHs-contaminated soil. The enrichment behavior of soil-bound PAHs was investigated. The results show that soil organic matters (SOM), rather than clay particles, seem to be the main carrier of PAHs. The enrichment is highly conditioned on runoff and erosion processes, and its magnitude varies among PAH compounds. It is not feasible to build a simple and universal relationship between enrichment ratio and sediment discharge following the traditional enrichment theory. To estimate the flux of PAHs from pervious areas, soil erosion process has to be clearly understood, and both organic carbon content and composition of SOM should be factored into the calculation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Atmospheric polycyclic aromatic hydrocarbons (PAHs) in Asia: A review from 1999 to 2004

International Nuclear Information System (INIS)

Chang, K.-F.; Fang, G.-C.; Chen, J.-C.; Wu, Y.-S.

2006-01-01

Polycyclic aromatic hydrocarbons (PAHs) are present in both gaseous and particulate phases. These compounds are considered to be atmospheric contaminants and are human carcinogens. Many studies have monitored atmospheric particulate and gaseous phases of PAH in Asia over the past 5 years. This work compares and discusses different sample collection, pretreatment and analytical methods. The main PAH sources are traffic exhausts (AcPy, FL, Flu, PA, Pyr, CHR, BeP) and industrial emissions (BaP, BaA, PER, BeP, COR, CYC). PAH concentrations are highest in areas of traffic, followed by the urban sites, and lowest in rural sites. Meteorological conditions, such as temperature, wind speed and humidity, strongly affect PAH concentrations at all sampling sites. This work elucidates the characteristics, sources and distribution, and the healthy impacts of atmospheric PAH species in Asia. - This work summarizes the characteristics, sources and distribution, and the healthy impacts of atmospheric PAH species in Asia

Source apportionment of elevated wintertime PAHs by compound-specific radiocarbon analysis

Directory of Open Access Journals (Sweden)

R. J. Sheesley

2009-05-01

Full Text Available Natural abundance radiocarbon analysis facilitates distinct source apportionment between contemporary biomass/biofuel (¹⁴C "alive" versus fossil fuel (¹⁴C "dead" combustion. Here, the first compound-specific radiocarbon analysis (CSRA of atmospheric polycyclic aromatic hydrocarbons (PAHs was demonstrated for a set of samples collected in Lycksele, Sweden a small town with frequent episodes of severe atmospheric pollution in the winter. Renewed interest in using residential wood combustion (RWC means that this type of seasonal pollution is of increasing concern in many areas. Five individual/paired PAH isolates from three pooled fortnight-long filter collections were analyzed by CSRA: phenanthrene, fluoranthene, pyrene, benzo[b+k]fluoranthene and indeno[cd]pyrene plus benzo[ghi]perylene; phenanthrene was the only compound also analyzed in the gas phase. The measured Δ¹⁴C for PAHs spanned from −138.3‰ to 58.0‰. A simple isotopic mass balance model was applied to estimate the fraction biomass (f_biomass contribution, which was constrained to 71–87% for the individual PAHs. Indeno[cd]pyrene plus benzo[ghi]perylene had an f_biomass of 71%, while fluoranthene and phenanthrene (gas phase had the highest biomass contribution at 87%. The total organic carbon (TOC, defined as carbon remaining after removal of inorganic carbon f_biomass was estimated to be 77%, which falls within the range for PAHs. This CSRA data of atmospheric PAHs established that RWC is the dominating source of atmospheric PAHs to this region of the boreal zone with some variations among RWC contributions to specific PAHs.

PAH dissipation in a contaminated river sediment under oxic and anoxic conditions

International Nuclear Information System (INIS)