Modulation of homocysteine toxicity by S-nitrosothiol formation: a mechanistic approach.

Science.gov (United States)

Morakinyo, Moshood K; Strongin, Robert M; Simoyi, Reuben H

2010-08-05

The metabolic conversion of homocysteine (HCYSH) to homocysteine thiolactone (HTL) has been reported as the major cause of HCYSH pathogenesis. It was hypothesized that inhibition of the thiol group of HCYSH by S-nitrosation will prevent its metabolic conversion to HTL. The kinetics, reaction dynamics, and mechanism of reaction of HCYSH and nitrous acid to produce S-nitrosohomocysteine (HCYSNO) was studied in mildly to highly acidic pHs. Transnitrosation of this non-protein-forming amino acid by S-nitrosoglutathione (GSNO) was also studied at physiological pH 7.4 in phosphate buffer. In both cases, HCYSNO formed quantitatively. Copper ions were found to play dual roles, catalyzing the rate of formation of HCYSNO as well as its rate of decomposition. In the presence of a transition-metal ions chelator, HCYSNO was very stable with a half-life of 198 h at pH 7.4. Nitrosation by nitrous acid occurred via the formation of more powerful nitrosating agents, nitrosonium cation (NO(+)) and dinitrogen trioxide (N(2)O(3)). In highly acidic environments, NO(+) was found to be the most effective nitrosating agent with a first-order dependence on nitrous acid. N(2)O(3) was the most relevant nitrosating agent in a mildly acidic environment with a second-order dependence on nitrous acid. The bimolecular rate constants for the direct reactions of HCYSH and nitrous acid, N(2)O(3), and NO(+) were 9.0 x 10(-2), 9.50 x 10(3), and 6.57 x 10(10) M(-1) s(-1), respectively. These rate constant values agreed with the electrophilic order of these nitrosating agents: HNO(2) formation kinetics of HCYSNO. This study has shown that it is possible to modulate homocysteine toxicity by preventing its conversion to a more toxic HTL by S-nitrosation.

Abrin Toxicity and Bioavailability after Temperature and pH Treatment

Directory of Open Access Journals (Sweden)

Christina C. Tam

2017-10-01

Full Text Available Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea, Abrus precatorius and is a potential bioterror weapon. The temperature and pH stability of abrin was evaluated with an in vitro cell free translation (CFT assay, a Vero cell culture cytotoxicity assay, and an in vivo mouse bioassay. pH treatment of abrin had no detrimental effect on its stability and toxicity as seen either in vitro or in vivo. Abrin exposure to increasing temperatures did not completely abrogate protein translation. In both the cell culture cytotoxicity model and the mouse bioassay, abrin’s toxic effects were completely abrogated if the toxin was exposed to temperatures of 74 °C or higher. In the cell culture model, 63 °C-treated abrin had a 30% reduction in cytotoxicity which was validated in the in vivo mouse bioassay with all mice dying but with a slight time-to-death delay as compared to the non-treated abrin control. Since temperature inactivation did not affect abrin’s ability to inhibit protein synthesis (A-chain, we hypothesize that high temperature treatment affected abrin’s ability to bind to cellular receptors (affecting B-chain. Our results confirm the absolute need to validate in vitro cytotoxicity assays with in vivo mouse bioassays.

Zinc toxicity on antioxidative response in (Zea mays L. at two different pH

Directory of Open Access Journals (Sweden)

Hosseini, Zahra

2013-02-01

Full Text Available Zn is the second most abundant transition metal after iron (Fe. Excess Zn can have negative effects on plants. The effect of Zn at two different pH on lipid peroxidation (MDA, membrane permeability (EC, hydrogen peroxide (H2O2,non-protein thiols (NPT and the activities of major antioxidant enzymes Zea mays were investigated under controlled growth conditions. Zn-excess conditions increased the EC, MDA, H2O2 content and non-protein thiols and also activities of antioxidant enzymes were increased. Also zinc toxicity was higher in 4.5 pH than 7.5 pH.

pH and ion strength modulated ionic species loading in mesoporous silica nanoparticles

International Nuclear Information System (INIS)

Liu, Wei; Liu, Jianbo; Yang, Xiaohai; Wang, Kemin; Wang, Qing; Yang, Meng; Li, Li; Xu, Jianguo

2013-01-01

Mesoporous silica nanoparticles (MSN) have emerged as appealing host materials to accommodate guest molecules for biomedical applications, and recently various methods have been developed to modulate the loading of guest molecules in the silica matrix. Herein, it was demonstrated that pH and ion strength showed great influence on the loading of charged species into the nanoparticles, taking MCM-41 as a host MSN model and methylviologen (MV 2+ ) and 1,5-naphthalene disulfonate (NDS 2− ) as typical charged ionic guest molecules. As the pH increased from 3.0 to 8.0, the loading amount of MV 2+ increased gradually, while on the contrary, it decreased gradually for NDS 2− , for the solution pH changed the electrostatic interaction between the silica matrix and the ionic guest molecules. Additionally, the adding of NaCl reduced the electrostatic interaction, which resulted in a decreasing of the electrostatic rejection and electrostatic accumulation for the molecules carrying the same and the opposite charge to the particle respectively. Thus, pH and ion strength can be employed as simple approaches to modulate the loading of charged molecules and permselectivity in MSN. This work has a definite guidance function for molecule loading, transport modulation, controlled release as well as sensors based on MSN. (paper)

Dietary compounds as modulators of metals and metalloids toxicity.

Science.gov (United States)

Jadán-Piedra, Carlos; Chiocchetti, Gabriela Matuoka; Clemente, María Jesús; Vélez, Dinoraz; Devesa, Vicenta

2017-07-07

A large part of the population is exposed to metals and metalloids through the diet. Most of the in vivo studies on its toxicokinetics and toxicity are conducted by means of exposure through drinking water or by intragastric or intraperitoneal administration of aqueous standards, and therefore they do not consider the effect of the food matrix on the exposure. Numerous studies show that some components of the diet can modulate the toxicity of these food contaminants, reducing their effect on a systemic level. Part of this protective role may be due to a reduction of intestinal absorption and subsequent tissue accumulation of the toxic element, although it may also be a consequence of their ability to counteract the toxicity directly by their antioxidant and/or anti-inflammatory activity, among other factors. The present review provides a compilation of existing information about the effect that certain components of the diet have on the toxicokinetics and toxicity of the metals and metalloids of greatest toxicological importance that are present in food (arsenic, cadmium, lead, and mercury), and of their most toxic chemical species.

Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

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Chen, Z L; Huang, R Q

2014-06-20

Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 μM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Is Selectively Toxic to Primary Dopaminergic Neurons In Vitro

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Griggs, Amy M.; Agim, Zeynep S.; Mishra, Vartika R.; Tambe, Mitali A.; Director-Myska, Alison E.; Turteltaub, Kenneth W.; McCabe, George P.; Rochet, Jean-Christophe; Cannon, Jason R.

2014-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. Much data has linked the etiology of PD to a variety of environmental factors. The majority of cases are thought to arise from a combination of genetic susceptibility and environmental factors. Chronic exposures to dietary factors, including meat, have been identified as potential risk factors. Although heterocyclic amines that are produced during high-temperature meat cooking are known to be carcinogenic, their effect on the nervous system has yet to be studied in depth. In this study, we investigated neurotoxic effects of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a highly abundant heterocyclic amine in cooked meat, in vitro. We tested toxicity of PhIP and the two major phase I metabolites, N-OH-PhIP and 4′-OH-PhIP, using primary mesencephalic cultures from rat embryos. This culture system contains both dopaminergic and nondopaminergic neurons, which allows specificity of neurotoxicity to be readily examined. We find that exposure to PhIP or N-OH-PhIP is selectively toxic to dopaminergic neurons in primary cultures, resulting in a decreased percentage of dopaminergic neurons. Neurite length is decreased in surviving dopaminergic neurons. Exposure to 4′-OH-PhIP did not produce significant neurotoxicity. PhIP treatment also increased formation of oxidative damage markers, 4-hydroxy-2-nonenal (HNE) and 3-nitrotyrosine in dopaminergic neurons. Pretreatment with N-acetylcysteine was protective. Finally, treatment with blueberry extract, a dietary factor with known antioxidant and other protective mechanisms, prevented PhIP-induced toxicity. Collectively, our study suggests, for the first time, that PhIP is selectively toxic to dopaminergic neurons likely through inducing oxidative stress. PMID:24718704

Modulation of parathion toxicity by glucose feeding: Is nitric oxide involved?

International Nuclear Information System (INIS)

Liu Jing; Gupta, Ramesh C.; Goad, John T.; Karanth, Subramanya; Pope, Carey

2007-01-01

Glucose feeding can markedly exacerbate the toxicity of the anticholinesterase insecticide, parathion. We determined the effects of parathion on brain nitric oxide and its possible role in potentiation of toxicity by glucose feeding. Adult rats were given water or 15% glucose in water for 3 days and challenged with vehicle or parathion (18 mg/kg, s.c.) on day 4. Functional signs, plasma glucose and brain cholinesterase, citrulline (an indicator of nitric oxide production) and high-energy phosphates (HEPs) were measured 1-3 days after parathion. Glucose feeding exacerbated cholinergic toxicity. Parathion increased plasma glucose (15-33%) and decreased cortical cholinesterase activity (81-90%), with no significant differences between water and glucose treatment groups. In contrast, parathion increased brain regional citrulline (40-47%) and decreased HEPs (18-40%) in rats drinking water, with significantly greater changes in glucose-fed rats (248-363% increase and 31-61% decrease, respectively). We then studied the effects of inhibiting neuronal nitric oxide synthase (nNOS) by 7-nitroindazole (7NI, 30 mg/kg, i.p. x4) on parathion toxicity and its modulation by glucose feeding. Co-exposure to parathion and 7NI led to a marked increase in cholinergic signs of toxicity and lethality, regardless of glucose intake. Thus, glucose feeding enhanced the accumulation of brain nitric oxide following parathion exposure, but inhibition of nitric oxide synthesis was ineffective at counteracting increased parathion toxicity associated with glucose feeding. Evidence is therefore presented to suggest that nitric oxide may play both toxic and protective roles in cholinergic toxicity, and its precise contribution to modulation by glucose feeding requires further investigation

Influence of soil pH on the toxicity of zinc oxide nanoparticles to the terrestrial isopod Porcellionides pruinosus.

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Tourinho, Paula S; van Gestel, Cornelis A M; Lofts, Stephen; Soares, Amadeu M V M; Loureiro, Susana

2013-12-01

The effects of soil pH on the toxicity of ZnO nanoparticles (NPs) to the terrestrial isopod Porcellionides pruinosus were evaluated. Isopods were exposed to a natural soil amended with CaCO3 to reach 3 different pH(CaCl2) levels (4.5, 6.2, and 7.3) and to standard LUFA 2.2 soil (pH 5.5) spiked with ZnO NPs (30 nm), non-nano ZnO (200 nm), and ionic Zn as ZnCl₂. Toxicity was expressed based on total Zn concentration in soil, as well as total Zn and free Zn²⁺ ion concentrations in porewater. Compared with ZnO-spiked soils, the ZnCl₂-spiked soils had lower pH and higher porewater Ca²⁺ and Zn levels. Isopod survival did not differ between Zn forms and soils, but survival was higher for isopods exposed to ZnO NPs at pH 4.5. Median effect concentrations (EC50s) for biomass change showed similar trends for all Zn forms in all soils, with higher values at intermediate pH. Median lethal concentration (LC50) and EC50 values based on porewater Zn or free Zn ion concentrations were much lower for ZnO than for ionic zinc. Zn body concentrations increased in a dose-related manner, but no effect of soil pH was found. It is suggested not only that dissolved or free Zn in porewater contributed to uptake and toxicity, but also that oral uptake (i.e., ingestion of soil particles) could be an important additional route of exposure. © 2013 SETAC.

Gut microbiota modulation of chemotherapy efficacy and toxicity

OpenAIRE

Alexander, James L.; Wilson, Ian D.; Teare, Julian; Marchesi, Julian Roberto; Nicholson, Jeremy K.; Kinross, James M.

2017-01-01

Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidenc...

Toxicity evaluation of pH dependent stable Achyranthes aspera herbal gold nanoparticles

Science.gov (United States)

Tripathi, Alok; Kumari, Sarika; Kumar, Arvind

2016-01-01

Nanoparticles have gained substantial attention for the control of various diseases. However, any adverse effect of herbal gold nanoparticles (HGNPs) on animals including human being has not been investigated in details. The objectives of current study are to assess the cytotoxicity of HGNPs synthesized by using leaf extract of Achyranthes aspera, and long epoch stability. The protocol deals with stability of HGNPs in pH dependent manner. Visually, HGNPs formation is characterized by colour change of extract from dark brown to dark purple after adding gold chloride solution (1 mM). The 100 μg/ml HGNPs concentration has been found nontoxic to the cultured spleenocyte cells. Spectrophotometric analysis of nanoparticles solution gave a peak at 540 nm which corresponds to surface plasmon resonance absorption band. As per scanning electron microscopy and Transmission electron microscopy (TEM), size of HGNPs are in the range of 50-80 nm (average size 70 nm) with spherical morphology. TEM-selected area electron diffraction observation showed hexagonal texture. HGNPs showed substantial stability at higher temperature (85 °C), pH 10 and salt concentration (5 M). The zeta potential value of HGNPs is -35.9 mV at temperature 25 °C, pH 10 showing its good quality with better stability in comparison to pH 6 and pH 7. The findings advocate that the protocol for the synthesis of HGNPs is easy and quick with good quality and long epoch stability at pH 10. Moreover, non-toxic dose could be widely applicable for human health as a potential nano-medicine in the future to cure diseases.

Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer

International Nuclear Information System (INIS)

Flentje, Michael; Guckenberger, Matthias; Ok, Sami; Polat, Buelent; Sweeney, Reinhart A.

2010-01-01

Purpose: To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. Patients and Methods: 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). Results: Treatment was completed as planned by all patients. Acute GI and GU toxicity grade ≥ 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade ≥ 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade ≥ 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). Conclusion: High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising. (orig.)

Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Flentje, Michael [Dept. of Radiotherapy, Univ. Hospital Wuerzburg (Germany); Guckenberger, Matthias; Ok, Sami; Polat, Buelent; Sweeney, Reinhart A.

2010-10-15

Purpose: To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. Patients and Methods: 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). Results: Treatment was completed as planned by all patients. Acute GI and GU toxicity grade {>=} 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade {>=} 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade {>=} 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). Conclusion: High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising. (orig.)

The effect of pH on the toxicity of zinc oxide nanoparticles to Folsomia candida in amended field soil.

Science.gov (United States)

Waalewijn-Kool, Pauline L; Ortiz, Maria Diez; Lofts, Stephen; van Gestel, Cornelis A M

2013-10-01

The effect of soil pH on the toxicity of 30 nm ZnO to Folsomia candida was assessed in Dorset field soils with pHCaCl2 adjusted to 4.31, 5.71, and 6.39. To unravel the contribution of particle size and dissolved Zn, 200 nm ZnO and ZnCl2 were tested. Zinc sorption increased with increasing pH, and Freundlich kf values ranged from 98.9 (L/kg)(1/n) to 333 (L/kg)(1/n) for 30 nm ZnO and from 64.3 (L/kg)(1/n) to 187 (L/kg)(1/n) for ZnCl2. No effect of particle size was found on sorption, and little difference was found in toxicity between 30 nm and 200 nm ZnO. The effect on reproduction decreased with increasing pH for all Zn forms, with 28-d median effective concentrations (EC50s) of 553 mg Zn/kg, 1481 mg Zn/kg, and 3233 mg Zn/kg for 30 nm ZnO and 331 mg Zn/kg, 732 mg Zn/kg, and 1174 mg Zn/kg for ZnCl2 at pH 4.31, 5.71, and 6.39, respectively. The EC50s based on porewater Zn concentrations increased with increasing pH for 30 nm ZnO from 4.77 mg Zn/L to 18.5 mg Zn/L, while for ZnCl2 no consistent pH-related trend in EC50s was found (21.0-63.3 mg Zn/L). Porewater calcium levels were 10 times higher in ZnCl2 -spiked soils than in ZnO-spiked soils. The authors' results suggest that the decreased toxicity of ZnCl2 compared with 30 nm ZnO based on porewater concentrations was because of a protective effect of calcium and not a particle effect. © 2013 SETAC.

Release of copper from sintered tungsten-bronze shot under different pH conditions and its potential toxicity to aquatic organisms

International Nuclear Information System (INIS)

Thomas, Vernon G.; Santore, Robert C.; McGill, Ian

2007-01-01

Sintered tungsten-bronze is a new substitute for lead shot, and is about to be deposited in and around the wetlands of North America. This material contains copper in the alloyed form of bronze. This in vitro study was performed according to U.S. Fish and Wildlife Service criteria to determine the dissolution rate of copper from the shot, and to assess the toxic risk that it may present to aquatic organisms. The dissolution of copper from tungsten-bronze shot, pure copper shot, and glass beads was measured in a buffered, moderately hard, synthetic water of pH 5.5, 6.6, and 7.8 over a 28-day period. The dissolution of copper from both the control copper shot and the tungsten-bronze shot was affected significantly by the pH of the water and the duration of dissolution (all p values < 0.000). The rate of copper release from tungsten bronze shot was 30 to 50 times lower than that from the copper shot, depending on pH (p < 0.0000). The observed expected environmental concentration of copper released from tungsten-bronze shot after 28 days was 0.02 μg/L at pH 7.8, and 0.4 μg/L at pH 5.6, using a loading and exposure scenario specific in a U.S. Fish and Wildlife Service protocol. Ratio Quotient values derived from the highest EEC observed in this study (0.4 μg/L), and the copper toxic effect levels for all aquatic species listed in the U.S. Environmental Protection Agency ambient water quality criteria database, were all far less than the 0.1 criterion value. Given the conditions stipulated by the U.S. Fish and Wildlife Service and the U.S. Environmental Protection Agency, heavy loading from discharged tungsten-bronze shot would not pose a toxic risk to potable water, or to soil. Consequently, it would appear that no toxic risks to aquatic organisms will attend the use of tungsten-bronze shot of the approved composition. Given the likelihood that sintered tungsten-bronze of the same formula will be used for fishing weights, bullets, and wheel balance weights, it is

Modulation of prion polymerization and toxicity by rationally designed peptidomimetics.

Science.gov (United States)

Srivastava, Ankit; Sharma, Sakshi; Sadanandan, Sandhya; Gupta, Sakshi; Singh, Jasdeep; Gupta, Sarika; Haridas, V; Kundu, Bishwajit

2017-01-01

Misfolding and aggregation of cellular prion protein is associated with a large array of neurological disorders commonly called the transmissible spongiform encephalopathies. Designing inhibitors against prions has remained a daunting task owing to limited information about mechanism(s) of their pathogenic self-assembly. Here, we explore the anti-prion properties of a combinatorial library of bispidine-based peptidomimetics (BPMs) that conjugate amino acids with hydrophobic and aromatic side chains. Keeping the bispidine unit unaltered, a series of structurally diverse BPMs were synthesized and tested for their prion-modulating properties. Administration of Leu- and Trp-BPMs delayed and completely inhibited the amyloidogenic conversion of human prion protein (HuPrP), respectively. We found that each BPM induced the HuPrP to form unique oligomeric nanostructures differing in their biophysical properties, cellular toxicities and response to conformation-specific antibodies. While Leu-BPMs were found to stabilize the oligomers, Trp-BPMs effected transient oligomerization, resulting in the formation of non-toxic, non-fibrillar aggregates. Yet another aromatic residue, Phe, however, accelerated the aggregation process in HuPrP. Molecular insights obtained through MD (molecular dynamics) simulations suggested that each BPM differently engages a conserved Tyr 169 residue at the α2-β2 loop of HuPrP and affects the stability of α2 and α3 helices. Our results demonstrate that this new class of molecules having chemical scaffolds conjugating hydrophobic/aromatic residues could effectively modulate prion aggregation and toxicity. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Toxicity after post-prostatectomy image-guided intensity-modulated radiotherapy using Australian guidelines.

Science.gov (United States)

Chin, Stephen; Aherne, Noel J; Last, Andrew; Assareh, Hassan; Shakespeare, Thomas P

2017-12-01

We evaluated single institution toxicity outcomes after post-prostatectomy radiotherapy (PPRT) via image-guided intensity-modulated radiation therapy (IG-IMRT) with implanted fiducial markers following national eviQ guidelines, for which late toxicity outcomes have not been published. Prospectively collected toxicity data were retrospectively reviewed for 293 men who underwent 64-66 Gy IG-IMRT to the prostate bed between 2007 and 2015. Median follow-up after PPRT was 39 months. Baseline grade ≥2 genitourinary (GU), gastrointestinal (GI) and sexual toxicities were 20.5%, 2.7% and 43.7%, respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥2 GU and GI toxicity was 5.8% and 10.6%, respectively. New late grade ≥2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2%, respectively. However, many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥2 GU, GI and sexual toxicities 4 years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4%, respectively). There were no grade ≥4 toxicities. Post-prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The 4-year prevalence of grade ≥2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT. © 2017 The Royal Australian and New Zealand College of Radiologists.

The effect of pH on the bioconcentration and toxicity of weak organic electrolytes

DEFF Research Database (Denmark)

Rendal, Cecilie

to the bioconcentration of ionizing organic compounds showed that this fraction cannot safely be overlooked. The work presented in this thesis suggests that the standard test procedures used to test toxicity and bioconcentration are not sufficient to fully illuminate the ecotoxicity of ionizing organic compounds unless......Many of the compounds in use today have ionizing properties. Investigations have shown that around half of the compounds preregistered for REACH and over 70% of all pharmaceuticals are ionizing organic compounds. These compounds may pose a risk when they are released into the environment....... Ionization, however, complicates the environmental risk assessment of these compounds because the uptake processes of the neutral fraction differ from the processes of the ionized fraction. Acids are increasingly neutral at pH levels below the pKa while bases are increasingly neutral at pH levels above the p...

Multiwall carbon nanotubes modulate paraquat toxicity in Arabidopsis thaliana.

Science.gov (United States)

Fan, Xiaoji; Xu, Jiahui; Lavoie, Michel; Peijnenburg, W J G M; Zhu, Youchao; Lu, Tao; Fu, Zhengwei; Zhu, Tingheng; Qian, Haifeng

2018-02-01

Carbon nanotubes can be either toxic or beneficial to plant growth and can also modulate toxicity of organic contaminants through surface sorption. The complex interacting toxic effects of carbon nanotubes and organic contaminants in plants have received little attention in the literature to date. In this study, the toxicity of multiwall carbon nanotubes (MWCNT, 50 mg/L) and paraquat (MV, 0.82 mg/L), separately or in combination, were evaluated at the physiological and the proteomic level in Arabidopsis thaliana for 7-14 days. The results revealed that the exposure to MWCNT had no inhibitory effect on the growth of shoots and leaves. Rather, MWCNT stimulated the relative electron transport rate and the effective photochemical quantum yield of PSII value as compared to the control by around 12% and lateral root production up to nearly 4-fold as compared to the control. The protective effect of MWCNT on MV toxicity on the root surface area could be quantitatively explained by the extent of MV adsorption on MWCNT and was related to stimulation of photosynthesis, antioxidant protection and number and area of lateral roots which in turn helped nutrient assimilation. The influence of MWCNT and MV on photosynthesis and oxidative stress at the physiological level was consistent with the proteomics analysis, with various over-expressed photosynthesis-related proteins (by more than 2 folds) and various under-expressed oxidative stress related proteins (by about 2-3 folds). This study brings new insights into the interactive effects of two xenobiotics (MWCNT and MV) on the physiology of a model plant. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of soil organic matter content and pH on the toxicity of ZnO nanoparticles to Folsomia candida.

Science.gov (United States)

Waalewijn-Kool, Pauline L; Rupp, Svenja; Lofts, Stephen; Svendsen, Claus; van Gestel, Cornelis A M

2014-10-01

Organic matter (OM) and pH may influence nanoparticle fate and effects in soil. This study investigated the influence of soil organic matter content and pH on the toxicity of ZnO-NP and ZnCl2 to Folsomia candida in four natural soils, having between 2.37% and 14.7% OM and [Formula: see text] levels between 5.0 and 6.8. Porewater Zn concentrations were much lower in ZnO-NP than in ZnCl2 spiked soils, resulting in higher Freundlich sorption constants for ZnO-NP. For ZnCl2 the porewater Zn concentrations were significantly higher in less organic soils, while for ZnO-NP the highest soluble Zn level (23mgZn/l) was measured in the most organic soil, which had the lowest pH. Free Zn(2+) ion concentrations were higher for ZnCl2 than for ZnO-NP and were greatly dependent on pH (pHpw) and dissolved organic carbon content of the pore water. The 28-d EC50 values for the effect of ZnCl2 on the reproduction of F. candida increased with increasing OM content from 356 to 1592mgZn/kg d.w. For ZnO-NP no correlation between EC50 values and OM content was found and EC50 values ranged from 1695 in the most organic soil to 4446mgZn/kg d.w. in the higher pH soil. When based on porewater and free Zn(2+) concentrations, EC50 values were higher for ZnCl2 than for ZnO-NP, and consistently decreased with increasing pHpw. This study shows that ZnO-NP toxicity is dependent on soil properties, but is mainly driven by soil pH. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypofractionated Intensity-Modulated Radiotherapy for Carcinoma of the Prostate: Analysis of Toxicity

International Nuclear Information System (INIS)

Coote, Joanna H.; Wylie, James P.; Cowan, Richard A.; Logue, John P.; Swindell, Ric; Livsey, Jacqueline E.

2009-01-01

Purpose: Dose escalation for prostate cancer improves biological control but with a significant increase in late toxicity. Recent estimates of low α/β ratio for prostate cancer suggest that hypofractionation may result in biological advantage. Intensity-modulated radiotherapy (IMRT) should enable dose escalation to the prostate while reducing toxicity to local organs. We report late toxicity data of a hypofractionated IMRT regime. Methods and Materials: Eligible men had T2-3N0M0 adenocarcinoma prostate, and either Gleason score ≥ 7 or prostate-specific antigen 20-50 ng/L. Patients received 57-60 Gy to prostate in 19-20 fractions using five-field IMRT. All received hormonal therapy for 3 months before radiotherapy to a maximum of 6 months. Toxicity was assessed 2 years postradiotherapy using the RTOG criteria, LENT/SOMA, and UCLA prostate index assessment tools. Results: Acute toxicity was favorable with no RTOG Grade 3 or 4 toxicity. At 2 years, there was 4% Grade 2 bowel and 4.25% Grade 2 bladder toxicity. There was no Grade 3 or 4 bowel toxicity; one patient developed Grade 3 bladder toxicity. UCLA data showed a slight improvement in urinary function at 2 years compared with pretreatment. LENT/SOMA assessments demonstrated general worsening of bowel function at 2 years. Patients receiving 60 Gy were more likely to develop problems with bowel function than those receiving 57 Gy. Conclusions: These data demonstrate that hypofractionated radiotherapy using IMRT for prostate cancer is well tolerated with minimal late toxicity at 2 years posttreatment. Ongoing studies are looking at the efficacy of hypofractionated regimes with respect to biological control.

Identification of causes of oil sands coke leachate toxicity

International Nuclear Information System (INIS)

Puttaswamy, N.; Liber, K.

2010-01-01

The potential causes of oil sands coke leachate toxicity were investigated. Chronic 7-day toxicity tests were conducted to demonstrate that oil sands coke leachates (CL) are acutely toxic to Ceriodaphnia dubia (C. dubia). CLs were generated in a laboratory to perform toxicity identification evaluation (TIE) tests in order to investigate the causes of the CL toxicity. The coke was subjected to a 15-day batch leaching process at 5.5 and 9.5 pH values. The leachates were then filtered and used for chemical and toxicological characterization. The 7-day estimates for the C. dubia survival were 6.3 for a pH of 5.5 and 28.7 per cent for the 9.5 CLs. The addition of EDTA significantly improved survival and reproduction in a pH of 5.5 CL, but not in a pH of 9.5 CL. The toxicity of the pH 5.5 CL was removed with a cationic resin treatment. The toxicity of the 9.5 pH LC was removed using an anion resin treatment. Toxicity re-appeared when nickel (Ni) and vanadium (V) were added back to the resin-treated CLs. Results of the study suggested that Ni and V were acting as primary toxicants in the pH 5.5 CL, while V was the primary cause of toxicity in the pH 9.5 CL.

Can dosimetric parameters predict acute hematologic toxicity in rectal cancer patients treated with intensity-modulated pelvic radiotherapy?

International Nuclear Information System (INIS)

Wan, Juefeng; Liu, Kaitai; Li, Kaixuan; Li, Guichao; Zhang, Zhen

2015-01-01

To identify dosimetric parameters associated with acute hematologic toxicity (HT) in rectal cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. Ninety-three rectal cancer patients receiving concurrent capecitabine and pelvic intensity-modulated radiation therapy (IMRT) were analyzed. Pelvic bone marrow (PBM) was contoured for each patient and divided into three subsites: lumbosacral spine (LSS), ilium, and lower pelvis (LP). The volume of each site receiving 5–40 Gy (V 5, V10, V15, V20, V30, and V40, respectively) as well as patient baseline clinical characteristics was calculated. The endpoint for hematologic toxicity was grade ≥ 2 (HT2+) leukopenia, neutropenia, anemia or thrombocytopenia. Logistic regression was used to analyze correlation between dosimetric parameters and grade ≥ 2 hematologic toxicity. Twenty-four in ninety-three patients experienced grade ≥ 2 hematologic toxicity. Only the dosimetric parameter V40 of lumbosacral spine was correlated with grade ≥ 2 hematologic toxicity. Increased pelvic lumbosacral spine V40 (LSS-V40) was associated with an increased grade ≥ 2 hematologic toxicity (p = 0.041). Patients with LSS-V40 ≥ 60 % had higher rates of grade ≥ 2 hematologic toxicity than did patients with lumbosacral spine V40 < 60 % (38.3 %, 18/47 vs.13 %, 6/46, p =0.005). On univariate and multivariate logistic regression analysis, lumbosacral spine V40 and gender was also the variable associated with grade ≥ 2 hematologic toxicity. Female patients were observed more likely to have grade ≥ 2 hematologic toxicity than male ones (46.9 %, 15/32 vs 14.8 %, 9/61, p =0.001). Lumbosacral spine -V40 was associated with clinically significant grade ≥ 2 hematologic toxicity. Keeping the lumbosacral spine -V40 < 60 % was associated with a 13 % risk of grade ≥ 2 hematologic toxicity in rectal cancer patients undergoing concurrent chemoradiotherapy

Plasmodium falciparum chloroquine resistance transporter (PfCRT) isoforms PH1 and PH2 perturb vacuolar physiology.

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Callaghan, Paul S; Siriwardana, Amila; Hassett, Matthew R; Roepe, Paul D

2016-03-31

Recent work has perfected yeast-based methods for measuring drug transport by the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT). The approach relies on inducible heterologous expression of PfCRT in Saccharomyces cerevisiae yeast. In these experiments selecting drug concentrations are not toxic to the yeast, nor is expression of PfCRT alone toxic. Only when PfCRT is expressed in the presence of CQ is the growth of yeast impaired, due to inward transport of chloroquine (CQ) via the transporter. During analysis of all 53 known naturally occurring PfCRT isoforms, two isoforms (PH1 and PH2 PfCRT) were found to be intrinsically toxic to yeast, even in the absence of CQ. Additional analysis of six very recently identified PfCRT isoforms from Malaysia also showed some toxicity. In this paper the nature of this yeast toxicity is examined. Data also show that PH1 and PH2 isoforms of PfCRT transport CQ with an efficiency intermediate to that catalyzed by previously studied CQR conferring isoforms. Mutation of PfCRT at position 160 is found to perturb vacuolar physiology, suggesting a fitness cost to position 160 amino acid substitutions. These data further define the wide range of activities that exist for PfCRT isoforms found in P. falciparum isolates from around the globe.

The effects of salinity, pH, and dissolved organic matter on acute copper toxicity to the rotifer, Brachionus plicatilis ("L" strain).

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Arnold, W R; Diamond, R L; Smith, D S

2010-08-01

This paper presents data from original research for use in the development of a marine biotic ligand model and, ultimately, copper criteria for the protection of estuarine and marine organisms and their uses. Ten 48-h static acute (unfed) copper toxicity tests using the euryhaline rotifer Brachionus plicatilis ("L" strain) were performed to assess the effects of salinity, pH, and dissolved organic matter (measured as dissolved organic carbon; DOC) on median lethal dissolved copper concentrations (LC50). Reconstituted and natural saltwater samples were tested at seven salinities (6, 11, 13, 15, 20, 24, and 29 g/L), over a pH range of 6.8-8.6 and a range of dissolved organic carbon of <0.5-4.1 mg C/L. Water chemistry analyses (alkalinity, calcium, chloride, DOC, hardness, magnesium, potassium, sodium, salinity, and temperature) are presented for input parameters to the biotic ligand model. In stepwise multiple regression analysis of experimental results where salinity, pH, and DOC concentrations varied, copper toxicity was significantly related only to the dissolved organic matter content (pH and salinity not statistically retained; alpha=0.05). The relationship of the 48-h dissolved copper LC50 values and dissolved organic carbon concentrations was LC50 (microg Cu/L)=27.1xDOC (mg C/L)1.25; r2=0.94.

Integration into Big Data: First Steps to Support Reuse of Comprehensive Toxicity Model Modules (SOT)

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Data surrounding the needs of human disease and toxicity modeling are largely siloed limiting the ability to extend and reuse modules across knowledge domains. Using an infrastructure that supports integration across knowledge domains (animal toxicology, high-throughput screening...

Rationally Engineering Phototherapy Modules of Eosin-Conjugated Responsive Polymeric Nanocarriers via Intracellular Endocytic pH Gradients.

Science.gov (United States)

Liu, Guhuan; Hu, Jinming; Zhang, Guoying; Liu, Shiyong

2015-07-15

Spatiotemporal switching of respective phototherapy modes at the cellular level with minimum side effects and high therapeutic efficacy is a major challenge for cancer phototherapy. Herein we demonstrate how to address this issue by employing photosensitizer-conjugated pH-responsive block copolymers in combination with intracellular endocytic pH gradients. At neutral pH corresponding to extracellular and cytosol milieu, the copolymers self-assemble into micelles with prominently quenched fluorescence emission and low (1)O2 generation capability, favoring a highly efficient photothermal module. Under mildly acidic pH associated with endolysosomes, protonation-triggered micelle-to-unimer transition results in recovered emission and enhanced photodynamic (1)O2 efficiency, which synergistically actuates release of encapsulated drugs, endosomal escape, and photochemical internalization processes.

Modulation of leak K(+) channel in hypoglossal motoneurons of rats by serotonin and/or variation of pH value.

Science.gov (United States)

Xu, Xue-Feng; Tsai, Hao-Jan; Li, Lin; Chen, Yi-Fan; Zhang, Cheng; Wang, Guang-Fa

2009-08-25

The cloned TWIK-related acid-sensitive K(+) channel (TASK-1) is sensitive to the pH changes within physiological pH range (pK~7.4). Recently, the native TASK-1-like channel was suggested to be the main contributor to the background (or leak) K(+) conductance in the motoneurons of the brain stem. Serotonin (5-HT) and variation of pH value in perfused solution could modulate these currents. Here we aimed to examine the properties and modulation of the currents by serotonin or variation of pH value in hypoglossal motoneurons of rats. Transverse slices were prepared from the brainstem of neonatal Sprague-Dawley rats (postnatal days 7-8). Hypoglossal motoneurons were used for the study. The leak K(+) current (TASK-1-like current) and hyperpolarization-activated cationic current (I(h)) were recorded with the whole-cell patch-clamp technique. The results showed that these currents were inhibited by acidified artificial cerebrospinal fluid (ACSF, pH 6.0) and activated by alkalized ACSF (pH 8.5). 5-HT (10 mumol/L) significantly inhibited both leak K(+) current and I(h) with depolarization of membrane potential and the occurrence of oscillation and/or spikes. Bath application of Ketanserine, an antagonist of 5-HT₂ receptor, reversed or reduced the inhibitory effect of acidified solution on leak K(+) current and I(h). The results suggest that 5-HT₂ receptors mediate the effects of acidified media on leak K(+) current and I(h) in hypoglossal motoneurons.

Effect of pH and ionic strength on exposure and toxicity of encapsulated lambda-cyhalothrin to Daphnia magna.

Science.gov (United States)

Son, Jino; Hooven, Louisa A; Harper, Bryan; Harper, Stacey L

2015-12-15

Encapsulation of pesticide active ingredients in polymers has been widely employed to control the release of poorly water-soluble active ingredients. Given the high dispersibility of these encapsulated pesticides in water, they are expected to behave differently compared to their active ingredients; however, our current understanding of the fate and effects of encapsulated pesticides is still limited. In this study, we employed a central composite design (CCD) to investigate how pH and ionic strength (IS) affect the hydrodynamic diameter (HDD) and zeta potential of encapsulated λ-cyhalothrin and how those changes affect the exposure and toxicity to Daphnia magna. R(2) values greater than 0.82 and 0.84 for HDD and zeta potential, respectively, irrespective of incubation time suggest those changes could be predicted as a function of pH and IS. For HDD, the linear factor of pH and quadratic factor of pH×pH were found to be the most significant factors affecting the change of HDD at the beginning of incubation, whereas the effects of IS and IS×IS became significant as incubation time increased. For zeta potential, the linear factor of IS and quadratic factor of IS×IS were found to be the most dominant factors affecting the change of zeta potential of encapsulated λ-cyhalothrin, irrespective of incubation time. The toxicity tests with D. magna under exposure conditions in which HDD or zeta potential of encapsulated λ-cyhalothrin was maximized or minimized in the overlying water also clearly showed the worst-case exposure condition to D. magna was when the encapsulated λ-cyhalothrin is either stable or small in the overlying water. Our results show that water quality could modify the fate and toxicity of encapsulated λ-cyhalothrin in aquatic environments, suggesting understanding their aquatic interactions are critical in environmental risk assessment. Herein, we discuss the implications of our findings for risk assessment. Copyright © 2015 Elsevier B.V. All

DOPA Decarboxylase Modulates Tau Toxicity.

Science.gov (United States)

Kow, Rebecca L; Sikkema, Carl; Wheeler, Jeanna M; Wilkinson, Charles W; Kraemer, Brian C

2018-03-01

The microtubule-associated protein tau accumulates into toxic aggregates in multiple neurodegenerative diseases. We found previously that loss of D 2 -family dopamine receptors ameliorated tauopathy in multiple models including a Caenorhabditis elegans model of tauopathy. To better understand how loss of D 2 -family dopamine receptors can ameliorate tau toxicity, we screened a collection of C. elegans mutations in dopamine-related genes (n = 45) for changes in tau transgene-induced behavioral defects. These included many genes responsible for dopamine synthesis, metabolism, and signaling downstream of the D 2 receptors. We identified one dopamine synthesis gene, DOPA decarboxylase (DDC), as a suppressor of tau toxicity in tau transgenic worms. Loss of the C. elegans DDC gene, bas-1, ameliorated the behavioral deficits of tau transgenic worms, reduced phosphorylated and detergent-insoluble tau accumulation, and reduced tau-mediated neuron loss. Loss of function in other genes in the dopamine and serotonin synthesis pathways did not alter tau-induced toxicity; however, their function is required for the suppression of tau toxicity by bas-1. Additional loss of D 2 -family dopamine receptors did not synergize with bas-1 suppression of tauopathy phenotypes. Loss of the DDC bas-1 reduced tau-induced toxicity in a C. elegans model of tauopathy, while loss of no other dopamine or serotonin synthesis genes tested had this effect. Because loss of activity upstream of DDC could reduce suppression of tau by DDC, this suggests the possibility that loss of DDC suppresses tau via the combined accumulation of dopamine precursor levodopa and serotonin precursor 5-hydroxytryptophan. Published by Elsevier Inc.

Evaluation of buffers toxicity in tobacco cells: Homopiperazine-1,4-bis (2-ethanesulfonic acid) is a suitable buffer for plant cells studies at low pH.

Science.gov (United States)

Borgo, Lucélia

2017-06-01

Low pH is an important environmental stressor of plant root cells. Understanding the mechanisms of stress and tolerance to acidity is critical; however, there is no widely accepted pH buffer for studies of plant cells at low pH. Such a buffer might also benefit studies of Al toxicity, in which buffering at low pH is also important. The challenge is to find a buffer with minimal cellular effects. We examined the cytotoxicity and possible metabolic disturbances of four buffers that have adequate pK a values and potential use for studies in the pH range of 4.0-5.0. These were homopipes (homopiperazine-1,4-bis (2-ethanesulfonic acid); pK a1 4.4), 3,3-dimethylglutaric acid (pK a1 3.73), β-alanine (pK a1 3.70) and potassium biphthalate (pK a1 2.95; pK a2 5.41). First, tobacco BY-2 cells were grown in a rich medium containing 10 mM of each buffer or MES (2-(N-morpholino) ethanesulfonic acid) as a control, with the pH initially adjusted to 5.7. β-alanine was clearly toxic and dimethylgluturate and biphthalate were found to be cytostatic, in which no culture growth occurred but cell viability was either unaffected or decreased only after 5 days. Only homopipes allowed normal culture growth and cell viability. Homopipes (10 mM) was then tested in cell cultures with an initial pH of 4.3 ± 0.17 in minimal medium to examine whether its undissociated species (H 2 A) displayed any cellular effects and no cytotoxic effects were observed. It is possible to conclude that among tested buffers, homopipes is the most suitable for studies at low pH, and may be especially useful for aluminum toxicity experiments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

pH Modulates the Binding of EGR1 Transcription Factor to DNA

Science.gov (United States)

Mikles, David C.; Bhat, Vikas; Schuchardt, Brett J.; Deegan, Brian J.; Seldeen, Kenneth L.; McDonald, Caleb B.; Farooq, Amjad

2013-01-01

EGR1 transcription factor orchestrates a plethora of signaling cascades involved in cellular homeostasis and its down-regulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with increasing pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as H382 by virtue of the fact that its substitution to non-ionizable residues abolishes pH-dependence of the binding of EGR1 to DNA. Notably, H382 inserts into the major groove of DNA and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, H382 is predominantly conserved across other members of EGR1 family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating protein-DNA interactions central to this family of transcription factors. Collectively, our findings uncover an unexpected but a key step in the molecular recognition of EGR1 family of transcription factors and suggest that they may act as sensors of pH within the intracellular environment. PMID:23718776

The toxicity of zinc oxide nanoparticles to Lemna minor (L.) is predominantly caused by dissolved Zn.

Science.gov (United States)

Chen, Xiaolin; O'Halloran, John; Jansen, Marcel A K

2016-05-01

Nano-ZnO particles have been reported to be toxic to many aquatic organisms, although it is debated whether this is caused by nanoparticles per sé, or rather dissolved Zn. This study investigated the role of dissolved Zn in nano-ZnO toxicity to Lemna minor. The technical approach was based on modulating nano-ZnO dissolution by either modifying the pH of the growth medium and/or surface coating of nano-ZnO, and measuring resulting impacts on L. minor growth and physiology. Results show rapid and total dissolution of nano-ZnO in the medium (pH 4.5). Quantitatively similar toxic effects were found when L. minor was exposed to nano-ZnO or the "dissolved Zn equivalent of dissolved nano-ZnO". The conclusion that nano-ZnO toxicity is primarily caused by dissolved Zn was further supported by the observation that phytotoxicity was absent on medium with higher pH-values (>7), where dissolution of nano-ZnO almost ceased. Similarly, the reduced toxicity of coated nano-ZnO, which displays a slower Zn dissolution, is also consistent with a major role for dissolved Zn in nano-ZnO toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

International Nuclear Information System (INIS)

Lim, Tee S.; Cheung, Patrick; Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

2008-01-01

Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score ≥8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity

Sorption, dissolution and pH determine the long-term equilibration and toxicity of coated and uncoated ZnO nanoparticles in soil.

Science.gov (United States)

Waalewijn-Kool, Pauline L; Diez Ortiz, Maria; van Straalen, Nico M; van Gestel, Cornelis A M

2013-07-01

To assess the effect of long-term dissolution on bioavailability and toxicity, triethoxyoctylsilane coated and uncoated zinc oxide nanoparticles (ZnO-NP), non-nano ZnO and ZnCl2 were equilibrated in natural soil for up to twelve months. Zn concentrations in pore water increased with time for all ZnO forms but peaked at intermediate concentrations of ZnO-NP and non-nano ZnO, while for coated ZnO-NP such a clear peak only was seen after 12 months. Dose-related increases in soil pH may explain decreased soluble Zn levels due to fixation of Zn released from ZnO at higher soil concentrations. At T = 0 uncoated ZnO-NP and non-nano ZnO were equally toxic to the springtail Folsomia candida, but not as toxic as coated ZnO-NP, and ZnCl2 being most toxic. After three months equilibration toxicity to F. candida was already reduced for all Zn forms, except for coated ZnO-NP which showed reduced toxicity only after 12 months equilibration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modulation of hexavalent chromium toxicity on Οriganum vulgare in an acidic soil amended with peat, lime, and zeolite.

Science.gov (United States)

Antoniadis, Vasileios; Zanni, Anna A; Levizou, Efi; Shaheen, Sabry M; Dimirkou, Anthoula; Bolan, Nanthi; Rinklebe, Jörg

2018-03-01

Dynamics of chromate (Cr(VI)) in contaminated soils may be modulated by decreasing its phytoavailability via the addition of organic matter-rich amendments, which might accelerate Cr(VI) reduction to inert chromite (Cr(III)) or high-cation exchange capacity amendments. We studied Cr(VI) phytoavailability of oregano in a Cr(VI)-spiked acidic soil non-treated (S) and treated with peat (SP), lime (SL), and zeolite (SZ). The addition of Cr(VI) increased the concentrations of Cr(VI) and Cr(III) in soils and plants, especially in the lime-amended soil. The plant biomass decreased in the lime-amended soil compared to the un-spiked soil (control) due to decreased plant phosphorus concentrations and high Cr(VI) concentrations in root at that treatment. Oregano in the peat-amended soil exhibited significantly less toxic effects, due to the role of organic matter in reducing toxic Cr(VI) to Cr(III) and boosted plant vigour in this treatment. In the lime-amended soil, the parameters of soil Cr(VI), soil Cr(III), and root Cr(III) increased significantly compared to the non-amended soil, indicating that Cr(VI) reduction to Cr(III) was accelerated at high pH. Added zeolite failed to decreased Cr(VI) level to soil and plant. Oregano achieved a total uptake of Cr(III) and Cr(VI) of 0.275 mg in plant kg -1 soil in a pot in the non-amended soil. We conclude that peat as soil amendment might be considered as a suitable option for decreasing Cr(VI) toxicity in soil and plant, and that oregano as tolerant plant species has a certain potential to be used as a Cr accumulator. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coral calcifying fluid pH is modulated by seawater carbonate chemistry not solely seawater pH.

Science.gov (United States)

Comeau, S; Tambutté, E; Carpenter, R C; Edmunds, P J; Evensen, N R; Allemand, D; Ferrier-Pagès, C; Tambutté, S; Venn, A A

2017-01-25

Reef coral calcification depends on regulation of pH in the internal calcifying fluid (CF) in which the coral skeleton forms. However, little is known about calcifying fluid pH (pH CF ) regulation, despite its importance in determining the response of corals to ocean acidification. Here, we investigate pH CF in the coral Stylophora pistillata in seawater maintained at constant pH with manipulated carbonate chemistry to alter dissolved inorganic carbon (DIC) concentration, and therefore total alkalinity (A T ). We also investigate the intracellular pH of calcifying cells, photosynthesis, respiration and calcification rates under the same conditions. Our results show that despite constant pH in the surrounding seawater, pH CF is sensitive to shifts in carbonate chemistry associated with changes in [DIC] and [A T ], revealing that seawater pH is not the sole driver of pH CF Notably, when we synthesize our results with published data, we identify linear relationships of pH CF with the seawater [DIC]/[H + ] ratio, [A T ]/ [H + ] ratio and [[Formula: see text

A novel approach for rapidly and cost-effectively assessing toxicity of toxic metals in acidic water using an acidophilic iron-oxidizing biosensor.

Science.gov (United States)

Yang, Shih-Hung; Cheng, Kuo-Chih; Liao, Vivian Hsiu-Chuan

2017-11-01

Contamination by heavy metals and metalloids is a serious environmental and health concern. Acidic wastewaters are often associated with toxic metals which may enter and spread into agricultural soils. Several biological assays have been developed to detect toxic metals; however, most of them can only detect toxic metals in a neutral pH, not in an acidic environment. In this study, an acidophilic iron-oxidizing bacterium (IOB) Strain Y10 was isolated, characterized, and used to detect toxic metals toxicity in acidic water at pH 2.5. The colorimetric acidophilic IOB biosensor was based on the inhibition of the iron oxidizing ability of Strain Y10, an acidophilic iron-oxidizing bacterium, by metals toxicity. Our results showed that Strain Y10 is acidophilic iron-oxidizing bacterium. Thiobacillus caldus medium (TCM) (pH 2.5) supplied with both S 4 O 6 2- and glucose was the optimum growth medium for Strain Y10. The optimum temperature and pH for the growth of Strain Y10 was 45 °C and pH 2.5, respectively. Our study demonstrates that the color-based acidophilic IOB biosensor can be semi-quantitatively observed by eye or quantitatively measured by spectrometer to detect toxicity from multiple toxic metals at pH 2.5 within 45 min. Our study shows that monitoring toxic metals in acidic water is possible by using the acidophilic IOB biosensor. Our study thus provides a novel approach for rapid and cost-effective detection of toxic metals in acidic conditions that can otherwise compromise current methods of chemical analysis. This method also allows for increased efficiency when screening large numbers of environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Postoperative Intensity-Modulated Arc Therapy for Cervical and Endometrial Cancer: A Prospective Report on Toxicity

International Nuclear Information System (INIS)

Vandecasteele, Katrien; Tummers, Philippe; Makar, Amin; Eijkeren, Marc van; Delrue, Louke; Denys, Hannelore; Lambert, Bieke; Beerens, Anne-Sophie; Van den Broecke, Rudy; Lambein, Kathleen; Fonteyne, Valérie; De Meerleer, Gert

2012-01-01

Purpose: To report on toxicity after postoperative intensity-modulated arc therapy (IMAT) for cervical (CC) and endometrial cancer (EC). Methods and Materials: Twenty-four CC and 41 EC patients were treated with postoperative IMAT. If indicated, para-aortic lymph node irradiation (preventive or when affected, PALN) and/or concomitant cisplatin (40 mg/m², weekly) was administered. The prescribed dose for IMAT was 45 Gy (CC, 25 fractions) and 46 Gy (EC, 23 fractions), followed by a brachytherapeutic boost if possible. Radiation-related toxicity was assessed prospectively. The effect of concomitant cisplatin and PALN irradiation was evaluated. Results: Regarding acute toxicity (n = 65), Grade 3 and 2 acute gastrointestinal toxicity was observed in zero and 63% of patients (79% CC, 54% EC), respectively. Grade 3 and 2 acute genitourinary toxicity was observed in 1% and 18% of patients, respectively. Grade 2 (21%) and 3 (12%) hematologic toxicity (n = 41) occurred only in CC patients. Seventeen percent of CC patients and 2% of EC patients experienced Grade 2 fatigue and skin toxicity, respectively. Adding cisplatin led to an increase in Grade >2 nausea (57% vs. 9%; p = 0.01), Grade 2 nocturia (24% vs. 4%; p = 0.03), Grade ≥2 hematologic toxicity (38% vs. nil, p = 0.003), Grade ≥2 leukopenia (33% vs. nil, p = 0.009), and a strong trend toward more fatigue (14% vs. 2%; p = 0.05). Para-aortic lymph node irradiation led to an increase of Grade 2 nocturia (31% vs. 4%, p = 0.008) and a strong trend toward more Grade >2 nausea (44% vs. 18%; p = 0.052). Regarding late toxicity (n = 45), no Grade 3 or 4 late toxicity occurred. Grade 2 gastrointestinal toxicity, genitourinary toxicity, and fatigue occurred in 4%, 9%, and 1% of patients. Neither concomitant cisplatin nor PALN irradiation increased late toxicity rates. Conclusions: Postoperative IMAT for EC or CC is associated with low acute and late toxicity. Concomitant chemotherapy and PALN irradiation influences acute but

Medium pH in submerged cultivation modulates differences in the intracellular protein profile of Fusarium oxysporum.

Science.gov (United States)

da Rosa-Garzon, Nathália Gonsales; Laure, Hélen Julie; Souza-Motta, Cristina Maria de; Rosa, José César; Cabral, Hamilton

2017-08-09

Fusarium oxysporum is a filamentous fungus that damages a wide range of plants and thus causes severe crop losses. In fungal pathogens, the genes and proteins involved in virulence are known to be controlled by environmental pH. Here, we report the influence of culture-medium pH (5, 6, 7, and 8) on the production of degradative enzymes involved in the pathogenesis of F. oxysporum URM 7401 and on the 2D-electrophoresis profile of intracellular proteins in this fungus. F. oxysporum URM 7401 was grown in acidic, neutral, and alkaline culture media in a submerged bioprocess. After 96 hr, the crude extract was processed to enzyme activity assays, while the intracellular proteins were obtained from mycelium and analyzed using 2D electrophoresis and mass spectrometry. We note that the diversity of secreted enzymes was changed quantitatively in different culture-medium pH. Also, the highest accumulated biomass and the intracellular protein profile of F. oxysporum URM 7401 indicate an increase in metabolism in neutral-alkaline conditions. The differential profiles of secreted enzymes and intracellular proteins under the evaluated conditions indicate that the global protein content in F. oxysporum URM 7401 is modulated by extracellular pH.

PhD on Track – designing learning for PhD students

Directory of Open Access Journals (Sweden)

Gunhild Austrheim

2013-12-01

Full Text Available Three years ago we started the project "Information Management for Knowledge Creation". The project was initiated to create online information literacy modules for PhD students. The result of our endeavours, PhD on Track, will be launched in May 2013. The initial stage of the project was mapping out the information behaviour of PhD students, as well as what services they require from the library through a literature review and a focus group study. The findings of these inquiries formed the knowledge base from which we developed our information literacy modules. Our paper will focus on the interaction between content production and user testing when creating PhD on Track. Methods: User testing has been employed throughout the production stage. We have tested navigation and organisation of the web site, content and usability. The project team have conducted expert testing. Analysis: The results from our user testing have played an important part in decisions concerning content production. Our working hypothesis was that the PhD students would want an encyclopaedic website, a place to quickly find answers. However, the user tests revealed that PhD students understood and expected the website to be learning modules. Conclusions: The PhD students in the tests agreed that a site such as this would be useful, especially to new PhD students. They also liked the design, but had some qualms with the level of information. They preferred shorter text, but with more depth. The students would likewise have preferred more practical examples, more illustrations and more discipline specific information. The current content of PhD on Track reflects the feedback from the user testing. We have retained initial ideas such as one section for reviewing and discovering research literature and one section for publishing PhD research work. In addition, we have included more practical examples to indicate efficient workflows or relevant actions in context. Illustrations

Modulating β-lactoglobulin nanofibril self-assembly at pH 2 using glycerol and sorbitol.

Science.gov (United States)

Dave, Anant C; Loveday, Simon M; Anema, Skelte G; Jameson, Geoffrey B; Singh, Harjinder

2014-01-13

β-Lactoglobulin (β-lg) forms fibrils when heated at 80 °C, pH 2, and low ionic strength (sorbitol (0-50% w/v) on β-lg self-assembly at pH 2. Glycerol and sorbitol stabilize native protein structure and modulate protein functionality by preferential exclusion. In our study, both polyols decreased the rate of β-lg self-assembly but had no effect on the morphology of fibrils. The mechanism of these effects was studied using circular dichroism spectroscopy and SDS-PAGE. Sorbitol inhibited self-assembly by stabilizing β-lg against unfolding and hydrolysis, resulting in fewer fibrillogenic species, whereas glycerol inhibited nucleation without inhibiting hydrolysis. Both polyols increased the viscosity of the solutions, but viscosity appeared to have little effect on fibril assembly, and we believe that self-assembly was not diffusion-limited under these conditions. This is in agreement with previous reports for other proteins assembling under different conditions. The phenomenon of peptide self-assembly can be decoupled from protein hydrolysis using glycerol.

Toxicity of oils and petroleum hydrocarbons to estuarine crustaceans

Energy Technology Data Exchange (ETDEWEB)

Tatem, H.E. (Army Engineer Waterways Experiment Station, Vicksburg, MS); Cox, B.A.; Anderson, J.W.

1978-04-01

Bioassay experiments with various life stages of three estuarine shrimp and soluble petroleum hydrocarbons (PH) revealed residual Bunker C oil and refined No. 2 fuel oil to be more toxic than two crude oils tested. Larvae of Palaemonetes pugio were slightly more sensitive to the PH than adults, while young penaeid shrimp were shown to be more resistant than older, larger individuals. Shrimp exposed to PH in conjunction with temperature and salinity changes were more susceptible to the PH. Some common aromatic and diaromatic PH, including three naphthalene compounds, were utilized in bioassays. Naphthalenes were highly toxic. The toxicity of petroleum products is closely related to aromatic hydrocarbon content, especially the naphthalenes and related hydrocarbons.

Toxic Hazards Research Unit Annual Report: 1986

Science.gov (United States)

1987-04-01

mediated hemolysis by mercapto compounds. Journal of Applied Toxicology, Volume 6, Number 5, pages 336-370, 1986. Hydrophobic tributyltin ( TBT ...7 ~OF~ AAMRL-TR-87-020 NMRI-87-2 ’~LRES 4 Iq 1986 TOXIC HAZARDS RESEARCH UNIT ANNUAL REPORT WILLIAM E. HOUSTON, Ph.D. RAYMOND S. KUTZMAN, Ph.D...and is approved for publication. FOR THE COMMANDElRi BRUCE 0. STUART, Ph.D. Director, Toxic Hazards Division Harry G. Armstrong Aerospace Medical

pH modulates the binding of early growth response protein 1 transcription factor to DNA.

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Mikles, David C; Bhat, Vikas; Schuchardt, Brett J; Deegan, Brian J; Seldeen, Kenneth L; McDonald, Caleb B; Farooq, Amjad

2013-08-01

The transcription factor early growth response protein (EGR)1 orchestrates a plethora of signaling cascades involved in cellular homeostasis, and its downregulation has been implicated in the development of prostate cancer. Herein, using a battery of biophysical tools, we show that the binding of EGR1 to DNA is tightly regulated by solution pH. Importantly, the binding affinity undergoes an enhancement of more than an order of magnitude with an increase in pH from 5 to 8, implying that the deprotonation of an ionizable residue accounts for such behavior. This ionizable residue is identified as His382 by virtue of the fact that its replacement by nonionizable residues abolishes the pH dependence of the binding of EGR1 to DNA. Notably, His382 inserts into the major groove of DNA, and stabilizes the EGR1-DNA interaction via both hydrogen bonding and van der Waals contacts. Remarkably, His382 is mainly conserved across other members of the EGR family, implying that histidine protonation-deprotonation may serve as a molecular switch for modulating the protein-DNA interactions that are central to this family of transcription factors. Collectively, our findings reveal an unexpected but a key step in the molecular recognition of the EGR family of transcription factors, and suggest that they may act as sensors of pH within the intracellular environment. © 2013 FEBS.

CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals

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Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

Science.gov (United States)

Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

2016-08-26

An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats

International Nuclear Information System (INIS)

Tang, Lili; Guan Hongxia; Ding Xiaolin; Wang Jiasheng

2007-01-01

Modulation by lycopene of aflatoxin B 1 (AFB 1 )-induced toxic effects, metabolism, and metabolic activations was studied in young F344 rats. Animals were pretreated orally with either corn oil (control group) or lycopene [100 mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control animals were then treated daily with AFB 1 (250 μg/kg b.w) alone. Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following a daily treatment with AFB 1 (250 μg/kg b.w.). Pretreatment and intervention with lycopene significantly reduced the toxic effect caused by AFB 1 and greatly modulated AFB 1 metabolism and metabolic activation. Urinary excretion of AFB 1 phase 1 metabolites, AFM 1 , AFQ 1 , and AFP 1 , was significantly decreased in lycopene-treated animals. Formation of serum AFB 1 -albumin adducts was also significantly reduced. The rate of reduction was from approximately 30% on day 1 (p 1 -DNA adducts in liver compared to control animals, with the highest reduction (52.7%) occurring on day 3 (p 1 -N 7 -guanine excreted in urine were also significantly decreased. Urinary excretion of the phase 2 detoxification metabolite, AFB 1 -mecapturic acid, was significantly increased in lycopene-intervened animals. AFB 1 -induced urinary excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after lycopene intervention. Collectively, these results suggest that inhibition of phase 1 metabolism and metabolic activation, as well as induction of phase 2 detoxification enzyme activity are the potential mechanisms for the chemopreventive effects of lycopene

Toxic essential oils. Part V: Behaviour modulating and toxic properties of thujones and thujone-containing essential oils of Salvia officinalis L., Artemisia absinthium L., Thuja occidentalis L. and Tanacetum vulgare L.

Science.gov (United States)

Radulović, Niko S; Genčić, Marija S; Stojanović, Nikola M; Randjelović, Pavle J; Stojanović-Radić, Zorica Z; Stojiljković, Nenad I

2017-07-01

Neurotoxic thujones (α- and β-diastereoisomers) are common constituents of plant essential oils. In this study, we employed a statistical approach to determine the contribution of thujones to the overall observed behaviour-modulating and toxic effects of essential oils (Salvia officinalis L., Artemisia absinthium L., Thuja occidentalis L. and Tanacetum vulgare L.) containing these monoterpene ketones. The data from three in vivo neuropharmacological tests on rats (open field, light-dark, and diazepam-induced sleep), and toxicity assays (brine shrimp, and antimicrobial activity against a panel of microorganisms), together with the data from detailed chemical analyses, were subjected to a multivariate statistical treatment to reveal the possible correlation(s) between the content of essential-oil constituents and the observed effects. The results strongly imply that the toxic and behaviour-modulating activity of the oils (hundreds of constituents) should not be associated exclusively with thujones. The statistical analyses pinpointed to a number of essential-oil constituents other than thujones that demonstrated a clear correlation with either the toxicity, antimicrobial effect or the activity on CNS. Thus, in addition to the thujone content, the amount and toxicity of other constituents should be taken into consideration when making risk assessment and determining the regulatory status of plants in food and medicines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional toxicogenomic profiling expands insight into modulators of formaldehyde toxicity in yeast

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Matthew North

2016-11-01

Full Text Available Formaldehyde (FA is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways–including homologous recombination, single strand annealing, and postreplication repair–were sensitive to FA, indicating FA may cause various forms of DNA damage in yeast. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance, suggesting FA may have unappreciated effects on RNA stability. Furthermore, various strains involved in osmoregulation and stress response were sensitive to FA. Together, our results are generally consistent with FA-mediated damage to both DNA and RNA. Considering DNA repair and RNA degradation pathways are evolutionarily conserved from yeast to humans, mechanisms of FA toxicity identified in yeast may be relevant to human disease and genetic susceptibility.

Effect of Low pH and Aluminum Toxicity on the Photosynthetic Characteristics of Different Fast-Growing Eucalyptus Vegetatively Propagated Clones.

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Yang, Mei; Tan, Ling; Xu, Yuanyuan; Zhao, Yihui; Cheng, Fei; Ye, Shaoming; Jiang, Weixin

2015-01-01

Knowing how acid soils and aluminum in soils may limit the growth of Eucalyptus trees in plantations is important because these plantations grow in many tropical and subtropical regions. Seedlings of four vegetatively propagated Eucalyptus clones, E. grandis × E. urophylla 'GLGU9'(G9), E. grandis × E. urophylla 'GLGU12' (G12), E. urophylla × E. camaldulensis 'GLUC3' (G3) and E. urophylla 'GLU4'(G4), were subjected to liquid culture with Hoagland nutrient solution for 40 days, then treated with four different treatments of acid and aluminum for 1 day. The four treatments used either pH 3.0 or 4.0 with or without added aluminum (4.4 mM) in all possible combinations; a control used no added aluminum at pH 4.8. Subsequently, the photosynthetic parameters and morphology of leaves from eucalypt seedlings were determined and observed. The results showed that the tested chlorophyll content, net photosynthetic rate, transpiration rate and water use efficiency were apparently inhibited by aluminum. Under uniform Al concentration (4.4 mM), the Al-induced limitation to photosynthetic parameters increased with pH, indicating acid stimulation to Al toxicity. Among all treatments, the most significant reduction was found in the combination of pH 3.0 and 4.4 mM Al. The photosynthetic and transpiration rates showed similar trends with G9 > G12 > G3 > G4, suggesting that G9 and G12 had higher Al-tolerance than other two clones. Microscopic observation revealed changes in leaf morphology when exposed to Al stress; for example, a reduced thickness of leaf epidermis and palisade tissue, the descendant palisade tissue/spongy tissue ratio and leaf tissue looseness. Overall, the acid and aluminum stress exerted negative effects on the photosynthetic activity of eucalypt seedlings, but the differences in tolerance to Al toxicity between the clones were favorable, offering potential to improve Eucalyptus plantation productivity by selecting Al tolerant clones.

Effect of Low pH and Aluminum Toxicity on the Photosynthetic Characteristics of Different Fast-Growing Eucalyptus Vegetatively Propagated Clones

Science.gov (United States)

Yang, Mei; Tan, Ling; Xu, Yuanyuan; Zhao, Yihui; Cheng, Fei; Ye, Shaoming; Jiang, Weixin

2015-01-01

Knowing how acid soils and aluminum in soils may limit the growth of Eucalyptus trees in plantations is important because these plantations grow in many tropical and subtropical regions. Seedlings of four vegetatively propagated Eucalyptus clones, E. grandis × E. urophylla ‘GLGU9’(G9), E. grandis × E. urophylla ‘GLGU12’ (G12), E. urophylla × E. camaldulensis ‘GLUC3’ (G3) and E. urophylla ‘GLU4’(G4), were subjected to liquid culture with Hoagland nutrient solution for 40 days, then treated with four different treatments of acid and aluminum for 1 day. The four treatments used either pH 3.0 or 4.0 with or without added aluminum (4.4 mM) in all possible combinations; a control used no added aluminum at pH 4.8. Subsequently, the photosynthetic parameters and morphology of leaves from eucalypt seedlings were determined and observed. The results showed that the tested chlorophyll content, net photosynthetic rate, transpiration rate and water use efficiency were apparently inhibited by aluminum. Under uniform Al concentration (4.4 mM), the Al-induced limitation to photosynthetic parameters increased with pH, indicating acid stimulation to Al toxicity. Among all treatments, the most significant reduction was found in the combination of pH 3.0 and 4.4 mM Al. The photosynthetic and transpiration rates showed similar trends with G9 > G12 > G3 > G4, suggesting that G9 and G12 had higher Al-tolerance than other two clones. Microscopic observation revealed changes in leaf morphology when exposed to Al stress; for example, a reduced thickness of leaf epidermis and palisade tissue, the descendant palisade tissue/spongy tissue ratio and leaf tissue looseness. Overall, the acid and aluminum stress exerted negative effects on the photosynthetic activity of eucalypt seedlings, but the differences in tolerance to Al toxicity between the clones were favorable, offering potential to improve Eucalyptus plantation productivity by selecting Al tolerant clones. PMID

Effect of Low pH and Aluminum Toxicity on the Photosynthetic Characteristics of Different Fast-Growing Eucalyptus Vegetatively Propagated Clones.

Directory of Open Access Journals (Sweden)

Mei Yang

Full Text Available Knowing how acid soils and aluminum in soils may limit the growth of Eucalyptus trees in plantations is important because these plantations grow in many tropical and subtropical regions. Seedlings of four vegetatively propagated Eucalyptus clones, E. grandis × E. urophylla 'GLGU9'(G9, E. grandis × E. urophylla 'GLGU12' (G12, E. urophylla × E. camaldulensis 'GLUC3' (G3 and E. urophylla 'GLU4'(G4, were subjected to liquid culture with Hoagland nutrient solution for 40 days, then treated with four different treatments of acid and aluminum for 1 day. The four treatments used either pH 3.0 or 4.0 with or without added aluminum (4.4 mM in all possible combinations; a control used no added aluminum at pH 4.8. Subsequently, the photosynthetic parameters and morphology of leaves from eucalypt seedlings were determined and observed. The results showed that the tested chlorophyll content, net photosynthetic rate, transpiration rate and water use efficiency were apparently inhibited by aluminum. Under uniform Al concentration (4.4 mM, the Al-induced limitation to photosynthetic parameters increased with pH, indicating acid stimulation to Al toxicity. Among all treatments, the most significant reduction was found in the combination of pH 3.0 and 4.4 mM Al. The photosynthetic and transpiration rates showed similar trends with G9 > G12 > G3 > G4, suggesting that G9 and G12 had higher Al-tolerance than other two clones. Microscopic observation revealed changes in leaf morphology when exposed to Al stress; for example, a reduced thickness of leaf epidermis and palisade tissue, the descendant palisade tissue/spongy tissue ratio and leaf tissue looseness. Overall, the acid and aluminum stress exerted negative effects on the photosynthetic activity of eucalypt seedlings, but the differences in tolerance to Al toxicity between the clones were favorable, offering potential to improve Eucalyptus plantation productivity by selecting Al tolerant clones.

High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

International Nuclear Information System (INIS)

Lips, Irene M; Dehnad, Homan; Gils, Carla H van; Boeken Kruger, Arto E; Heide, Uulke A van der; Vulpen, Marco van

2008-01-01

We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used

High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

Directory of Open Access Journals (Sweden)

Boeken Kruger Arto E

2008-05-01

Full Text Available Abstract We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment and weekly during treatment (acute toxicity were scored using the Common Toxicity Criteria (CTC. The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU complaints and 2% experienced grade 2 gastrointestinal (GI complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4. In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose-Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

Energy Technology Data Exchange (ETDEWEB)

Pederson, Aaron W.; Fricano, Janine; Correa, David; Pelizzari, Charles A. [Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Chicago, IL (United States); Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu [Department of Radiation and Cellular Oncology, Pritzker School of Medicine, University of Chicago, Chicago, IL (United States)

2012-01-01

Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose-volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V{sub 70}), 65 Gy (V{sub 65}), and 40 Gy (V{sub 40}). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V{sub 70} {<=}10%, V{sub 65} {<=}20%, and V{sub 40} {<=}40%; 92% for men with rectal V{sub 70} {<=}20%, V{sub 65} {<=}40%, and V{sub 40} {<=}80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged {>=}70 years (p = 0.07). No bladder dose-volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints

Late Toxicity After Intensity-Modulated Radiation Therapy for Localized Prostate Cancer: An Exploration of Dose–Volume Histogram Parameters to Limit Genitourinary and Gastrointestinal Toxicity

International Nuclear Information System (INIS)

Pederson, Aaron W.; Fricano, Janine; Correa, David; Pelizzari, Charles A.; Liauw, Stanley L.

2012-01-01

Purpose: To characterize the late genitourinary (GU) and gastrointestinal (GI) toxicity for prostate cancer patients treated with intensity-modulated radiation therapy (IMRT) and propose dose–volume histogram (DVH) guidelines to limit late treatment-related toxicity. Methods and Materials: In this study 296 consecutive men were treated with IMRT for adenocarcinoma of the prostate. Most patients received treatment to the prostate with or without proximal seminal vesicles (90%), to a median dose of 76 Gy. Concurrent androgen deprivation therapy was given to 150 men (51%) for a median of 4 months. Late toxicity was defined by Common Toxicity Criteria version 3.0 as greater than 3 months after radiation therapy completion. Four groupings of DVH parameters were defined, based on the percentage of rectal or bladder tissue receiving 70 Gy (V 70 ), 65 Gy (V 65 ), and 40 Gy (V 40 ). These DVH groupings, as well as clinical and treatment characteristics, were correlated to maximal Grade 2+ GU and GI toxicity. Results: With a median follow-up of 41 months, the 4-year freedom from maximal Grade 2+ late toxicity was 81% and 91% for GU and GI systems, respectively, and by last follow-up, the rates of Grade 2+ GU and GI toxicity were 9% and 5%, respectively. On multivariate analysis, whole-pelvic IMRT was associated with Grade 2+ GU toxicity and age was associated with Grade 2+ GI toxicity. Freedom from Grade 2+ GI toxicity at 4 years was 100% for men with rectal V 70 ≤10%, V 65 ≤20%, and V 40 ≤40%; 92% for men with rectal V 70 ≤20%, V 65 ≤40%, and V 40 ≤80%; and 85% for men exceeding these criteria (p = 0.13). These criteria were more highly associated with GI toxicity in men aged ≥70 years (p = 0.07). No bladder dose–volume relationships were associated with the risk of GU toxicity. Conclusions: IMRT is associated with low rates of severe GU or GI toxicity after treatment for prostate cancer. Rectal dose constraints may help limit late GI morbidity.

A plant-wide aqueous phase chemistry module describing pH variations and ion speciation/pairing in wastewater treatment process models.

Science.gov (United States)

Flores-Alsina, Xavier; Kazadi Mbamba, Christian; Solon, Kimberly; Vrecko, Darko; Tait, Stephan; Batstone, Damien J; Jeppsson, Ulf; Gernaey, Krist V

2015-11-15

There is a growing interest within the Wastewater Treatment Plant (WWTP) modelling community to correctly describe physico-chemical processes after many years of mainly focusing on biokinetics. Indeed, future modelling needs, such as a plant-wide phosphorus (P) description, require a major, but unavoidable, additional degree of complexity when representing cationic/anionic behaviour in Activated Sludge (AS)/Anaerobic Digestion (AD) systems. In this paper, a plant-wide aqueous phase chemistry module describing pH variations plus ion speciation/pairing is presented and interfaced with industry standard models. The module accounts for extensive consideration of non-ideality, including ion activities instead of molar concentrations and complex ion pairing. The general equilibria are formulated as a set of Differential Algebraic Equations (DAEs) instead of Ordinary Differential Equations (ODEs) in order to reduce the overall stiffness of the system, thereby enhancing simulation speed. Additionally, a multi-dimensional version of the Newton-Raphson algorithm is applied to handle the existing multiple algebraic inter-dependencies. The latter is reinforced with the Simulated Annealing method to increase the robustness of the solver making the system not so dependent of the initial conditions. Simulation results show pH predictions when describing Biological Nutrient Removal (BNR) by the activated sludge models (ASM) 1, 2d and 3 comparing the performance of a nitrogen removal (WWTP1) and a combined nitrogen and phosphorus removal (WWTP2) treatment plant configuration under different anaerobic/anoxic/aerobic conditions. The same framework is implemented in the Benchmark Simulation Model No. 2 (BSM2) version of the Anaerobic Digestion Model No. 1 (ADM1) (WWTP3) as well, predicting pH values at different cationic/anionic loads. In this way, the general applicability/flexibility of the proposed approach is demonstrated, by implementing the aqueous phase chemistry module in some

Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility.

Science.gov (United States)

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Kyoung-Ho; Kim, Dong-Jin; Lee, Beom-Jin

2010-05-01

Although the solid dispersion method has been known to increase the dissolution rate of poorly water-soluble drugs by dispersing them in hydrophilic carriers, one obstacle of the solid dispersion method is its limited solubilization capacity, especially for pH-dependent soluble drugs. pH-modified solid dispersion, in which pH modifiers are incorporated, may be a useful method for increasing the dissolution rate of weakly acidic or basic drugs. Sufficient research, including the most recent reports, was undertaken in this review. How could the inclusion of the pH the pH modifiers in the solid dispersion system change drug structural behaviors, molecular interactions, microenvironmental pH, and/or release rate of pH modifiers, relating with the enhanced dissolution of weakly acidic or weakly basic drugs with poor water solubility? These questions have been investigated to determine the dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs. It is believed that step-by-step mechanistic approaches could provide the ultimate solution for solubilizing several poorly water-soluble drugs with pH-dependent solubility from a solid dispersion system, as well as provide ideas for developing future dosage systems.

Assessment of citalopram and escitalopram on neuroblastoma cell lines: Cell toxicity and gene modulation

Science.gov (United States)

Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

2017-01-01

Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram. PMID:28467792

Assessment of citalopram and escitalopram on neuroblastoma cell lines. Cell toxicity and gene modulation.

Science.gov (United States)

Sakka, Laurent; Delétage, Nathalie; Chalus, Maryse; Aissouni, Youssef; Sylvain-Vidal, Valérie; Gobron, Stéphane; Coll, Guillaume

2017-06-27

Selective serotonin reuptake inhibitors (SSRI) are common antidepressants which cytotoxicity has been assessed in cancers notably colorectal carcinomas and glioma cell lines. We assessed and compared the cytotoxicity of 2 SSRI, citalopram and escitalopram, on neuroblastoma cell lines. The study was performed on 2 non-MYCN amplified cell lines (rat B104 and human SH-SY5Y) and 2 human MYCN amplified cell lines (IMR32 and Kelly). Citalopram and escitalopram showed concentration-dependent cytotoxicity on all cell lines. Citalopram was more cytotoxic than escitalopram. IMR32 was the most sensitive cell line. The absence of toxicity on human primary Schwann cells demonstrated the safety of both molecules for myelin. The mechanisms of cytotoxicity were explored using gene-expression profiles and quantitative real-time PCR (qPCR). Citalopram modulated 1 502 genes and escitalopram 1 164 genes with a fold change ≥ 2. 1 021 genes were modulated by both citalopram and escitalopram; 481 genes were regulated only by citalopram while 143 genes were regulated only by escitalopram. Citalopram modulated 69 pathways (KEGG) and escitalopram 42. Ten pathways were differently modulated by citalopram and escitalopram. Citalopram drastically decreased the expression of MYBL2, BIRC5 and BARD1 poor prognosis factors of neuroblastoma with fold-changes of -107 (pescitalopram.

Two rhodamine lactam modulated lysosome-targetable fluorescence probes for sensitively and selectively monitoring subcellular organelle pH change

Energy Technology Data Exchange (ETDEWEB)

Li, Hongmei [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Wang, Cuiling [Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi' an 710069 (China); She, Mengyao; Zhu, Yuelu; Zhang, Jidong; Yang, Zheng [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Liu, Ping, E-mail: liuping@nwu.edu.cn [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Wang, Yaoyu [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China); Li, Jianli, E-mail: lijianli@nwu.edu.cn [Ministry of Education Key Laboratory of Synthetic and Natural Functional Molecule Chemistry, College of Chemistry & Materials Science, Northwest University, Xi' an 710069 (China)

2015-11-05

Be a powerful technique for convenient detection of pH change in living cells, especially at subcellular level, fluorescent probes has attracted more and more attention. In this work, we designed and synthesized three rhodamine lactam modulated fluorescent probes RS1, RS2 and RS3, which all respond sensitively toward weak acidity (pH range 4–6) via the photophysical property in buffer solution without interference from the other metal ions, and they also show ideal pKa values and excellent reversibility. Particularly, by changing the lone pair electrons distribution of lactam-N atom with different conjugations, RS2 and RS3 exhibit high quantum yield, negligible cytotoxicity and excellent permeability. They are suitable to stain selectively lysosomes of tumor cells and monitor its pH changes sensitively via optical molecular imaging. The above findings suggest that the probes we designed could act as ideal and easy method for investigating the pivotal role of H{sup +} in lysosomes and are potential pH detectors in disease diagnosis through direct intracellular imaging. - Highlights: • Two probes for sensitively and selectively monitoring weak acidic pH change. • The pKa of the probes was highly suitable for staining lysosomes in tumor cells. • The properties of those probes were changed by different conjugate system. • These probes have negligible cytotoxicity and good sensitivity in vivo.

Two rhodamine lactam modulated lysosome-targetable fluorescence probes for sensitively and selectively monitoring subcellular organelle pH change

International Nuclear Information System (INIS)

Li, Hongmei; Wang, Cuiling; She, Mengyao; Zhu, Yuelu; Zhang, Jidong; Yang, Zheng; Liu, Ping; Wang, Yaoyu; Li, Jianli

2015-01-01

Be a powerful technique for convenient detection of pH change in living cells, especially at subcellular level, fluorescent probes has attracted more and more attention. In this work, we designed and synthesized three rhodamine lactam modulated fluorescent probes RS1, RS2 and RS3, which all respond sensitively toward weak acidity (pH range 4–6) via the photophysical property in buffer solution without interference from the other metal ions, and they also show ideal pKa values and excellent reversibility. Particularly, by changing the lone pair electrons distribution of lactam-N atom with different conjugations, RS2 and RS3 exhibit high quantum yield, negligible cytotoxicity and excellent permeability. They are suitable to stain selectively lysosomes of tumor cells and monitor its pH changes sensitively via optical molecular imaging. The above findings suggest that the probes we designed could act as ideal and easy method for investigating the pivotal role of H + in lysosomes and are potential pH detectors in disease diagnosis through direct intracellular imaging. - Highlights: • Two probes for sensitively and selectively monitoring weak acidic pH change. • The pKa of the probes was highly suitable for staining lysosomes in tumor cells. • The properties of those probes were changed by different conjugate system. • These probes have negligible cytotoxicity and good sensitivity in vivo.

CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Detailed Conceptual Diagram

Science.gov (United States)

Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Simple Conceptual Diagram

Science.gov (United States)

Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

pH- and temperature-sensitive polymeric microspheres for drug delivery: the dissolution of copolymers modulates drug release.

Science.gov (United States)

Fundueanu, Gheorghe; Constantin, Marieta; Stanciu, Cristina; Theodoridis, Georgios; Ascenzi, Paolo

2009-12-01

Most pH-/temperature-responsive polymers for controlled release of drugs are used as cross-linked hydrogels. However, the solubility properties of the linear polymers below and above the lower critical solution temperature (LCST) are not exploited. Here, the preparation and characterization of poly (N-isopropylacrylamide-co-methacrylic acid-co-methyl methacrylate) (poly (NIPAAm-co-MA-co-MM)) and poly (N-isopropylacrylamide-co-acrylamide) (poly (NIPAAm-co-AAm)), known as "smart" polymers (SP), is reported. Both poly (NIPAAm-co-MA-co-MM) and poly (NIPAAm-co-AAm) display pH- and temperature-responsive properties. Poly (NIPAAm-co-MA-co-MM) was designed to be insoluble in the gastric fluid (pH = 1.2), but soluble in the intestinal fluid (pH = 6.8 and 7.4), at the body temperature (37 degrees C). Poly (NIPAAm-co-AAm) was designed to have a lower critical solution temperature (LCST) corresponding to 37 degrees C at pH = 7.4, therefore it is not soluble above the LCST. The solubility characteristics of these copolymers were exploited to modulate the rate of release of drugs by changing pH and/or temperature. These copolymers were solubilized with hydrophobic cellulose acetate butyrate (CAB) and vitamin B(12) (taken as a water soluble drug model system) in an acetone/methanol mixture and dispersed in mineral oil. By a progressive evaporation of the solvent, the liquid droplets were transformed into loaded CAB/SP microspheres. Differential scanning calorimetric studies and scanning electron microscopy analysis demonstrated that the polymeric components of the microspheres precipitated separately during solvent evaporation forming small microdomains. Moreover, vitamin B(12) was found to be molecularly dispersed in both microdomains with no specific affinity for any polymeric component of microspheres. The release of vitamin B(12) was investigated as a function of temperature, pH, and the CAB/SP ratio.

Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

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Samuelian, Jason M. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Callister, Matthew D., E-mail: Callister.matthew@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Ashman, Jonathan B. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Young-Fadok, Tonia M. [Division of Colorectal Surgery, Mayo Clinic, Scottsdale, AZ (United States); Borad, Mitesh J. [Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ (United States); Gunderson, Leonard L. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

2012-04-01

Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

International Nuclear Information System (INIS)

Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

2012-01-01

Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced ≥Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, ≥Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

International Nuclear Information System (INIS)

Sharma, Navesh K.; Li Tianyu; Chen, David Y.; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

2011-01-01

Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; ≥6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. ≥6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

Intensity modulated radiotherapy for localized prostate cancer: rigid compliance to dose-volume constraints as a warranty of acceptable toxicity?

International Nuclear Information System (INIS)

Chen, Michael J; Nadalin, Wladmir; Weltman, Eduardo; Hanriot, Rodrigo M; Luz, Fábio P; Cecílio, Paulo J; Cruz, José C da; Moreira, Frederico R; Santos, Adriana S; Martins, Lidiane C

2007-01-01

To report the toxicity after intensity modulated radiotherapy (IMRT) for patients with localized prostate cancer, as a sole treatment or after radical prostatectomy. Between August 2001 and December 2003, 132 patients with prostate cancer were treated with IMRT and 125 were evaluable to acute and late toxicity analysis, after a minimum follow-up time of one year. Clinical and treatment data, including normal tissue dose-volume histogram (DVH) constraints, were reviewed. Gastro-intestinal (GI) and genito-urinary (GU) signs and symptoms were evaluated according to the Radiation Therapy Oncology Group (RTOG) toxicity scales. Median prescribed dose was 76 Gy. Median follow-up time was of 26.1 months. From the 125 patients, 73 (58.4%) presented acute Grade 1 or Grade 2 GI and 97 (77.2%) presented acute Grade 1 or Grade 2 GU toxicity. Grade 3 GI acute toxicity occurred in only 2 patients (1.6%) and Grade 3 GU acute toxicity in only 3 patients (2.4%). Regarding Grade 1 and 2 late toxicity, 26 patients (20.8%) and 21 patients (16.8%) presented GI and GU toxicity, respectively. Grade 2 GI late toxicity occurred in 6 patients (4.8%) and Grade 2 GU late toxicity in 4 patients (3.2%). None patient presented any Grade 3 or higher late toxicity. Non-conformity to DVH constraints occurred in only 11.2% of treatment plans. On univariate analysis, no significant risk factor was identified for Grade 2 GI late toxicity, but mean dose delivered to the PTV was associated to higher Grade 2 GU late toxicity (p = 0.042). IMRT is a well tolerable technique for routine treatment of localized prostate cancer, with short and medium-term acceptable toxicity profiles. According to the data presented here, rigid compliance to DHV constraints might prevent higher incidences of normal tissue complication

Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy

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Maclean, Jillian, E-mail: jillian.maclean@uclh.nhs.uk [Radiotherapy Department, University College London Hospital, London (United Kingdom); Fersht, Naomi [Radiotherapy Department, University College London Hospital, London (United Kingdom); Bremner, Fion [Neuro-Ophthalmology Department, National Hospital for Neurology and Neurosurgery, London (United Kingdom); Stacey, Chris; Sivabalasingham, Suganya [Radiotherapy Department, University College London Hospital, London (United Kingdom); Short, Susan [Radiotherapy Department, University College London Hospital, London (United Kingdom); Leeds Institute of Molecular Medicine, St James University Hospital, Leeds (United Kingdom)

2013-03-15

Purpose: To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. Methods and Materials: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3 optic nerve sheath meningiomas); 4 were posterior to the chiasm. Results: Vision improved objectively in 12 patients (40%). Improvements were in visual field (5/16 patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2 keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. Conclusion: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of radiological change.

CO2-induced pH reduction increases physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus

Science.gov (United States)

Hu, Menghong; Lin, Daohui; Shang, Yueyong; Hu, Yi; Lu, Weiqun; Huang, Xizhi; Ning, Ke; Chen, Yimin; Wang, Youji

2017-01-01

The increasing usage of nanoparticles has caused their considerable release into the aquatic environment. Meanwhile, anthropogenic CO2 emissions have caused a reduction of seawater pH. However, their combined effects on marine species have not been experimentally evaluated. This study estimated the physiological toxicity of nano-TiO2 in the mussel Mytilus coruscus under high pCO2 (2500-2600 μatm). We found that respiration rate (RR), food absorption efficiency (AE), clearance rate (CR), scope for growth (SFG) and O:N ratio were significantly reduced by nano-TiO2, whereas faecal organic weight rate and ammonia excretion rate (ER) were increased under nano-TiO2 conditions. High pCO2 exerted lower effects on CR, RR, ER and O:N ratio than nano-TiO2. Despite this, significant interactions of CO2-induced pH change and nano-TiO2 were found in RR, ER and O:N ratio. PCA showed close relationships among most test parameters, i.e., RR, CR, AE, SFG and O:N ratio. The normal physiological responses were strongly correlated to a positive SFG with normal pH and no/low nano-TiO2 conditions. Our results indicate that physiological functions of M. coruscus are more severely impaired by the combination of nano-TiO2 and high pCO2.

Effect of Microenvironmental pH Modulation on the Dissolution Rate and Oral Absorption of the Salt of a Weak Acid - Case Study of GDC-0810.

Science.gov (United States)

Hou, Hao Helen; Jia, Wei; Liu, Lichuan; Cheeti, Sravanthi; Li, Jane; Nauka, Ewa; Nagapudi, Karthik

2018-01-29

The purpose of this work is to investigate the effect of microenvironmental pH modulation on the in vitro dissolution rate and oral absorption of GDC-0810, an oral anti-cancer drug, in human. The pH-solubility profile of GDC-0810 free acid and pH max of its N-Methyl-D-glucamine (NMG) salt were determined. Precipitation studies were conducted for GDC-0810 NMG salt at different pH values. GDC-0810 200-mg dose NMG salt tablet formulations containing different levels of sodium bicarbonate as the pH modifier were tested for dissolution under the dual pH-dilution scheme. Three tablet formulations were evaluated in human as a part of a relative bioavailability study. A 200-mg dose of GDC-0810 was administered QD with low fat food. Intrinsic solubility of GDC-0810 free acid was found to be extremely low. The pH max of the NMG salt suggested a strong tendency for form conversion to the free acid under GI conditions. In vitro dissolution profiles showed that the dissolution rate and extent of GDC-0810 increased with increasing the level of sodium bicarbonate in the formulation. The human PK data showed a similar trend for the geometric mean of C max and AUC 0-t for formulations containing 5%, 10%, and 15% sodium bicarbonate, but the difference is not statistically significant. Incorporation of a basic pH modifier, sodium bicarbonate, in GDC-0810 NMG salt tablet formulations enhanced in vitro dissolution rate of GDC-0810 via microenvironmental pH modulation. The human PK data showed no statistically significant difference in drug exposure from tablets containing 5%, 10%, and 15% sodium bicarbonate.

Toxicity identification evaluations of produced-water effluents

International Nuclear Information System (INIS)

Sauer, T.C.; Costa, H.J.; Brown, J.S.; Ward, T.J.

1997-01-01

Toxicity identification evaluations (TIEs) were performed on 14 produced-water (PW) samples of various salinities from inland and offshore oil- and gas-production facilities operated by different companies in Wyoming, Texas, California, and Louisiana (USA) to evaluate the efficacy of TIE procedures in determining potential toxicants in PW effluents. The research involved acute (24- and 48-h) freshwater and marine toxicity tests on whole PW and PW fractions generated by standard US Environmental Protection Agency and PW-specific fractionation schemes. Factors influencing PW TIEs were investigated, such as the effect of salinity in selecting fractionation manipulations, the effect of toxicity test replication (i.e., reproducibility) in distinguishing changes in toxicities between whole PW and its fractions, and the suitability of different test species in PW TIEs. The results obtained and lessons learned from conducting these PW TIEs are presented in this article. Components, or fractions, contributing to toxicity differed for each PW with no specific fraction being consistently toxic. For most PW samples, toxicity attributed to any one fraction represented only part of the toxicity of the whole sample. However, no more than two fraction types were identified as potential toxicants in any sample. Potential toxicants identified during this study, besides salinity, included acidic and basic organic compound class fractions, particulates removed by filtration at pH 11, ammonia, hydrocarbons, hydrogen sulfide, material removed by pH change, and volatile compounds

Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

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Deville, Curtiland, E-mail: deville@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Lin Haibo; Bar Ad, Voichita; Tochner, Zelig; Both, Stefan [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2012-03-15

Purpose: To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. Methods and Materials: All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluated uni- and multivariate associations between pretreatment demographics and toxicities. Results: Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade {>=}2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade {>=}2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade {>=}2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade {>=}2 late GU toxicity (p = 0.02). Conclusion: Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.

Toxicity identification evaluation methods for identification of toxicants in refinery effluents

International Nuclear Information System (INIS)

Barten, K.A.; Mount, D.R.; Hackett, J.R.

1993-01-01

During the last five years, the authors have used Toxicity Identification Evaluation (TIE) methods to characterize and identify the source(s) of toxicity in effluents from dozens of municipal and industrial facilities. In most cases, specific chemicals responsible for toxicity have been identified. Although generally successful, the initial experience was that for several refinery effluents, they were able only to qualitatively characterize the presence of organic toxicants; standard toxicant identification procedures were not able to isolate specific organic chemicals. They believe that organic toxicity in these refinery effluents is caused by multiple organic compounds rather than by just a few; evidence for this includes an inability to isolate toxicity in a small number of fractions using liquid chromatography and the presence of very large numbers of compounds in isolated fractions. There is also evidence that the toxicant(s) may be ionic, in that the toxicity of whole effluent and isolated fractions often show increasing toxicity with decreasing pH. Finally, positive-pressure filtration has also reduced toxicity in some samples. In this presentation the authors summarize their experiences with refinery effluents, focusing on typical patterns they have observed and alternative procedures they have used to better understand the nature of these toxicants

On the Toxicity of the Aromatic Diamines and their Tetramethylcarboxylic Acid Derivatives

OpenAIRE

Gili, Pedro; Mederos, Alfredo

2000-01-01

The use of the theoretical PALLAS 3.0 program, to study the toxic behaviour of tetramethylcarboxylic acids, potential pharmaceuticals derived from o-phenylenediamines, indicates that o-phenylenediamines are highly toxic (level 1), while the tetramethycarboxylic acid derivatives (o-PhDTA and 3,4-TDTA) are slightly toxic, similar to EDTA (level 3). Therefore these ligands o-PhDTA and 3,4-TDTA, similar to EDTA, can be used as sequestering agents of toxic metals and overload of essential metals i...

Modulation of Ras signaling alters the toxicity of hydroquinone, a benzene metabolite and component of cigarette smoke

International Nuclear Information System (INIS)

North, Matthew; Shuga, Joe; Fromowitz, Michele; Loguinov, Alexandre; Shannon, Kevin; Zhang, Luoping; Smith, Martyn T; Vulpe, Chris D

2014-01-01

Benzene is an established human leukemogen, with a ubiquitous environmental presence leading to significant population exposure. In a genome-wide functional screen in the yeast Saccharomyces cerevisiae, inactivation of IRA2, a yeast ortholog of the human tumor suppressor gene NF1 (Neurofibromin), enhanced sensitivity to hydroquinone, an important benzene metabolite. Increased Ras signaling is implicated as a causal factor in the increased pre-disposition to leukemia of individuals with mutations in NF1. Growth inhibition of yeast by hydroquinone was assessed in mutant strains exhibiting varying levels of Ras activity. Subsequently, effects of hydroquinone on both genotoxicity (measured by micronucleus formation) and proliferation of WT and Nf1 null murine hematopoietic precursors were assessed. Here we show that the Ras status of both yeast and mammalian cells modulates hydroquinone toxicity, indicating potential synergy between Ras signaling and benzene toxicity. Specifically, enhanced Ras signaling increases both hydroquinone-mediated growth inhibition in yeast and genotoxicity in mammalian hematopoetic precursors as measured by an in vitro erythroid micronucleus assay. Hydroquinone also increases proliferation of CFU-GM progenitor cells in mice with Nf1 null bone marrow relative to WT, the same cell type associated with benzene-associated leukemia. Together our findings show that hydroquinone toxicity is modulated by Ras signaling. Individuals with abnormal Ras signaling could be more vulnerable to developing myeloid diseases after exposure to benzene. We note that hydroquinone is used cosmetically as a skin-bleaching agent, including by individuals with cafe-au-lait spots (which may be present in individuals with neurofibromatosis who have a mutation in NF1), which could be unadvisable given our findings

One-step synthesis, toxicity assessment and degradation in tumoral pH environment of SiO2@Ag core/shell nanoparticles

Science.gov (United States)

De Matteis, Valeria; Rizzello, Loris; Di Bello, Maria Pia; Rinaldi, Rosaria

2017-06-01

The unique physicochemical properties of SiO2@Ag core/shell nanoparticles make them a promising tool in nanomedicine, where they are used as nanocarriers for several biomedical applications, including (but not restricted to) cancer treatment. However, a comprehensive estimation of their potential toxicity, as well as their degradation in the tumor microenvironment, has not been extensively addressed yet. We investigated in vitro the viability, the reactive oxygen species (ROS) production, the DNA damage level, and the nanoparticle uptake on HeLa cells, used as model cancer cells. In addition, we studied the NPs degradation profile at pH 6.5, to mimic the tumor microenvironment, and at the neutral and physiological (pH 7-7.4). Our experiments demonstrate that the silver shell dissolution is promoted under acidic conditions, which could be related to cell death induction. Our evidences demonstrate that SiO2@Ag nanoparticles possess the ability of combining an effective cancer cell treatment (through local silver ions release) together with a possible controlled release of bioactive compounds encapsulated in the silica as future application.

Modulation of phosducin-like protein 3 (PhLP3 levels promotes cytoskeletal remodelling in a MAPK and RhoA-dependent manner.

Directory of Open Access Journals (Sweden)

Nandini V L Hayes

Full Text Available Phosducin-like protein 3 (PhLP3 forms a ternary complex with the ATP-dependent molecular chaperone CCT and its folding client tubulin. In vitro studies suggest PhLP3 plays an inhibitory role in β-tubulin folding while conversely in vivo genetic studies suggest PhLP3 is required for the correct folding of β-tubulin. We have a particular interest in the cytoskeleton, its chaperones and their role in determining cellular phenotypes associated with high level recombinant protein expression from mammalian cell expression systems.As studies into PhLP3 function have been largely carried out in non mammalian systems, we examined the effect of human PhLP3 over-expression and siRNA silencing using a single murine siRNA on both tubulin and actin systems in mammalian Chinese hamster ovary (CHO cell lines. We show that over-expression of PhLP3 promotes an imbalance of α and β tubulin subunits, microtubule disassembly and cell death. In contrast, β-actin levels are not obviously perturbed. On-the-other-hand, RNA silencing of PhLP3 increases RhoA-dependent actin filament formation and focal adhesion formation and promotes a dramatic elongated fibroblast-like change in morphology. This was accompanied by an increase in phosphorylated MAPK which has been associated with promoting focal adhesion assembly and maturation. Transient overexpression of PhLP3 in knockdown experiments rescues cells from the morphological change observed during PhLP3 silencing but mitosis is perturbed, probably reflecting a tipping back of the balance of PhLP3 levels towards the overexpression state.Our results support the hypothesis that PhLP3 is important for the maintenance of β-tubulin levels in mammalian cells but also that its modulation can promote actin-based cytoskeletal remodelling by a mechanism linked with MAPK phosphorylation and RhoA-dependent changes. PhLP3 levels in mammalian cells are thus finely poised and represents a novel target for engineering industrially

Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation.

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Agnello, M; Cen, L; Tran, N C; Shi, W; McLean, J S; He, X

2017-07-01

Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis. There is evidence that the use of arginine in dentifrices helps protect against caries. The aim of the current study was to investigate the mechanistic and ecological effect of arginine treatment on the oral microbiome and its regulation of pH dynamics, using an in vitro multispecies oral biofilm model that was previously shown to be highly reflective of the in vivo oral microbiome. Pooled saliva from 6 healthy subjects was used to generate overnight biofilms, reflecting early stages of biofilm maturation. First, we investigated the uptake of arginine by the cells of the biofilm as well as the metabolites generated. We next explored the effect of arginine on pH dynamics by pretreating biofilms with 75 mM arginine, followed by the addition of sucrose (15 mM) after 0, 6, 20, or 48 h. pH was measured at each time point and biofilms were collected for 16S sequencing and targeted arginine quantification, and supernatants were prepared for metabolomic analysis. Treatment with only sucrose led to a sustained pH drop from 7 to 4.5, while biofilms treated with sucrose after 6, 20, or 48 h of preincubation with arginine exhibited a recovery to higher pH. Arginine was detected within the cells of the biofilms, indicating active uptake, and arginine catabolites citrulline, ornithine, and putrescine were detected in supernatants, indicating active metabolism. Sequencing analysis revealed a shift in the microbial community structure in arginine-treated biofilms as well as increased species diversity. Overall, we show that arginine improved pH homeostasis through a remodeling of the oral microbial community.

Use of zeolite for removing ammonia and ammonia-caused toxicity in marine toxicity identification evaluations.

Science.gov (United States)

Burgess, R M; Perron, M M; Cantwell, M G; Ho, K T; Serbst, J R; Pelletier, M C

2004-11-01

Ammonia occurs in marine waters including effluents, receiving waters, and sediment interstitial waters. At sufficiently high concentrations, ammonia can be toxic to aquatic species. Toxicity identification evaluation (TIE) methods provide researchers with tools for identifying aquatic toxicants. For identifying ammonia toxicity, there are several possible methods including pH alteration and volatilization, Ulva lactuca addition, microbial degradation, and zeolite addition. Zeolite addition has been used successfully in freshwater systems to decrease ammonia concentrations and toxicity for several decades. However, zeolite in marine systems has been used less because ions in the seawater interfere with zeolite's ability to adsorb ammonia. The objective of this study was to develop a zeolite method for removing ammonia from marine waters. To accomplish this objective, we performed a series of zeolite slurry and column chromatography studies to determine uptake rate and capacity and to evaluate the effects of salinity and pH on ammonia removal. We also assessed the interaction of zeolite with several toxic metals. Success of the methods was also evaluated by measuring toxicity to two marine species: the mysid Americamysis bahia and the amphipod Ampelisca abdita. Column chromatography proved to be effective at removing a wide range of ammonia concentrations under several experimental conditions. Conversely, the slurry method was inconsistent and variable in its overall performance in removing ammonia and cannot be recommended. The metals copper, lead, and zinc were removed by zeolite in both the slurry and column treatments. The zeolite column was successful in removing ammonia toxicity for both the mysid and the amphipod, whereas the slurry was less effective. This study demonstrated that zeolite column chromatography is a useful tool for conducting marine water TIEs to decrease ammonia concentrations and characterize toxicity.

Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

Directory of Open Access Journals (Sweden)

Tao HM

2016-03-01

Full Text Available Hengmin Tao,1,2 Yumei Wei,1 Wei Huang,1 Xiujuan Gai,1,2 Baosheng Li11Department of 6th Radiation Oncology, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaAim: In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF have been involved in the treatment of nasopharyngeal carcinoma (NPC. However, the potential clinical effects and toxicities are still controversial.Methods: Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS, 5-year progression-free survival (PFS, 5-year locoregional recurrence-free survival (LRFS, and relevant toxicities were analyzed.Results: In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months. The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568. In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773 and 5-year LRFS (88.1% vs 90.8%, P=0.903. Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05.Conclusion: Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.Keywords: intensity-modulated

Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.

Science.gov (United States)

Campion, Katherine L; McCormick, Wanda D; Warwicker, Jim; Khayat, Mohd Ezuan Bin; Atkinson-Dell, Rebecca; Steward, Martin C; Delbridge, Leigh W; Mun, Hee-Chang; Conigrave, Arthur D; Ward, Donald T

2015-09-01

The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo. Copyright © 2015 by the American Society of

pH modulation of glial glutamate transporters regulates synaptic transmission in the nucleus of the solitary tract

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McCrimmon, Donald R.; Martina, Marco

2013-01-01

The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K+-selective membrane currents. NTS glia also showed functional expression of voltage-sensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with dl-threo-β-benzyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter d-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents. PMID:23615553

Curcumin Modulates α-Synuclein Aggregation and Toxicity

Science.gov (United States)

2012-01-01

In human beings, Parkinson’s disease (PD) is associated with the oligomerization and amyloid formation of α-synuclein (α-Syn). The polyphenolic Asian food ingredient curcumin has proven to be effective against a wide range of human diseases including cancers and neurological disorders. While curcumin has been shown to significantly reduce cell toxicity of α-Syn aggregates, its mechanism of action remains unexplored. Here, using a series of biophysical techniques, we demonstrate that curcumin reduces toxicity by binding to preformed oligomers and fibrils and altering their hydrophobic surface exposure. Further, our fluorescence and two-dimensional nuclear magnetic resonance (2D-NMR) data indicate that curcumin does not bind to monomeric α-Syn but binds specifically to oligomeric intermediates. The degree of curcumin binding correlates with the extent of α-Syn oligomerization, suggesting that the ordered structure of protein is required for effective curcumin binding. The acceleration of aggregation by curcumin may decrease the population of toxic oligomeric intermediates of α-Syn. Collectively; our results suggest that curcumin and related polyphenolic compounds can be pursued as candidate drug targets for treatment of PD and other neurological diseases. PMID:23509976

Acute toxicity profile of craniospinal irradiation with intensity-modulated radiation therapy in children with medulloblastoma: A prospective analysis

International Nuclear Information System (INIS)

Cox, Maurice C.; Kusters, Johannes M.; Gidding, Corrie E.; Schieving, Jolanda H.; Lindert, Erik J. van; Kaanders, Johannes H.; Janssens, Geert O.

2015-01-01

To report on the acute toxicity in children with medulloblastoma undergoing intensity-modulated radiation therapy (IMRT) with daily intrafractionally modulated junctions. Newly diagnosed patients, aged 3–21, with standard-risk (SR) or high-risk (HR) medulloblastoma were eligible. A dose of 23.4 or 36.0Gy in daily fractions of 1.8Gy was prescribed to the craniospinal axis, followed by a boost to the primary tumor bed (54 or 55.8Gy) and metastases (39.6–55.8Gy), when indicated. Weekly, an intravenous bolus of vincristine was combined for patients with SR medulloblastoma and patients participating in the COG-ACNS-0332 study. Common toxicity criteria (CTC, version 2.0) focusing on skin, alopecia, voice changes, conjunctivitis, anorexia, dysphagia, gastro-intestinal symptoms, headache, fatigue and hematological changes were scored weekly during radiotherapy. From 2010 to 2014, data from 15 consecutive patients (SR, n = 7; HR, n = 8) were collected. Within 72 h from onset of treatment, vomiting (66 %) and headache (46 %) occurred. During week 3 of treatment, a peak incidence in constipation (33 %) and abdominal pain/cramping (40 %) was observed, but only in the subgroup of patients (n = 9) receiving vincristine (constipation: 56 vs 0 %, P = .04; pain/cramping: 67 vs 0 %, P = .03). At week 6, 73 % of the patients developed faint erythema of the cranial skin with dry desquamation (40 %) or moist desquamation confined to the skin folds of the auricle (33 %). No reaction of the skin overlying the spinal target volume was observed. Headache at onset and gastro-intestinal toxicity, especially in patients receiving weekly vincristine, were the major complaints of patients with medulloblastoma undergoing craniospinal irradiation with IMRT

High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients

International Nuclear Information System (INIS)

Zelefsky, Michael J.; Fuks, Zvi; Hunt, Margie; Yamada, Yoshiya; Marion, Christine; Ling, C. Clifton; Amols, Howard; Venkatraman, E.S.; Leibel, Steven A.

2002-01-01

Purpose: To report the acute and late toxicity and preliminary biochemical outcomes in 772 patients with clinically localized prostate cancer treated with high-dose intensity-modulated radiotherapy (IMRT). Methods and Materials: Between April 1996 and January 2001, 772 patients with clinically localized prostate cancer were treated with IMRT. Treatment was planned using an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. A total of 698 patients (90%) were treated to 81.0 Gy, and 74 patients (10%) were treated to 86.4 Gy. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. PSA relapse was defined according to The American Society of Therapeutic Radiation Oncology Consensus Statement. The median follow-up time was 24 months (range: 6-60 months). Results: Thirty-five patients (4.5%) developed acute Grade 2 rectal toxicity, and no patient experienced acute Grade 3 or higher rectal symptoms. Two hundred seventeen patients (28%) developed acute Grade 2 urinary symptoms, and one experienced urinary retention (Grade 3). Eleven patients (1.5%) developed late Grade 2 rectal bleeding. Four patients (0.1%) experienced Grade 3 rectal toxicity requiring either one or more transfusions or a laser cauterization procedure. No Grade 4 rectal complications have been observed. The 3-year actuarial likelihood of ≥ late Grade 2 rectal toxicity was 4%. Seventy-two patients (9%) experienced late Grade 2 urinary toxicity, and five (0.5%) developed Grade 3 urinary toxicity (urethral stricture). The 3-year actuarial likelihood of ≥ late Grade 2 urinary toxicity was 15%. The 3-year actuarial PSA relapse-free survival rates for favorable, intermediate, and unfavorable risk group patients were 92%, 86%, and 81%, respectively. Conclusions: These data demonstrate the feasibility of high-dose IMRT in a large number of patients. Acute and late rectal toxicities seem to be

Studying the effect of CO2-induced acidification on sediment toxicity using acute amphipod toxicity test.

Science.gov (United States)

Basallote, M Dolores; De Orte, Manoela R; DelValls, T Ángel; Riba, Inmaculada

2014-01-01

Carbon capture and storage is increasingly being considered one of the most efficient approaches to mitigate the increase of CO2 in the atmosphere associated with anthropogenic emissions. However, the environmental effects of potential CO2 leaks remain largely unknown. The amphipod Ampelisca brevicornis was exposed to environmental sediments collected in different areas of the Gulf of Cádiz and subjected to several pH treatments to study the effects of CO2-induced acidification on sediment toxicity. After 10 days of exposure, the results obtained indicated that high lethal effects were associated with the lowest pH treatments, except for the Ría of Huelva sediment test. The mobility of metals from sediment to the overlying seawater was correlated to a pH decrease. The data obtained revealed that CO2-related acidification would lead to lethal effects on amphipods as well as the mobility of metals, which could increase sediment toxicity.

The Impact of Pretreatment Prostate Volume on Severe Acute Genitourinary Toxicity in Prostate Cancer Patients Treated With Intensity-Modulated Radiation Therapy

International Nuclear Information System (INIS)

Aizer, Ayal A.; Anderson, Nicole S.; Oh, Steven C.; Yu, James B.; McKeon, Anne M.; Decker, Roy H.; Peschel, Richard E.

2011-01-01

Purpose: To assess the impact of pretreatment prostate volume on the development of severe acute genitourinary toxicity in patients undergoing intensity-modulated radiation therapy (IMRT) for prostate cancer. Methods and Materials: Between 2004 and 2007, a consecutive sample of 214 patients who underwent IMRT (75.6 Gy) for prostate cancer at two referral centers was analyzed. Prostate volumes were obtained from computed tomography scans taken during treatment simulation. Genitourinary toxicity was defined using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0 guidelines. Acute toxicity was defined as any toxicity originating within 90 days of the completion of radiation therapy. Patients were characterized as having a small or large prostate depending on whether their prostate volume was less than or greater than 50 cm 3 , respectively. Genitourinary toxicity was compared in these groups using the chi-square or Fisher's exact test, as appropriate. Bivariate and multivariate logistic regression analysis was performed to further assess the impact of prostate volume on severe (Grade 3) acute genitourinary toxicity. Results: Patients with large prostates (>50 cm 3 ) had a higher rate of acute Grade 3 genitourinary toxicity (p = .02). Prostate volume was predictive of the likelihood of developing acute Grade 3 genitourinary toxicity on bivariate (p = .004) and multivariate (p = .006) logistic regression. Every 27.0 cm 3 increase in prostate volume doubled the likelihood of acute Grade 3 genitourinary toxicity. Conclusions: Patients with larger prostates are at higher risk for the development of severe acute genitourinary toxicity when treated with IMRT for prostate cancer.

A plant-wide aqueous phase chemistry module describing pH variations and ion speciation/pairing in wastewater treatment process models

DEFF Research Database (Denmark)

Flores Alsina, Xavier; Kazadi Mbamba, Christian; Solon, Kimberly

2015-01-01

at different cationic/anionic loads. In this way, the general applicability/flexibility of the proposed approach is demonstrated, by implementing the aqueous phase chemistry module in some of the most frequently used WWTP process simulation models. Finally, it is shown how traditional wastewater modelling......, but unavoidable, additional degree of complexity when representing cationic/anionic behaviour in Activated Sludge (AS)/Anaerobic Digestion (AD) systems. In this paper, a plant-wide aqueous phase chemistry module describing pH variations plus ion speciation/pairing is presented and interfaced with industry......) in order to reduce the overall stiffness of the system, thereby enhancing simulation speed. Additionally, a multi-dimensional version of the Newton-Raphson algorithm is applied to handle the existing multiple algebraic inter-dependencies. The latter is reinforced with the Simulated Annealing method...

Modulation of the epithelial Ca2+ channel ECaC by extracellular pH.

NARCIS (Netherlands)

Vennekens, R.; Prenen, J.; Hoenderop, J.G.J.; Bindels, R.J.M.; Droogmans, G.; Nilius, B.

2001-01-01

We investigated the effect of extracellular pH on whole-cell currents through the epithelial Ca2+ channel, ECaC, expressed in HEK 293 cells. Both mono- and divalent current densities were significantly smaller at pH 6.0 than at pH 7.4. At pH 8.5 they were slightly larger. Lowering extracellular pH

Dosimetric Predictors of Duodenal Toxicity After Intensity Modulated Radiation Therapy for Treatment of the Para-aortic Nodes in Gynecologic Cancer

Energy Technology Data Exchange (ETDEWEB)

Verma, Jonathan [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Sulman, Erik P.; Jhingran, Anuja [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tucker, Susan L. [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rauch, Gaiane M. [Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Eifel, Patricia J. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Klopp, Ann H., E-mail: aklopp@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-02-01

Purpose: To determine the incidence of duodenal toxicity in patients receiving intensity modulated radiation therapy (IMRT) for treatment of para-aortic nodes and to identify dosimetric parameters predictive of late duodenal toxicity. Methods and Materials: We identified 105 eligible patients with gynecologic malignancies who were treated with IMRT for gross metastatic disease in the para-aortic nodes from January 1, 2005, through December 31, 2009. Patients were treated to a nodal clinical target volume to 45 to 50.4 Gy with a boost to 60 to 66 Gy. The duodenum was contoured, and dosimetric data were exported for analysis. Duodenal toxicity was scored according to Radiation Therapy Oncology Group criteria. Univariate Cox proportional hazards analysis and recursive partitioning analysis were used to determine associations between dosimetric variables and time to toxicity and to identify the optimal threshold that separated patients according to risk of toxicity. Results: Nine of the 105 patients experienced grade 2 to grade 5 duodenal toxicity, confirmed by endoscopy in all cases. The 3-year actuarial rate of any duodenal toxicity was 11.7%. A larger volume of the duodenum receiving 55 Gy (V55) was associated with higher rates of duodenal toxicity. The 3-year actuarial rates of duodenal toxicity with V55 above and below 15 cm{sup 3} were 48.6% and 7.4%, respectively (P<.01). In Cox univariate analysis of dosimetric variables, V55 was associated with duodenal toxicity (P=.029). In recursive partitioning analysis, V55 less than 13.94% segregated all patients with duodenal toxicity. Conclusions: Dose-escalated IMRT can safely and effectively treat para-aortic nodal disease in gynecologic malignancies, provided that care is taken to limit the dose to the duodenum to reduce the risk of late duodenal toxicity. Limiting V55 to below 15 cm{sup 3} may reduce the risk of duodenal complications. In cases where the treatment cannot be delivered within these constraints

Label-Free Carbon-Dots-Based Ratiometric Fluorescence pH Nanoprobes for Intracellular pH Sensing.

Science.gov (United States)

Shangguan, Jingfang; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Xu, Fengzhou; Liu, Jinquan; Tang, Jinlu; Yang, Xue; Huang, Jin

2016-08-02

Measuring pH in living cells is of great importance for better understanding cellular functions as well as providing pivotal assistance for early diagnosis of diseases. In this work, we report the first use of a novel kind of label-free carbon dots for intracellular ratiometric fluorescence pH sensing. By simple one-pot hydrothermal treatment of citric acid and basic fuchsin, the carbon dots showing dual emission bands at 475 and 545 nm under single-wavelength excitation were synthesized. It is demonstrated that the fluorescence intensities of the as-synthesized carbon dots at the two emissions are pH-sensitive simultaneously. The intensity ratio (I475 nm/I545 nm) is linear against pH values from 5.2 to 8.8 in buffer solution, affording the capability as ratiometric probes for intracellular pH sensing. It also displays that the carbon dots show excellent reversibility and photostability in pH measurements. With this nanoprobe, quantitative fluorescence imaging using the ratio of two emissions (I475 nm/I545 nm) for the detection of intracellular pH were successfully applied in HeLa cells. In contrast to most of the reported nanomaterials-based ratiometric pH sensors which rely on the attachment of additional dyes, these carbon-dots-based ratiometric probes are low in toxicity, easy to synthesize, and free from labels.

Acute toxicity of copper oxide nanoparticles to Daphnia magna under different test conditions

DEFF Research Database (Denmark)

Thit, Amalie; Huggins, Krista; Selck, Henriette

2017-01-01

suspensions changed in a way similar to what is known for dissolved Cu: first in ISO standard test conditions (pH 7.8), second with slight acidity (pH 6.5), third in the presence of citric acid, and fourth in the presence of humic acid. For all four exposure conditions, the toxicity of Cu employed...... in the three forms followed the same sequence, i.e., CuSO4 > monodispersed 6 nm CuO ≫ poly-dispersed CuO. The toxicity of all Cu forms decreased from pH 6.5, ≫ pH 7.8, > pH 7.8 + citric acid, to ≫ pH 7.8 + humic acid. This pattern is in agreement with concentrations of Cu2+ calculated using the equilibrium...

Mechanisms of Phosphine Toxicity

Directory of Open Access Journals (Sweden)

Nisa S. Nath

2011-01-01

Full Text Available Fumigation with phosphine gas is by far the most widely used treatment for the protection of stored grain against insect pests. The development of high-level resistance in insects now threatens its continued use. As there is no suitable chemical to replace phosphine, it is essential to understand the mechanisms of phosphine toxicity to increase the effectiveness of resistance management. Because phosphine is such a simple molecule (PH3, the chemistry of phosphorus is central to its toxicity. The elements above and below phosphorus in the periodic table are nitrogen (N and arsenic (As, which also produce toxic hydrides, namely, NH3 and AsH3. The three hydrides cause related symptoms and similar changes to cellular and organismal physiology, including disruption of the sympathetic nervous system, suppressed energy metabolism and toxic changes to the redox state of the cell. We propose that these three effects are interdependent contributors to phosphine toxicity.

UV-photodegradation of desipramine: Impact of concentration, pH and temperature on formation of products including their biodegradability and toxicity

Energy Technology Data Exchange (ETDEWEB)

Khaleel, Nareman D.H.; Mahmoud, Waleed M.M. [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Scharnhorststraße 1 C13, DE 21335 Lüneburg (Germany); Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia 41522 (Egypt); Olsson, Oliver [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Scharnhorststraße 1 C13, DE 21335 Lüneburg (Germany); Kümmerer, Klaus, E-mail: klaus.kuemmerer@leuphana.de [Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, Scharnhorststraße 1 C13, DE 21335 Lüneburg (Germany)

2016-10-01

Desipramine (DMI) is a widely used tricyclic antidepressant, and it is the major metabolite of imipramine (IMI) and lofepramine (LMI); IMI and LMI are two of the most commonly used tricyclic antidepressants. If DMI enters the aquatic environment, it can be transformed by the environmental bacteria or UV radiation. Therefore, photolysis of DMI in water was performed using a simulated sunlight Xenon-lamp and a UV-lamp. Subsequently, the biodegradability of DMI and its photo-transformation products (PTPs) formed during its UV photolysis was studied. The influence of variable conditions, such as initial DMI concentration, solution pH, and temperature, on DMI UV photolysis behavior was also studied. The degree of mineralization of DMI and its PTPs was monitored. A Shimadzu HPLC-UV apparatus was used to follow the kinetic profile of DMI during UV-irradiation; after that, ion-trap and high-resolution mass spectrometry coupled with chromatography were used to monitor and identify the possible PTPs. The environmentally relevant properties and selected toxicity properties of DMI and the non-biodegradable PTPs were predicted using different QSAR models. DMI underwent UV photolysis with first-order kinetics. Quantum yields were very low. DOC values indicated that DMI formed new PTPs and was not completely mineralized. Analysis by means of high-resolution mass spectrometry revealed that the photolysis of DMI followed three main photolysis pathways: isomerization, hydroxylation, and ring opening. The photolysis rate was inversely proportional to initial DMI concentration. The pH showed a significant impact on the photolysis rate of DMI, and on the PTPs in terms of both formation kinetics and mechanisms. Although temperature was expected to increase the photolysis rate, it showed a non-significant impact in this study. Results from biodegradation tests and QSAR analysis revealed that DMI and its PTPs are not readily biodegradable and that some PTPs may be human and/or eco-toxic

Late toxicity and quality of life after definitive treatment of prostate cancer: redefining optimal rectal sparing constraints for intensity-modulated radiation therapy

International Nuclear Information System (INIS)

Chennupati, Sravana K; Pelizzari, Charles A; Kunnavakkam, Rangesh; Liauw, Stanley L

2014-01-01

The objective of this study was to assess late toxicity and quality of life (QOL) for patients receiving definitive intensity-modulated radiotherapy (IMRT) and image-guided radiation therapy (IGRT) with regard to normal tissue sparing objectives. Three hundred and seventy-two consecutive men treated with definitive IMRT for prostate adenocarcinoma. Toxicity was graded by CTC v3.0 genitourinary (GU) and gastrointestinal (GI) toxicity at each follow-up visit. Patient-reported QOL (EPIC-26) was prospectively collected for a subset of men. Dosimetric data for bladder and rectum were compared to toxicity and QOL global domain scores, specifically analyzing outcomes for men who met ideal rectal constraints (V70 <10%, V65 <20%, V40 <40%). The median age and prescription dose was 69 years and 76 Gy, respectively. Median follow-up was 47 months. At 4 years, freedom from Grade 2 (FFG2) GI toxicity was 92% and FFG2 GU toxicity was 76%. On univariate analysis, current smoking, larger bladder volume, and higher RT dose were associated with decreased FFG2 GU toxicity, while use of anticoagulation, increasing age, and not meeting ideal rectal constraints were associated with decreased FFG2 GI toxicity (all P ≤ 0.05). Bowel QOL remained stable over the 2-year follow-up period and was higher for patients who met ideal rectal constraints (P = 0.05). IMRT with IGRT is associated with low rates of severe toxicity and a high GI and GU QOL. The use of strict rectal constraints can further improve GI QOL and reduce GI toxicity

Modulating Pluronics micellar rupture with cyclodextrins and drugs: effect of pH and temperature

International Nuclear Information System (INIS)

Valero, M; Dreiss, C A

2014-01-01

Micelles of the triblock copolymer Pluronic F127 can encapsulate drugs with various chemical structures and their architecture has been studied by small-angle neutron scattering (SANS). Interaction with a derivative of β-cyclodextrin, namely, heptakis(2,6-di-O- methyl)-β-cyclodextrin (DIMEB), induces a complete break-up of the micelles, providing a mechanism for drug release. In the presence of drugs partitioned within the micelles, competitive interactions between polymer, drug and cyclodextrin lead to a modulation of the micellar rupture, depending on the nature of the drug and the exact composition of the ternary system. These interactions can be further adjusted by temperature and pH. While the most widely accepted mechanism for the interaction between Pluronics and cyclodextrins is through polypseudorotaxane (PR) formation, involving the threading of β-CD on the polymer backbone, time-resolved SANS experiments show that de-micellisation takes place in less than 100 ms, thus unambiguously ruling out an inclusion complex between the cyclodextrin and the polymer chains

Astrocyte-neuron interaction in diphenyl ditelluride toxicity directed to the cytoskeleton

International Nuclear Information System (INIS)

Heimfarth, Luana; Silva Ferreira, Fernanda da; Pierozan, Paula; Mingori, Moara Rodrigues; Moreira, José Cláudio Fonseca; Batista Teixeira da Rocha, João; Pessoa-Pureur, Regina

2017-01-01

Highlights: • Diphenyl ditelluride is toxic to the cytoskeleton of neural cells in vitro. • Hypophosphorylation disrupts cytoskeletal homeostasis and causes cell dysfunction. • Calcium signaling underlies hypophosphorylation of intermediate filaments. • Actin disorganization causes altered astrocyte morphology. • Astrocyte cytoskeleton is more susceptible than neuronal cytoskeleton. - Abstract: Diphenylditelluride (PhTe) 2 is a neurotoxin that disrupts cytoskeletal homeostasis. We are showing that different concentrations of (PhTe) 2 caused hypophosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) and altered actin organization in co-cultured astrocytes and neurons from cerebral cortex of rats. These mechanisms were mediated by N-methyl-D-aspartate (NMDA) receptors without participation of either L-type voltage-dependent calcium channels (L-VDCC) or metabotropic glutamate receptors. Upregulated Ca 2+ influx downstream of NMDA receptors activated Ca 2+ -dependent protein phosphatase 2B (PP2B) causing hypophosphorylation of astrocyte and neuron IFs. Immunocytochemistry showed that hypophosphorylated intermediate filaments (IF) failed to disrupt their organization into the cytoskeleton. However, phalloidin-actin-FITC stained cytoskeleton evidenced misregulation of actin distribution, cell spreading and increased stress fibers in astrocytes. βIII tubulin staining showed that neurite meshworks are not altered by (PhTe) 2 , suggesting greater susceptibility of astrocytes than neurons to (PheTe) 2 toxicity. These findings indicate that signals leading to IF hypophosphorylation fail to disrupt the cytoskeletal IF meshwork of interacting astrocytes and neurons in vitro however astrocyte actin network seems more susceptible. Our findings support that intracellular Ca 2+ is one of the crucial signals that modulate the action of (PhTe) 2 in co-cultured astrocytes and neurons and highlights the cytoskeleton

Investigating copper toxicity in the tropical fish cardinal tetra (Paracheirodon axelrodi) in natural Amazonian waters: Measurements, modeling, and reality

International Nuclear Information System (INIS)

Crémazy, Anne; Wood, Chris M.; Smith, D. Scott; Ferreira, Márcio S.; Johannsson, Ora E.; Giacomin, Marina; Val, Adalberto L.

2016-01-01

Highlights: • Copper toxicity to a tropical fish varied greatly in different Amazonian waters. • The biotic ligand model could not capture this variability. • Possible physiological protection was offered by natural organic matter. • Care must be used in applying BLM to fish in tropical waters. - Abstract: Copper at high concentrations is an ionoregulatory toxicant in fish and its toxicity is known to be strongly modulated by the water chemistry. The toxicity of Cu to the tropical fish cardinal tetra (Paracheirodon axelrodi) was investigated in waters from two major rivers of the Amazon watershed: the Rio Negro (filtered <0.45 μm, pH 5.6, DOC = 8.4 mg L"−"1, Na = 33 μM, Ca = 8 μM) and the Rio Solimões (filtered <0.45 μm, pH 6.7, DOC = 2.8 mg L"−"1, Na = 185 μM, Ca = 340 μM), as well as in a natural “reference water” (groundwater) which was almost DOC-free (pH 6.0, DOC = 0.34 mg L"−"1, Na = 53 μM, Ca = 5 μM). Acute 96-h mortality, Cu bioaccumulation and net flux rates of Na"+, Cl"−, K"+ and total ammonia were determined in P. axelrodi exposed in each water. Copper speciation in each water was determined by two thermodynamic models and by potentiometry, and its toxicity was predicted based on the biotic ligand model (BLM) framework. Our results indicate that high Na"+ loss is the main mode of toxic action of Cu in P. axelrodi, in accordance with general theory. Cardinal tetra showed a particularly high ability to tolerate Cu and to maintain Na"+ balance, similar to the ability of this and other endemic Rio Negro species to tolerate low pH and ion-poor conditions. Cu toxicity was lower in Rio Negro than in the other two waters tested, and the free [Cu"2"+] at the LC50, as determined by any of the three speciation methods tested, was approximately 10-fold higher. This variation could not be captured by a realistic set of BLM parameters. At least in part, this observation may be due to gill physiological alterations induced by the abundant

Investigating copper toxicity in the tropical fish cardinal tetra (Paracheirodon axelrodi) in natural Amazonian waters: Measurements, modeling, and reality

Energy Technology Data Exchange (ETDEWEB)

Crémazy, Anne, E-mail: acremazy@zoology.ubc.ca [Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4 (Canada); Wood, Chris M. [Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4 (Canada); Smith, D. Scott [Department of Chemistry and Biochemistry, Wilfrid Laurier University, Waterloo, ON N2L 3C5 (Canada); Ferreira, Márcio S. [Laboratory of Ecophysiology and Molecular Evolution, National Institute for Amazonian Research, Manaus, AM (Brazil); Johannsson, Ora E.; Giacomin, Marina [Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4 (Canada); Val, Adalberto L. [Laboratory of Ecophysiology and Molecular Evolution, National Institute for Amazonian Research, Manaus, AM (Brazil)

2016-11-15

Highlights: • Copper toxicity to a tropical fish varied greatly in different Amazonian waters. • The biotic ligand model could not capture this variability. • Possible physiological protection was offered by natural organic matter. • Care must be used in applying BLM to fish in tropical waters. - Abstract: Copper at high concentrations is an ionoregulatory toxicant in fish and its toxicity is known to be strongly modulated by the water chemistry. The toxicity of Cu to the tropical fish cardinal tetra (Paracheirodon axelrodi) was investigated in waters from two major rivers of the Amazon watershed: the Rio Negro (filtered <0.45 μm, pH 5.6, DOC = 8.4 mg L{sup −1}, Na = 33 μM, Ca = 8 μM) and the Rio Solimões (filtered <0.45 μm, pH 6.7, DOC = 2.8 mg L{sup −1}, Na = 185 μM, Ca = 340 μM), as well as in a natural “reference water” (groundwater) which was almost DOC-free (pH 6.0, DOC = 0.34 mg L{sup −1}, Na = 53 μM, Ca = 5 μM). Acute 96-h mortality, Cu bioaccumulation and net flux rates of Na{sup +}, Cl{sup −}, K{sup +} and total ammonia were determined in P. axelrodi exposed in each water. Copper speciation in each water was determined by two thermodynamic models and by potentiometry, and its toxicity was predicted based on the biotic ligand model (BLM) framework. Our results indicate that high Na{sup +} loss is the main mode of toxic action of Cu in P. axelrodi, in accordance with general theory. Cardinal tetra showed a particularly high ability to tolerate Cu and to maintain Na{sup +} balance, similar to the ability of this and other endemic Rio Negro species to tolerate low pH and ion-poor conditions. Cu toxicity was lower in Rio Negro than in the other two waters tested, and the free [Cu{sup 2+}] at the LC50, as determined by any of the three speciation methods tested, was approximately 10-fold higher. This variation could not be captured by a realistic set of BLM parameters. At least in part, this observation may be due to gill

Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes.

Science.gov (United States)

Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J; Shakespeare, Thomas P

2013-08-01

There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64 Gy (19%) or 66 Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy < 60% and V60Gy < 40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy < 35% and V65Gy < 17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy < 50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastroinestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes

International Nuclear Information System (INIS)

Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J.; Shakespeare, Thomas P.

2013-01-01

There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64Gy (19%) or 66Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy<60% and V60Gy<40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy<35% and V65Gy<17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy<50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastrointestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy.

Hypofractionated intensity-modulated arc therapy for lymph node metastasized prostate cancer: Early late toxicity and 3-year clinical outcome

International Nuclear Information System (INIS)

Fonteyne, Valérie; Lumen, Nicolaas; Ost, Piet; Van Praet, Charles; Vandecasteele, Katrien; De Gersem Ir, Werner; Villeirs, Geert; De Neve, Wilfried; Decaestecker, Karel; De Meerleer, Gert

2013-01-01

Background and purpose: For patients with N1 prostate cancer (PCa) aggressive local therapies can be advocated. We evaluated clinical outcome, gastro-intestinal (GI) and genito-urinary (GU) toxicity after intensity modulated arc radiotherapy (IMAT) + androgen deprivation (AD) for N1 PCa. Material and methods: Eighty patients with T1-4N1M0 PCa were treated with IMAT and 2–3 years of AD. A median dose of 69.3 Gy (normalized isoeffective dose at 2 Gy per fraction: 80 Gy [α/β = 3]) was prescribed in 25 fractions to the prostate. The pelvic lymph nodes received a minimal dose of 45 Gy. A simultaneous integrated boost to 72 Gy and 65 Gy was delivered to the intraprostatic lesion and/or pathologically enlarged lymph nodes, respectively. GI and GU toxicity was scored using the RTOG/RILIT and RTOG-SOMA/LENT-CTC toxicity scoring system respectively. Three-year actuarial risk of grade 2 and 3/4 GI–GU toxicity and biochemical and clinical relapse free survival (bRFS and cRFS) were calculated with Kaplan–Meier statistics. Results: Median follow-up was 36 months. Three-year actuarial risk for late grade 3 and 2 GI toxicity is 8% and 20%, respectively. Three-year actuarial risk for late grade 3–4 and 2 GU toxicity was 6% and 34%, respectively. Actuarial 3-year bRFS and cRFS was 81% and 89%, respectively. Actuarial 3-year bRFS and cRFS was, respectively 26% and 32% lower for patients with cN1 disease when compared to patients with cN0 disease. Conclusion: IMAT for N1 PCa offers good clinical outcome with moderate toxicity. Patients with cN1 disease have poorer outcome

Late toxicity after conformal and intensity-modulated radiation therapy for prostate cancer. Impact of previous surgery for benign prostatic hyperplasia

International Nuclear Information System (INIS)

Odrazka, K.; Dolezel, M.; Vanasek, J.

2010-01-01

The objective of this study was to retrospectively compare late toxicity of conventional-dose three-dimensional conformal radiation therapy (3D-CRT) and high-dose intensity-modulated radiation therapy (IMRT) for prostate cancer. A total of 340 patients with T1-3 prostate cancer were treated with 3D-CRT (n=228) and IMRT (n=112). The median follow-up time was 5.9 years and 3.0 years, respectively. The prescription dose was 70 Gy for 3D-CRT and 78 Gy for IMRT. Late gastrointestinal (GI) and genitourinary (GU) toxicities were graded according to the Fox Chase modification of the Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. There was no difference between 3D-CRT and IMRT in the incidence of GI and GU toxicity at 3 years. On multivariate analysis, transurethral resection of prostate/open transvesical prostatectomy (TURP/TVPE) for benign prostatic hyperplasia, carried out before radiotherapy, significantly increased the risk of Grade ≥2 GU toxicity (risk ratio 1.88). Among patients who experienced TURP/TVPE, the 5-year actuarial likelihood of Grade 2-3 urinary incontinence was 23%, compared with 9% for those without prostate surgery (P=0.01). Tolerance of 3D-CRT and IMRT was similar, despite the use of high radiation dose with IMRT. Previous TURP/TVPE increased the risk of GU toxicity. (author)

Intensity-modulated arc therapy with cisplatin as neo-adjuvant treatment for primary irresectable cervical cancer. Toxicity, tumour response and outcome

Energy Technology Data Exchange (ETDEWEB)

Vandecasteele, K.; Eijkeren, M. van; Meerleer, G. de [Ghent University Hospital (Belgium). Dept. of Radiotherapy; Makar, A.; Broecke, R. van den; Tummers, P. [Ghent University Hospital (Belgium). Dept. of Gynecology; Delrue, L. [Ghent University Hospital (Belgium). Dept. of Radiology; Denys, H. [Ghent University Hospital (Belgium). Dept. of Medical Oncology; Lambein, K. [Ghent University Hospital (Belgium). Dept. of Pathology; Lambert, B. [Ghent University Hospital (Belgium). Dept. of Nuclear Medicine

2012-07-15

Purpose: The goal of this work was to evaluate the feasibility and outcome of intensity-modulated arc therapy {+-} cisplatin (IMAT {+-} C) followed by hysterectomy for locally advanced cervical cancer. Patients and methods: A total of 30 patients were included in the study. The primary tumour and PET-positive lymph node(s) received a simultaneous integrated boost. Four weeks after IMAT {+-} C treatment, response was evaluated. Resection consisted of hysterectomy with or without lymphadenectomy. Tumour response, acute and late radiation toxicity, postoperative morbidity and outcome were evaluated. Results: All hysterectomy specimens were macroscopically tumour-free with negative resection margins; pathological complete response was 40%. In 2 patients, one resected lymph node was positive. There was no excess in postoperative morbidity. Apart from two grade 3 hematologic toxicities, no grade 3 or 4 acute radiation toxicity was observed. No grade 3, 1 grade 4 (4%) intestinal, and 4 grade 3 (14%) urinary late toxicities were observed. The 2-year local and regional control rates were 96% and 100%, respectively. The 2-year distant control rate was 92%. Actuarial 2-year progression free survival rate was 89%. Actuarial 1- and 2-year overall survival rates were 96% and 91%, while 3-year overall survival was 84%. Conclusion: Surgery after IMAT {+-} C is feasible with low postoperative morbidity and radiation toxicity. Local, regional, distant control and survival rates are promising. (orig.)

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

Energy Technology Data Exchange (ETDEWEB)

Poorvu, Philip D. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Sadow, Cheryl A. [Department of Radiology, Brigham and Women' s Hospital, and Harvard Medical School, Boston, Massachusetts (United States); Townamchai, Kanokpis; Damato, Antonio L. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States); Viswanathan, Akila N., E-mail: aviswanathan@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts (United States)

2013-04-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy.

Duodenal and Other Gastrointestinal Toxicity in Cervical and Endometrial Cancer Treated With Extended-Field Intensity Modulated Radiation Therapy to Paraaortic Lymph Nodes

International Nuclear Information System (INIS)

Poorvu, Philip D.; Sadow, Cheryl A.; Townamchai, Kanokpis; Damato, Antonio L.; Viswanathan, Akila N.

2013-01-01

Purpose: To characterize the rates of acute and late duodenal and other gastrointestinal (GI) toxicities among patients treated for cervical and endometrial cancers with extended-field intensity modulated radiation therapy (EF-IMRT) to the paraaortic nodes and to analyze dose-volume relationships of GI toxicities. Methods and Materials: Fifty-three patients with endometrial or cervical cancer underwent EF-IMRT to the paraaortic nodes, of whom 46 met the inclusion criteria for GI toxicity and 45 for duodenal toxicity analysis. The median prescribed dose to the paraaortic nodes was 54 Gy (range, 41.4-65 Gy). The 4 duodenal segments, whole duodenum, small bowel loops, peritoneum, and peritoneum plus retroperitoneal segments of colon were contoured retrospectively, and dosimetric analysis was performed to identify dose-volume relationships to grade ≥3 acute (<90 day) and late (≥90 day) GI toxicity. Results: Only 3/46 patients (6.5%) experienced acute grade ≥3 GI toxicity and 3/46 patients (6.5%) experienced late grade ≥3 GI toxicity. The median dose administered to these 6 patients was 50.4 Gy. One of 12 patients who received 63 to 65 Gy at the level of the renal hilum experienced grade 3 GI toxicity. Dosimetric analysis of patients with and without toxicity revealed no differences between the mean absolute or fractional volumes at any 5-Gy interval between 5 Gy and the maximum dose. None of the patients experienced duodenal toxicity. Conclusions: Treatment of paraaortic nodes with IMRT is associated with low rates of GI toxicities and no duodenal-specific toxicity, including patients treated with concurrent chemotherapy. This technique may allow sufficient dose sparing of the bowel to enable safe dose escalation to at least 65 Gy

Acute gastrointestinal and genitourinary toxicity of image-guided intensity modulated radiation therapy for prostate cancer using a daily water-filled endorectal balloon

Directory of Open Access Journals (Sweden)

Deville Curtiland

2012-05-01

Full Text Available Abstract Background Our purpose was to report acute gastrointestinal (GI and genitourinary (GU toxicity rates for prostate cancer patients undergoing image-guided intensity modulated radiation therapy (IG-IMRT with a daily endorectal water-filled balloon (ERBH2O, and assess associations with planning parameters and pretreatment clinical characteristics. Methods The first 100 patients undergoing prostate and proximal seminal vesicle IG-IMRT with indexed-lumen 100 cc ERBH2O to 79.2 Gy in 1.8 Gy fractions at our institution from 12/2008- 12/2010 were assessed. Pretreatment characteristics, organ-at-risk dose volume histograms, and maximum GU and GI toxicities (CTCAE 3.0 were evaluated. Logistic regression models evaluated univariate association between toxicities and dosimetric parameters, and uni- and multivariate association between toxicities and pretreatment characteristics. Results Mean age was 68 (range 51–88. Thirty-two, 49, and 19 patients were low, intermediate, and high-risk, respectively; 40 received concurrent androgen deprivation. No grade 3 or greater toxicities were recorded. Maximum GI toxicity was grade 0, 1, and 2 in 69%, 23%, and 8%, respectively. Infield (defined as 1 cm above/below the CTV rectal mean/median doses, D75, V30, and V40 and hemorrhoid history were associated with grade 2 GI toxicity (Ps  Conclusion Prostate IG-IMRT using a daily ERBH2O shows low rates of acute GI toxicity compared to previous reports of air-filled ERB IMRT when using stringent infield rectum constraints and comparable GU toxicities.

PhEDEx Data Service

International Nuclear Information System (INIS)

Egeland, Ricky; Wildish, Tony; Huang, Chih-Hao

2010-01-01

The PhEDEx Data Service provides access to information from the central PhEDEx database, as well as certificate-authenticated managerial operations such as requesting the transfer or deletion of data. The Data Service is integrated with the 'SiteDB' service for fine-grained access control, providing a safe and secure environment for operations. A plug-in architecture allows server-side modules to be developed rapidly and easily by anyone familiar with the schema, and can automatically return the data in a variety of formats for use by different client technologies. Using HTTP access via the Data Service instead of direct database connections makes it possible to build monitoring web-pages with complex drill-down operations, suitable for debugging or presentation from many aspects. This will form the basis of the new PhEDEx website in the near future, as well as providing access to PhEDEx information and certificate-authenticated services for other CMS dataflow and workflow management tools such as CRAB, WMCore, DBS and the dashboard. A PhEDEx command-line client tool provides one-stop access to all the functions of the PhEDEx Data Service interactively, for use in simple scripts that do not access the service directly. The client tool provides certificate-authenticated access to managerial functions, so all the functions of the PhEDEx Data Service are available to it. The tool can be expanded by plug-ins which can combine or extend the client-side manipulation of data from the Data Service, providing a powerful environment for manipulating data within PhEDEx.

Polyaluminium chloride (PAX-18) - acute toxicity and toxicity for early development stages of common carp (Cyprinus carpio)

Czech Academy of Sciences Publication Activity Database

Mácová, S.; Máchová, J.; Prokeš, Miroslav; Plhalová, L.; Široká, Z.; Dlesková, K.; Doleželová, P.; Svobodová, Z.

2009-01-01

Roč. 30, Suppl. 1 (2009), s. 192-198 ISSN 0172-780X. [Interdisciplinary Czech-Slovak Toxicological Conference /14./. Brno, 01.06.2009-03.06.2009] R&D Projects: GA MZe QH71305 Institutional research plan: CEZ:AV0Z60930519 Keywords : fish * acute toxicity test * embryo-larval toxicity test * pH Subject RIV: GL - Fishing Impact factor: 1.047, year: 2009 http://node.nel.edu/?node_id=9497

Interactive effects of pH and metals on mitochondrial functions of intertidal bivalves Crassostrea virginica and Mercenaria mercenaria

International Nuclear Information System (INIS)

Ivanina, Anna V.; Sokolova, Inna M.

2013-01-01

Highlights: •Interactive effects of trace metals Cd and Cu and pH were studied in mitochondria of clams and oysters. •Mitochondrial respiration and membrane potential of bivalves were robust to pH variation (6.6–7.8). •Elevated levels of Cd and Cu inhibited mitochondrial respiration in the pH-dependent manner but did not affect the membrane potential. •Negative effects of Cd and Cd on mitochondrial respiration were alleviated at low pH (7.0 and below). •Moderate acidosis may protect molluscan mitochondria from metal toxicity. -- Abstract: Intertidal bivalves experience broad fluctuations of environmental temperature, pH and oxygen content which could change their intracellular pH. They are also exposed to trace metals such as cadmium (Cd) and copper (Cu) that accumulate in their tissues and may negatively affect mitochondrial functions and bioenergetics. We determined the interactive effects of pH and trace metals (25 μM Cd or Cu) on mitochondrial functions (including respiration and membrane potentials in both ADP-stimulated (state 3) and resting (state 4) states) of two common marine bivalves, the hard clams (Mercenaria mercenaria) and eastern oysters (Crassostrea virginica). In the absence of the trace metals, mitochondrial functions of C. virginica and M. mercenaria were insensitive to pH in a broad physiologically relevant range (6.6–7.8). Mitochondrial respiration was generally suppressed by 25 μM Cd or Cu (with the stronger effects observed for ADP-stimulated compared to the resting respiration) while the mitochondrial membrane potential was unaffected. pH modulated the effects of Cu and Cd on mitochondrial respiration of the bivalves. In oysters, Cu suppressed ADP-stimulated mitochondrial respiration at high and low pH values (6.6 and 7.8, respectively), but had no effect in the intermediate pH range (7.0–7.4). In clams, the negative effect of Cu on ADP-stimulated respiration was only observed at extremely high pH (7.8). A decrease in pH

Interactive effects of pH and metals on mitochondrial functions of intertidal bivalves Crassostrea virginica and Mercenaria mercenaria

Energy Technology Data Exchange (ETDEWEB)

Ivanina, Anna V.; Sokolova, Inna M., E-mail: isokolov@uncc.edu

2013-11-15

Highlights: •Interactive effects of trace metals Cd and Cu and pH were studied in mitochondria of clams and oysters. •Mitochondrial respiration and membrane potential of bivalves were robust to pH variation (6.6–7.8). •Elevated levels of Cd and Cu inhibited mitochondrial respiration in the pH-dependent manner but did not affect the membrane potential. •Negative effects of Cd and Cd on mitochondrial respiration were alleviated at low pH (7.0 and below). •Moderate acidosis may protect molluscan mitochondria from metal toxicity. -- Abstract: Intertidal bivalves experience broad fluctuations of environmental temperature, pH and oxygen content which could change their intracellular pH. They are also exposed to trace metals such as cadmium (Cd) and copper (Cu) that accumulate in their tissues and may negatively affect mitochondrial functions and bioenergetics. We determined the interactive effects of pH and trace metals (25 μM Cd or Cu) on mitochondrial functions (including respiration and membrane potentials in both ADP-stimulated (state 3) and resting (state 4) states) of two common marine bivalves, the hard clams (Mercenaria mercenaria) and eastern oysters (Crassostrea virginica). In the absence of the trace metals, mitochondrial functions of C. virginica and M. mercenaria were insensitive to pH in a broad physiologically relevant range (6.6–7.8). Mitochondrial respiration was generally suppressed by 25 μM Cd or Cu (with the stronger effects observed for ADP-stimulated compared to the resting respiration) while the mitochondrial membrane potential was unaffected. pH modulated the effects of Cu and Cd on mitochondrial respiration of the bivalves. In oysters, Cu suppressed ADP-stimulated mitochondrial respiration at high and low pH values (6.6 and 7.8, respectively), but had no effect in the intermediate pH range (7.0–7.4). In clams, the negative effect of Cu on ADP-stimulated respiration was only observed at extremely high pH (7.8). A decrease in pH

Comparison of conformal and intensity modulated radiation therapy techniques for treatment of pelvic tumors. Analysis of acute toxicity

International Nuclear Information System (INIS)

Ferrigno, Robson; Santos, Adriana; Martins, Lidiane C; Weltman, Eduardo; Chen, Michael J; Sakuraba, Roberto; Lopes, Cleverson P; Cruz, José C

2010-01-01

This retrospective analysis reports on the comparative outcome of acute gastrointestinal (GI) and genitourinary (GU) toxicities between conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) techniques in the treatment of patients with pelvic tumors. From January 2002 to December 2008, 69 patients with pelvic tumors underwent whole pelvic CRT and 65 underwent whole pelvic IMRT to treat pelvic lymph nodes and primary tumor regions. Total dose to the whole pelvis ranged from 50 to 50.4 Gy in 25 to 28 daily fractions. Chemotherapy (CT) regimen, when employed, was based upon primary tumor. Acute GI and GU toxicities were graded by RTOG/EORTC acute radiation morbidity criteria. Absence of GI symptoms during radiotherapy (grade 0) was more frequently observed in the IMRT group (43.1% versus 8.7; p < 0.001) and medication for diarrhea (Grade 2) was more frequently used in the CRT group (65.2% versus 38.5%; p = 0.002). Acute GI grade 1 and 3 side effects incidence was similar in both groups (18.5% versus 18.8%; p = 0.95 and 0% versus 7.2%; p = 0.058, respectively). Incidence of GU toxicity was similar in both groups (grade 0: 61.5% versus 66.6%, p = 0.54; grade 1: 20% versus 8.7%, p = 0.06; grade 2: 18.5% versus 23.5%, p = 0.50 and grade 3: 0% versus 1.5%, p > 0.99). This comparative case series shows less grade 2 acute GI toxicity in patients treated with whole pelvic IMRT in comparison with those treated with CRT. Incidence of acute GU toxicity was similar in both groups

Acute gastrointestinal and genitourinary toxicity of image-guided intensity modulated radiation therapy for prostate cancer using a daily water-filled endorectal balloon

International Nuclear Information System (INIS)

Deville, Curtiland; Both, Stefan; Bui, Viet; Hwang, Wei-Ting; Tan, Kay-See; Schaer, Mattia; Tochner, Zelig; Vapiwala, Neha

2012-01-01

Our purpose was to report acute gastrointestinal (GI) and genitourinary (GU) toxicity rates for prostate cancer patients undergoing image-guided intensity modulated radiation therapy (IG-IMRT) with a daily endorectal water-filled balloon (ERB H2O ), and assess associations with planning parameters and pretreatment clinical characteristics. The first 100 patients undergoing prostate and proximal seminal vesicle IG-IMRT with indexed-lumen 100 cc ERB H2O to 79.2 Gy in 1.8 Gy fractions at our institution from 12/2008- 12/2010 were assessed. Pretreatment characteristics, organ-at-risk dose volume histograms, and maximum GU and GI toxicities (CTCAE 3.0) were evaluated. Logistic regression models evaluated univariate association between toxicities and dosimetric parameters, and uni- and multivariate association between toxicities and pretreatment characteristics. Mean age was 68 (range 51–88). Thirty-two, 49, and 19 patients were low, intermediate, and high-risk, respectively; 40 received concurrent androgen deprivation. No grade 3 or greater toxicities were recorded. Maximum GI toxicity was grade 0, 1, and 2 in 69%, 23%, and 8%, respectively. Infield (defined as 1 cm above/below the CTV) rectal mean/median doses, D75, V30, and V40 and hemorrhoid history were associated with grade 2 GI toxicity (Ps < 0.05). Maximum acute GU toxicity was grade 0, 1, and 2 for 17%, 41%, and 42% of patients, respectively. Infield bladder V20 (P = 0.03) and pretreatment International Prostate Symptom Scale (IPSS) (P = 0.003) were associated with grade 2 GU toxicity. Prostate IG-IMRT using a daily ERB H2O shows low rates of acute GI toxicity compared to previous reports of air-filled ERB IMRT when using stringent infield rectum constraints and comparable GU toxicities

Influence of pH, light cycle, and temperature on ecotoxicity of four sulfonylurea herbicides towards Lemna gibba

DEFF Research Database (Denmark)

Rosenkrantz, Rikke Tjørnhøj; Cedergreen, Nina; Baun, Anders

2013-01-01

test conditions on the toxicity of four sulfonylurea herbicides (SUs). The toxicity of the four SUs towards Lemna gibba was investigated at three pH levels (6, 7.5 and 9), at two temperatures (15 and 24 °C) and two light regimes (continuous and 12:12 h light:dark cycle) The EC50 increased twofold...... conditions e.g. specific temperature, pH, light intensity etc. However, environmental conditions under which the organisms live are rarely identical to the standard conditions. Thus, the ecotoxicity of compounds found in standard test is not only a function of the compounds inherent physico...... to tenfold for the four SUs when pH was increased from 6 to 9. Decreasing the temperature from 24 to 15 °C or introducing a dark:light cycle did not cause any trends in changes in toxicity. The results show that test conditions can have an effect on the toxicity and this should be considered when...

Nickel toxicity to cardinal tetra (Paracheirodon axelrodi) differs seasonally and among the black, white and clear river waters of the Amazon basin.

Science.gov (United States)

Holland, Aleicia; Wood, Chris M; Smith, D Scott; Correia, Tiago Gabriel; Val, Adalberto L

2017-10-15

This study investigated the acute toxicity of nickel (Ni) to cardinal tetra (Paracheirodon axelrodi), within the three main water types of the Amazon basin: black (Rio Negro), white (Rio Solimões) and clear (Rio Tapajós) during the wet and dry season at pH 7 (representative of white and clear rivers) and pH 4 (representative of black waters). The influence of dissolved organic carbon (DOC) quality on Ni toxicity within the three waters was also explored via the use of DOC isolates. Differences in water chemistry, DOC quality and ion concentrations were shown between waters and between seasons. Toxicity of Ni was shown to vary between river waters, seasons, and pHs. Ni was significantly less toxic during the dry season at pH 4 in all three river waters; for example, black water during the wet season had an LC 50 of 9.72 mg Ni/L compared to 41.5 mg Ni/L during the dry season. At pH 7, contrasting effects in toxicity between seasons were shown between black and clear waters (black: wet = 28.9 mg/L, dry = 17.3 mg/L; clear: wet = 13.8 mg/L, dry = 24.1 mg/L). There were no significant differences in Ni toxicity for white waters at pH 7 (white: wet = 22.2 mg/L, dry = 21.8). Overall, Ni was shown to be more toxic at pH 7 than at pH 4 except in black water during the wet season. Toxicity of Ni at pH 4 was positively related to DOC concentration and amount of humic-like and fulvic-like DOC and negatively related to fluorescence index. Therefore, at pH 4, Ni is more toxic in waters containing more allochthonous DOC, consisting of higher amounts of humic-like and fulvic-like components. LC 50 values for the different DOC concentrates at the same DOC concentration of 4.5 mg/L (black: 26.8 mg/L; white: 73.3 mg/L; clear: 49.2) support the river water findings at pH 4 (Ni more toxic in presence of black DOC) indicating that DOC quality alone can influence Ni toxicity at this pH. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancement of Radiotherapeutic Efficacy by Paclitaxel-Loaded ph-Sensitive Block Copolymer Micelles

International Nuclear Information System (INIS)

Jinhyang, C.; Jaesook, P.; Dong-Hoon, J.

2012-01-01

Radiotherapy (RT) is a major modality for cancer treatment, but its efficacy is often compromised by the resistance caused by tumor-specific microenvironment including acidosis and hypoxia. For an effective RT, concurrent administration of radiosensitizer with RT has been emphasized. However, most anticancer agents enhancing radiotherapeutic efficacy have obstacles such as poor solubility and severe toxicity. Paclitaxel (PTX), a well-known radiosensitizer, is insoluble in water and needs toxic solvent like Cremophor EL. Nano materials in drug delivery systems have been utilized for improving the drawbacks of anti-cancer drugs. Solubilization, tumor accumulation, and toxicity attenuation of drug by nano materials are suitable for enhancement of radiotherapeutic efficacy. In this study, PTX was incorporated into ph-sensitive block copolymer micelle (psm-PTX), polyethylene glycol-graft-poly(β-amino ester), and pre clinically evaluated for its effect on RT. The size of psm-PTX was 125. 4.4±nm at ph 7.4. psm-PTX released PTX rapidly in the acidic condition (ph 6.5), while it was reasonably stable in the physiologic condition (ph 7.4). The clonogenic assay showed that psm-PTX greatly sensitized human non-small-cell lung cancer A549 cells to radiation. In the xenograft tumor model, the combination of psm-PTX and radiation significantly delayed the tumor growth. These results demonstrated the feasibility of psm-PTX to enhance the chemo radiotherapeutic efficacy.

Relationships between soil properties and toxicity of copper and nickel to bok choy and tomato in Chinese soils.

Science.gov (United States)

Li, Bo; Zhang, Hongtao; Ma, Yibing; McLaughlin, Mike J

2013-10-01

The toxicity of copper (Cu) and nickel (Ni) to bok choy and tomato shoot growth was investigated in a wide range of Chinese soils with and without leaching with artificial rainwater. The results showed that the variations of Ni toxicity induced by soil properties were wider than those of Cu toxicity to both tomato and bok choy plant growth. Leaching generally decreased the toxicity of Cu and Ni added to soils, which also depended on soils, metals, and test plant species. Soil factors controlling metal phytotoxicity were found to be soil pH and soil organic carbon content for Cu, and soil pH for Ni. It was also found that soil pH had stronger effects on Ni toxicity than on Cu toxicity. Predictive toxicity models based on these soil factors were developed. These toxicity models for Cu and Ni toxicity to tomato plant growth were validated using an independent data set for European soils. These models could be applied to predict the Cu and Ni phytotoxicity in not only Chinese soils but also European soils. © 2013 SETAC.

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

Energy Technology Data Exchange (ETDEWEB)

Hoffman, Karen E., E-mail: khoffman1@mdanderson.org; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

2014-04-01

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

Risk of Late Toxicity in Men Receiving Dose-Escalated Hypofractionated Intensity Modulated Prostate Radiation Therapy: Results From a Randomized Trial

International Nuclear Information System (INIS)

Hoffman, Karen E.; Voong, K. Ranh; Pugh, Thomas J.; Skinner, Heath; Levy, Lawrence B.; Takiar, Vinita; Choi, Seungtaek; Du, Weiliang; Frank, Steven J.; Johnson, Jennifer; Kanke, James; Kudchadker, Rajat J.; Lee, Andrew K.; Mahmood, Usama; McGuire, Sean E.; Kuban, Deborah A.

2014-01-01

Objective: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. Methods and Materials: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. Results: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). Conclusions: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this

Bovine colostrum modulates myeloablative chemotherapy-induced gut toxicity in piglets

DEFF Research Database (Denmark)

Pontoppidan, Peter Erik Lotko; Shen, René Liang; Cilieborg, Malene Skovsted

2015-01-01

BACKGROUND: Intensive chemotherapy frequently results in gut toxicity, indicated by oral and intestinal mucositis, resulting in poor treatment outcomes and increased mortality. There are no effective preventive strategies against gut toxicity and the role of diet is unknown. OBJECTIVE: We...

Abrin toxicity and bioavailability after temperature and pH treatment

Science.gov (United States)

Abrin, one of most potent toxins known to man, is derived from the rosary pea (jequirity pea), Abrus precatorius. Due to its potential use as a bioterror weapon, the efficacy of standard food processing methods must be evaluated for its effectiveness against abrin. The temperature and pH stability o...

Development of Low-Toxicity Wastewater Stabilization for Spacecraft Water Recovery Systems

Science.gov (United States)

Adam, Niklas; Mitchell, Julie; Pickering, Karen; Carrier, Chris; Vega, Letty; Muirhead, Dean

2014-01-01

Wastewater stabilization was an essential component of the spacecraft water cycle. The purpose of stabilizing wastewater was two-fold. First, stabilization prevents the breakdown of urea into ammonia, a toxic gas at high concentrations. Second, it prevents the growth of microorganisms, thereby mitigating hardware and water quality issues due to due biofilm and planktonic growth. Current stabilization techniques involve oxidizers and strong acids (pH=2) such as chromic and sulfuric acid, which are highly toxic and pose a risk to crew health. The purpose of this effort was to explore less toxic stabilization techniques, such as food-grade and commercial care preservatives. Additionally, certain preservatives were tested in the presence of a low-toxicity organic acid. Triplicate 300-mL volumes of urine were dosed with a predetermined quantity of stabilizer and stored for two weeks. During that time, pH, total organic carbon (TOC), ammonia, and turbidity were monitored. Those preservatives that showed the lowest visible microbial growth and stable pH were further tested in a six-month stability study. The results of the six-month study are also included in this paper.

The concept of bio-corona in modulating the toxicity of engineered nanomaterials (ENM)

International Nuclear Information System (INIS)

Westmeier, Dana; Stauber, Roland H.; Docter, Dominic

2016-01-01

Besides the wide use of engineered nanomaterials (ENM) in technical products, their application spectrum in biotechnology and biomedicine is steadily increasing. In complex physiological environments the physico-chemical properties and the behavior of nanoparticles (NPs) are challenging to characterize. Biomolecules rapidly adsorb to the nanomaterial, leading to the formation of the protein/biomolecule corona, which critically affects the nanomaterials' (patho)biological and technical identities. This formation can trigger an immune response and affect nanoparticles' toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the (protein)corona-nanoparticle interaction and discuss how the corona modulates both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers. - Highlights: • “Nanotoxicology” has emerged an autonomous field with an explosive growth. • Nanomaterials adsorb (bio)molecules forming the so-called (bio)molecule corona. • (Fine-)tune of the corona composition could enable new possibilities in nanomedicine.

The concept of bio-corona in modulating the toxicity of engineered nanomaterials (ENM)

Energy Technology Data Exchange (ETDEWEB)

Westmeier, Dana; Stauber, Roland H.; Docter, Dominic, E-mail: docter@uni-mainz.de

2016-05-15

Besides the wide use of engineered nanomaterials (ENM) in technical products, their application spectrum in biotechnology and biomedicine is steadily increasing. In complex physiological environments the physico-chemical properties and the behavior of nanoparticles (NPs) are challenging to characterize. Biomolecules rapidly adsorb to the nanomaterial, leading to the formation of the protein/biomolecule corona, which critically affects the nanomaterials' (patho)biological and technical identities. This formation can trigger an immune response and affect nanoparticles' toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the (protein)corona-nanoparticle interaction and discuss how the corona modulates both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers. - Highlights: • “Nanotoxicology” has emerged an autonomous field with an explosive growth. • Nanomaterials adsorb (bio)molecules forming the so-called (bio)molecule corona. • (Fine-)tune of the corona composition could enable new possibilities in nanomedicine.

Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial

Energy Technology Data Exchange (ETDEWEB)

Michalski, Jeff M., E-mail: jmichalski@radonc.wustl.edu [Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri (United States); Yan, Yan [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Watkins-Bruner, Deborah [Emory University School of Nursing, Atlanta, Georgia (United States); Bosch, Walter R. [Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri (United States); Winter, Kathryn [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Galvin, James M. [Department of Radiation Oncology Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Department of Radiation Oncology Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, QC (Canada); Morton, Gerard C. [Department of Radiation Oncology Toronto-Sunnybrook Regional Cancer Centre, Toronto, ON (Canada); Parliament, Matthew B. [Department of Oncology Cross Cancer Institute, Edmonton, AB (Canada); Sandler, Howard M. [Department of Radiation Oncology Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California (United States)

2013-12-01

Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a

Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

International Nuclear Information System (INIS)

Simpson, Daniel R.; Song, William Y.; Moiseenko, Vitali; Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

2012-01-01

Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I–III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade ≥2 GI toxicity and the volume of bowel receiving ≥45 Gy (V 45 ) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V 45 was 143 mL (99). The mean V 45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V 45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V 45 >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and γ were 161 mL (95% confidence interval [CI] 60–399) and 0.31 (95% CI 0.04–0.63), respectively. On multivariable logistic regression, increased V 45 was associated with an increased odds of Grade ≥2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04–4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V 45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V 45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared.

Remote loading of doxorubicin into liposomes by transmembrane pH gradient to reduce toxicity toward H9c2 cells

Directory of Open Access Journals (Sweden)

Mohamed Alyane

2016-03-01

Full Text Available The use of doxorubicin (DOX is limited by its dose-dependent cardiotoxicity. Entrapped DOX in liposome has been shown to reduce cardiotoxicity. Results showed that about 92% of the total drug was encapsulated in liposome. The release experiments showed a weak DOX leakage in both culture medium and in PBS, more than 98% and 90% of the encapsulated DOX respectively was still retained in liposomes after 24 h of incubation. When the release experiments were carried out in phosphate buffer pH5.3, the leakage of DOX from liposomes reached 37% after 24 h of incubation. Evaluation of cellular uptake of the liposomal DOX indicated the possible endocytosis of liposomes because the majority of visible fluorescence of DOX was mainly in the cytoplasm, whereas the nuclear compartment showed a weak intensity. When using unloaded fluorescent-liposomes, the fluorescence was absent in nuclei suggests that liposomes cannot cross the nuclear membrane. MTT assay and measurement of LDH release suggest that necrosis is the form of cellular death predominates in H9c2 cells exposed to high doses of DOX, while for weak doses apoptosis could be the predominate form. Entrapped DOX reduced significantly DOX toxicity after 3 and 6 h of incubation, but after 20 h entrapped DOX is more toxic than free one.

Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual 3.2

Science.gov (United States)

The Web-ICE Endangered Species module simultaneously estimates toxicity to taxa representing threatened or endangered species using up to 25 surrogates. This module batch processes toxicity values for endangered species from all species, genus, and family level models available f...

Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

Directory of Open Access Journals (Sweden)

Richard Sauerheber

2013-01-01

Full Text Available The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

Physiologic conditions affect toxicity of ingested industrial fluoride.

Science.gov (United States)

Sauerheber, Richard

2013-01-01

The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

Regulation of pH During Amelogenesis.

Science.gov (United States)

Lacruz, Rodrigo S; Nanci, Antonio; Kurtz, Ira; Wright, J Timothy; Paine, Michael L

2010-02-01

During amelogenesis, extracellular matrix proteins interact with growing hydroxyapatite crystals to create one of the most architecturally complex biological tissues. The process of enamel formation is a unique biomineralizing system characterized first by an increase in crystallite length during the secretory phase of amelogenesis, followed by a vast increase in crystallite width and thickness in the later maturation phase when organic complexes are enzymatically removed. Crystal growth is modulated by changes in the pH of the enamel microenvironment that is critical for proper enamel biomineralization. Whereas the genetic bases for most abnormal enamel phenotypes (amelogenesis imperfecta) are generally associated with mutations to enamel matrix specific genes, mutations to genes involved in pH regulation may result in severely affected enamel structure, highlighting the importance of pH regulation for normal enamel development. This review summarizes the intra- and extracellular mechanisms employed by the enamel-forming cells, ameloblasts, to maintain pH homeostasis and, also, discusses the enamel phenotypes associated with disruptions to genes involved in pH regulation.

Comparison of mucous and cutaneous toxicity of IMRT and of conventional radiotherapy associated with cetuximab

International Nuclear Information System (INIS)

Kreps, S.; Tamby, E.; Dessard Diana, B.; Berges, O.; Botti, M.; Deberne, M.; Henni, M.; Durdux, C.; Housset, M.; Giraud, P.

2011-01-01

The authors report a retrospective assessment of acute, cutaneous and mucous toxicity resulting from an association of cetuximab and conventional conformational radiotherapy, and from an intensity-modulated conformational radiotherapy (IMRT). Seven patients presenting nasopharyngeal, oropharyngeal or hypopharyngeal tumours have been irradiated with intensity modulation, and seven without. It appears that the association of cetuximab and radiotherapy is not well tolerated and requires a close monitoring. Intensity-modulated radiotherapy allows a significant reduction of dose and of toxicity. However, mucous toxicity remains significant. Short communication

The neutral species of the weak base trimethoprim is more toxic to willow trees (Salix viminalis) than the cation

DEFF Research Database (Denmark)

Mikes, O.; Trapp, Stefan

2011-01-01

The acute toxicity of the veterinary antibiotic trimethoprim (TMP) to willow trees was tested at three different pH levels in hydroponic solutions with TMP concentrations of 1, 10, 100 or 1000 mg/L. The pH variation was achieved by using ammonium (pH 4.3, low) or nitrate (pH 6.4, medium) as nitro......The acute toxicity of the veterinary antibiotic trimethoprim (TMP) to willow trees was tested at three different pH levels in hydroponic solutions with TMP concentrations of 1, 10, 100 or 1000 mg/L. The pH variation was achieved by using ammonium (pH 4.3, low) or nitrate (pH 6.4, medium...

Long-term toxicity assessment of soils in a recovered area affected by a mining spill

International Nuclear Information System (INIS)

Romero-Freire, A.; García Fernández, I.; Simón Torres, M.; Martínez Garzón, F.J.; Martín Peinado, F.J.

2016-01-01

Residual pollution in the Guadiamar Green Corridor still remains after Aználcollar mine spill in 1998. The polluted areas are identified by the absence of vegetation, soil acidic pH and high concentrations of As, Pb, Zn and Cu. Soil toxicity was assessed by lettuce root elongation and induced soil respiration bioassays. In bare soils, total As and Pb concentrations and water-extractable levels for As, Zn and Cu exceeded the toxicity guidelines. Pollutants responsible for toxicity were different depending on the tested organism, with arsenic being most toxic for lettuce and the metal mixture to soil respiration. Soil properties, such as pH or organic carbon content, are key factors to control metal availability and toxicity in the area. According to our results, there is a risk of pollution to living organisms and the soil quality criteria established in the area should be revised to reduce the risk of toxicity. - Highlights: • 15 years after the Aznalcóllar mine spill residual pollution remains in some areas. • Toxic levels were exceeded for total As and Pb and for soluble As, Zn and Cu. • Metals responsible for soil toxicity are different depending on the tested organism. • pH and organic carbon content reduce metal availability and therefore soil toxicity. • Regulatory guidelines in the area should be revised to reduce the risk of toxicity. - Residual pollution in the Guadiamar Green Corridor remains in some areas after long-term stabilization, with some risk of pollution according to toxicity bioassays.

Ph3CCOOSnPh3.Ph3PO AND Ph3CCOOSnPh3.Ph3AsO: SYNTHESIS AND INFRARED STUDY

Directory of Open Access Journals (Sweden)

ABDOU MBAYE

2014-08-01

Full Text Available The mixture of ethanolic solutions of Ph3CCOOSnPh3 and Ph3PO or Ph3AsO gives Ph3CCOOSnPh3.Ph3PO and Ph3CCOOSnPh3.Ph3AsO adducts which have been characterized by infrared spectroscopy. A discrete structure is suggested for both, the environment around the tin centre being trigonal bipyramidal, the triphenylacetate anion behaving as a mondentate ligand.

Economical wireless optical ratiometric pH sensor

International Nuclear Information System (INIS)

Vuppu, Sandeep; Kostov, Yordan; Rao, Govind

2009-01-01

The development and application of a portable, wireless fluorescence-based optical pH sensor is presented. The design incorporates the MSP430 microcontroller as the control unit, an RF transceiver for wireless communication, digital filters and amplifiers and a USB-based communication module for data transmission. The pH sensor is based on ratiometric fluorescence detection from pH sensitive dye incorporated in a peel-and-stick patch. The ability of the instrument to detect the pH of the solution with contact only between the sensor patch and the solution makes it partially non-invasive. The instrument also has the ability to transmit data wirelessly, enabling its use in processes that entail stringent temperature control and sterility. The use of the microcontroller makes it a reliable, low-cost and low-power device. The luminous intensity of the light source can be digitally controlled to maximize the sensitivity of the instrument. It has a resolution of 0.05 pH. The sensor is accurate and reversible over the pH range of 6.5–9

Biosorption and toxicity responses to arsenite (As[III]) in Scenedesmus quadricauda.

Science.gov (United States)

Zhang, Jianying; Ding, Tengda; Zhang, Chunlong

2013-08-01

Toxicity and biosorption responses to arsenite (As[III]) were examined in a 96-h exposure study using Scenedesmus quadricauda, one of the most popular green algae distributed in freshwaters in China. Results indicated that the pH-dependent distribution of two arsenite species (H2AsO3(-) and H3AsO3) played an important role in biosorption and toxicity. The undissociated H3AsO3 was more toxic than its monoanionic H2AsO3(-) through comparison of algal cell numbers, chlorophyll-a contents, and algal ultrastructural changes observed with transmission electron microscopy. An effective biosorption of 89.0mgg(-1) at 100mgL(-1) As[III] was found in the treatments with an initial pH of 9.3 and 25.2μgg(-1) at 0.03mgL(-1) As[III] at an initial pH of 8.2 as a result of the predominant species of H2AsO3(-) under the ambient pH and Eh conditions. Our results imply that S. quadricauda may provide a new means for the removal of toxic arsenite species present in contaminated surface water. Copyright © 2013 Elsevier Ltd. All rights reserved.

Equilibrium leaching of toxic elements from cement stabilized soil.

Science.gov (United States)

Voglar, Grega E; Leštan, Domen

2013-02-15

The toxicity characteristics leaching procedure (TCLP) is commonly used to assess the efficiency of solidification/stabilization (S/S) of pollutants in wastes, despite recent objections to this method. In this study, formulations of 7, 10, 15 and 20% (w/w) of calcium aluminate cement (CAC) and sulfate resistant Portland cement (SRC) were used for S/S of soil from brownfield contaminated with 43,149, 10,115, 7631, 6130, 90, 82 mg kg(-1) of Zn, Pb, Cu, As, Cd and Ni, respectively. CAC produced S/S soil monoliths of higher mechanical strength (up to 7.65 N mm(-2)). Mass-transfer analysis indicated surface wash-off as a mechanism of toxic elements release, and equilibrium leaching as a crucial parameter of S/S efficiency assessment. In the expected range of field soil pH after S/S (pH 7-9), the TCLP gave markedly different results than the multi-point pH equilibrium leaching method (using nine targeted pH values): up to 2953-, 94-, 483-, 1.3-, 27- and 1.5-times more Zn, Pb, Cu, As, Cd and Ni, respectively, was determined in the TCLP leachate. S/S with CAC reduced leachability of toxic elements more effectively than SRC. Our results indicate that, under given field conditions, the TCLP significantly underrates the efficiency of S/S of contaminated soil with cementitious binders. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of water quality parameters on boron toxicity to Ceriodaphnia dubia.

Science.gov (United States)

Dethloff, Gail M; Stubblefield, William A; Schlekat, Christian E

2009-07-01

The potential modifying effects of certain water quality parameters (e.g., hardness, alkalinity, pH) on the acute toxicity of boron were tested using a freshwater cladoceran, Ceriodaphnia dubia. By comparison, boron acute toxicity was less affected by water quality characteristics than some metals (e.g., copper and silver). Increases in alkalinity over the range tested did not alter toxicity. Increases in water hardness appeared to have an effect with very hard waters (>500 mg/L as CaCO(3)). Decreased pH had a limited influence on boron acute toxicity in laboratory waters. Increasing chloride concentration did not provide a protective effect. Boron acute toxicity was unaffected by sodium concentrations. Median acute lethal concentrations (LC(50)) in natural water samples collected from three field sites were all greater than in reconstituted laboratory waters that matched natural waters in all respects except for dissolved organic carbon. Water effect ratios in these waters ranged from 1.4 to 1.8. In subsequent studies using a commercially available source of natural organic matter, acute toxicity decreased with increased dissolved organic carbon, suggesting, along with the natural water studies, that dissolved organic carbon should be considered further as a modifier of boron toxicity in natural waters where it exceeds 2 mg/L.

Plumbagin Nanoparticles Induce Dose and pH Dependent Toxicity on Prostate Cancer Cells.

Science.gov (United States)

Nair, Harikrishnan A; Snima, K S; Kamath, Ravindranath C; Nair, Shantikumar V; Lakshmanan, Vinoth-Kumar

2015-01-01

Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer. Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer.

pH-dependent toxicity of sulphur mustard in vitro

International Nuclear Information System (INIS)

Sawyer, Thomas W.; Vair, Cory; Nelson, Peggy; Shei Yimin; Bjarnason, Stephen; Tenn, Catherine; McWilliams, Michael; Villanueva, Mercy; Burczyk, Andrew

2007-01-01

The dependence of sulphur mustard (HD) toxicity on intracellular (pH i ) and extracellular pH was examined in CHO-K1 cells. HD produced an immediate and significant concentration-dependent decline in cytosolic pH, and also inhibited the mechanisms responsible for restoring pH i to physiological values. The concentration-response of HD-induced cytosolic acidification, closely paralleled the acidification of the extracellular buffer through HD hydrolysis. A viability study was carried out in order to assess the importance of HD-induced cytosolic acidification. Cultures were exposed to HD for 1 h in media that were adjusted through a pH range (pH 5.0-10), and the 24 h LC 50 values were assessed using the viability indicator dye alamarBlue TM . The toxicity of HD was found to be dependent on extracellular pH, with a greater than eight-fold increase in LD 50 obtained in cultures treated with HD at pH 9.5, compared to those treated at pH 5.0. Assays of apoptotic cell death, including morphology, soluble DNA, caspase-3 activity and TUNEL also showed that as pH was increased, much greater HD concentrations were required to cause cell death. The modest decline in HD half-life measured in buffers of increasing pH, did not account for the protective effects of basic pH. The early event(s) that HD initiates to eventually culminate in cell death are not known. However, based on the data obtained in this study, we propose that HD causes an extracellular acidification through chemical hydrolysis and that this, in both a concentration and temporally related fashion, results in cytosolic acidification. Furthermore, HD also acts to poison the antiporter systems responsible for maintaining physiological pH i , so that the cells are unable to recover from this insult. It is this irreversible decline in pH i that initiates the cascade of events that results in HD-induced cell death

Human vaginal pH and microbiota: an update.

Science.gov (United States)

Godha, Keshav; Tucker, Kelly M; Biehl, Colton; Archer, David F; Mirkin, Sebastian

2018-06-01

A woman's vaginal pH has many implications on her health and it can be a useful tool in disease diagnosis and prevention. For that reason, the further examination of the relationship between the human vaginal pH and microbiota is imperative. In the past several decades, much has been learned about the physiological mechanisms modulating the vaginal pH, and exogenous/genetic factors that may influence it. A unified, coherent understanding of these concepts is presented to comprehend their interrelationships and their cumulative effect on a woman's health. In this review, we explore research on vaginal pH and microbiota throughout a woman's life, vaginal intermediate cell anaerobic metabolism and net proton secretion by the vaginal epithelial, and the way these factors interact to acidify the vaginal pH. This review provides foundational information about what a microbiota is and its relationship with human physiology and vaginal pH. We then evaluate the influence of physiological mechanisms, demographic factors, and propose ideas for the mechanisms behind their action on the vaginal pH.

Lysosomal Re-acidification Prevents Lysosphingolipid-Induced Lysosomal Impairment and Cellular Toxicity.

Directory of Open Access Journals (Sweden)

Christopher J Folts

2016-12-01

Full Text Available Neurodegenerative lysosomal storage disorders (LSDs are severe and untreatable, and mechanisms underlying cellular dysfunction are poorly understood. We found that toxic lipids relevant to three different LSDs disrupt multiple lysosomal and other cellular functions. Unbiased drug discovery revealed several structurally distinct protective compounds, approved for other uses, that prevent lysosomal and cellular toxicities of these lipids. Toxic lipids and protective agents show unexpected convergence on control of lysosomal pH and re-acidification as a critical component of toxicity and protection. In twitcher mice (a model of Krabbe disease [KD], a central nervous system (CNS-penetrant protective agent rescued myelin and oligodendrocyte (OL progenitors, improved motor behavior, and extended lifespan. Our studies reveal shared principles relevant to several LSDs, in which diverse cellular and biochemical disruptions appear to be secondary to disruption of lysosomal pH regulation by specific lipids. These studies also provide novel protective strategies that confer therapeutic benefits in a mouse model of a severe LSD.

Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Wortel, Ruud C.; Incrocci, Luca [Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; Heide, Uulke A. van der; Herk, Marcel van [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Heemsbergen, Wilma D., E-mail: w.heemsbergen@nki.nl [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands)

2015-03-15

Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

Effect of pH on Pulp Potential and Sulphide Mineral Flotation

OpenAIRE

GÖKTEPE, Ferihan

2014-01-01

Control of pH is one of the most widely applied methods for the modulation of mineral flotation. In this study the effect of pH on potential in solution and sulphur minerals flotation is discussed with various electrodes. The electrodes were platinum, gold, chalcopyrite, pyrite and galena. In solution, potentials were linearly dependent on pH with a different slope for each electrode. Chalcopyrite, pyrite, sphalerite and galena minerals flotation tests were performed in a microflot...

Intracellular pH gradients in migrating cells

DEFF Research Database (Denmark)

Martin, Christine; Pedersen, Stine Helene Falsig; Schwab, Albrecht

2011-01-01

might function as such unevenly distributed regulators as they modulate the interaction of focal adhesion proteins and components of the cytoskeleton in vitro. However, an intracellular pH (pH(i)) gradient reflecting a spatial asymmetry of protons has not been shown so far. One major regulator of p...

Predicting molybdenum toxicity to higher plants: Influence of soil properties

International Nuclear Information System (INIS)

McGrath, S.P.; Mico, C.; Curdy, R.; Zhao, F.J.

2010-01-01

The effect of soil properties on the toxicity of molybdenum (Mo) to four plant species was investigated. Soil organic carbon or ammonium-oxalate extractable Fe oxides were found to be the best predictors of the 50% effective dose (ED 50 ) of Mo in different soils, explaining > 65% of the variance in ED 50 for four species except for ryegrass (26-38%). Molybdenum concentrations in soil solution and consequently plant uptake were increased when soil pH was artificially raised because sorption of Mo to amorphous oxides is greatly reduced at high pH. The addition of sulphate significantly decreased Mo uptake by oilseed rape. For risk assessment, we suggest that Mo toxicity values for plants should be normalised using soil amorphous iron oxide concentrations. - Amorphous iron oxides or organic carbon were found to be the best predictors of the toxicity threshold values of Mo to higher plants on different soils.

Stabilizing the baseline current of a microbial fuel cell-based biosensor through overpotential control under non-toxic conditions.

Science.gov (United States)

Stein, Nienke E; Hamelers, Hubertus V M; Buisman, Cees N J

2010-04-01

A MFC-based biosensor can act as online toxicity sensor. Electrical current is a direct linear measure for metabolic activity of electrochemically active microorganisms. Microorganisms gain energy from anodic overpotential and current strongly depends on anodic overpotential. Therefore control of anodic overpotential is necessary to detect toxic events and prevent false positive alarms. Anodic overpotential and thus current is influenced by anode potential, pH, substrate and bicarbonate concentrations. In terms of overpotential all factor showed a comparable effect, anode potential 1.2% change in current density per mV, pH 0.43%/mV, bicarbonate 0.75%/mV and acetate 0.8%/mV. At acetate saturation the maximum acetate conversion rate is reached and with that a constant bicarbonate concentration. Control of acetate and bicarbonate concentration can be less strict than control of anode potential and pH. Current density changes due to changing anode potential and pH are in the same order of magnitude as changes due to toxicity. Strict control of pH and anode potential in a small range is required. The importance of anodic overpotential control for detection of toxic compounds is shown. To reach a stable baseline current under nontoxic conditions a MFC-based biosensor should be operated at controlled anode potential, controlled pH and saturated substrate concentrations. 2009 Elsevier B.V. All rights reserved.

Effects of water chemistry on the dissolution of ZnO nanoparticles and their toxicity to Escherichia coli

International Nuclear Information System (INIS)

Li Mei; Lin Daohui; Zhu Lizhong

2013-01-01

The dissolution of ZnO nanoparticles (nano-ZnO) plays an important role in the toxicity of nano-ZnO to the aquatic organisms. The effects of water chemistry such as pH, ionic components, and dissolved organic matter (DOM) on the dissolution of nano-ZnO and its toxicity to Escherichia coli (E. coli) were investigated in synthetic and natural water samples. The results showed that the toxicity of nano-ZnO to E. coli depended on not only free Zn 2+ but also the coexisting cations which could reduce the toxicity of Zn 2+ . Increasing solution pH, HPO 4 2− , and DOM reduced the concentration of free Zn 2+ released from nano-ZnO, and thus lowered the toxicity of nano-ZnO. In addition, both Ca 2+ and Mg 2+ dramatically reduced the toxicity of Zn 2+ to E. coli. These results highlight the importance of water chemistry on the toxicity evaluation of nano-ZnO in natural waters. - Highlights: ► The effects of water chemistry on the toxicity of nano-ZnO were investigated. ► Increasing solution pH, HPO 4 2− , and DOM reduced nano-ZnO toxicity to E. coli. ► Ca 2+ and Mg 2+ could dramatically reduce the toxicity of nano-ZnO to E. coli. ► Free Zn 2+ ions and water hardness together controlled nano-ZnO toxicity in waters. - The toxicity of nano-ZnO to E. coli depended on not only free Zn 2+ but also Ca 2+ and Mg 2+ which could reduce the toxicity of Zn 2+ .

Seasonal variability in irradiance affects herbicide toxicity to the marine flagellate Dunaliella tertiolecta

Directory of Open Access Journals (Sweden)

Sascha eSjollema

2014-06-01

Full Text Available Photosynthetically Active Radiation (PAR and Ultraviolet Radiation (UVR of the solar spectrum affect microalgae directly and modify the toxicity of phytotoxic compounds present in water. As a consequence seasonal variable PAR and UVR levels are likely to modulate the toxic pressure of contaminants in the field. Therefore the present study aimed to determine the toxicity of two model contaminants, the herbicides diuron and Irgarol®1051, under simulated irradiance conditions mimicking different seasons. Irradiance conditions of spring and autumn were simulated with a set of Light Emitting Diodes (LEDs. Toxicity of both herbicides was measured individually and in a mixture by determining the inhibition of photosystem II efficiency (ΦPSII of the marine flagellate Dunaliella teriolecta using Pulse Amplitude Modulation (PAM fluorometry. Toxicity of the single herbicides was higher under simulated spring irradiance than under autumn irradiance and this effect was also observed for mixtures of the herbicides. This irradiance dependent toxicity indicates that herbicide toxicity in the field is seasonally variable. Consequently toxicity tests under standard light conditions may overestimate or underestimate the toxic effect of phytotoxic compounds.

Hemithoracic Intensity Modulated Radiation Therapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Toxicity, Patterns of Failure, and a Matched Survival Analysis

Energy Technology Data Exchange (ETDEWEB)

Chance, William W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rice, David C. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsao, Anne S. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fontanilla, Hiral P. [Princeton Radiation Oncology, Monroe Township, New Jersey (United States); Liao, Zhongxing; Chang, Joe Y.; Tang, Chad; Pan, Hubert Y.; Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza J. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-01-01

Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but

Preparation and toxicity evaluation of a novel nattokinase-tauroursodeoxycholate complex

Directory of Open Access Journals (Sweden)

Rui Feng

2018-03-01

Full Text Available Nattokinase (NK, which has been identified as a potent fibrinolytic protease, has remarkable potential in treatment of thrombolysis, and even has the ability to ameliorate chronic vein thrombosis. To reduce the hemorrhagic risk from an intravenous injection of NK, nattokinase-tauroursodeoxycholate (NK-TUDCA complex was prepared at different pH values and with different ratios of NK and TUDCA. When assessing survival time, survival state, tail injury, and the body weight of mice, it was found that the NK-TUDCA complex (NK: 10 kIU/ml; TUDCA: 10 mg/ml; pH 5.0 had a lower toxicity when administered at an NK dosage of 130 kIU/kg in the acute toxicity test and 13 kIU/kg in the repeated low-dose challenge. From the results of the in vitro thrombolytic test and characterization of NK-TUDCA, we speculated that the delayed release of NK-TUDCA might be the main cause of toxicity reduction by the complex. This study described the preparation of an NK complex with low toxicity following intravenous administration, which could be utilized for further clinical study of NK. Keywords: Nattokinase, Tauroursodeoxycholate, Complex, Toxicity test, In vitro thrombolytic test

Toxicity of acid mine pit lake water remediated with limestone and phosphorus

Energy Technology Data Exchange (ETDEWEB)

Neil, L.L.; McCullough, C.D.; Lund, M.A.; Evans, L.H.; Tsvetnenko, Y. [Edith Cowan University, Joondalup, WA (Australia)

2009-11-15

Pit lakes are increasingly common worldwide and have potential to provide many benefits. However, lake water toxicity may require remediation before beneficial end uses can be realised. Three treatments to remediate AMD (pH similar to 4.8) pit lake water containing elevated concentrations of Al and Zn from Collie, Western Australia were tested in mesocosms. Treatments were: (a) limestone neutralisation (L), (b) phosphorus amendment (P), and c) combined limestone neutralisation and phosphorus amendment (L+P). Laboratory bioassays with Ceriodaphnia cf. dubia, Chlorella protothecoides and Tetrahymena thermophila assessed remediation. Limestone neutralisation increased pH and reduced heavy metal concentrations by 98% (Al) to 14% (Mg), removing toxicity to the three test species within 2 months. Phosphorus amendment removed toxicity after 6 months of treatment. However, phosphorus amendment to prior limestone neutralisation failed to reduce toxicity more than limestone neutralisation alone. Low concentrations of both phosphorus and nitrogen appear to limit phytoplankton population growth in all treatments.

Toxicity of acid mine pit lake water remediated with limestone and phosphorus.

Science.gov (United States)

Neil, Luke L; McCullough, Clint D; Lund, Mark A; Evans, Louis H; Tsvetnenko, Yuri

2009-11-01

Pit lakes are increasingly common worldwide and have potential to provide many benefits. However, lake water toxicity may require remediation before beneficial end uses can be realised. Three treatments to remediate AMD (pH approximately 4.8) pit lake water containing elevated concentrations of Al and Zn from Collie, Western Australia were tested in mesocosms. Treatments were: (a) limestone neutralisation (L), (b) phosphorus amendment (P), and (c) combined limestone neutralisation and phosphorus amendment (L+P). Laboratory bioassays with Ceriodaphnia cf. dubia, Chlorella protothecoides and Tetrahymena thermophila assessed remediation. Limestone neutralisation increased pH and reduced heavy metal concentrations by 98% (Al) to 14% (Mg), removing toxicity to the three test species within 2 months. Phosphorus amendment removed toxicity after 6 months of treatment. However, phosphorus amendment to prior limestone neutralisation failed to reduce toxicity more than limestone neutralisation alone. Low concentrations of both phosphorus and nitrogen appear to limit phytoplankton population growth in all treatments.

Mercury and other element exposure in tree swallows nesting at low pH and neutral pH lakes in northern Wisconsin USA

International Nuclear Information System (INIS)

Custer, Thomas W.; Custer, Christine M.; Thogmartin, Wayne E.; Dummer, Paul M.; Rossmann, Ronald; Kenow, Kevin P.; Meyer, Michael W.

2012-01-01

The primary objective of this study was to determine whether tree swallows (Tachycineta bicolor) demonstrate similar responses to lake pH and mercury (Hg) contamination in northern Wisconsin as do common loons (Gavia immer). Similar to common loons, Hg concentrations in the blood of tree swallow nestlings were higher, Hg concentrations in eggs tended to be higher, and egg size tended to be smaller at low (<6.2) pH lakes. In contrast to common loons, tree swallow nestling production was not lower at low pH lakes. Based on modeling associations, Hg concentrations in tree swallow eggs and nestling blood can be used to predict Hg concentrations in common loons without the invasive or destructive sampling of loons. Mean concentrations of cadmium, manganese, and mercury in nestling livers were higher at low pH lakes than neutral pH lakes. Concentrations of cadmium, chromium, mercury, selenium, and zinc were not at toxic levels. - Highlights: ► Mercury concentrations in tree swallow nestling livers were higher in low than neutral pH lakes. ► Tree swallow eggs were smaller at low than neutral pH lakes. ► Tree swallow hatching success was not correlated with mercury concentrations in eggs. ► Mercury concentrations in tree swallows can be used to predict common loon exposure. - Mercury concentrations in tree swallows were higher at low pH lakes.

Sulfate Reduction at Low Ph To Remediate Acid Mine Drainage

NARCIS (Netherlands)

Sánchez-Andrea, I.; Sanz, J.L.; Bijmans, M.F.M.; Stams, A.J.M.

2014-01-01

Industrial activities and the natural oxidation of metallic sulfide-ores produce sulfate-rich waters with low pH and high heavy metals content, generally termed acid mine drainage (AMD). This is of great environmental concern as some heavy metals are highly toxic. Within a number of possibilities,

Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

Science.gov (United States)

Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

2016-01-01

The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model

Energy Technology Data Exchange (ETDEWEB)

Neuwoehner, Judith [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Uberlandstr. 133, 8600 Duebendorf (Switzerland); Institute of Biogeochemistry and Pollutant Dynamics (IBP), ETH Zuerich, 8092 Zuerich (Switzerland); Escher, Beate I., E-mail: b.escher@uq.edu.au [The University of Queensland, National Research Centre for Environmental Toxicology (Entox), 39 Kessels Road, Brisbane, QLD 4108 (Australia); Eawag, Swiss Federal Institute of Aquatic Science and Technology, Uberlandstr. 133, 8600 Duebendorf (Switzerland)

2011-01-17

Several previous studies revealed that pharmaceuticals with aliphatic amine function exhibit a higher toxicity toward algae than toward other aquatic organisms. Here we investigated the pH-dependent toxicity of the five basic pharmaceuticals fluoxetine, its metabolite norfluoxetine, propranolol, lidocaine, and trimipramine. For all of them, the toxicity increased with increasing pH when aqueous effect concentrations were considered. Since these pharmaceuticals contain a basic amine group that is protonated and thus positively charged at physiological pH and because algae are capable of biological homeostasis, i.e., pH inside the algal cell remains virtually independent of variable external pH, the speciation of aliphatic amines can be different inside the algal cell compared to the external medium. Therefore, we hypothesized that the high toxicity of aliphatic amines in algae is a toxicokinetic effect caused by speciation and not a toxicodynamic effect caused by a specific mode of toxic action. This hypothesis also implies that internal effect concentrations are independent on external pH. On this basis we developed a simple toxicokinetic model, which assumes that only the neutral molecule is bioavailable and can pass the plasma membrane. This assumption is likely to be valid at pH values down to two units below the acidity constant (pK{sub a}). For lower pH values a more complex model would have to be evoked that includes, an, albeit smaller, permeability of the charged species. For pH > pK{sub a} - 2, we can safely assume that the outer membrane serves as insulator and that the charged species is formed inside the cell according to the pH in the cytoplasm. Thus this toxicokinetic model is an ion-trapping model. The input parameters of this model are the measured aqueous effect concentrations determined as a function of pH and the membrane-water partitioning, which was modelled by the liposome-water partition coefficients of the neutral and cationic species. They

The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model

International Nuclear Information System (INIS)

Neuwoehner, Judith; Escher, Beate I.

2011-01-01

Several previous studies revealed that pharmaceuticals with aliphatic amine function exhibit a higher toxicity toward algae than toward other aquatic organisms. Here we investigated the pH-dependent toxicity of the five basic pharmaceuticals fluoxetine, its metabolite norfluoxetine, propranolol, lidocaine, and trimipramine. For all of them, the toxicity increased with increasing pH when aqueous effect concentrations were considered. Since these pharmaceuticals contain a basic amine group that is protonated and thus positively charged at physiological pH and because algae are capable of biological homeostasis, i.e., pH inside the algal cell remains virtually independent of variable external pH, the speciation of aliphatic amines can be different inside the algal cell compared to the external medium. Therefore, we hypothesized that the high toxicity of aliphatic amines in algae is a toxicokinetic effect caused by speciation and not a toxicodynamic effect caused by a specific mode of toxic action. This hypothesis also implies that internal effect concentrations are independent on external pH. On this basis we developed a simple toxicokinetic model, which assumes that only the neutral molecule is bioavailable and can pass the plasma membrane. This assumption is likely to be valid at pH values down to two units below the acidity constant (pK a ). For lower pH values a more complex model would have to be evoked that includes, an, albeit smaller, permeability of the charged species. For pH > pK a - 2, we can safely assume that the outer membrane serves as insulator and that the charged species is formed inside the cell according to the pH in the cytoplasm. Thus this toxicokinetic model is an ion-trapping model. The input parameters of this model are the measured aqueous effect concentrations determined as a function of pH and the membrane-water partitioning, which was modelled by the liposome-water partition coefficients of the neutral and cationic species. They were

Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies

International Nuclear Information System (INIS)

Brixey, Clark J.; Roeske, John C.; Lujan, Anthony E.; Yamada, S. Diane; Rotmensch, Jacob; Mundt, Arno J.

2002-01-01

Purpose: To evaluate the impact of intensity-modulated whole pelvic radiotherapy (IM-WPRT) on acute hematologic toxicity (HT) in gynecology patients. Methods and Materials: Between February 2000 and June 2001, 36 patients (24 cervix, 12 uterus) received IM-WPRT. The target consisted of the upper vagina, parametria, uterus, and presacral and pelvic lymph nodes. Using commercially available software, seven or nine coplanar IM-WPRT plans were generated. The planning goals were to irradiate the target while minimizing the dose to the small bowel, bladder, and rectum. Pelvic bone marrow (BM) was not a constraint in the planning process. The variables analyzed included white blood count (WBC), absolute neutrophil count (ANC), platelets, and hemoglobin (Hgb) obtained before and weekly during RT. As a comparison, the HT in 88 patients (44 cervix, 44 uterus) treated to the same target volume and total dose (45 Gy) with conventional four-field WPRT was analyzed. In addition, the medullary spaces within the pelvic bones in 10 women were contoured and the average dose-volume histograms representing the pelvic BM were compared between the two groups. Results: IM-WPRT patients had a lower median age (p=0.008), higher percentage of squamous histologic features (p=0.04), and were more likely to receive chemotherapy (CTX) (p=0.02) than were the WPRT patients. No differences were seen in the baseline WBC, ANC, platelet, or Hgb levels between the two groups. Grade 2 or greater WBC, ANC, and Hgb toxicity was seen in 19.4%, 9.1%, and 8.6% of the IM-WPRT patients, respectively. Comparable rates were seen in the WPRT patients (WBC 21.6%, p=0.79; ANC 8.3%, p=0.91; Hgb 9.2%, p=0.94). No Grade 2 or greater platelet toxicity was seen in either group. Significant HT was infrequent in women treated with RT alone and was comparable in the two groups. In contrast, WPRT + CTX patients experienced more Grade 2 or greater WBC toxicity (60% vs. 31.2%, p=0.08) and developed lower median WBC (2.8 vs

Predicting molybdenum toxicity to higher plants: Influence of soil properties

Energy Technology Data Exchange (ETDEWEB)

McGrath, S.P., E-mail: steve.mcgrath@bbsrc.ac.u [Soil Science Department, Centre for Soils and Ecosystems Functions, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Mico, C. [Soil Science Department, Centre for Soils and Ecosystems Functions, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom); Curdy, R. [Laboratory for Environmental Biotechnology (LBE), Swiss Federal Institute of Technology Lausanne (EPFL) Station 6 CH, 1015 Lausanne (Switzerland); Zhao, F.J. [Soil Science Department, Centre for Soils and Ecosystems Functions, Rothamsted Research, Harpenden, Hertfordshire AL5 2JQ (United Kingdom)

2010-10-15

The effect of soil properties on the toxicity of molybdenum (Mo) to four plant species was investigated. Soil organic carbon or ammonium-oxalate extractable Fe oxides were found to be the best predictors of the 50% effective dose (ED{sub 50}) of Mo in different soils, explaining > 65% of the variance in ED{sub 50} for four species except for ryegrass (26-38%). Molybdenum concentrations in soil solution and consequently plant uptake were increased when soil pH was artificially raised because sorption of Mo to amorphous oxides is greatly reduced at high pH. The addition of sulphate significantly decreased Mo uptake by oilseed rape. For risk assessment, we suggest that Mo toxicity values for plants should be normalised using soil amorphous iron oxide concentrations. - Amorphous iron oxides or organic carbon were found to be the best predictors of the toxicity threshold values of Mo to higher plants on different soils.

Hydrogel-coated fiber Bragg grating sensor for pH monitoring

Science.gov (United States)

Pabbisetti, Vayu Nandana Kishore; Madhuvarasu, Sai Shankar

2016-06-01

We present a fiber-optic wavelength-modulated sensor for pH applications. Fiber Bragg grating (FBG) is functionalized with a stimulus-responsive hydrogel that induces a strain on FBG due to mechanical expansion of the gel in response to ambient pH changes. The gel is synthesized from the blends of poly (vinyl alcohol)/poly (acrylic acid). The induced strain results in a shift of FBG reflected peak that is monitored by an interrogator. The sensor system shows good linearity in the acidic pH range of 3 to 7 with a sensitivity of 12.16 pm/pH. In addition, it shows good repeatability and oscillator behavior, which proves it to be fit for pH sensing applications.

The Role of the Plasma Membrane H+-ATPase in Plant Responses to Aluminum Toxicity

Directory of Open Access Journals (Sweden)

Jiarong Zhang

2017-10-01

Full Text Available Aluminum (Al toxicity is a key factor limiting plant growth and crop production on acid soils. Increasing the plant Al-detoxification capacity and/or breeding Al-resistant cultivars are a cost-effective strategy to support crop growth on acidic soils. The plasma membrane H+-ATPase plays a central role in all plant physiological processes. Changes in the activity of the plasma membrane H+-ATPase through regulating the expression and phosphorylation of this enzyme are also involved in many plant responses to Al toxicity. The plasma membrane H+-ATPase mediated H+ influx may be associated with the maintenance of cytosolic pH and the plasma membrane gradients as well as Al-induced citrate efflux mediated by a H+-ATPase-coupled MATE co-transport system. In particular, modulating the activity of plasma membrane H+-ATPase through application of its activators (e.g., magnesium or IAA or using transgenics has effectively enhanced plant resistance to Al stress in several species. In this review, we critically assess the available knowledge on the role of the plasma membrane H+-ATPase in plant responses to Al stress, incorporating physiological and molecular aspects.

A new mechanism of macrophyte mitigation: how submerged plants reduce malathion's acute toxicity to aquatic animals.

Science.gov (United States)

Brogan, William R; Relyea, Rick A

2014-08-01

A growing body of evidence suggests that aquatic plants can mitigate the toxicity of insecticides to sensitive aquatic animals. The current paradigm is that this ability is driven primarily by insecticide sorption to plant tissues, especially for hydrophobic compounds. However, recent work shows that submerged plants can strongly mitigate the toxicity of the relatively hydrophilic insecticide malathion, despite the fact that this compound exhibits a slow sorption rate to plants. To examine this disparity, we tested the hypothesis that the mitigating effect of submerged plants on malathion's toxicity is driven primarily by the increased water pH from plant photosynthesis causing the hydrolysis of malathion, rather than by sorption. To do this, we compared zooplankton (Daphnia magna) survival across five environmentally relevant malathion concentrations (0, 1, 4, 6, or 36 μg L(-1)) in test containers where we chemically manipulated water pH in the absence of plants or added the submerged plant (Elodea canadensis) but manipulated plant photosynthetic activity via shading or no shading. We discovered that malathion was equally lethal to Daphnia at all concentrations tested when photosynthetically inactive (i.e. shaded) plants were present (pH at time of dosing=7.8) or when pH was chemically decreased (pH=7.7). In contrast, when photosynthetically active (i.e. unshaded) plants were present (pH=9.8) or when pH was chemically increased (pH=9.5), the effects of 4 and 6 μg L(-1) of malathion on Daphnia were mitigated strongly and to an equal degree. These results demonstrate that the mitigating effect of submerged plants on malathion's toxicity can be explained entirely by a mechanism of photosynthesizing plants causing an increase in water pH, resulting in rapid malathion hydrolysis. Our findings suggest that current ecotoxicological models and phytoremediation strategies may be overlooking a critical mechanism for mitigating pesticides. Copyright © 2014 Elsevier Ltd

Biochar application to hardrock mine tailings: Soil quality, microbial activity, and toxic element sorption

Science.gov (United States)

Kelly, Charlene N.; Peltz, Christopher D.; Stanton, Mark R.; Rutherford, David W.; Rostad, Colleen E.

2014-01-01

Waste rock piles from historic mining activities remain unvegetated as a result of metal toxicity and high acidity. Biochar has been proposed as a low-cost remediation strategy to increase soil pH and reduce leaching of toxic elements, and improve plant establishment. In this laboratory column study, biochar made from beetle-killed pine wood was assessed for utility as a soil amendment by mixing soil material from two mine sites collected near Silverton, Colorado, USA with four application rates of biochar (0%, 10%, 20%, 30% vol:vol). Columns were leached seven times over 65 days and leachate pH and concentration of toxic elements and base cations were measured at each leaching. Nutrient availability and soil physical and biological parameters were determined following the incubation period. We investigated the hypotheses that biochar incorporation into acidic mine materials will (1) reduce toxic element concentrations in leaching solution, (2) improve soil parameters (i.e. increase nutrient and water holding capacity and pH, and decrease compaction), and (3) increase microbial populations and activity. Biochar directly increased soil pH (from 3.33 to 3.63 and from 4.07 to 4.77 in the two materials) and organic matter content, and decreased bulk density and extractable salt content in both mine materials, and increased nitrate availability in one material. No changes in microbial population or activity were detected in either mine material upon biochar application. In leachate solution, biochar increased base cations from both materials and reduced the concentrations of Al, Cd, Cu, Pb, and Zn in leachate solution from one material. However, in the material with greater toxic element content, biochar did not reduce concentrations of any measured dissolved toxic elements in leachate and resulted in a potentially detrimental release of Cd and Zn into solution at concentrations above that of the pure mine material. The length of time of effectiveness and specific

[Toxicity and influencing factors of liquid chlorine on chironomid larvae].

Science.gov (United States)

Sun, Xing-Bin; Cui, Fu-Yi; Zhang, Jin-Song; Guo, Zhao-Hai; Xu, Feng; Liu, Li-Jun

2005-09-01

The excessive propagation of Chironomid larvae (red worm) in the sedimentation tanks is a difficult problem for the normal function of waterworks. The toxic effect of liquid chlorine on the different instar larvae of Chironomid was studied using distilled water as test sample. Furthermore, the effect of pH value, organic matter content, ammonia nitrogen, and algae content on toxicity of liquid chlorine was observed. The results show that the tolerance of Chironomid larvae to liquid chlorine is strengthened with the increase in instar. The 24h semi-lethal concentration (LC50) of liquid chlorine to the 4th instar larvae of Chironomid is 3.39 mg/L. Low pH value and high algae content are helpful to improve the toxic effect of liquid chlorine to Chironomid larvae. In neutral water body, the increase in organic matter content results in the decrease in the death rate of Chironomid larvae. The toxicity of liquid chlorine differs greatly in different concentrations of ammonia nitrogen. The death rate of the 4th instar larvae of Chironomid in raw water is higher by contrast with that in sedimentation tanks water for 24h disposal with various amount of liquid chlorine.

Photocatalytic degradation of rosuvastatin: Analytical studies and toxicity evaluations

Energy Technology Data Exchange (ETDEWEB)

Machado, Tiele Caprioli, E-mail: tiele@enq.ufrgs.br [Chemical Engineering Department, Federal University of Rio Grande do Sul, Rua Engenheiro Luiz Englert s/n, CEP: 90040-040 Porto Alegre, RS (Brazil); Pizzolato, Tânia Mara [Chemical Institute, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Arenzon, Alexandre [Ecology Center, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Segalin, Jeferson [Biotechnology Center, Federal University of Rio Grande do Sul, Avenida Bento Gonçalves, 9500, CEP: 91501-970 Porto Alegre, RS (Brazil); Lansarin, Marla Azário [Chemical Engineering Department, Federal University of Rio Grande do Sul, Rua Engenheiro Luiz Englert s/n, CEP: 90040-040 Porto Alegre, RS (Brazil)

2015-01-01

Photocatalytic degradation of rosuvastatin, which is a drug that has been used to reduce blood cholesterol levels, was studied in this work employing ZnO as catalyst. The experiments were carried out in a temperature-controlled batch reactor that was irradiated with UV light. Preliminary the effects of the photocatalyst loading, the initial pH and the initial rosuvastatin concentration were evaluated. The experimental results showed that rosuvastatin degradation is primarily a photocatalytic process, with pseudo-first order kinetics. The byproducts that were generated during the oxidative process were identified using nano-ultra performance liquid chromatography tandem mass spectrometry (nano-UPLC–MS/MS) and acute toxicity tests using Daphnia magna were done to evaluate the toxicity of the untreated rosuvastatin solution and the reactor effluent. - Highlights: • The photocatalytic degradation of rosuvastatin was studied under UV irradiation. • Commercial catalyst ZnO was used. • Initial rosuvastatin concentration, photocatalyst loading and pH were evaluated. • The byproducts generated during the oxidative process were detected and identified. • Acute toxicity tests using Daphnia magna were carried out.

Herbicide toxicity on river biofilms assessed by pulse amplitude modulated (PAM) fluorometry

International Nuclear Information System (INIS)

Kim Tiam, Sandra; Laviale, Martin; Feurtet-Mazel, Agnès; Jan, Gwilherm; Gonzalez, Patrice; Mazzella, Nicolas; Morin, Soizic

2015-01-01

Highlights: • Rapid Light Curves were shown to be early markers of toxicant exposure. • Diuron and norflurazon effects were significant at environmentally realistic concentrations. • Toxic effects in intact biofilms seem to be delayed compared to disrupted biofilms. - Abstract: The use of Rapid light curves (RLCs) as a toxicity endpoint for river biofilms was examined in this study and compared to “classical fluorescence parameters” i.e. minimal fluorescence (F 0 ), optimal and effective quantum yields of photosystem II (F v /F m and Φ PSII ). Measurements were performed after exposure to five concentrations of diuron (from 0.3 to 33.4 μg L −1 ), its main degradation product (DCPMU) (from 1.0 to 1014 μg L −1 ) and norflurazon (from 0.6 to 585 μg L −1 ) with the lowest exposure concentrations corresponding to levels regularly encountered in chronically contaminated sites. Biofilm responses were evaluated after 1, 5, 7 and 14 days of exposure to the different toxicants. Overall, the responses of both “classical fluorescence parameters” and RLC endpoints were highly time dependent and related to the mode of action of the different compounds. Interestingly, parameters calculated from RLCs (α, ETR max and I k ) were useful early markers of pesticide exposure since they revealed significant effects of all the tested toxicants from the first day of exposure. In comparison, classical fluorescence endpoints (F 0 and F v /F m ) measured at day 1 were only affected in the DCPMU treatment. Our results demonstrated the interest of RLCs as early markers of toxicant exposure particularly when working with toxicants with less specific mode of action than PSII inhibitors

Aluminium Toxicity Targets in Plants

Directory of Open Access Journals (Sweden)

Sónia Silva

2012-01-01

Full Text Available Aluminium (Al is the third most abundant metallic element in soil but becomes available to plants only when the soil pH drops below 5.5. At those conditions, plants present several signals of Al toxicity. As reported by literature, major consequences of Al exposure are the decrease of plant production and the inhibition of root growth. The root growth inhibition may be directly/indirectly responsible for the loss of plant production. In this paper the most remarkable symptoms of Al toxicity in plants and the latest findings in this area are addressed. Root growth inhibition, ROS production, alterations on root cell wall and plasma membrane, nutrient unbalances, callose accumulation, and disturbance of cytoplasmic Ca2+ homeostasis, among other signals of Al toxicity are discussed, and, when possible, the behavior of Al-tolerant versus Al-sensitive genotypes under Al is compared.

Toxicity of lead (Pb) to freshwater green algae: Development and validation of a bioavailability model and inter-species sensitivity comparison

Energy Technology Data Exchange (ETDEWEB)

De Schamphelaere, K.A.C., E-mail: karel.deschamphelaere@ugent.be; Nys, C., E-mail: chnys.nys@ugent.be; Janssen, C.R., E-mail: colin.janssen@ugent.be

2014-10-15

Highlights: • Chronic toxicity of Pb varied 4-fold among three algae species. • The use of an organic P avoided Pb precipitation in the experiments. • pH and Dissolved Organic Carbon strongly affect Pb toxicity, Ca and Mg do not. • A bioavailability model was developed that accurately predicts toxicity. • Algae may become the most sensitive species to Pb above pH 7.4. - Abstract: Scientifically sound risk assessment and derivation of environmental quality standards for lead (Pb) in the freshwater environment are hampered by insufficient data on chronic toxicity and bioavailability to unicellular green algae. Here, we first performed comparative chronic (72-h) toxicity tests with three algal species in medium at pH 6, containing 4 mg fulvic acid (FA)/L and containing organic phosphorous (P), i.e. glycerol-2-phosphate, instead of PO{sub 4}{sup 3−} to prevent lead-phosphate mineral precipitation. Pseudokirchneriella subcapitata was 4-fold more sensitive to Pb than Chlorella kesslerii, with Chlamydomonas reinhardtii in the middle. The influence of medium physico-chemistry was therefore investigated in detail with P. subcapitata. In synthetic test media, higher concentrations of fulvic acid or lower pH protected against toxicity of (filtered) Pb to P. subcapitata, while effects of increased Ca or Mg on Pb toxicity were less clear. When toxicity was expressed on a free Pb{sup 2+} ion activity basis, a log-linear, 260-fold increase of toxicity was observed between pH 6.0 and 7.6. Effects of fulvic acid were calculated to be much more limited (1.9-fold) and were probably even non-existent (depending on the affinity constant for Pb binding to fulvic acid that was used for calculating speciation). A relatively simple bioavailability model, consisting of a log-linear pH effect on Pb{sup 2+} ion toxicity linked to the geochemical speciation model Visual Minteq (with the default NICA-Donnan description of metal and proton binding to fulvic acid), provided relatively

Toxicity of lead (Pb) to freshwater green algae: Development and validation of a bioavailability model and inter-species sensitivity comparison

International Nuclear Information System (INIS)

De Schamphelaere, K.A.C.; Nys, C.; Janssen, C.R.

2014-01-01

Highlights: • Chronic toxicity of Pb varied 4-fold among three algae species. • The use of an organic P avoided Pb precipitation in the experiments. • pH and Dissolved Organic Carbon strongly affect Pb toxicity, Ca and Mg do not. • A bioavailability model was developed that accurately predicts toxicity. • Algae may become the most sensitive species to Pb above pH 7.4. - Abstract: Scientifically sound risk assessment and derivation of environmental quality standards for lead (Pb) in the freshwater environment are hampered by insufficient data on chronic toxicity and bioavailability to unicellular green algae. Here, we first performed comparative chronic (72-h) toxicity tests with three algal species in medium at pH 6, containing 4 mg fulvic acid (FA)/L and containing organic phosphorous (P), i.e. glycerol-2-phosphate, instead of PO 4 3− to prevent lead-phosphate mineral precipitation. Pseudokirchneriella subcapitata was 4-fold more sensitive to Pb than Chlorella kesslerii, with Chlamydomonas reinhardtii in the middle. The influence of medium physico-chemistry was therefore investigated in detail with P. subcapitata. In synthetic test media, higher concentrations of fulvic acid or lower pH protected against toxicity of (filtered) Pb to P. subcapitata, while effects of increased Ca or Mg on Pb toxicity were less clear. When toxicity was expressed on a free Pb 2+ ion activity basis, a log-linear, 260-fold increase of toxicity was observed between pH 6.0 and 7.6. Effects of fulvic acid were calculated to be much more limited (1.9-fold) and were probably even non-existent (depending on the affinity constant for Pb binding to fulvic acid that was used for calculating speciation). A relatively simple bioavailability model, consisting of a log-linear pH effect on Pb 2+ ion toxicity linked to the geochemical speciation model Visual Minteq (with the default NICA-Donnan description of metal and proton binding to fulvic acid), provided relatively accurate toxicity

Intensity-modulated radiotherapy vs. parotid-sparing 3D conformal radiotherapy. Effect on outcome and toxicity in locally advanced head and neck cancer

Energy Technology Data Exchange (ETDEWEB)

Lambrecht, M.; Nevens, D.; Nuyts, S. [University Hospitals Leuven (Belgium). Dept. of Radiation Oncology

2013-03-15

Background and purpose: Intensity-modulated radiotherapy (IMRT) has rapidly become standard of care in the management of locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, our aim was to retrospectively investigate the effect of the introducing IMRT on outcome and treatment-related toxicity compared to parotid-sparing 3D conformal radiotherapy (3DCRT). Material and methods: A total of 245 patients with stage III and IV HNSCC treated with primary radiotherapy between January 2003 and December 2010 were included in this analysis: 135 patients were treated with 3DCRT, 110 patients with IMRT. Groups were compared for acute and late toxicity, locoregional control (LRC), and overall survival (OS). Oncologic outcomes were estimated using Kaplan-Meier analysis and compared using a log-rank test. Acute toxicity was analyzed according to the Common Terminology Criteria for Adverse Events v3.0 and late toxicity was scored using the RTOG/EORTC late toxicity scoring system. Results: Median follow-up was 35 months in the IMRT group and 68 months in the 3DCRT group. No significant differences were found in 3-year LRC and OS rates between the IMRT group and 3DCRT group. Significantly less acute mucositis {>=} grade 3 was observed in the IMRT group (32% vs. 44%, p = 0.03). There was significantly less late xerostomia {>=} grade 2 in the IMRT group than in the 3DCRT group (23% vs. 68%, p < 0.001). After 24 months, there was less dysphagia {>=} grade 2 in the IMRT group although differences failed to reach statistical significance. Conclusion: The introduction of IMRT in the radiotherapeutic management of locally advanced head and neck cancer significantly improved late toxicity without compromising tumor control compared to a parotid-sparing 3D conformal radiotherapy technique. (orig.)

Effects of toxic cyanobacteria and ammonia on flesh quality of blunt snout bream (Megalobrama amblycephala).

Science.gov (United States)

Wang, Li; Chen, Chuanyue; Liu, Wanjing; Xia, Hu; Li, Jian; Zhang, Xuezhen

2017-03-01

Toxic cyanobacterial blooms result in the production of an organic biomass containing cyanotoxins (e.g. microcystins) and an elevated ammonia concentration in the water environment. The ingestion of toxic cyanobacteria and exposure to ammonia are grave hazards for fish. The present study assessed the effects of dietary toxic cyanobacteria and ammonia exposure on the flesh quality of blunt snout bream (Megalobrama amblycephala). Dietary toxic cyanobacteria and ammonia exposure had no impact on fish growth performance, fillet proximate composition and drip loss, whereas it significantly decreased fillet total amino acids, total essential amino acids, hardness and gumminess, and increased fillet ultimate pH as well as malondialdehyde content. However, there was no significant interaction between dietary toxic cyanobacteria and ammonia exposure on these parameters. Additionally, dietary toxic cyanobacteria significantly increased fillet initial pH, thaw loss and protein carbonyl content, whereas ammonia exposure did not. The results of the present study indicate that dietary toxic cyanobacteria and ammonia exposure reduced the quality of blunt snout bream fillet. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Astrocyte-neuron interaction in diphenyl ditelluride toxicity directed to the cytoskeleton.

Science.gov (United States)

Heimfarth, Luana; da Silva Ferreira, Fernanda; Pierozan, Paula; Mingori, Moara Rodrigues; Moreira, José Cláudio Fonseca; da Rocha, João Batista Teixeira; Pessoa-Pureur, Regina

2017-03-15

Diphenylditelluride (PhTe) 2 is a neurotoxin that disrupts cytoskeletal homeostasis. We are showing that different concentrations of (PhTe) 2 caused hypophosphorylation of glial fibrillary acidic protein (GFAP), vimentin and neurofilament subunits (NFL, NFM and NFH) and altered actin organization in co-cultured astrocytes and neurons from cerebral cortex of rats. These mechanisms were mediated by N-methyl-d-aspartate (NMDA) receptors without participation of either L-type voltage-dependent calcium channels (L-VDCC) or metabotropic glutamate receptors. Upregulated Ca 2+ influx downstream of NMDA receptors activated Ca 2+ -dependent protein phosphatase 2B (PP2B) causing hypophosphorylation of astrocyte and neuron IFs. Immunocytochemistry showed that hypophosphorylated intermediate filaments (IF) failed to disrupt their organization into the cytoskeleton. However, phalloidin-actin-FITC stained cytoskeleton evidenced misregulation of actin distribution, cell spreading and increased stress fibers in astrocytes. βIII tubulin staining showed that neurite meshworks are not altered by (PhTe) 2 , suggesting greater susceptibility of astrocytes than neurons to (PheTe) 2 toxicity. These findings indicate that signals leading to IF hypophosphorylation fail to disrupt the cytoskeletal IF meshwork of interacting astrocytes and neurons in vitro however astrocyte actin network seems more susceptible. Our findings support that intracellular Ca 2+ is one of the crucial signals that modulate the action of (PhTe) 2 in co-cultured astrocytes and neurons and highlights the cytoskeleton as an end-point of the neurotoxicity of this compound. Cytoskeletal misregulation is associated with cell dysfunction, therefore, the understanding of the molecular mechanisms mediating the neurotoxicity of this compound is a matter of increasing interest since tellurium compounds are increasingly released in the environment. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

Directory of Open Access Journals (Sweden)

Rui Guo

Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

Herbicide toxicity on river biofilms assessed by pulse amplitude modulated (PAM) fluorometry

Energy Technology Data Exchange (ETDEWEB)

Kim Tiam, Sandra, E-mail: sandra.kimtiam@gmail.com [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France); Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Laviale, Martin [Departamento de Biologia and CESAM – Centro de Estudos do Ambiente e do Mar Universidade de Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Sorbonne Universités, UPMC Univ Paris 06, UMR 7093, LOV, Observatoire Océanologique, F-06230, Villefranche-Sur-Mer (France); CNRS, UMR 7093, LOV, Observatoire Océanologique, F-06230, Villefranche-Sur-Mer France (France); Feurtet-Mazel, Agnès [Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Jan, Gwilherm [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France); Gonzalez, Patrice [Université de Bordeaux, EPOC, UMR 5805, F-33120 Arcachon (France); Mazzella, Nicolas; Morin, Soizic [Irstea, UR EABX, 50 Avenue de Verdun, F-33612, Cestas Cedex (France)

2015-08-15

Highlights: • Rapid Light Curves were shown to be early markers of toxicant exposure. • Diuron and norflurazon effects were significant at environmentally realistic concentrations. • Toxic effects in intact biofilms seem to be delayed compared to disrupted biofilms. - Abstract: The use of Rapid light curves (RLCs) as a toxicity endpoint for river biofilms was examined in this study and compared to “classical fluorescence parameters” i.e. minimal fluorescence (F{sub 0}), optimal and effective quantum yields of photosystem II (F{sub v}/F{sub m} and Φ{sub PSII}). Measurements were performed after exposure to five concentrations of diuron (from 0.3 to 33.4 μg L{sup −1}), its main degradation product (DCPMU) (from 1.0 to 1014 μg L{sup −1}) and norflurazon (from 0.6 to 585 μg L{sup −1}) with the lowest exposure concentrations corresponding to levels regularly encountered in chronically contaminated sites. Biofilm responses were evaluated after 1, 5, 7 and 14 days of exposure to the different toxicants. Overall, the responses of both “classical fluorescence parameters” and RLC endpoints were highly time dependent and related to the mode of action of the different compounds. Interestingly, parameters calculated from RLCs (α, ETR{sub max} and I{sub k}) were useful early markers of pesticide exposure since they revealed significant effects of all the tested toxicants from the first day of exposure. In comparison, classical fluorescence endpoints (F{sub 0} and F{sub v}/F{sub m}) measured at day 1 were only affected in the DCPMU treatment. Our results demonstrated the interest of RLCs as early markers of toxicant exposure particularly when working with toxicants with less specific mode of action than PSII inhibitors.

Catalytic Ozonation of Phenolic Wastewater: Identification and Toxicity of Intermediates

Directory of Open Access Journals (Sweden)

Mahdi Farzadkia

2014-01-01

Full Text Available A new strategy in catalytic ozonation removal method for degradation and detoxification of phenol from industrial wastewater was investigated. Magnetic carbon nanocomposite, as a novel catalyst, was synthesized and then used in the catalytic ozonation process (COP and the effects of operational conditions such as initial pH, reaction time, and initial concentration of phenol on the degradation efficiency and the toxicity assay have been investigated. The results showed that the highest catalytic potential was achieved at optimal neutral pH and the removal efficiency of phenol and COD is 98.5% and 69.8%, respectively. First-order modeling demonstrated that the reactions were dependent on the initial concentration of phenol, with kinetic constants varying from 0.038 min−1  ([phenol]o = 1500 mg/L to 1.273 min−1 ([phenol]o = 50 mg/L. Bioassay analysis showed that phenol was highly toxic to Daphnia magna (LC50 96 h=5.6 mg/L. Comparison of toxicity units (TU of row wastewater (36.01 and the treated effluent showed that TU value, after slightly increasing in the first steps of ozonation for construction of more toxic intermediates, severely reduced at the end of reaction (2.23. Thus, COP was able to effectively remove the toxicity of intermediates which were formed during the chemical oxidation of phenolic wastewaters.

ELEMENTAL ANALYSIS OF RESPIRABLE TIRE PARTICLES AND ASSESSMENT OF CARDIO-PULMONARY TOXICITY IN RATS

Science.gov (United States)

Elemental Analysis of Respirable Tire Particles and Assessment of Cardio-pulmonary Toxicity in RatsR.R. Gottipolu, PhD1, E. Landa, PhD2, J.K. McGee, MS1, M.C. Schladweiler, BS1, J.G. Wallenborn, MS3, A.D. Ledbetter, BS1, J.E. Richards, MS1 and U.P. Kodavanti, PhD1. 1NHEER...

Organophosphorus insecticides: Toxic effects and bioanalytical tests for evaluating toxicity during degradation processes

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Čolović Mirjana B.

2013-01-01

Full Text Available Organophosphorus insecticides have been the most applied group of insecticides for the last two decades. Their main toxic effects are related to irreversible inactivation of acetylcholinesterase (AChE. Actually, they covalently bind to serine OH group in the enzyme active site forming phosphorylated enzyme that cannot hydrolyze acetylcholine. Organophosphorus insecticides in the environment undergo the natural degradation pathway including mainly homogeneous and heterogeneous hydrolysis (especially at high pH generating non-inhibiting products. Additionally, thio organophosphates are easily oxidized by naturally present oxidants and UV light, forming more toxic and stable oxons. Thus, oxidative degradation procedures, generally referred as advanced oxidation processes (AOP, have been applied for their efficient removal from contaminated waters. The most applied bioassays to monitor the organophosphate toxicity i.e. the detoxification degree during AOP are Vibrio fischeri and AChE bioassays. Vibrio fischeri toxicity test exploits bioluminescence as the measure of luciferase activity of this marine bacterium, whereas AChE bioassay is based on AChE activity inhibition. Both bioanalytical techniques are rapid (several minutes, simple, sensitive and reproducible. Vibrio fischeri test seems to be a versatile indicator of toxic compounds generated in AOP for organophosphorus insecticides degradation. However, detection of neurotoxic AChE inhibitors, which can be formed in AOP of some organophosphates, requires AChE bioassays. Therefore, AChE toxicity test is more appropriate for monitoring the degradation processes of thio organophosphates, because more toxic oxo organophosphates might be formed and overlooked by Vibrio fischeri bioluminescence inhibition. In addition, during organophosphates removal by AOP, compounds with strong genotoxic potential may be formed, which cannot be detected by standard toxicity tests. For this reason, determination of

Stabilization of pH in solid-matrix hydroponic systems

Science.gov (United States)

Frick, J.; Mitchell, C. A.

1993-01-01

2-[N-morpholino]ethanesulfonic acid (MES) buffer or Amberlite DP-1 (cation-exchange resin beads) were used to stabilize substrate pH of passive-wicking, solid-matrix hydroponic systems in which small canopies of Brassica napus L. (CrGC 5-2, genome : ACaacc) were grown to maturity. Two concentrations of MES (5 or 10 mM) were included in Hoagland 1 nutrient solution. Alternatively, resin beads were incorporated into the 2 vermiculite : 1 perlite (v/v) growth medium at 6% or 12% of total substrate volume. Both strategies stabilized pH without toxic side effects on plants. Average seed yield rates for all four pH stabilization treatments (13.3 to 16.9 g m-2 day-1) were about double that of the control (8.2 g m-2 day-1), for which there was no attempt to buffer substrate pH. Both the highest canopy seed yield rate (16.9 g m-2 day-1) and the highest shoot harvest index (19.5%) occurred with the 6% resin bead treatment, even though the 10 mM MES and 12% bead treatments maintained pH within the narrowest limits. The pH stabilization methods tested did not significantly affect seed oil and protein contents.

Removal of organic matter and toxicity in hospital wastewaters by ozone

International Nuclear Information System (INIS)

Grisales Penagos, Dayana; Ortega Lopez, Joela; Rodriguez Chaparro, Tatiana

2012-01-01

Hospital wastewaters are considered to be one of the major sources of emergent contaminants as result of the dairy activities and excretion of the patients. Several studies have demonstrated that these compounds are not easily removed in conventional wastewater treatments that use biological process. This study evaluated the removal of the organic matter present in real hospital effluent applying ozone at different pH conditions (3,0, 6,7, 10). Parameters such as UV254, biodegradability ratio (COD/BOD) and color (VIS436) were measured. Moreover, it was assessed the acute toxicity with Allium cepa L. The results demonstrated that with an ozone dosage of 187 mgO3/h and pH = 10 the biodegradability increased by 70% and the acute toxicity decreased by 62%, whereas for pH =3,0 both UV254 and color removal was notable. The ozone application seems to be a viable alternative to treat hospital effluents as a pretreatment of a biological process.

Removal of organic matter and toxicity in hospital wastewaters by ozone

International Nuclear Information System (INIS)

Grisales Penagos Dayana; Ortega Lopez Joela; Rodriguez Chaparro Tatiana

2012-01-01

Hospital wastewaters are considered to be one of the major sources of emergent contaminants as result of the dairy activities and excretion of the patients. Several studies have demonstrated that these compounds are not easily removed in conventional wastewater treatments that use biological process. This study evaluated the removal of the organic matter present in real hospital effluent applying ozone at different pH conditions (3,0, 6,7, 10). Parameters such as UV254, biodegradability ratio (COD/BOD) and color (VIS436) were measured. Moreover, it was assessed the acute toxicity with Allium cepa L. The results demonstrated that with an ozone dosage of 187 MgO 3 /h and pH = 10 the biodegradability increased by 70% and the acute toxicity decreased by 62%, whereas for pH =3,0 both UV254 and color removal was notable. The ozone application seems to be a viable alternative to treat hospital effluents as a pretreatment of a biological process. Allium cepa L., biodegradability, emergent compounds, recalcitrance

Short - Term Exposure To Visible And Ultraviolet Light Modulates Dacarbazine Toxicity To Human Blood Cells In Vitro

International Nuclear Information System (INIS)

Kopjar, N.; Zunec, S.; Lucic Vrdoljak, A.; Zeljezic, D.; Mladinic, M.

2015-01-01

Dacarbazine (DTIC), i.e. 5-(3,3-dimethyltriazeno)imidazol-4-carboxamide, is an alkylating cytostatic used in the treatment of various types of human cancer. It is prone to photodegradation, the products of which cause adverse effects in treated patients. In the present study, we evaluated the relationships between photo genotoxicity, cytotoxicity, lipid peroxidation and AChE activity in in vitro DTIC - treated human blood after illumination with visible and ultraviolet light for 30 and 60 minutes. AChE activity was measured in erythrocytes. The extent of lipid peroxidation was measured in plasma. Cell death and morphological changes in the nuclei were studied in isolated peripheral blood lymphocytes using the fluorescent dye exclusion method. Primary DNA damage in lymphocytes was studied by alkaline comet assay immediately after treatment and 60 minutes later. The obtained results suggest that short-term exposure to UV and visible light modulated DTIC toxicity. Most of the effects were dose-dependent. We assume that photodegradation products, together with the parent compound, were responsible for increased LPO in plasma, along with cytotoxicity and infliction of primary DNA damage in lymphocytes. Erythrocyte AChE activity, on the other hand, was strongly impaired by the parent drug. Our findings suggest the need for a simultaneous evaluation of cyto-/genotoxicity and biochemical markers, as such an approach would provide much better insight into the mechanisms underlying drug toxicity in general. (author).

Pharmacological modulation of late radio-induced side effects; Modulation pharmacologique des effets tardifs de l'irradiation

Energy Technology Data Exchange (ETDEWEB)

Bourgier, C.; Bourhis, J.; Deutsch, E. [Departement de radiotherapie, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Unite mixte de recherche ' radiotherapie moleculaire' , Inserm unite 1030, 114, rue edouard-Vaillant, 94805 Villejuif (France); UMR 1030, universite Paris Sud 11, 114, rue edouard-Vaillant, 94805 Villejuif (France); UMR 1030, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Monceau, V. [Unite mixte de recherche ' radiotherapie moleculaire' , Inserm unite 1030, 114, rue edouard-Vaillant, 94805 Villejuif (France); UMR 1030, universite Paris Sud 11, 114, rue edouard-Vaillant, 94805 Villejuif (France); UMR 1030, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Vozenin, M.C. [Unite mixte de recherche ' radiotherapie moleculaire' , Inserm unite 1030, 114, rue edouard-Vaillant, 94805 Villejuif (France); UMR 1030, universite Paris Sud 11, 114, rue edouard-Vaillant, 94805 Villejuif (France); UMR 1030, institut de cancerologie Gustave-Roussy, 114, rue edouard-Vaillant, 94805 Villejuif (France); Unite mixte de recherche ' cellules souches et radiations' , Inserm unite 967, 18, route du Panorama, 92265 Fontenay-aux-Roses cedex (France); UMR 967, institut de radiobiologie cellulaire et moleculaire (iRCM), direction des sciences du vivant, CEA, 18, route du Panorama, 92265 Fontenay-aux-Roses cedex (France); UMR 967, universite Paris-Diderot Paris 7, 18, route du Panorama, 92265 Fontenay-aux-Roses cedex (France); UMR 967, universite Paris Sud 11, 18, route du Panorama, 92265 Fontenay-aux-Roses cedex (France)

2011-08-15

After normal tissue exposure to radiation therapy, late side effects can occur and may reduce patients' quality of life due to their progressive nature. Late toxicities occurrence is the main limiting factor of radiotherapy. Various biological disorders related to irradiation are involved in the development of late toxicities including fibrosis. The present review will focus on the recent physiopathological and molecular mechanisms described to be involved in the development of late radio-induced toxicities, that provide therapeutic perspective for pharmaco-modulation. (authors)

Preoperative intensity-modulated and image-guided radiotherapy with a simultaneous integrated boost in locally advanced rectal cancer: Report on late toxicity and outcome

International Nuclear Information System (INIS)

Engels, Benedikt; Platteaux, Nele; Van den Begin, Robbe; Gevaert, Thierry; Sermeus, Alexandra; Storme, Guy; Verellen, Dirk; De Ridder, Mark

2014-01-01

Background and purpose: The addition of chemotherapy to preoperative radiotherapy has been established as the standard of care for patients with cT3-4 rectal cancer. As an alternative strategy, we explored intensity-modulated and image-guided radiotherapy (IMRT–IGRT) with a simultaneous integrated boost (SIB) in a prospective phase II study. Here, we report outcome and late toxicity after a median follow-up of 54 months. Methods and materials: A total of 108 patients were treated preoperatively with IMRT–IGRT, delivering a dose of 46 Gy in fractions of 2 Gy. Patients (n = 57) displaying an anticipated circumferential resection margin (CRM) of less than 2 mm based on magnetic resonance imaging received a SIB to the tumor up to a total dose of 55.2 Gy. Results: The absolute incidence of grade ⩾3 late gastrointestinal and urinary toxicity was 9% and 4%, respectively, with a 13% rate of any grade ⩾3 late toxicity. The actuarial 5-year local control (LC), progression-free survival (PFS) and overall survival (OS) were 97%, 57%, and 68%. On multivariate analysis, R1 resection and pN2 disease were associated with significantly impaired OS. Conclusions: The use of preoperative IMRT–IGRT with a SIB resulted in a high 5-year LC rate and non-negligible late toxicity

Light modulated toxicity of isoproturon toward natural stream periphyton photosynthesis: a comparison between constant and dynamic light conditions.

Science.gov (United States)

Laviale, Martin; Prygiel, Jean; Créach, Anne

2010-05-10

This study tested if a variation in light intensity, in comparison to constant light required in well-designed toxicity test, could have measurable consequences on the sensitivity of phototrophic biofilms (periphyton) to isoproturon. Two independent experiments were carried out to investigate the combined effects of light and isoproturon on the photochemical behavior of intact natural biofilms by measurements of chlorophyll fluorescence and pigment composition. Experiment 1 consisted of exposing biofilms to series of isoproturon concentrations (0-2 mg L(-1)) for 7 h under constant light at different irradiance levels (25-300 micromol m(-2) s(-1)). In experiment 2, biofilms were exposed using more environmentally realistic conditions to three selected concentrations of isoproturon (2, 6 and 20 microg L(-1)) during a 7-h-simulated daily light cycle. Our results demonstrated that light, considered here as a direct physical stressor, slightly modulated the acute toxicity of isoproturon on these diatom dominated communities. This was attributed to the fact that these two factors act specifically on the photosynthetic activity. Furthermore, it was shown that a dynamic light regime increased periphyton sensitivity to isoproturon by challenging its photoprotective mechanisms such as the xanthophyll cycle, therefore implying that traditional ecotoxicological bioassays lead to underestimate the effect of isoproturon. 2010 Elsevier B.V. All rights reserved.

Differential gene expression in tomato fruit and Colletotrichum gloeosporioides during colonization of the RNAi-SlPH tomato line with reduced fruit acidity and higher pH.

Science.gov (United States)

Barad, Shiri; Sela, Noa; Dubey, Amit K; Kumar, Dilip; Luria, Neta; Ment, Dana; Cohen, Shahar; Schaffer, Arthur A; Prusky, Dov

2017-08-04

The destructive phytopathogen Colletotrichum gloeosporioides causes anthracnose disease in fruit. During host colonization, it secretes ammonia, which modulates environmental pH and regulates gene expression, contributing to pathogenicity. However, the effect of host pH environment on pathogen colonization has never been evaluated. Development of an isogenic tomato line with reduced expression of the gene for acidity, SlPH (Solyc10g074790.1.1), enabled this analysis. Total RNA from C. gloeosporioides colonizing wild-type (WT) and RNAi-SlPH tomato lines was sequenced and gene-expression patterns were compared. C. gloeosporioides inoculation of the RNAi-SlPH line with pH 5.96 compared to the WT line with pH 4.2 showed 30% higher colonization and reduced ammonia accumulation. Large-scale comparative transcriptome analysis of the colonized RNAi-SlPH and WT lines revealed their different mechanisms of colonization-pattern activation: whereas the WT tomato upregulated 13-LOX (lipoxygenase), jasmonic acid and glutamate biosynthesis pathways, it downregulated processes related to chlorogenic acid biosynthesis II, phenylpropanoid biosynthesis and hydroxycinnamic acid tyramine amide biosynthesis; the RNAi-SlPH line upregulated UDP-D-galacturonate biosynthesis I and free phenylpropanoid acid biosynthesis, but mainly downregulated pathways related to sugar metabolism, such as the glyoxylate cycle and L-arabinose degradation II. Comparison of C. gloeosporioides gene expression during colonization of the WT and RNAi-SlPH lines showed that the fungus upregulates ammonia and nitrogen transport and the gamma-aminobutyric acid metabolic process during colonization of the WT, while on the RNAi-SlPH tomato, it mainly upregulates the nitrate metabolic process. Modulation of tomato acidity and pH had significant phenotypic effects on C. gloeosporioides development. The fungus showed increased colonization on the neutral RNAi-SlPH fruit, and limited colonization on the WT acidic fruit

Early Clinical Outcomes and Toxicity of Intensity Modulated Versus Conventional Pelvic Radiation Therapy for Locally Advanced Cervix Carcinoma: A Prospective Randomized Study

Energy Technology Data Exchange (ETDEWEB)

Gandhi, Ajeet Kumar, E-mail: ajeetgandhi23@gmail.com [Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi (India); Sharma, Daya Nand; Rath, Goura Kisor; Julka, Pramod Kumar; Subramani, Vellaiyan; Sharma, Seema; Manigandan, Durai; Laviraj, M.A. [Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi (India); Kumar, Sunesh [Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi (India); Thulkar, Sanjay [Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi (India)

2013-11-01

Purpose: To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). Methods and Materials: Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m{sup 2}. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was graded according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. Results: Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). Conclusion: WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify

Acute dysprosium toxicity to Daphnia pulex and Hyalella azteca and development of the biotic ligand approach

Energy Technology Data Exchange (ETDEWEB)

Vukov, Oliver, E-mail: vuko3930@mylaurier.ca [Biology Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada); Smith, D. Scott [Chemistry Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada); McGeer, James C. [Biology Department, Wilfrid Laurier University, Waterloo, Ontario N2L 3C5 (Canada)

2016-01-15

The toxicological understanding of rare earth elements (REEs) in the aquatic environment is very limited but of increasing concern. The objective of this research is to compare the toxicological effect of the REE dysprosium to the freshwater invertebrates Daphnia pulex and Hyalella azteca and in the more sensitive organism, understand the toxicity modifying influence of Ca, Na, Mg, pH and dissolved organic matter (DOM). Standard methods (Environment Canada) were followed for testing and culture in media of intermediate hardness (60 mg CaCO{sub 3} mg/L) at pH 7.8 with Ca at 0.5, Na 0.5, Mg 0.125 (mM) and 23 °C. Acute toxicity tests were done with <24 h old neonates for 48 h in the case of D. pulex and with 2–9 days old offspring for 96 h tests with Hyalella. The potential protective effect of cationic competition was tested with Ca (0.5–2.0 mM), Na (0.5–2.0 mM) and Mg (0.125–0.5 mM). The effect of pH (6.5–8.0) and Suwannee River DOM complexation (at dissolved organic carbon (DOC) concentrations of 9 and 13 mg C/L) were evaluated. Dissolved Dy concentrations were lower than total (unfiltered) indicating precipitation, particularly at higher concentrations. Acute toxicity of Dy to H. azteca and D. pulex revealed Hyalella to be 1.4 times more sensitive than Daphnia. Additions of Ca and Na but not Mg provided significant protection against Dy toxicity to Hyalella. Similarly, low pH was associated with reduction in toxicity. Exposures which were pH buffered with and without MOPS were significantly different and indicated that MOPS enhanced Dy toxicity. DOM also mitigated Dy toxicity. Biotic ligand based parameters (Log K values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The log K value for Dy{sup 3+} toxicity to Hyalella was 7.75 while the protective influence of Ca and Na were 3.95 and 4.10, respectively. This study contributes data towards the development of site specific

Acute dysprosium toxicity to Daphnia pulex and Hyalella azteca and development of the biotic ligand approach

International Nuclear Information System (INIS)

Vukov, Oliver; Smith, D. Scott; McGeer, James C.

2016-01-01

The toxicological understanding of rare earth elements (REEs) in the aquatic environment is very limited but of increasing concern. The objective of this research is to compare the toxicological effect of the REE dysprosium to the freshwater invertebrates Daphnia pulex and Hyalella azteca and in the more sensitive organism, understand the toxicity modifying influence of Ca, Na, Mg, pH and dissolved organic matter (DOM). Standard methods (Environment Canada) were followed for testing and culture in media of intermediate hardness (60 mg CaCO 3 mg/L) at pH 7.8 with Ca at 0.5, Na 0.5, Mg 0.125 (mM) and 23 °C. Acute toxicity tests were done with <24 h old neonates for 48 h in the case of D. pulex and with 2–9 days old offspring for 96 h tests with Hyalella. The potential protective effect of cationic competition was tested with Ca (0.5–2.0 mM), Na (0.5–2.0 mM) and Mg (0.125–0.5 mM). The effect of pH (6.5–8.0) and Suwannee River DOM complexation (at dissolved organic carbon (DOC) concentrations of 9 and 13 mg C/L) were evaluated. Dissolved Dy concentrations were lower than total (unfiltered) indicating precipitation, particularly at higher concentrations. Acute toxicity of Dy to H. azteca and D. pulex revealed Hyalella to be 1.4 times more sensitive than Daphnia. Additions of Ca and Na but not Mg provided significant protection against Dy toxicity to Hyalella. Similarly, low pH was associated with reduction in toxicity. Exposures which were pH buffered with and without MOPS were significantly different and indicated that MOPS enhanced Dy toxicity. DOM also mitigated Dy toxicity. Biotic ligand based parameters (Log K values) were calculated based on free ion relationships as determined by geochemical equilibrium modeling software (WHAM ver. 7.02). The log K value for Dy 3+ toxicity to Hyalella was 7.75 while the protective influence of Ca and Na were 3.95 and 4.10, respectively. This study contributes data towards the development of site specific water quality

Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages.

Directory of Open Access Journals (Sweden)

Lydia Kasper

Full Text Available Candida glabrata currently ranks as the second most frequent cause of invasive candidiasis. Our previous work has shown that C. glabrata is adapted to intracellular survival in macrophages and replicates within non-acidified late endosomal-stage phagosomes. In contrast, heat killed yeasts are found in acidified matured phagosomes. In the present study, we aimed at elucidating the processes leading to inhibition of phagosome acidification and maturation. We show that phagosomes containing viable C. glabrata cells do not fuse with pre-labeled lysosomes and possess low phagosomal hydrolase activity. Inhibition of acidification occurs independent of macrophage type (human/murine, differentiation (M1-/M2-type or activation status (vitamin D3 stimulation. We observed no differential activation of macrophage MAPK or NFκB signaling cascades downstream of pattern recognition receptors after internalization of viable compared to heat killed yeasts, but Syk activation decayed faster in macrophages containing viable yeasts. Thus, delivery of viable yeasts to non-matured phagosomes is likely not triggered by initial recognition events via MAPK or NFκB signaling, but Syk activation may be involved. Although V-ATPase is abundant in C. glabrata phagosomes, the influence of this proton pump on intracellular survival is low since blocking V-ATPase activity with bafilomycin A1 has no influence on fungal viability. Active pH modulation is one possible fungal strategy to change phagosome pH. In fact, C. glabrata is able to alkalinize its extracellular environment, when growing on amino acids as the sole carbon source in vitro. By screening a C. glabrata mutant library we identified genes important for environmental alkalinization that were further tested for their impact on phagosome pH. We found that the lack of fungal mannosyltransferases resulted in severely reduced alkalinization in vitro and in the delivery of C. glabrata to acidified phagosomes. Therefore

Identification and modulation of the key amino acid residue responsible for the pH sensitivity of neoculin, a taste-modifying protein.

Directory of Open Access Journals (Sweden)

Ken-ichiro Nakajima

Full Text Available Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS and a neoculin basic subunit (NBS. Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor-taste substance in particular.

Validation of a biotic ligand model on site-specific copper toxicity to Daphnia magna in the Yeongsan River, Korea.

Science.gov (United States)

Park, Jinhee; Ra, Jin-Sung; Rho, Hojung; Cho, Jaeweon; Kim, Sang Don

2018-03-01

The objective of this study was to determine whether the water effect ratio (WER) or biotic ligand model (BLM) could be applied to efficiently develop water quality criteria (WQC) in Korea. Samples were collected from 12 specific sites along the Yeongsan River (YSR), Korea, including two sewage treatment plants and one estuary lake. A copper toxicity test using Daphnia magna was performed to determine the WER and to compare to the BLM prediction. The results of the WER from YSR samples also indicated significantly different copper toxicities in all sites. The model-based predictions showed that effluent and estuary waters had significantly different properties in regard to their ability to be used to investigate water characteristics and copper toxicity. It was supposed that the slight water characteristics changes, such as pH, DOC, hardness, conductivity, among others, influence copper toxicity, and these variable effects on copper toxicity interacted with the water composition. The 38% prediction was outside of the validation range by a factor of two in all sites, showing a poor predictive ability, especially in STPs and streams adjacent to the estuary, while the measured toxicity was more stable. The samples that ranged from pH 7.3-7.7 generated stable predictions, while other samples, including those with lower and the higher pH values, led to more unstable predictions. The results also showed that the toxicity of Cu in sample waters to D. magna was closely proportional to the amounts of acidity, including the carboxylic and phenolic groups, as well as the DOC concentrations. Consequently, the acceptable prediction of metal toxicity in various water samples needs the site-specific results considering the water characteristics such as pH and DOC properties particularly in STPs and estuary regions. Copyright © 2017 Elsevier Inc. All rights reserved.

Membrane Cholesterol Modulates Superwarfarin Toxicity

Energy Technology Data Exchange (ETDEWEB)

Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan; Braun, David; Polak, Paul E.; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L.

2016-04-26

Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

pH controlled gating of toxic protein pores by dendrimers

Science.gov (United States)

Mandal, Taraknath; Kanchi, Subbarao; Ayappa, K. G.; Maiti, Prabal K.

2016-06-01

Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent bacterial strains, on a target cell membrane is a challenging and active area of research. Here we demonstrate that PAMAM dendrimers can act as effective pH controlled gating devices once the pore has been formed. We have used fully atomistic molecular dynamics (MD) simulations to characterize the cytolysin A (ClyA) protein pores modified with fifth generation (G5) PAMAM dendrimers. Our results show that the PAMAM dendrimer, in either its protonated (P) or non-protonated (NP) states can spontaneously enter the protein lumen. Protonated dendrimers interact strongly with the negatively charged protein pore lumen. As a consequence, P dendrimers assume a more expanded configuration efficiently blocking the pore when compared with the more compact configuration adopted by the neutral NP dendrimers creating a greater void space for the passage of water and ions. To quantify the effective blockage of the protein pore, we have calculated the pore conductance as well as the residence times by applying a weak force on the ions/water. Ionic currents are reduced by 91% for the P dendrimers and 31% for the NP dendrimers. The preferential binding of Cl- counter ions to the P dendrimer creates a zone of high Cl- concentration in the vicinity of the internalized dendrimer and a high concentration of K+ ions in the transmembrane region of the pore lumen. In addition to steric effects, this induced charge segregation for the P dendrimer effectively blocks ionic transport through the pore. Our investigation shows that the bio-compatible PAMAM dendrimers can potentially be used to develop therapeutic protocols based on the pH sensitive gating of pores formed by pore forming toxins to mitigate bacterial infections.Designing effective nanoscale blockers for membrane inserted pores formed by pore forming toxins, which are expressed by several virulent

Electrochemical oxidation of selective estrogen receptor modulator raloxifene

International Nuclear Information System (INIS)

Li, Xi-Qian; He, Jian-Bo; Liu, Lu; Cui, Ting

2013-01-01

Highlights: ► Application and analysis of in situ thin-layer spectroelectrochemistry. ► Cyclic voltabsorptometry used for a drug study. ► Highly pH-dependent oxidative metabolism of raloxifene. ► A complex parallel-consecutive mechanism proposed for oxidation of raloxifene. -- Abstract: Raloxifene is a selective estrogen receptor modulator that may produce toxic oxidative species in metabolism. The oxidation mechanism of raloxifene with different pH values was studied by cyclic voltammetry, X-ray photoelectron spectroscopy (XPS), in situ UV–vis spectral analysis and cyclic voltabsorptometry based on a long optical-path thin-layer electrochemical cell. Time-derivative cyclic voltabsorptograms were obtained for comparative discussion with the corresponding cyclic voltammograms. Raloxifene was initially oxidized to reactive phenoxyl radicals, followed by a series of transformation steps leading to different final products in different pH media. A parallel-consecutive reaction mechanism was proposed for the pH-dependent formation of 7-hydroxyraloxifene, raloxifene 6,7-o-quinone and two raloxifene dimers, each pathway following a complex electrochemical-chemical mechanism. Both raloxifene diquinone methide and its N-oxides were not detected by in situ UV–vis spectroscopy and XPS analysis. This work provides an electrochemical viewpoint and comparable information for better understanding of the oxidative metabolism and chemical toxicology of raloxifene under physiological conditions in vivo or in vitro

Tomotherapy for prostate adenocarcinoma: A report on acute toxicity

International Nuclear Information System (INIS)

Keiler, Louis; Dobbins, Donald; Kulasekere, Ravi; Einstein, Douglas

2007-01-01

Background and purpose: To analyze the impact of Tomotherapy (TOMO) intensity modulated radiotherapy (IMRT) on acute gastrointestinal (GI) and genitourinary (GU) toxicity in prostate cancer. Materials and methods: The records of 55 consecutively treated TOMO patients were reviewed. Additionally a well-matched group of 43 patients treated with LINAC-based step and shoot IMRT (LINAC) was identified. Acute toxicity was scored according to Radiation Therapy Oncology Group acute toxicity criterion. Results: The grade 2-3 acute GU toxicity rates for the TOMO vs. LINAC groups were 51% vs. 28% (p = 0.001). Acute grade 2 GI toxicity was 25% vs. 40% (p = 0.024), with no grade 3 GI toxicity in either group. In univariate analysis, androgen deprivation, prostate volume, pre-treatment urinary toxicity, and prostate dose homogeneity correlated with acute GI and GU toxicity. With multivariate analysis use of Tomotherapy, median bladder dose and bladder dose homogeneity remained significantly correlated with GU toxicity. Conclusions: Acute GI toxicity for prostate cancer is improved with Tomotherapy at a cost of increased acute GU toxicity possibly due to differences in bladder and prostate dose distribution

Toxicity of proton-metal mixtures in the field: Linking stream macroinvertebrate species diversity to chemical speciation and bioavailability

Energy Technology Data Exchange (ETDEWEB)

Stockdale, Anthony [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Tipping, Edward, E-mail: et@ceh.ac.uk [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Lofts, Stephen [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Ormerod, Stephen J. [Catchment Research Group, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US (United Kingdom); Clements, William H. [Department of Fish, Wildlife, and Conservation Biology, Colorado State University, Fort Collins, CO 80523 (United States); Blust, Ronny [Ecophysiology, Biochemistry and Toxicology Group, Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp (Belgium)

2010-10-01

Understanding metal and proton toxicity under field conditions requires consideration of the complex nature of chemicals in mixtures. Here, we demonstrate a novel method that relates streamwater concentrations of cationic metallic species and protons to a field ecological index of biodiversity. The model WHAM-F{sub TOX} postulates that cation binding sites of aquatic macroinvertebrates can be represented by the functional groups of natural organic matter (humic acid), as described by the Windermere Humic Aqueous Model (WHAM6), and supporting field evidence is presented. We define a toxicity function (F{sub TOX}) by summing the products: (amount of invertebrate-bound cation) x (cation-specific toxicity coefficient, {alpha}{sub i}). Species richness data for Ephemeroptera, Plecoptera and Trichoptera (EPT), are then described with a lower threshold of F{sub TOX}, below which all organisms are present and toxic effects are absent, and an upper threshold above which organisms are absent. Between the thresholds the number of species declines linearly with F{sub TOX}. We parameterised the model with chemistry and EPT data for low-order streamwaters affected by acid deposition and/or abandoned mines, representing a total of 412 sites across three continents. The fitting made use of quantile regression, to take into account reduced species richness caused by (unknown) factors other than cation toxicity. Parameters were derived for the four most common or abundant cations, with values of {alpha}{sub i} following the sequence (increasing toxicity) H{sup +} < Al < Zn < Cu. For waters affected mainly by H{sup +} and Al, F{sub TOX} shows a steady decline with increasing pH, crossing the lower threshold near to pH 7. Competition effects among cations mean that toxicity due to Cu and Zn is rare at lower pH values, and occurs mostly between pH 6 and 8.

Do diosgenin ameliorate urinary bladder toxic effect of ...

African Journals Online (AJOL)

SWEET

2012-01-26

Jan 26, 2012 ... experimental animal models? ... BSO doses using a Swiss albino mouse model. Toxicity modulation ... bladder inflammation induced by CP in rats and mice .... 0.1 ml NADPH (nicotinamide adenine dinucleotide phosphate.

Environmentally safe management of radioactive and toxic sludges

International Nuclear Information System (INIS)

Shingarev, N.E.; Mukhin, I.V.; Polyakov, A.S.; Raginsky, L.S.; Semenov, B.A.

2000-01-01

Toxic industrial wastes constitute a significant part of Russian natural environment. The most reliable route to provide the long-term ecologic safety involves removal of toxicants or radioactive substances from polluted sites. With a view of processing toxic and radioactive sludges available in reservoirs, a process flowsheet is suggested that comprises the operations of sludge concentration, dehydration and granulation.Flocculation is an operation required to concentrate a solid phase. Polyacrylamide (PAA) and hydrolyzed PAA (HPAA) are standard flocculating agents used in the processing of sludges coming from storage facilities of radioactive wastes. HPAA is less efficient and it is shown that the optimized concentration of PAA is 4 mg/g solid. Flotation agents are used to extract the solid phase of sludges, it is shown that the process of extraction has to be carried out in 2 stages, the first flotation cycle with a Ph value between 7.5 and 9.5 and the second with a Ph adjustment to 3.5-6.0.The cake resulting from the sludge filtration has poor technological properties, it is advisable to produce a granular material. Hydro-granulation using hydrophobic flocculating agents may be implemented immediately after sludge concentration. The other granulation technique involves the sol-gel process used to incorporate sludge into a ceramic (aluminium oxide) matrix

Modulation of physiological responses with TiO2 nano-particle in Azolla pinnata R.Br. under 2,4-D toxicity.

Science.gov (United States)

De, Arnab Kumar; Ghosh, Arijit; Debnath, Subhas Chandra; Sarkar, Bipul; Saha, Indraneel; Adak, Malay Kumar

2018-06-05

The present work is emphasised with the herbicidal tolerance of Azolla pinnata R.Br. and its modulation with TiO 2 nano-particle. Both carbohydrate and nitrogen metabolism were effected with 2,4-D as herbicide and in few cases TiO 2 -NP had recovered few detrimental effects. From the nutrient status in Azolla it recorded the recovery of nitrogen as well as potassium by TiO 2 -NP but not in case of phosphorus. However, a conversion of nitrate to ammonium was more induced by TiO 2 -NP under herbicidal toxicity. Similar results were obtained for inter-conversion of amino acid-nitrate pool, but no changes with glutamine synthase activity with TiO 2 -NP. Initially, the effects of 2,4-D was monitored with changes of chlorophyll content but had not been recovered with nanoparticle. Photosynthetic reserves expressed as both total and reducing sugar were insensitive to TiO 2 -NP interference but activity of soluble and wall bound invertase was in reverse trend as compared to control. The 2,4-D mediated changes of redox and its oxidative stress was ameliorated in plants with over expressed ADH activity. As a whole the Azolla bio system with TiO 2 supplementation may be useful in sustenance against 2,4-D toxicity through recovery of nitrogen metabolism. Thus, Azolla-TiO 2 -NP bio system would be realised to monitor the herbicidal toxicity in soil and its possible bioremediation.

Determining the bioavailability and toxicity of lead contamination to earthworms requires using a combination of physicochemical and biological methods

International Nuclear Information System (INIS)

Luo, Wei; Verweij, Rudo A.; Gestel, Cornelis A.M. van

2014-01-01

This study aimed at assessing the bioavailability and toxicity of lead to Eisenia andrei in shooting range soils representing different land uses (forest, grassland, bullet plot). Soils contained 47–2398 mg Pb/kg dry weight (dw), but also had different pH-CaCl 2 (3.2–6.8) and organic matter contents (3.8–13%). Therefore artificial soils with different pH and organic matter contents and two natural soils were included as control soils. Earthworms were exposed for 28 days and toxicity and uptake of Pb were related to total, water and 0.01 M CaCl 2 extractable and porewater Pb concentrations as well as to soil characteristics. Pb uptake in the earthworms linearly increased with increasing soil concentrations. At >2000 mg Pb/kg dw and pH 3.3–3.5, high earthworm mortality with significant weight loss and complete inhibition of reproduction were recorded. At <1000 mg/kg dw, earthworm reproduction was more related to differences in pH and other soil characteristics than to Pb. -- Highlights: • Availability and earthworm toxicity of Pb determined in field-contaminated soils. • Earthworm toxicity of most-polluted soils explained from available Pb levels. • Earthworm response in less polluted soils mainly determined by soil pH. • Earthworm toxicity correlated with Pb uptake from the soil. • Soil properties explained differences in earthworm Pb uptake and effects. -- Combination of physicochemical and biological assays helped explaining Pb toxicity in shooting range soils from available Pb concentrations and soil characteristics

Narrow pH Range of Surface Water Bodies Receiving Pesticide Input in Europe.

Science.gov (United States)

Bundschuh, Mirco; Weyers, Arnd; Ebeling, Markus; Elsaesser, David; Schulz, Ralf

2016-01-01

Fate and toxicity of the active ingredients (AI's) of plant protection products in surface waters is often influenced by pH. Although a general range of pH values is reported in literature, an evaluation targeting aquatic ecosystems with documented AI inputs is lacking at the larger scale. Results show 95% of European surface waters (n = 3075) with a documented history of AI exposure fall within a rather narrow pH range, between 7.0 and 8.5. Spatial and temporal variability in the data may at least be partly explained by the calcareous characteristics of parental rock material, the affiliation of the sampling site to a freshwater ecoregion, and the photosynthetic activity of macrophytes (i.e., higher pH values with photosynthesis). Nonetheless, the documented pH range fits well with the standard pH of most ecotoxicological test guidelines, confirming the fate and ecotoxicity of AIs are usually adequately addressed.

Sulfate transport kinetics and toxicity are modulated by sodium in aquatic insects.

Science.gov (United States)

Scheibener, Shane; Conley, Justin M; Buchwalter, David

2017-09-01

The salinization of freshwater ecosystems is emerging as a major ecological issue. Several anthropogenic causes of salinization (e.g. surface coal mining, hydro-fracking, road de-icing, irrigation of arid lands, etc.) are associated with biodiversity losses in freshwater ecosystems. Because insects tend to dominate freshwater ecology, it is important that we develop a better understanding of how and why different species respond to salinity matrices dominated by different major ions. This study builds upon previous work demonstrating that major ion toxicity to the mayfly Neocloeon triangulifer was apparently due to the ionic composition of water rather than specific conductance. Synthetic waters with low Ca:Mg ratios and high SO 4 :Na ratios produced toxicity, whereas waters with higher Ca:Mg ratios and lower SO 4 :Na ratios were not toxic to mayflies at comparable conductivities. Here we used a radiotracer approach to show that Mg did not competitively exclude Ca uptake at environmentally realistic ratios in 4 aquatic insect species. We characterized SO 4 uptake kinetics in 5 mayflies and assessed the influence of different ions on SO 4 uptake. Dual label experiments show an inverse relationship between SO 4 and Na transport rates as SO 4 was held constant and Na was increased, suggesting that Na (and not Cl or HCO 3 ) is antagonistic to SO 4 transport. Based on this observation, we tested the hypothesis that increasing Na would protect against SO 4 induced toxicity in a Na-dependent manner. Increasing Na from 0.7 to 10.9mM improved 96-h survivorship associated with 20.8mM SO 4 from 44% to 73% in a concentration dependent manner. However, when Na reached 21.8mM, survivorship decreased to 16%, suggesting that other interactive effects of major ions caused toxicity under those conditions. Thus, the combination of elevated sulfate and low sodium commonly observed in streams affected by mountaintop coal mining has the potential to cause toxicity in sensitive aquatic

Dietary Chemoprevention of PhIP Induced Carcinogenesis in Male Fischer 344 Rats with Tomato and Broccoli

Science.gov (United States)

Canene-Adams, Kirstie; Sfanos, Karen S.; Liang, Chung-Tiang; Yegnasubramanian, Srinivasan; Nelson, William G.; Brayton, Cory; De Marzo, Angelo M.

2013-01-01

The heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-B]pyridine (PhIP), found in meats cooked at high temperatures, has been implicated in epidemiological and rodent studies for causing breast, prostate, and colorectal cancers. A previous animal study using a xenograft model has shown that whole tomato and broccoli, when eaten in combination, exhibit a marked effect on tumor reduction compared to when eaten alone. Our aim was to determine if PhIP-induced carcinogenesis can be prevented by dietary consumption of whole tomato + broccoli powders. Male Fischer 344 rats (n = 45) were randomized into the following treatment groups: control (AIN93G diet), PhIP (200 ppm in AIN93G diet for the first 20 weeks of the study), or tomato + broccoli + PhIP (mixed in AIN93G diet at 10% each and fed with PhIP for 20 weeks, and then without PhIP for 32 weeks). Study animals were monitored for 52 weeks and were euthanized as necessary based on a set of criteria for health status and tumor burden. Although there appeared to be some hepatic and intestinal toxicity due to the combination of PhIP and tomato + broccoli, these rodents had improved survival and reduced incidence and/or severity of PhIP-induced neoplastic lesions compared to the PhIP-alone treated group. Rats eating tomato + broccoli exhibited a marked decrease in the number and size of cribiform prostatic intraepitheilial neoplasia/carcinoma in situ (cribiform PIN/CIS) lesions and in the incidence of invasive intestinal adenocarcinomas and skin carcinomas. Although the apparent toxic effects of combined PhIP and tomato + broccoli need additional study, the results of this study support the hypothesis that a diet rich in tomato and broccoli can reduce or prevent dietary carcinogen-induced cancers. PMID:24312188

pH during non-synaptic epileptiform activity—computational simulations

Science.gov (United States)

Márcio Rodrigues, Antônio; Canton Santos, Luiz Eduardo; Covolan, Luciene; Hamani, Clement; Guimarães de Almeida, Antônio-Carlos

2015-10-01

The excitability of neuronal networks is strongly modulated by changes in pH. The origin of these changes, however, is still under debate. The high complexity of neural systems justifies the use of computational simulation to investigate mechanisms that are possibly involved. Simulated neuronal activity includes non-synaptic epileptiform events (NEA) induced in hippocampal slices perfused with high-K+ and zero-Ca2+, therefore in the absence of the synaptic circuitry. A network of functional units composes the NEA model. Each functional unit represents one interface of neuronal/extracellular space/glial segments. Each interface contains transmembrane ionic transports, such as ionic channels, cotransporters, exchangers and pumps. Neuronal interconnections are mediated by gap-junctions, electric field effects and extracellular ionic fluctuations modulated by extracellular electrodiffusion. Mechanisms investigated are those that change intracellular and extracellular ionic concentrations and are able to affect [H+]. Our simulations suggest that the intense fluctuations in intra and extracellular concentrations of Na+, K+ and Cl- that accompany NEA are able to affect the combined action of the Na+/H+ exchanger (NHE), {{{HCO}}}3-/Cl- exchanger (HCE), H+ pump and the catalytic activity of intra and extracellular carbonic anhydrase. Cellular volume changes and extracellular electrodiffusion are responsible for modulating pH.

Oxidation of iodide and iodine on birnessite (delta-MnO2) in the pH range 4-8.

Science.gov (United States)

Allard, Sébastien; von Gunten, Urs; Sahli, Elisabeth; Nicolau, Rudy; Gallard, Hervé

2009-08-01

The oxidation of iodide by synthetic birnessite (delta-MnO(2)) was studied in perchlorate media in the pH range 4-8. Iodine (I(2)) was detected as an oxidation product that was subsequently further oxidized to iodate (IO(3)(-)). The third order rate constants, second order on iodide and first order on manganese oxide, determined by extraction of iodine in benzene decreased with increasing pH (6.3-7.5) from 1790 to 3.1M(-2) s(-1). Both iodine and iodate were found to adsorb significantly on birnessite with an adsorption capacity of 12.7 microM/g for iodate at pH 5.7. The rate of iodine oxidation by birnessite decreased with increasing ionic strength, which resulted in a lower rate of iodate formation. The production of iodine in iodide-containing waters in contact with manganese oxides may result in the formation of undesired iodinated organic compounds (taste and odor, toxicity) in natural and technical systems. The probability of the formation of such compounds is highest in the pH range 5-7.5. For pH iodine is quickly oxidized to iodate, a non-toxic and stable sink for iodine. At pH >7.5, iodide is not oxidized to a significant extent.

Analyzing the capacity of the Daphnia magna and Pseudokirchneriella subcapitata bioavailability models to predict chronic zinc toxicity at high pH and low calcium concentrations and formulation of a generalized bioavailability model for D. magna.

Science.gov (United States)

Van Regenmortel, Tina; Berteloot, Olivier; Janssen, Colin R; De Schamphelaere, Karel A C

2017-10-01

Risk assessment in the European Union implements Zn bioavailability models to derive predicted-no-effect concentrations for Zn. These models are validated within certain boundaries (i.e., pH ≤ 8 and Ca concentrations ≥ 5mg/L), but a substantial fraction of the European surface waters falls outside these boundaries. Therefore, we evaluated whether the chronic Zn biotic ligand model (BLM) for Daphnia magna and the chronic bioavailability model for Pseudokirchneriella subcapitata could be extrapolated to pH > 8 and Ca concentrations model can accurately predict Zn toxicity for Ca concentrations down to 0.8 mg/L and pH values up to 8.5. Because the chronic Zn BLM for D. magna could not be extrapolated beyond its validity boundaries for pH, a generalized bioavailability model (gBAM) was developed. Of 4 gBAMs developed, we recommend the use of gBAM-D, which combines a log-linear relation between the 21-d median effective concentrations (expressed as free Zn 2+ ion activity) and pH, with more conventional BLM-type competition constants for Na, Ca, and Mg. This model is a first step in further improving the accuracy of chronic toxicity predictions of Zn as a function of water chemistry, which can decrease the uncertainty in implementing the bioavailability-based predicted-no-effect concentration in the risk assessment of high-pH and low-Ca concentration regions in Europe. Environ Toxicol Chem 2017;36:2781-2798. © 2017 SETAC. © 2017 SETAC.

Macroinvertebrate response to acid mine drainage: community metrics and on-line behavioural toxicity bioassay

International Nuclear Information System (INIS)

Gerhardt, A.; Janssens de Bisthoven, L.; Soares, A.M.V.M.

2004-01-01

The hypothesis is tested that toxicity of acid mine drainage can be detected by a selection of existing macroinvertebrate community and bioindicator metrices supplemented by toxicity tests with the local mosquitofish Gambusia holbrooki Girard and the shrimp Atyaephyra desmaresti Millet. The behavioural responses of A. desmaresti to acid mine drainage were recorded in the Multispecies Freshwater Biomonitor[reg], based on behaviour and survival as parameters. Bioassessment methods were based on community diversity, structure, function, and bioindicators and supplemented by chemical analysis (temperature, pH, metals). The Biological Monitoring Working Party adapted for the Iberian Peninsula, the number of predators (Coleoptera, Hemiptera) and the number of Ephemeroptera and Trichoptera taxa differentiated the sites well. The on-line toxicity test revealed pH-dependent acute toxicity of the acid mine drainage for the shrimp (LC 50 -48 h: pH-AMD=5.8) and a pH- dependent decrease in locomotory activity with the lowest-observed-response-times (LORTs) within 5 h of exposure. Shrimp were more sensitive to acid mine drainage than fish (LC 50 -48 h: pH-AMD=4.9). A new multimetric index combining toxicity testing and bioassessment methods is proposed. - Toxicity of acid mine drainage was evaluated by macroinvertebrate bioassessment and a new on-line rapid behavioural toxicity test with Atyaephyra desmaresti (Crustacea)

Macroinvertebrate response to acid mine drainage: community metrics and on-line behavioural toxicity bioassay

Energy Technology Data Exchange (ETDEWEB)

Gerhardt, A.; Janssens de Bisthoven, L.; Soares, A.M.V.M

2004-07-01

The hypothesis is tested that toxicity of acid mine drainage can be detected by a selection of existing macroinvertebrate community and bioindicator metrices supplemented by toxicity tests with the local mosquitofish Gambusia holbrooki Girard and the shrimp Atyaephyra desmaresti Millet. The behavioural responses of A. desmaresti to acid mine drainage were recorded in the Multispecies Freshwater Biomonitor[reg], based on behaviour and survival as parameters. Bioassessment methods were based on community diversity, structure, function, and bioindicators and supplemented by chemical analysis (temperature, pH, metals). The Biological Monitoring Working Party adapted for the Iberian Peninsula, the number of predators (Coleoptera, Hemiptera) and the number of Ephemeroptera and Trichoptera taxa differentiated the sites well. The on-line toxicity test revealed pH-dependent acute toxicity of the acid mine drainage for the shrimp (LC{sub 50}-48 h: pH-AMD=5.8) and a pH- dependent decrease in locomotory activity with the lowest-observed-response-times (LORTs) within 5 h of exposure. Shrimp were more sensitive to acid mine drainage than fish (LC{sub 50}-48 h: pH-AMD=4.9). A new multimetric index combining toxicity testing and bioassessment methods is proposed. - Toxicity of acid mine drainage was evaluated by macroinvertebrate bioassessment and a new on-line rapid behavioural toxicity test with Atyaephyra desmaresti (Crustacea)

Inorganic carbon acquisition in potentially toxic and non-toxic diatoms: the effect of pH-induced changes in the seawater carbonate chemistry

DEFF Research Database (Denmark)

Trimborn, S; Lundholm, Nina; Thoms, S

2008-01-01

. In terms of carbon source, all species took up both CO2 and HCO3-. K-1/2 values for inorganic carbon uptake decreased with increasing pH in two species, while in N. navis-varingica apparent affinities did not change. While the contribution of HCO3- to net fixation was more than 85% in S. stellaris......The effects of pH-induced changes in seawater carbonate chemistry on inorganic carbon (C-i) acquisition and domoic acid (DA) production were studied in two potentially toxic diatom species, Pseudo-nitzschia multiseries and Nitzschia navis-varingica, and the non-toxic Stellarima stellaris. In vivo...... activities of carbonic anhydrase (CA), photosynthetic O-2 evolution and CO2 and HCO3- uptake rates were measured by membrane inlet MS in cells acclimated to low (7.9) and high pH (8.4 or 8.9). Species-specific differences in the mode of carbon acquisition were found. While extracellular carbonic anhydrase (e...

Dredged Material Evaluations: Review of Zooplankton Toxicity Test Methods for Marine Water Quality Evaluations

Science.gov (United States)

2016-09-01

term impacts of the DM while settling through the water column (elutriate toxicity tests), and long-term toxicity (whole sediment toxicity tests) and...elutriates are prepared according to guidance (USEPA/USACE 1991; 1998) by mixing sediment and site water and allowing settling for prescribed periods...of water and waste water . 17th ed. Washington, DC: APHA. Arnold, W. R., R. L. Diamond, and D. S. Smith. 2010a. The effects of salinity, pH, and

Accounting for dissociation and photolysis: a review of the algal toxicity of triclosan.

Science.gov (United States)

Roberts, Jayne; Price, Oliver R; Bettles, Nicola; Rendal, Cecilie; van Egmond, Roger

2014-11-01

Triclosan, an antimicrobial agent commonly used in down-the-drain consumer products, is toxic to freshwater microalgae. However, the rapid photolysis and pH-dependent dissociation of this compound may give rise to uncertainty in growth inhibition tests with freshwater microalgae, if these are not well characterized. Methods are presented to minimize these uncertainties by stabilizing pH with an organic buffering agent (Bis-Tris) and by the application of ultraviolet (UV) covers to remove UV wavelengths. Toxicity tests with these methods were in compliance with the validity criteria of the Organisation for Economic Co-operation and Development test 201, and no negative effects were seen in controls relative to the unmodified method. The methods were used for toxicity tests with triclosan at pH levels of 7.0, 8.0, and 8.5, yielding effective concentration, 10% values of 0.5 µg/L, 0.6 µg/L, and 12.1 µg/L, respectively. The observed change in toxicity with pH was proportional to the change in bioconcentration factor (BCF) as calculated using the cell model (a dynamic flux model based on the Fick-Nernst-Planck equations, in this case parameterized for an algal cell). Effect concentrations produced with the methods presented in the present study offer robust data on which to base risk assessment, and it is suggested that similar approaches be used to minimize uncertainty when other compounds that dissociate and photolyse are tested. © 2014 SETAC.

pH and the cytotoxicity of fluoride in an animal cell culture system

International Nuclear Information System (INIS)

Helgeland, K.; Leirskar, J.

1976-01-01

To investigate the mechanism for the toxicity of silicate cement as observed in a cell culture system, the effects of pH and fluoride were tested on human epithelial cells (NCTC 2544). At pH 7.3, fluoride concentrations from 15 to 25 μg/ml (0.79 to 1.3 mM) had a growth inhibitory effect. When the pH of the incubation medium was lowered to the range 7.0 to 6.4, an enhanced cytotoxic effect of fluoride was found, and even at 5 to 10 μg/ml growth inhibition occurred. Concomitant with the enhanced cytotoxicity of fluoride at low pH, there was an increased utilization of glucose and formation of lactate. Upon lowering the pH of the incubation medium from 7.4 to 6.7, a twofold increase in the intracellular concentration of fluoride was found. (author)

Effects of chelating agent CBMIDA on the toxicity of depleted uranium administered subcutaneously in rats

International Nuclear Information System (INIS)

Fukuda, Satoshi; Ikeda, Mizuyo; Nakamaura, Mariko

2008-01-01

We examined the acute toxicity of depleted uranium (DU) after subcutaneous injection as a simulated wounds model, and the effects of the chelating agent catechol-3,6-bis(methyliminodiacetic acid) (CBMIDA), by local treatment in rats. First, to examine the initial behavior and toxicity of uranium of different chemical forms, male Wistar rats were subcutaneously injected with 4 and 16 mg/kg DU (pH 1) in a solution of pH 1 and 7, respectively, and were killed 1, 3, 6 and 24 hours later. After the injection of DU(pH1), about 60% of the uranium was retained for first 1-3 hours at the injected sites, and then decreased to 16% at 24 hours in the 4 mg/kg DU group; however, the uranium did not change significantly in the 16 mg/kg DU group. Urinary excretion rates of uranium increased in a time-independent manner after the injection Depositions of uranium in the liver, kidneys and femur were found at 1 hour after DU injection, with significant increases in serum and urinary biochemical markers indicating acute and severe damage. The results of the DU (pH 7) injection were useful for estimating the toxicity of uranium by the chemical changes in the body. Second, CBMIDA (480 mg/kg) was infused into the DU-injected site at 0, 10, 30, 60 min and 24 hours after the subcutaneous injection of 4 mg/kg DU (pH 1 and 7). When CBMIDA was administered within 120 min after DU (pH 1) injection, the uranium at the injected sites decreased to 4-17% of that in the no-treatment DU (pH 1) group, and was excreted effectively in the urine and feces, with decreased levels in the kidneys and femur. The results indicated that the subcutaneously injected uranium acutely induced severe damage in the DU-injected sites and organs after DU intake, relating to chemical forms of uranium by pH and that local treatment of CBMIDA was effective in decreasing the acute toxicity of uranium if carried out as early as possible (at least within 2 hours) after DU administration. (author)

Protective influence of healthful nutrition on mechanisms of environmental pollutant toxicity and disease risks.

Science.gov (United States)

Hoffman, Jessie B; Hennig, Bernhard

2017-06-01

Human exposures to environmental contaminants around the world contribute to the global burden of disease and thus require urgent attention. Exploring preventive measures against environmental exposure and disease risk is essential. While a sedentary lifestyle and/or poor dietary habits can exacerbate the deleterious effects resulting from exposure to toxic chemicals, much emerging evidence suggests that positive lifestyle changes (e.g., healthful nutrition) can modulate and/or reduce the toxicity of environmental pollutants. Our work has shown that diets high in anti-inflammatory bioactive food components (e.g., phytochemicals or polyphenols) are possible strategies for modulating and reducing the disease risks associated with exposure to toxic pollutants in the environment. Thus, consuming healthy diets rich in plant-derived bioactive nutrients may reduce the vulnerability to diseases linked to environmental toxic insults. This nutritional paradigm in environmental toxicology requires further study in order to improve our understanding of the relationships between nutrition and other lifestyle modifications and toxicant-induced diseases. © 2017 New York Academy of Sciences.

Seasonal variability in irradiance affects herbicide toxicity to the marine flagellate Dunaliella tertiolecta

NARCIS (Netherlands)

Sjollema, S.B.; Vavourakis, C.D.; van der Geest, H.G.; Vethaak, A.D.; Admiraal, W.

2014-01-01

Photosynthetically Active Radiation (PAR) and Ultraviolet Radiation (UVR) of the solar spectrum affect microalgae directly and modify the toxicity of phytotoxic compounds present in water. As a consequence seasonal variable PAR and UVR levels are likely to modulate the toxic pressure of contaminants

Hydroxy-Al and cell-surface negativity are responsible for the enhanced sensitivity of Rhodotorula taiwanensis to aluminum by increased medium pH.

Science.gov (United States)

Zhao, Xue Qiang; Bao, Xue Min; Wang, Chao; Xiao, Zuo Yi; Hu, Zhen Min; Zheng, Chun Li; Shen, Ren Fang

2017-10-01

Aluminum (Al) is ubiquitous and toxic to microbes. High Al 3+ concentration and low pH are two key factors responsible for Al toxicity, but our present results contradict this idea. Here, an Al-tolerant yeast strain Rhodotorula taiwanensis RS1 was incubated in glucose media containing Al with a continuous pH gradient from pH 3.1-4.2. The cells became more sensitive to Al and accumulated more Al when pH increased. Calculations using an electrostatic model Speciation Gouy Chapman Stern indicated that, the increased Al sensitivity of cells was associated with AlOH 2+ and Al(OH) 2 + rather than Al 3+ . The alcian blue (a positively charged dye) adsorption and zeta potential determination of cell surface indicated that, higher pH than 3.1 increased the negative charge and Al adsorption at the cell surface. Taken together, the enhanced sensitivity of R. taiwanensis RS1 to Al from pH 3.1-4.2 was associated with increased hydroxy-Al and cell-surface negativity.

Role of soil properties in sewage sludge toxicity to soil collembolans

OpenAIRE

Domene, X.

2010-01-01

Soil properties are one of the most important factors explaining the different toxicity results found in different soils. Although there is knowledge about the role of soil properties on the toxicity of individual chemicals, not much is known about its relevance for sewage sludge amendments. In particular little is known about the effect of soil properties on the toxicity modulation of these complex wastes. In addition, in most studies on sewage sludges the identity of the main substances lin...

Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

International Nuclear Information System (INIS)

Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, José

2012-01-01

Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m²). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D mean and D max of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade ≥2 and grade ≥3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade ≥2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade ≥3 AET (P=.012). The derived V50 model was shown to predict grade ≥2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade ≥3 AET. There was no difference in the incidence of grade ≥2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

Measurements of spectral responses for developing fiber-optic pH sensor

Science.gov (United States)

Yoo, Wook Jae; Heo, Ji Yeon; Jang, Kyoung Won; Seo, Jeong Ki; Moon, Jin Soo; Park, Jang-Yeon; Park, Byung Gi; Cho, Seunghyun; Lee, Bongsoo

2011-01-01

In this study, we have fabricated a fiber-optic pH sensor, which is composed of a light source, a pH-sensing probe, plastic optical fibers and a spectrometer, for determining the degree of infection by Helicobacter pylori in the stomach. As pH indicators, phenol red and m-cresol purple are used, and pH liquid solutions are prepared by mixing phenol red or m-cresol purple solutions and various kinds of pH buffer solutions. The light emitted by a light source is guided by plastic optical fibers to the pH liquid solution, and the optical characteristic of a reflected light is changed according to the color variations of the pH indicator in the pH-sensing probe. Therefore, we have measured the intensities and wavelength shifts of the reflected lights, which change according to the color variations of indicators at different pH values, by using a spectrometer for spectral analysis. Also, the relationships between the pH values of liquid solutions and the optical properties of the modulated lights are obtained on the basis of the changes of the colors of indicators.

Hybrid silica materials for detection of toxic species and clinical diagnosis

OpenAIRE

Pascual Vidal, Lluís

2017-01-01

The present PhD thesis entitled "Silica Hybrid Materials for detection of toxic species and clinical diagnosis" is focused on the design and synthesis of new hybrid materials, using different silica supports as inorganic scaffolds, with applications in recognition, sensing and diagnostic protocols. The first chapter of the PhD thesis is devoted to the definition and classification of hybrid materials, relying on concepts of Nanotechnology, Supramolecular and Materials Chemistry. State o...

Design of a compact high-speed optical modulator based on a hybrid plasmonic nanobeam cavity

Science.gov (United States)

Javid, Mohammad Reza; Miri, Mehdi; Zarifkar, Abbas

2018-03-01

A hybrid plasmonic electro-optic modulator based on a polymer-filled one dimensional photonic crystal nanobeam (1D PhCNB) cavity is proposed here. In the proposed structure the optical intensity modulation is realized by shifting the resonant wavelength of the cavity through electrically tuning the refractive index of the electro-optic polymer in the hybrid plasmonic waveguide. As a result of the subwavelength light confinement in the hybrid plasmonic waveguide and the compact footprint of the 1D PhCNB cavity, the designed modulator has the small overall footprint of 3 . 6 μm2 and the required wavelength shift can be achieved by applying very small actuating power. Three dimensional finite-difference time-domain (3D-FDTD) simulations show that the modulation depth of 10.9 dB, and insertion loss of 1.14 dB, along with very high modulation speed of 224 GHz can be achieved in the proposed modulator with very low modulation energy of 0.75 fJ/bit. A comparison between the performance parameters of the proposed modulator and those of previously reported PhCNB based modulators reveals the superior performance of the proposed structure in terms of modulation speed, energy consumption and overall footprint.

Antitumour, antimicrobial and catalytic activity of gold nanoparticles synthesized by different pH propolis extracts

Science.gov (United States)

Gatea, Florentina; Teodor, Eugenia Dumitra; Seciu, Ana-Maria; Covaci, Ovidiu Ilie; Mănoiu, Sorin; Lazăr, Veronica; Radu, Gabriel Lucian

2015-07-01

The Romanian propolis was extracted in five different media, respectively, in water (pH 6.8), glycine buffer (pH 2.5), acetate buffer (pH 5), phosphate buffer (pH 7.4) and carbonate buffer (pH 9.2). The extracts presented different amounts of flavonoids and phenolic acids, increasing pH leading to higher concentrations of active compounds. Five variants of gold nanoparticles suspensions based on different pH Romanian propolis aqueous extracts were successfully synthesized. The obtained nanoparticles presented dimensions between 20 and 60 nm in dispersion form and around 18 nm in dried form, and different morphologies (spherical, hexagonal, triangular). Fourier transform infrared spectroscopy proved the attachment of organic compounds from propolis extracts to the colloidal gold suspensions and X-ray diffraction certified that the suspensions contain metallic gold. The obtained propolis gold nanoparticles do not exhibit any antibacterial or antifungal activity, but presented different catalytic activities and toxicity on tumour cells.

Antitumour, antimicrobial and catalytic activity of gold nanoparticles synthesized by different pH propolis extracts

Energy Technology Data Exchange (ETDEWEB)

Gatea, Florentina; Teodor, Eugenia Dumitra, E-mail: eu-teodor@yahoo.com [National Institute for Biological Sciences, Centre of Bioanalysis (Romania); Seciu, Ana-Maria [National Institute for Biological Sciences, Cellular and Molecular Biology Department (Romania); Covaci, Ovidiu Ilie [SARA Pharm Solutions (Romania); Mănoiu, Sorin [National Institute for Biological Sciences, Cellular and Molecular Biology Department (Romania); Lazăr, Veronica [University of Bucharest, Faculty of Biology (Romania); Radu, Gabriel Lucian [University “Politehnica” Bucharest, Faculty of Applied Chemistry and Materials Science (Romania)

2015-07-15

The Romanian propolis was extracted in five different media, respectively, in water (pH 6.8), glycine buffer (pH 2.5), acetate buffer (pH 5), phosphate buffer (pH 7.4) and carbonate buffer (pH 9.2). The extracts presented different amounts of flavonoids and phenolic acids, increasing pH leading to higher concentrations of active compounds. Five variants of gold nanoparticles suspensions based on different pH Romanian propolis aqueous extracts were successfully synthesized. The obtained nanoparticles presented dimensions between 20 and 60 nm in dispersion form and around 18 nm in dried form, and different morphologies (spherical, hexagonal, triangular). Fourier transform infrared spectroscopy proved the attachment of organic compounds from propolis extracts to the colloidal gold suspensions and X-ray diffraction certified that the suspensions contain metallic gold. The obtained propolis gold nanoparticles do not exhibit any antibacterial or antifungal activity, but presented different catalytic activities and toxicity on tumour cells.

Influence of potentially confounding factors on sea urchin porewater toxicity tests

Science.gov (United States)

Carr, R.S.; Biedenbach, J.M.; Nipper, M.

2006-01-01

The influence of potentially confounding factors has been identified as a concern for interpreting sea urchin porewater toxicity test data. The results from >40 sediment-quality assessment surveys using early-life stages of the sea urchin Arbacia punctulata were compiled and examined to determine acceptable ranges of natural variables such as pH, ammonia, and dissolved organic carbon on the fertilization and embryological development endpoints. In addition, laboratory experiments were also conducted with A. punctulata and compared with information from the literature. Pore water with pH as low as 6.9 is an unlikely contributor to toxicity for the fertilization and embryological development tests with A. punctulata. Other species of sea urchin have narrower pH tolerance ranges. Ammonia is rarely a contributing factor in pore water toxicity tests using the fertilization endpoint, but the embryological development endpoint may be influenced by ammonia concentrations commonly found in porewater samples. Therefore, ammonia needs to be considered when interpreting results for the embryological development test. Humic acid does not affect sea urchin fertilization at saturation concentrations, but it could have an effect on the embryological development endpoint at near-saturation concentrations. There was no correlation between sediment total organic carbon concentrations and porewater dissolved organic carbon concentrations. Because of the potential for many varying substances to activate parthenogenesis in sea urchin eggs, it is recommended that a no-sperm control be included with every fertilization test treatment. ?? 2006 Springer Science+Business Media, Inc.

A microfabricated fringing field capacitive pH sensor with an integrated readout circuit

International Nuclear Information System (INIS)

Arefin, Md Shamsul; Redoute, Jean-Michel; Rasit Yuce, Mehmet; Bulut Coskun, M.; Alan, Tuncay; Neild, Adrian

2014-01-01

This work presents a microfabricated fringe-field capacitive pH sensor using interdigitated electrodes and an integrated modulation-based readout circuit. The changes in capacitance of the sensor result from the permittivity changes due to pH variations and are converted to frequency shifts using a crossed-coupled voltage controlled oscillator readout circuit. The shift in resonant frequency of the readout circuit is 30.96 MHz for a change in pH of 1.0–5.0. The sensor can be used for the measurement of low pH levels, such as gastric acid, and can be integrated with electronic pills. The measurement results show high repeatability, low noise, and a stable output.

A microfabricated fringing field capacitive pH sensor with an integrated readout circuit

Energy Technology Data Exchange (ETDEWEB)

Arefin, Md Shamsul, E-mail: md.arefin@monash.edu; Redoute, Jean-Michel; Rasit Yuce, Mehmet [Electrical and Computer Systems Engineering, Monash University, Melbourne (Australia); Bulut Coskun, M.; Alan, Tuncay; Neild, Adrian [Mechanical and Aerospace Engineering, Monash University, Melbourne (Australia)

2014-06-02

This work presents a microfabricated fringe-field capacitive pH sensor using interdigitated electrodes and an integrated modulation-based readout circuit. The changes in capacitance of the sensor result from the permittivity changes due to pH variations and are converted to frequency shifts using a crossed-coupled voltage controlled oscillator readout circuit. The shift in resonant frequency of the readout circuit is 30.96 MHz for a change in pH of 1.0–5.0. The sensor can be used for the measurement of low pH levels, such as gastric acid, and can be integrated with electronic pills. The measurement results show high repeatability, low noise, and a stable output.

Particles in swimming pool filters – Does pH determine the DBP formation?

DEFF Research Database (Denmark)

Hansen, Kamilla Marie Speht; Willach, Sarah; Mosbæk, Hans

2012-01-01

The formation was investigated for different groups of disinfection byproducts (DBPs) during chlorination of filter particles from swimming pools at different pH-values and the toxicity was estimated. Specifically, the formation of the DBP group trihalomethanes (THMs), which is regulated in many...... or initial free chlorine concentrations the particles were chlorinated at different pH-values in the relevant range for swimming pools. THM and HAA formations were reduced by decreasing pH while HAN formation increased with decreasing pH. Based on the organic content the relative DBP formation from...

Ionoregulatory and toxicological responses of stonefly nymphs (Plecoptera) to acidic and alkaline pH

Energy Technology Data Exchange (ETDEWEB)

Lechleitner, R.A.; Cherry, D.S.; Cairns, J. Jr.; Stetler, D.A.

1985-03-01

The acute toxicities of acidic and alkaline pH to nymphs of the stoneflies Pteronarcys dorsata, P. proteus, and Tallaperla maria were determined in 96-hr static bioassays. The acidic and alkaline 96-hr LC/sub 50/ values were 2.8 to 3.3 and 12.1 to 10.3, respectively. Exposure to pH 3.0 for 72 hr or longer caused a significant loss of sodium from nymphs of P. proteus. Morphological changes, including distension of cuticular disk and increased number of vesicles, were observed in gill tissue from nymphs of P. dorsata exposed to pH 2.5 for 9 hr while minor changes were observed in nymphs exposed to pH 4.0 for 96 hr. Changes in gill tissue ultrastructure included an increase in number of vesicles and a decrease in number and size of mitochondria in nymphs exposed to alkaline pH of 11.75.

The Use of Stimulable Bioluminescence From Dinoflagellates as a Means of Detecting Toxicity in the Marine Environment

Science.gov (United States)

1993-03-01

AND SSTýTL FUNDINCG NUMI)) W, TIHE USE OF STIMt LABILE BIOLUMINESCENCE FROM DI NOIFLAGELLATk. PH: M1E69 AS A MEAN’S OF DETrECTING ToxicITY IN THE...bioluminescence dinoflagellates for asseossmnent of toxic effects when exposed to a single tox~icant or mixture. Successful use of this type of bioassav... tributyltin chloride (TFITCI), Copper (11) Sulfate (CuSO 4 I. zinc sulfate (ZnSO4 ), or storm drain effluent. Stimulable bioluminescence was measured at

Acute and chronic toxicity of boron to a variety of freshwater organisms.

Science.gov (United States)

Soucek, David J; Dickinson, Amy; Koch, Brian T

2011-08-01

Boron enters the aquatic environment from various sources, including weathering of borates, sewage effluents, coal combustion, use of cleaning compounds, and agrochemicals. The present study was designed to generate data on acute and chronic boron toxicity in support of an update of water quality standards in Illinois, USA. We examined the acute toxicity of boron to eight different freshwater organisms including a fish, an insect, two crustaceans, and four bivalve mollusks. To our knowledge, this is the first study to present data on the toxicity of boron to freshwater mollusks. We also sought to clarify whether hardness or pH affect boron toxicity to aquatic life, and to quantify chronic effect levels in two freshwater species. Sensitivity among the various species ranged widely, with the fathead minnow (Pimephales promelas) being the most sensitive. Neither pH nor hardness had a consistent effect on acute boron toxicity to two crustaceans (Ceriodaphnia dubia and Hyalella azteca), but we observed evidence that chloride reduces boron toxicity to H. azteca. The fathead minnow, while more acutely sensitive than the other species, had a lower acute to chronic ratio than did H. azteca, which had reduced reproduction at 13 mg/L. While we do not know the extent to which the eight tested species represent the range of sensitivities of native but untested species in Illinois, the current water quality standard for Illinois (1 mg/L) is conservative with regard to the native species tested thus far. Copyright © 2011 SETAC.

Homogeneous plate based antibody internalization assay using pH sensor fluorescent dye.

Science.gov (United States)

Nath, Nidhi; Godat, Becky; Zimprich, Chad; Dwight, Stephen J; Corona, Cesear; McDougall, Mark; Urh, Marjeta

2016-04-01

Receptor-mediated antibody internalization is a key mechanism underlying several anti-cancer antibody therapeutics. Delivering highly toxic drugs to cancer cells, as in the case of antibody drug conjugates (ADCs), efficient removal of surface receptors from cancer cells and changing the pharmacokinetics profile of the antibody drugs are some of key ways that internalization impacts the therapeutic efficacy of the antibodies. Over the years, several techniques have been used to study antibody internalization including radiolabels, fluorescent microscopy, flow cytometry and cellular toxicity assays. While these methods allow analysis of internalization, they have limitations including a multistep process and limited throughput and are generally endpoint assays. Here, we present a new homogeneous method that enables time and concentration dependent measurements of antibody internalization. The method uses a new hydrophilic and bright pH sensor dye (pHAb dye), which is not fluorescent at neutral pH but becomes highly fluorescent at acidic pH. For receptor mediated antibody internalization studies, antibodies against receptors are conjugated with the pHAb dye and incubated with the cells expressing the receptors. Upon binding to the receptor, the dyes conjugated to the antibody are not fluorescent because of the neutral pH of the media, but upon internalization and trafficking into endosomal and lysosomal vesicles the pH drops and dyes become fluorescent. The enabling attributes of the pHAb dyes are the hydrophilic nature to minimize antibody aggregation and bright fluorescence at acidic pH which allows development of simple plate based assays using a fluorescent reader. Using two different therapeutic antibodies--Trastuzumab (anti-HER2) and Cetuximab (anti-EGFR)--we show labeling with pHAb dye using amine and thiol chemistries and impact of chemistry and dye to antibody ration on internalization. We finally present two new approaches using the pHAb dye, which will be

Influence of the pH value of anthocyanins on the electrical properties of dye-sensitized solar cells

Directory of Open Access Journals (Sweden)

Irén Juhász Junger

2017-03-01

Full Text Available In recent years the harvesting of renewable energies became of great importance. This led to a rapid development of dye-sensitized solar cells which can be produced from low-purity materials. The best electrical properties are provided by cells prepared using synthetical, ruthenium based dyes. Unfortunately, most of them are toxic and expensive. The anthocyanins extracted for example from hibiscus flowers yield a more cost-effective and eco-friendly alternative to toxic dyes, however, with a loss of solar cell efficiency. In this article the possibility of improvement of the conversion efficiency by modification of the pH value of the dye is investigated. By decrease of the pH value, an increase of efficiency by a factor of two was achieved.

Effects of pH on uranium uptake and oxidative stress responses induced in Arabidopsis thaliana

OpenAIRE

Saenen, Eline; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Biermans, Geert; Van Hees, May; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

2013-01-01

Uranium (U) causes oxidative stress in Arabidopsis thaliana plants grown at pH 5.5. However, U speciation and its toxicity strongly depend on environmental parameters, for example pH. It is unknown how different U species determine U uptake and translocation within plants and how they might affect the oxidative defense mechanisms of these plants. The present study analyzed U uptake and oxidative stress-related responses in A. thaliana (Columbia ecotype) under contrasted U chemical speciation ...

Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique

OpenAIRE

Md. Rajibur Rahaman Khan; Shin-Won Kang

2016-01-01

In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal?s pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The...

Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions.

Science.gov (United States)

Rimkute, Lina; Kraujalis, Tadas; Snipas, Mindaugas; Palacios-Prado, Nicolas; Jotautis, Vaidas; Skeberdis, Vytenis A; Bukauskas, Feliksas F

2018-01-01

Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pH i ) and cytosolic magnesium ion concentration ([Mg 2+ ] i ), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail. Our experimental results in HeLa cells expressing Cx36 show that changes in both pH i and [Mg 2+ ] i affect junctional conductance (g j ) in an interdependent manner; in other words, intracellular acidification cause increase or decay in g j depending on whether [Mg 2+ ] i is high or low, respectively, and intracellular alkalization cause reduction in g j independently of [Mg 2+ ] i . Our experimental and modelling data support the hypothesis that Cx36 GJ channels contain two separate gating mechanisms, and both are differentially sensitive to changes in pH i and [Mg 2+ ] i . Using recombinant Cx36 we found that two glutamate residues in the N-terminus could be partly responsible for the observed interrelated effect of pH i and [Mg 2+ ] i . Mutation of glutamate at position 8 attenuated the stimulatory effect of intracellular acidification at high [Mg 2+ ] i , while mutation at position 12 and double mutation at both positions reversed stimulatory effect to inhibition. Moreover, Cx36 * E8Q lost the initial increase of g j at low [Mg 2+ ] i and double mutation lost the sensitivity to high [Mg 2+ ] i . These results suggest that E8 and E12 are involved in regulation of Cx36 GJ channels by Mg 2+ and H + ions.

Data collection and analysis strategies for phMRI.

Science.gov (United States)

Mandeville, Joseph B; Liu, Christina H; Vanduffel, Wim; Marota, John J A; Jenkins, Bruce G

2014-09-01

Although functional MRI traditionally has been applied mainly to study changes in task-induced brain function, evolving acquisition methodologies and improved knowledge of signal mechanisms have increased the utility of this method for studying responses to pharmacological stimuli, a technique often dubbed "phMRI". The proliferation of higher magnetic field strengths and the use of exogenous contrast agent have boosted detection power, a critical factor for successful phMRI due to the restricted ability to average multiple stimuli within subjects. Receptor-based models of neurovascular coupling, including explicit pharmacological models incorporating receptor densities and affinities and data-driven models that incorporate weak biophysical constraints, have demonstrated compelling descriptions of phMRI signal induced by dopaminergic stimuli. This report describes phMRI acquisition and analysis methodologies, with an emphasis on data-driven analyses. As an example application, statistically efficient data-driven regressors were used to describe the biphasic response to the mu-opioid agonist remifentanil, and antagonism using dopaminergic and GABAergic ligands revealed modulation of the mesolimbic pathway. Results illustrate the power of phMRI as well as our incomplete understanding of mechanisms underlying the signal. Future directions are discussed for phMRI acquisitions in human studies, for evolving analysis methodologies, and for interpretative studies using the new generation of simultaneous PET/MRI scanners. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polyoxyethylene hydrogenated castor oil modulates benzalkonium chloride toxicity: comparison of acute corneal barrier dysfunction induced by travoprost Z and travoprost.

Science.gov (United States)

Uematsu, Masafumi; Kumagami, Takeshi; Shimoda, Kenichiro; Kusano, Mao; Teshima, Mugen; To, Hideto; Kitahara, Takashi; Kitaoka, Takashi; Sasaki, Hitoshi

2011-10-01

To determine the element that modulates benzalkonium chloride (BAC) toxicity by using a new electrophysiological method to evaluate acute corneal barrier dysfunction induced by travoprost Z with sofZia (Travatan Z(®)), travoprost with 0.015% BAC (Travatan(®)), and its additives. Corneal transepithelial electrical resistance (TER) was measured in live white Japanese rabbits by 2 Ag/AgCl electrodes placed in the anterior aqueous chamber and on the cornea. We evaluated corneal TER changes after a 60-s exposure to travoprost Z, travoprost, and 0.015% BAC. Similarly, TER changes were evaluated after corneas were exposed for 60 s to the travoprost additives ethylenediaminetetraacetic acid disodium salt, boric acid, mannitol, trometamol, and polyoxyethylene hydrogenated castor oil 40 (HCO-40) with or without BAC. Corneal damage was examined after exposure to BAC with or without travoprost additives using scanning electron microscopy (SEM) and a cytotoxicity assay. Although no decreases of TER were noted after exposure to travoprost Z with sofZia and travoprost with 0.015% BAC, a significant decrease of corneal TER was observed after 0.015% BAC exposure. With the exception of BAC, no corneal TER decreases were observed for any travoprost additives. After corneal exposure to travoprost additives with BAC, HCO-40 was able to prevent the BAC-induced TER decrease. SEM observations and the cytotoxicity assay confirmed that there was a remarkable improvement of BAC-induced corneal epithelial toxicity after addition of HCO-40 to the BAC. Travoprost Z with sofZia and travoprost with BAC do not induce acute corneal barrier dysfunction. HCO-40 provides protection against BAC-induced corneal toxicity.

The role of pH in heavy metal detoxification by biosorption from ...

African Journals Online (AJOL)

The high level of toxic metal pollution in the environment is a result of increased human activities. The hydrogen ion concentration of solutions has been known to affect reactions in solutions. The role of pH in As(V), Pb(II) and Hg(II) ions detoxification by bio-sorption from aqueous solutions using coconut fiber and sawdust ...

pH control structure design for a periodically operated membrane separation process

DEFF Research Database (Denmark)

Prado Rubio, Oscar Andres; Jørgensen, Sten Bay; Jonsson, Gunnar Eigil

2012-01-01

A bioreactor integrated with an electrically driven membrane separation process (Reverse Electro-Enhanced Dialysis – REED) is under investigation as potential technology for intensifying lactic acid bioproduction. In this contribution the pH regulation issue in the periodically operated REED module...

Influence of pH and media composition on suspension stability of silver, zinc oxide, and titanium dioxide nanoparticles and immobilization of Daphnia magna under guideline testing conditions.

Science.gov (United States)

Cupi, Denisa; Hartmann, Nanna B; Baun, Anders

2016-05-01

In aquatic toxicity testing of engineered nanoparticles (ENPs) the process of agglomeration is very important as it may alter bioavailability and toxicity. In the present study, we aimed to identify test conditions that are favorable for maintaining stable ENP suspensions. We evaluated the influence of key environmental parameters: pH (2-12) and ionic strength using M7, Soft EPA (S EPA) medium, and Very Soft EPA (VS EPA) medium; and observed the influence of these parameters on zeta potential, zeta average, and acute immobilization of Daphnia magna for three different ENPs. Despite being sterically stabilized, test suspensions of silver (Ag) ENPs formed large agglomerates in both VS EPA and M7 media; and toxicity was found to be higher in VS EPA medium due to increased dissolution. Low-agglomerate suspensions for zinc oxide (ZnO) could be obtained at pH 7 in VS EPA medium, but the increase in dissolution caused higher toxicity than in M7 medium. Titanium dioxide (TiO2) ENPs had a point of zero charge in the range of pH 7-8. At pH 7 in VS EPA, agglomerates with smaller hydrodynamic diameters (~200nm) were present compared to the high ionic strength M7 medium where hydrodynamic diameters reached micrometer range. The stable suspensions of TiO2 ENPs caused immobilization of D. magna, 48-h EC50 value of 13.7mgL(-1) (95% CI, 2.4mg-79.1mgL(-1)); whereas no toxicity was seen in the unstable, highly agglomerated M7 medium suspensions, 48-h EC50 >100mgL(-1). The current study provides a preliminary approach for methodology in testing and assessing stability and toxicity of ENPs in aquatic toxicity tests of regulatory relevance. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of a molecular pH sensor in coral.

Science.gov (United States)

Barott, Katie L; Barron, Megan E; Tresguerres, Martin

2017-11-15

Maintaining stable intracellular pH (pHi) is essential for homeostasis, and requires the ability to both sense pH changes that may result from internal and external sources, and to regulate downstream compensatory pH pathways. Here we identified the cAMP-producing enzyme soluble adenylyl cyclase (sAC) as the first molecular pH sensor in corals. sAC protein was detected throughout coral tissues, including those involved in symbiosis and calcification. Application of a sAC-specific inhibitor caused significant and reversible pHi acidosis in isolated coral cells under both dark and light conditions, indicating sAC is essential for sensing and regulating pHi perturbations caused by respiration and photosynthesis. Furthermore, pHi regulation during external acidification was also dependent on sAC activity. Thus, sAC is a sensor and regulator of pH disturbances from both metabolic and external origin in corals. Since sAC is present in all coral cell types, and the cAMP pathway can regulate virtually every aspect of cell physiology through post-translational modifications of proteins, sAC is likely to trigger multiple homeostatic mechanisms in response to pH disturbances. This is also the first evidence that sAC modulates pHi in any non-mammalian animal. Since corals are basal metazoans, our results indicate this function is evolutionarily conserved across animals. © 2017 The Author(s).

Modulation of mitochondrial bioenergetics in a skeletal muscle cell line model of mitochondrial toxicity

Directory of Open Access Journals (Sweden)

William Dott

2014-01-01

Full Text Available Mitochondrial toxicity is increasingly being implicated as a contributing factor to many xenobiotic-induced organ toxicities, including skeletal muscle toxicity. This has necessitated the need for predictive in vitro models that are able to sensitively detect mitochondrial toxicity of chemical entities early in the research and development process. One such cell model involves substituting galactose for glucose in the culture media. Since cells cultured in galactose are unable to generate sufficient ATP from glycolysis they are forced to rely on mitochondrial oxidative phosphorylation for ATP generation and consequently are more sensitive to mitochondrial perturbation than cells grown in glucose. The aim of this study was to characterise cellular growth, bioenergetics and mitochondrial toxicity of the L6 rat skeletal muscle cell line cultured in either high glucose or galactose media. L6 myoblasts proliferated more slowly when cultured in galactose media, although they maintained similar levels of ATP. Galactose cultured L6 cells were significantly more sensitive to classical mitochondrial toxicants than glucose-cultured cells, confirming the cells had adapted to galactose media. Analysis of bioenergetic function with the XF Seahorse extracellular flux analyser demonstrated that oxygen consumption rate (OCR was significantly increased whereas extracellular acidification rate (ECAR, a measure of glycolysis, was decreased in cells grown in galactose. Mitochondria operated closer to state 3 respiration and had a lower mitochondrial membrane potential and basal mitochondrial O2·– level compared to cells in the glucose model. An antimycin A (AA dose response revealed that there was no difference in the sensitivity of OCR to AA inhibition between glucose and galactose cells. Importantly, cells in glucose were able to up-regulate glycolysis, while galactose cells were not. These results confirm that L6 cells are able to adapt to growth in a

Toxic Anterior Segment Syndrome (TASS

Directory of Open Access Journals (Sweden)

Özlem Öner

2011-12-01

Full Text Available Toxic anterior segment syndrome (TASS is a sterile intraocular inflammation caused by noninfectious substances, resulting in extensive toxic damage to the intraocular tissues. Possible etiologic factors of TASS include surgical trauma, bacterial endotoxin, intraocular solutions with inappropriate pH and osmolality, preservatives, denatured ophthalmic viscosurgical devices (OVD, inadequate sterilization, cleaning and rinsing of surgical devices, intraocular lenses, polishing and sterilizing compounds which are related to intraocular lenses. The characteristic signs and symptoms such as blurred vision, corneal edema, hypopyon and nonreactive pupil usually occur 24 hours after the cataract surgery. The differential diagnosis of TASS from infectious endophthalmitis is important. The main treatment for TASS formation is prevention. TASS is a cataract surgery complication that is more commonly seen nowadays. In this article, the possible underlying causes as well as treatment and prevention methods of TASS are summarized. (Turk J Oph thal mol 2011; 41: 407-13

USE OF ULVA LACTUCA TO DISTINGUISH PH DEPENDENT TOXICANTS IN MARINE WATERS AND SEDIMENTS

Science.gov (United States)

Ulva lactuca (sea lettuce) is a cosmopolitan marine attached green seaweed capable of sequestering high environmental levels of ammonia. Ammonia can be acutely toxic to marine organisms and is often found in dredged sediments from highly industrial areas or from areas with high c...

Oxidative stress responses induced by uranium exposure at low pH in leaves of Arabidopsis thaliana plants

International Nuclear Information System (INIS)

Saenen, Eline; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Biermans, Geert; Hees, May van; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

2015-01-01

Anthropogenic activities have led to a widespread uranium (U) contamination in many countries. The toxic effects of U at the cellular level have mainly been investigated at a pH around 5.5, the optimal pH for hydroponically grown plants. However, since the speciation of U, and hence its toxicity, is strongly dependent on environmental factors such as the pH, it is important to investigate the effects of U at different environmentally relevant pH levels. Although U is poorly translocated from the roots to the shoots, resulting in a low U concentration in the leaves, it has been demonstrated that toxic effects in the leaves were already visible after 1 day exposure at pH 5.5, although only when exposed to relatively high U concentrations (100 μM). Therefore, the present study aimed to analyse the effects of different U concentrations (ranging from 0 to 100 μM) at pH 4.5 in leaves of Arabidopsis thaliana plants. Results indicate that U induces early senescence in A. thaliana leaves as was suggested by a decreased expression of CAT2 accompanied by an induction of CAT3 expression, a decreased CAT capacity and an increased lipid peroxidation. In addition, miRNA398b/c is involved in the regulation of the SOD response in the leaves. As such, an increased MIR398b/c expression was observed leading to a decreased transcript level of CSD1/2. Finally, the biosynthesis of ascorbate was induced after U exposure. This can point towards an important role for this metabolite in the scavenging of reactive oxygen species under U stress. - Highlights: • Uranium induces early senescence in A. thaliana after uranium exposure. • Ascorbate is involved in scavenging reactive oxygen species under uranium stress. • miRNA398b/c is involved in the regulation of the SOD response under uranium stress.

Development of innovative pH sensor to evaluate phagocytosis of nanoparticles

International Nuclear Information System (INIS)

Leclerc, L; Boudard, D; Pourchez, J; Cottier, M; Marmuse, L; Louis, C; Palle, S; Grosseau, P; Bernache, D

2011-01-01

The aim of this work was the development of pH-sensor-NP allowing the quantification of the amount of NP phagocytosed by macrophages. Two types of fluorescent NP with variable and well-characterized sizes and chemicals coatings have been synthesized: - NP with a FITC core (FITC-NP): green fluorescence (control). - FITC-NP functionalized with a pH sensitive probe (pH-sensor-NP): green fluorescence of the FITC and red fluorescence of the pH probe in acidic conditions. Our pH-sensor-NP model was first validated in acellular conditions. They were then incubated with a macrophage cell line allowing distinction and quantification of internalized NP with no major effects on biological toxicity.

Speciation, uptake and toxicity of uranium in Atlantic Salmon (Salmo salar)

Energy Technology Data Exchange (ETDEWEB)

Teien, Hans-Christian; Hertel-Aas, Turid; Lind, Ole Christian; Skipperud, Lindis; Oughton, Deborah H.; Salbu, Brit [Norwegian University of Life Sciences (NMBU), Center of Excellence in Environmental Radioactivity (CERAD). P.O. Box 5003, N-1432 Aas (Norway); Thoerring, Haavard [Norwegian Radiation Protection Authority (NRPA), P.O. Box 55, N-1332 Oesteraas (Norway)

2014-07-01

To obtain information about the bioavailability of uranium (U) and its chemical toxicity, a significant number of Atlantic Salmon (Salmo salar) juveniles (in total about 800 fish) were exposure to commercial available depleted uranium (DU) in controlled experiments conducted in accordance with the OECD guidelines for acute toxicity tests. Speciation, gill accumulation and induced toxicity of U as a function of varying water concentrations of H{sup +}, Ca{sup 2+}, Mg{sup 2+}, Na{sup +} and K{sup +} as well as U were studied. In addition to recording mortality, blood samples were collected and analysed for general stress parameters (plasma Cl and glucose) prior to fish dissection and collection of different tissues. The observed dose-response demonstrated that varying concentrations of K{sup +}, Na{sup +} or Mg{sup 2+} had no apparent effect on the U induced toxicity in terms of 96 h LC50-values. U toxicity was, however, strongly dependent on pH. Reducing pH from about 6.7 to 6.0 or 5.5 reduced the LC50-value from 3.1 to 1.4 mg U/l. However, by increasing pH to 7.9, LC50-values increased to 25 mg/L. Fractionation of the exposure waters, demonstrated that U was present as dissolved species less than 10 kDa in size predominantly as anion, and that a fraction (30%) was present as U colloids ( 3-10 kDa). Furthermore, U accumulated in fish gills, and the accumulation of U in the fish gills increased with increasing U concentration in the water. U accumulation at >50 μg U/g dry weight gill was correlated with ion regulation problems and stress response in fish, reflected by reduced plasma Cl concentration and increased blood glucose, and mortality was observed at concentration levels >300 μg/g gill dry weight. Thus, toxic effects in fish were correlated to U concentration in gills, and the concentration of U in gills was highly dependent upon pH in water and the U speciation. As presented in detail on a poster at the present conference (Cagno et al.), U did not only

A PhD is a PhD is a PhD

OpenAIRE

Ostrow, Deborah Anne

2017-01-01

A PhD is a PhD is a PhD is a practice-based project that interrogates the process of an artist undertaking PhD research under established criteria. It consists of an exegesis, an original screenplay, and a digital film made for online viewing, with images drawn from a range of documentaries and films found on YouTube. They have been dissected, re-assembled and then re-embedded to YouTube. The source material covers topics such as medicalization of madness, the conspicuous appropriation of uni...

PIXE analysis of mineral composition of alfalfa root-tip exposed to low pH or aluminum stress condition

International Nuclear Information System (INIS)

Yokota, Satoshi; Mae, Tadahiko; Ojima, Kunihiko; Ishii, Keizo.

1994-01-01

PIXE analysis was applied to study alteration of mineral composition (Al, P, K, and Cl) of alfalfa root-tip exposed to low pH or aluminum stress. These minerals were detectable using one or two pieces of root-tips. Short-term (within 4 h) decreases in K/P and Cl/P ratios were observed under low pH and aluminum stress conditions. However, degree of the decrease was not same. Differences in toxic effects of low pH and Al on the root-tip of alfalfa are discussed. (author)

Therapeutic Down-Modulators of Staphylococcal Superantigen-Induced Inflammation and Toxic Shock

Directory of Open Access Journals (Sweden)

Teresa Krakauer

2010-07-01

Full Text Available Staphylococcal enterotoxin B (SEB and related superantigenic toxins are potent stimulators of the immune system and cause a variety of diseases in humans, ranging from food poisoning to toxic shock. These toxins bind directly to major histocompatibility complex (MHC class II molecules on antigen-presenting cells and specific Vb regions of T-cell receptors (TCR, resulting in hyperactivation of both monocytes/macrophages and T lymphocytes. Activated host cells produce massive amounts of proinflammatory cytokines and chemokines, activating inflammation and coagulation, causing clinical symptoms that include fever, hypotension, and shock. This review summarizes the in vitro and in vivo effects of staphylococcal superantigens, the role of pivotal mediators induced by these toxins in the pathogenic mechanisms of tissue injury, and the therapeutic agents to mitigate the toxic effects of superantigens.

Cation modulation of hemoglobin interaction with sodium n-dodecyl sulphate (SDS iv: magnesium modulation at pH 7.20

Directory of Open Access Journals (Sweden)

Ali Akbar Moosavi-Movahedi

2016-03-01

Full Text Available We investigate the interaction of Mg2+ (0–2.30 mM and sodium n-dodecyl sulfate (SDS with hemoglobins (Hbs A and S at pH 7.20. SDS was used to model both membranes (0.60 mM SDS and proteases (5.0 mM SDS. Via UV-visible spectroscopy, second derivative and difference second derivative spectroscopy, we interrogated for difference(s in the interaction of these ligands with the proteins that can account for the HbS resistance to malaria parasite while been prone to sickling. Our results show that Mg2+ interaction with the proteins lowered the HbS oxygen affinity in comparison with the HbA. Additionally, [SDS]-protein interactions resulted in oxoferryl heme species formation that was prominent for the HbA and highly diminished for the HbS. [Mg2+] introduction to the [SDS]-protein mixture, however decreased the concentration of denatured protein species. The [Mg2+]-[SDS]-protein interactions suggest that while ionic or coulomb interactions for the HbA, in the presence of the surfactants, are [Mg2+] dependent, those of the HbS are not. Furthermore, hydrophobicity is a crucial force for the HbS interaction at neutral pH and is little-masked by ionic, electrostatic or coulombic interactions. In conclusion, at physiological pH, the Mg-SDS interaction decreased the HbS denaturation in comparison to the HbA.

Hazard and risk assessment of human exposure to toxic metals using in vitro digestion assay

Directory of Open Access Journals (Sweden)

Hani A. Alhadrami

2016-10-01

Full Text Available Clean-up targets for toxic metals require that the site be “fit for purpose”. This means that targets are set with respect to defined receptors that reflect intended land-use. In this study, the likely threat of human exposure to toxic metals has been evaluated by simulating the human digestion process in vitro. The effects of key attributes (i.e. sample fraction size, pH, Kd and total metal concentrations on the bioavailability of Cu and Ni were also investigated. Total metal concentration was the key explanatory factor for Cu and Ni bioavailability. A comparative ranking of metal concentrations in the context of tolerable daily intakes for Cu and Ni confirmed that the pH has the greatest impact on metals bioavailability. Rapid screening of key attributes and total toxic metal doses can reveal the relative hazard imposed on human, and this approach should be considered when defining threshold values for human protection.

A ratiometric approach for pH optosensing with a single fluorophore indicator

Energy Technology Data Exchange (ETDEWEB)

Sanchez-Barragan, I. [Department of Physical and Analytical Chemistry, University of Oviedo, c/ Julian Claveria 8, 33006 Oviedo (Spain); Costa-Fernandez, J.M. [Department of Physical and Analytical Chemistry, University of Oviedo, c/ Julian Claveria 8, 33006 Oviedo (Spain); Sanz-Medel, A. [Department of Physical and Analytical Chemistry, University of Oviedo, c/ Julian Claveria 8, 33006 Oviedo (Spain); Valledor, Marta [Department of Electric, Electronic, Computers and Systems Engineering, University of Oviedo, Edificio Departamental no. 3, Campus de Viesques, 33204 Gijon (Spain); Ferrero, Francisco J. [Department of Electric, Electronic, Computers and Systems Engineering, University of Oviedo, Edificio Departamental no. 3, Campus de Viesques, 33204 Gijon (Spain)]. E-mail: ferrero@ate.uniovi.es; Campo, Juan Carlos [Department of Electric, Electronic, Computers and Systems Engineering, University of Oviedo, Edificio Departamental no. 3, Campus de Viesques, 33204 Gijon (Spain)

2006-03-15

A new fiber-optic prototype of luminometer has been designed in order to perform ratiometric-based measurements for optical sensing purposes. The coupling of a pH-selective sensing phase to the fiber-optic prototype has been evaluated for robust pH optosensing in drinking water. The pH-sensitive material has been synthesized by entrapping a pH-sensitive luminescent indicator (mercurochrome) in a sol-gel inorganic matrix. The pH optosensing is based on the detection of pH-induced reversible changes in the mercurochrome fluorescent emission and in the light reflected by the sensing phase. The instrument has been constructed using low-cost and simple optoelectronic components. The active phase was excited by means of a visible 470 nm high intensity light emitting diode (LED). The radiant power of the LED was modulated using a sinusoidal function so that scattered light due to light sources of different frequency than the modulating signal (e.g. sunlight) can be easily removed by adequate electronic filtering of the emission signal. Both the fluorescence emission from the dye and the sensing phase reflected light were collected in a bifurcated fiber-optic to allow the ratiometric measurement. Two different ratiometric approaches have been evaluated. The analytical performance of the pH optrode using both measurement methods have been compared, between them and with simple fluorescence intensity measurements, in terms of sensitivity, measurement range, response time, repeatability and insensitivity to changes in excitation light intensity. The applicability of the developed pH optrode and methods has been tested for pH analysis in tap and bottled still mineral water samples. The results obtained showed good agreement with the corresponding pH values provided by a commercial glass electrode. In this work, pH was selected as a model analyte to evaluate the performance of the proposed methodology, although other optical sensors for different applications/analytes could

A ratiometric approach for pH optosensing with a single fluorophore indicator

International Nuclear Information System (INIS)

Sanchez-Barragan, I.; Costa-Fernandez, J.M.; Sanz-Medel, A.; Valledor, Marta; Ferrero, Francisco J.; Campo, Juan Carlos

2006-01-01

A new fiber-optic prototype of luminometer has been designed in order to perform ratiometric-based measurements for optical sensing purposes. The coupling of a pH-selective sensing phase to the fiber-optic prototype has been evaluated for robust pH optosensing in drinking water. The pH-sensitive material has been synthesized by entrapping a pH-sensitive luminescent indicator (mercurochrome) in a sol-gel inorganic matrix. The pH optosensing is based on the detection of pH-induced reversible changes in the mercurochrome fluorescent emission and in the light reflected by the sensing phase. The instrument has been constructed using low-cost and simple optoelectronic components. The active phase was excited by means of a visible 470 nm high intensity light emitting diode (LED). The radiant power of the LED was modulated using a sinusoidal function so that scattered light due to light sources of different frequency than the modulating signal (e.g. sunlight) can be easily removed by adequate electronic filtering of the emission signal. Both the fluorescence emission from the dye and the sensing phase reflected light were collected in a bifurcated fiber-optic to allow the ratiometric measurement. Two different ratiometric approaches have been evaluated. The analytical performance of the pH optrode using both measurement methods have been compared, between them and with simple fluorescence intensity measurements, in terms of sensitivity, measurement range, response time, repeatability and insensitivity to changes in excitation light intensity. The applicability of the developed pH optrode and methods has been tested for pH analysis in tap and bottled still mineral water samples. The results obtained showed good agreement with the corresponding pH values provided by a commercial glass electrode. In this work, pH was selected as a model analyte to evaluate the performance of the proposed methodology, although other optical sensors for different applications/analytes could

Effects of soil organic matter content on cadmium toxicity in Eisenia fetida: implications for the use of biomarkers and standard toxicity tests.

Science.gov (United States)

Irizar, A; Rodríguez, M P; Izquierdo, A; Cancio, I; Marigómez, I; Soto, M

2015-01-01

Bioavailability is affected by soil physicochemical characteristics such as pH and organic matter (OM) content. In addition, OM constitutes the energy source of Eisenia fetida, a well established model species for soil toxicity assessment. The present work aimed at assessing the effects of changes in OM content on the toxicity of Cd in E. fetida through the measurement of neutral red uptake (NRU) and mortality, growth, and reproduction (Organisation for Economic Co-operation and Development [OECD] Nos. 207 and 222). Complementarily, metallothionein (MT) and catalase transcription levels were measured. To decrease variability inherent to natural soils, artificial soils (Organization for Economic Cooperation and Development 1984) with different OM content (6, 10, and 14%) and spiked with Cd solutions at increasing concentrations were used. Low OM in soil decreased soil ingestion and Cd bioaccumulation but also increased Cd toxicity causing lower NRU of coelomocytes, 100 % mortality, and stronger reproduction impairment, probably due to the lack of energy to maintain protection mechanisms (production of MT).Cd bioaccumulation did not reflect toxicity, and OM played a pivotal role in Cd toxicity. Thus, OM content should be taken into account when using E. fetida in in vivo exposures for soil health assessment.

Analysis of late toxicity in nasopharyngeal carcinoma patients treated with intensity modulated radiation therapy

International Nuclear Information System (INIS)

Zheng, YingJie; Han, Fei; Xiao, WeiWei; Xiang, YanQun; Lu, LiXia; Deng, XiaoWu; Cui, NianJi; Zhao, Chong

2015-01-01

To observe the late toxicities in nasopharyngeal carcinoma (NPC) patients who achieved long-term survival after intensity modulated radiation therapy (IMRT). 208 untreated NPC patients who received IMRT and survived more than five years with locoregional disease control and no metastasis were evaluated in this study. The prescription dose to the gross target volume of nasopharynx (GTVnx), positive neck lymph nodes (GTVnd), clinical target volume 1 (CTV1) and 2 (CTV2) was 68Gy/30f, 60-66Gy/30f, 60 Gy/30f and 54Gy/30f, respectively. The nasopharynx and upper neck targets were irradiated using IMRT, and the lower neck and supraclavicular fossae targets were irradiated using the half-beam technique with conventional irradiation. The late toxicities were evaluated according to the LENT/SOMA criteria of 1995. The median follow-up time was 78 months (60–96 months). The occurrence rates of cervical subcutaneous fibrosis, hearing loss, skin dystrophy, xerostomia, trismus, temporal lobe injury, cranial nerve damage, cataract, and brain stem injury induced by radiotherapy were 89.9%, 67.8%, 47.6%, 40.9%, 7.21%, 4.33%, 2.88%, 1.44%, and 0.48%, respectively. No spinal cord injury and mandible damage were found. Grade 3–4 late injuries were observed as follows: 1 (0.48%) skin dystrophy, 4 (1.92%) cervical subcutaneous fibrosis, 2 (0.96%) hearing loss, 2 (0.96%) cranial nerve palsy, and 1 (0.48%) temporal lobe necrosis. No grade 3–4 late injuries occurred in parotid, temporomandibular joints and eyes. Xerostomia decreased gradually over time and then showed only slight changes after 4 years. The change in the incisor distance stabilised by 1 year after RT, however, the incidence of hearing loss, skin dystrophy, subcutaneous fibrosis and nervous system injuries increased over time after RT. The late injuries in most NPC patients who had long-term survivals after IMRT are alleviated. Within the 5 years of follow-up, we found xerostomia decreased gradually; The change in the

Fluorescent bioassays for toxic metals in milk and yoghurt

Science.gov (United States)

2012-01-01

Background From a human health viewpoint, contaminated milk and its products could be a source of long-term exposure to toxic metals. Simple, inexpensive, and on-site assays would enable constant monitoring of their contents. Bioassays that can measure toxic metals in milk or yoghurt might reduce the risk. For this purpose, the green fluorescent protein (GFP)-tagged trans factors, ArsR-GFP and CadC-GFP, together with their cis elements were used to develop such bioassays. Results ArsR-GFP or CadC-GFP, which binds either toxic metal or DNA fragment including cis element, was directly mixed with cow’s milk or yoghurt within a neutral pH range. The fluorescence of GFP, which is reflected by the association/dissociation ratio between cis element and trans factor, significantly changed with increasing externally added As (III) or Cd (II) whereas smaller responses to externally added Pb (II) and Zn (II) were found. Preparation and dilution of whey fraction at low pH were essential to intrinsic zinc quantification using CadC-GFP. Using the extraction procedure and bioassay, intrinsic Zn (II) concentrations ranging from 1.4 to 4.8 mg/l for milk brands and from 1.2 to 2.9 mg/kg for yoghurt brands were determined, which correlated to those determined using inductively coupled plasma atomic emission spectroscopy. Conclusions GFP-tagged bacterial trans factors and cis elements can work in the neutralized whole composition and diluted whey fraction of milk and yoghurt. The feature of regulatory elements is advantageous for establishment of simple and rapid assays of toxic metals in dairy products. PMID:23098077

Fluorescent bioassays for toxic metals in milk and yoghurt

Directory of Open Access Journals (Sweden)

Siddiki Mohammad Shohel

2012-10-01

Full Text Available Abstract Background From a human health viewpoint, contaminated milk and its products could be a source of long-term exposure to toxic metals. Simple, inexpensive, and on-site assays would enable constant monitoring of their contents. Bioassays that can measure toxic metals in milk or yoghurt might reduce the risk. For this purpose, the green fluorescent protein (GFP-tagged trans factors, ArsR-GFP and CadC-GFP, together with their cis elements were used to develop such bioassays. Results ArsR-GFP or CadC-GFP, which binds either toxic metal or DNA fragment including cis element, was directly mixed with cow’s milk or yoghurt within a neutral pH range. The fluorescence of GFP, which is reflected by the association/dissociation ratio between cis element and trans factor, significantly changed with increasing externally added As (III or Cd (II whereas smaller responses to externally added Pb (II and Zn (II were found. Preparation and dilution of whey fraction at low pH were essential to intrinsic zinc quantification using CadC-GFP. Using the extraction procedure and bioassay, intrinsic Zn (II concentrations ranging from 1.4 to 4.8 mg/l for milk brands and from 1.2 to 2.9 mg/kg for yoghurt brands were determined, which correlated to those determined using inductively coupled plasma atomic emission spectroscopy. Conclusions GFP-tagged bacterial trans factors and cis elements can work in the neutralized whole composition and diluted whey fraction of milk and yoghurt. The feature of regulatory elements is advantageous for establishment of simple and rapid assays of toxic metals in dairy products.

Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals

DEFF Research Database (Denmark)

Rendal, Cecilie; Kusk, Kresten Ole; Trapp, Stefan

2011-01-01

a dynamic flux model based on the Fick-Nernst-Planck diffusion equation known as the cell model. The cell model predicts that bases with delocalized charges may in some cases show declining bioaccumulation with increasing pH. Little information is available for amphoteric and zwitterionic compounds; however...

Salivary pH as a marker of plasma adiponectin concentrations in Women.

Science.gov (United States)

Tremblay, Monique; Loucif, Yacine; Methot, Julie; Brisson, Diane; Gaudet, Daniel

2012-02-03

Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status. Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW) and 98 menopausal women (MW)). Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH. Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p salivary pH (R2) was 10.8% (p salivary pH quartiles (p = 0.005). These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue.

Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs.

Science.gov (United States)

Oleaga, Carlota; Bernabini, Catia; Smith, Alec S T; Srinivasan, Balaji; Jackson, Max; McLamb, William; Platt, Vivien; Bridges, Richard; Cai, Yunqing; Santhanam, Navaneetha; Berry, Bonnie; Najjar, Sarah; Akanda, Nesar; Guo, Xiufang; Martin, Candace; Ekman, Gail; Esch, Mandy B; Langer, Jessica; Ouedraogo, Gladys; Cotovio, Jose; Breton, Lionel; Shuler, Michael L; Hickman, James J

2016-02-03

We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro "human-on-a-chip" assay for systemic toxicity screening.

Models for the field-based toxicity of copper and zinc salts to wheat in 11 Australian soils and comparison to laboratory-based models

International Nuclear Information System (INIS)

Warne, Michael St.J.; Heemsbergen, Diane; McLaughlin, Mike; Bell, Mike; Broos, Kris; Whatmuff, Mark; Barry, Glenn; Nash, David; Pritchard, Deb; Penney, Nancy

2008-01-01

Laboratory-based relationships that model the phytotoxicity of metals using soil properties have been developed. This paper presents the first field-based phytotoxicity relationships. Wheat (Triticum aestivum L.) was grown at 11 Australian field sites at which soil was spiked with copper (Cu) and zinc (Zn) salts. Toxicity was measured as inhibition of plant growth at 8 weeks and grain yield at harvest. The added Cu and Zn EC10 values for both endpoints ranged from approximately 3 to 4760 mg/kg. There were no relationships between field-based 8-week biomass and grain yield toxicity values for either metal. Cu toxicity was best modelled using pH and organic carbon content while Zn toxicity was best modelled using pH and the cation exchange capacity. The best relationships estimated toxicity within a factor of two of measured values. Laboratory-based phytotoxicity relationships could not accurately predict field-based phytotoxicity responses. - Field-based toxicity of Cu and Zn to wheat can be modelled using soil properties. Laboratory-based models should not be used to estimate toxicity in the field

Reduced Toxicity With Intensity Modulated Radiation Therapy (IMRT) for Desmoplastic Small Round Cell Tumor (DSRCT): An Update on the Whole Abdominopelvic Radiation Therapy (WAP-RT) Experience

Energy Technology Data Exchange (ETDEWEB)

Desai, Neil B. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Stein, Nicholas F. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); LaQuaglia, Michael P. [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Alektiar, Kaled M. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kushner, Brian H.; Modak, Shakeel; Magnan, Heather M. [Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Goodman, Karyn [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne L., E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

2013-01-01

Purpose: Desmoplastic small round cell tumor (DSRCT) is a rare malignancy typically involving the peritoneum in young men. Whole abdominopelvic radiation therapy (WAP-RT) using conventional 2-dimensional (2D) radiation therapy (RT) is used to address local recurrence but has been limited by toxicity. Our objectives were to assess the benefit of intensity modulated radiation therapy (IMRT) on toxicity and to update the largest series on radiation for DSRCT. Methods and Materials: The records of 31 patients with DSRCT treated with WAP-RT (22 with 2D-RT and 9 with IMRT) between 1992 and 2011 were retrospectively reviewed. All received multi-agent chemotherapy and maximal surgical debulking followed by 30 Gy of WAP-RT. A further focal boost of 12 to 24 Gy was used in 12 cases. Boost RT and autologous stem cell transplantation were nearly exclusive to patients treated with 2D-RT. Toxicities were assessed with the Common Terminology Criteria for Adverse Events. Dosimetric analysis compared IMRT and simulated 2D-RT dose distributions. Results: Of 31 patients, 30 completed WAP-RT, with a median follow-up after RT of 19 months. Acute toxicity was reduced with IMRT versus 2D-RT: P=.04 for gastrointestinal toxicity of grade 2 or higher (33% vs 77%); P=.02 for grade 4 hematologic toxicity (33% vs 86%); P=.01 for rates of granulocyte colony-stimulating factor; and P=.04 for rates of platelet transfusion. Post treatment red blood cell and platelet transfusion rates were also reduced (P=.01). IMRT improved target homogeneity ([D05-D95]/D05 of 21% vs 46%) and resulted in a 21% mean bone dose reduction. Small bowel obstruction was the most common late toxicity (23% overall). Updated 3-year overall survival and progression-free survival rates were 50% and 24%, respectively. Overall survival was associated with distant metastasis at diagnosis on multivariate analysis. Most failures remained intraperitoneal (88%). Conclusions: IMRT for consolidative WAP-RT in DSRCT improves

The effect of soil properties on the toxicity and bioaccumulation of Ag nanoparticles and Ag ions in Enchytraeus crypticus.

Science.gov (United States)

Topuz, Emel; van Gestel, Cornelis A M

2017-10-01

Standard natural Lufa soils (2.2, 2.3 and 5M) with different organic carbon contents (0.67-1.61%) and pH CaCl2 (5.5-7.3) were spiked with ionic Ag (AgNO 3 ) and polyvinyl pyrrolidone (AgNP-PVP) and citrate (AgNP-Cit) coated Ag nanoparticles (NPs). Enchytraeus crypticus were exposed for 21 days to assess effects on survival and reproduction. Soil, pore water and animals were analyzed for Ag. AgNP-Cit had a strong increasing effect on soil pH, leading to high enchytraeid mortality at concentrations higher than 60-100mg Ag/kg dry soil which made it impossible to determine the influence of soil properties on its toxicity. LC50s were lower for AgNO 3 than for AgNP-PVP (92-112 and 335-425mg Ag/kg dry soil, respectively) and were not affected by soil properties. AgNO 3 and AgNP-PVP had comparable reproductive toxicity with EC50s of 26.9-75.2 and 28.2-92.3mg Ag/kg dry soil, respectively; toxicity linearly increased with decreasing organic carbon content of the soils but did not show a clear effect of soil pH. Ag uptake in the enchytraeids was higher at higher organic carbon content, but could not explain differences in toxicity between soils. This study indicates that the bioavailability of both ionic and nanoparticulate Ag is mainly affected by soil organic carbon, with little effect of soil pH. Copyright © 2017. Published by Elsevier Inc.

A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial

Energy Technology Data Exchange (ETDEWEB)

Sayan, Mutlay; Nelson, Carl; Gagne, Havaleh; Rubin, Deborah; Heimann, Ruth [Dept. of Radiation Oncology, University of Vermont Medical Center, Burlington (United States); Wilson, Karen [University of Vermont Cancer Center, Burlington (United States)

2017-03-15

Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

Effect of water treatment residuals on soil phosphorus, copper and aluminium availability and toxicity

Energy Technology Data Exchange (ETDEWEB)

Lombi, E., E-mail: enzo.lombi@unisa.edu.a [CSIRO Land and Water, Centre for Environmental Contaminant Research, PMB 2, Glen Osmond, SA 5064 (Australia); Centre for Environmental Risk Assessment and Remediation, University of South Australia, Building X, Mawson Lakes Campus, Mawson Lakes, SA 5095 (Australia); CRC CARE, PO Box 486, Salisbury, SA 5106 (Australia); Stevens, D.P. [CSIRO Land and Water, Centre for Environmental Contaminant Research, PMB 2, Glen Osmond, SA 5064 (Australia); Arris Pty Ltd, PO Box 5143, Burnley, Victoria 3121 (Australia); McLaughlin, M.J. [CSIRO Land and Water, Centre for Environmental Contaminant Research, PMB 2, Glen Osmond, SA 5064 (Australia); Soil and Land Systems, University of Adelaide, PMB 1, Glen Osmond, SA 5064 (Australia)

2010-06-15

Water treatment residuals (WTRs) are produced by the treatment of potable water with coagulating agents. Beneficial recycling in agriculture is hampered by the fact that WTRs contain potentially toxic contaminants (e.g. copper and aluminium) and they bind phosphorus strongly. These issues were investigated using a plant bioassay (Lactuca sativa), chemical extractions and an isotopic dilution technique. Two WTRs were applied to an acidic and a neutral pH soil at six rates. Reductions in plant growth in amended soils were due to WTR-induced P deficiency, rather than Al or Cu toxicity. The release of potentially toxic Al from WTRs was found to be mitigated by their alkaline nature and pH buffering capacity. However, acidification of WTRs was shown to release more soluble Al than soil naturally high in Al. Copper availability was relatively low in all treatments. However, the lability of WTR-Cu increased when the WTR was applied to the soil. - The effect of water treatment residue application to soil was investigated in relation to phosphorus availability, and copper and aluminium phytotoxicity.

Effect of water treatment residuals on soil phosphorus, copper and aluminium availability and toxicity

International Nuclear Information System (INIS)

Lombi, E.; Stevens, D.P.; McLaughlin, M.J.

2010-01-01

Water treatment residuals (WTRs) are produced by the treatment of potable water with coagulating agents. Beneficial recycling in agriculture is hampered by the fact that WTRs contain potentially toxic contaminants (e.g. copper and aluminium) and they bind phosphorus strongly. These issues were investigated using a plant bioassay (Lactuca sativa), chemical extractions and an isotopic dilution technique. Two WTRs were applied to an acidic and a neutral pH soil at six rates. Reductions in plant growth in amended soils were due to WTR-induced P deficiency, rather than Al or Cu toxicity. The release of potentially toxic Al from WTRs was found to be mitigated by their alkaline nature and pH buffering capacity. However, acidification of WTRs was shown to release more soluble Al than soil naturally high in Al. Copper availability was relatively low in all treatments. However, the lability of WTR-Cu increased when the WTR was applied to the soil. - The effect of water treatment residue application to soil was investigated in relation to phosphorus availability, and copper and aluminium phytotoxicity.

Photo and pH dual-responsive polydiacetylene smart nanocontainer

International Nuclear Information System (INIS)

Li, Jingguo; Yu, Zhiqiang; Jiang, Hao; Zou, Gang; Zhang, Qijin

2012-01-01

Herein, a novel smart nanocontainer was developed by incorporating photo-responsive azobenzene derivative/cyclodextrin (Azo–CD) supramolecular complex into pH-responsive polydiacetylene (PDA) vesicles matrix. The designed nanocontainer exhibited excellent cell-toxicity, and the controlled release property response to external photo and pH stimuli. The photo-controlled inclusion and exclusion reaction between α-cyclodextrin (α-CD) and azobenzene moiety were used to act as the driving force to induce photo-triggered controlled release behavior of the designed nanocontainer. Moreover, the pH-responsive PDA vesicle matrix endowed the designed system with a controlled release property upon pH variation. The facile preparation procedures and their efficiency of response to the external stimuli render the novel smart nanocontainer potential candidate for future applications in remote controlled drug release. -- Graphical abstract: Herein, we developed a novel smart nanocontainer comprising the azobenzene derivative/cyclodextrin supramolecular complex and polydiacetylene vesicles, which exhibited excellent biocompatibility, and controlled release property response to external photo and pH stimuli. Highlights: ► We developed a novel dual-responsive smart polydiacetylene nanocontainer. ► The azobenzene/cyclodextrin complex was introduced into polydiacetylene vesicles. ► The designed nanocontainer exhibited excellent biocompatibility and stability. ► 365 and 435 nm light irradiations are used to realize photo controlled release. ► The smart nanocontainer exhibited controlled release property upon pH variation.

pH modulation and salivary sugar clearance of different chocolates in children: A randomized clinical trial

Directory of Open Access Journals (Sweden)

SVSG Nirmala

2016-01-01

Full Text Available Background: Sugars that occur naturally in foods and those added in processed foods may act as the source for fermentable carbohydrates and may initiate caries process. Among all the foods consumed by children, chocolates form an important constituent. A wide variety of chocolates are available in the Indian market and very few studies have compared their acidogenicity and salivary sugar clearance. Objectives: To compare the acidogenicity and salivary sugar clearance of 6 different commercially available chocolates in the Indian market. Materials and Methods: Thirty subjects aged 10-15 years were selected randomly from one of the available public schools in Nellore city. Six commercially available chocolates in the Indian market were divided into three groups, unfilled (dark and milk chocolate, filled (wafer and fruit and nuts chocolate, and candy (hard milk and mango-flavored candy groups. Plaque pH values and salivary sugar clearance rates are assessed at baseline, 5, 10, 15, 20, and 30 min after consumption. All the data obtained were statistically evaluated using independent sample t-test and one-way ANOVA for multiple group comparisons. Results: Mango-flavored candy had maximum fall in plaque pH and least fall in plaque pH was recorded with milk chocolate. Fruit and nuts chocolate had a maximum clearance of salivary sugar and least fall in the salivary sugar clearance was recorded with dark chocolate. When the plaque pH and salivary sugar clearance of all the chocolates were assessed, it was seen that the values were statistically significant at all the time intervals (P < 0.05. Conclusion: Dark chocolate had a high fall in pH and milk chocolate had low salivary sugar clearance which signifies that unfilled chocolates are more cariogenic than other chocolates. Even though mango-flavored candy had maximum fall in plaque pH, its salivary sugar clearance was high.

pH modulation and salivary sugar clearance of different chocolates in children: A randomized clinical trial.

Science.gov (United States)

Nirmala, Svsg; Quadar, Mohammed Akhil; Veluru, Sindhuri

2016-01-01

Sugars that occur naturally in foods and those added in processed foods may act as the source for fermentable carbohydrates and may initiate caries process. Among all the foods consumed by children, chocolates form an important constituent. A wide variety of chocolates are available in the Indian market and very few studies have compared their acidogenicity and salivary sugar clearance. To compare the acidogenicity and salivary sugar clearance of 6 different commercially available chocolates in the Indian market. Thirty subjects aged 10-15 years were selected randomly from one of the available public schools in Nellore city. Six commercially available chocolates in the Indian market were divided into three groups, unfilled (dark and milk chocolate), filled (wafer and fruit and nuts chocolate), and candy (hard milk and mango-flavored candy) groups. Plaque pH values and salivary sugar clearance rates are assessed at baseline, 5, 10, 15, 20, and 30 min after consumption. All the data obtained were statistically evaluated using independent sample t-test and one-way ANOVA for multiple group comparisons. Mango-flavored candy had maximum fall in plaque pH and least fall in plaque pH was recorded with milk chocolate. Fruit and nuts chocolate had a maximum clearance of salivary sugar and least fall in the salivary sugar clearance was recorded with dark chocolate. When the plaque pH and salivary sugar clearance of all the chocolates were assessed, it was seen that the values were statistically significant at all the time intervals (P pH and milk chocolate had low salivary sugar clearance which signifies that unfilled chocolates are more cariogenic than other chocolates. Even though mango-flavored candy had maximum fall in plaque pH, its salivary sugar clearance was high.

Levofloxacin oxidation by ozone and hydroxyl radicals: kinetic study, transformation products and toxicity.

Science.gov (United States)

Hamdi El Najjar, Nasma; Touffet, Arnaud; Deborde, Marie; Journel, Romain; Leitner, Nathalie Karpel Vel

2013-10-01

This work was carried out to investigate the fate of the antibiotic levofloxacin upon oxidation with ozone and hydroxyl radicals. A kinetic study was conducted at 20 °C for each oxidant. Ozonation experiments were performed using a competitive kinetic method with carbamazepin as competitor. Significant levofloxacin removal was observed during ozonation and a rate constant value of 6.0×10(4) M(-1) s(-1) was obtained at pH 7.2. An H2O2/UV system was used for the formation of hydroxyl radicals HO. The rate constant of HO was determined in the presence of a high H2O2 concentration. The kinetic expressions yielded a [Formula: see text] value of 4.5×10(9) M(-1) s(-1) at pH 6.0 and 5.2×10(9) M(-1) s(-1) at pH 7.2. These results were used to develop a model to predict the efficacy of the ozonation process and pharmaceutical removal was estimated under different ozonation conditions (i.e. oxidant concentrations and contact times). The results showed that levofloxacin was completely degraded by molecular ozone during ozonation of water and that hydroxyl radicals had no effect in real waters conditions. Moreover, LC/MS/MS and toxicity assays using Lumistox test were performed to identify ozonation transformation products. Under these conditions, four transformation products were observed and their chemical structures were proposed. The results showed an increase in toxicity during ozonation, even after degradation of all of the observed transformation products. The formation of other transformation products not identified under our experimental conditions could be responsible for the observed toxicity. These products might be ozone-resistant and more toxic to Vibrio fisheri than levofloxacin. Copyright © 2013 Elsevier Ltd. All rights reserved.

Definitive Reirradiation for Locoregionally Recurrent Non-Small Cell Lung Cancer With Proton Beam Therapy or Intensity Modulated Radiation Therapy: Predictors of High-Grade Toxicity and Survival Outcomes

Energy Technology Data Exchange (ETDEWEB)

McAvoy, Sarah; Ciura, Katherine; Wei, Caimiao; Rineer, Justin; Liao, Zhongxing; Chang, Joe Y.; Palmer, Matthew B.; Cox, James D.; Komaki, Ritsuko; Gomez, Daniel R., E-mail: DGomez@mdanderson.org

2014-11-15

Purpose: Intrathoracic recurrence of non-small cell lung cancer (NSCLC) after initial treatment remains a dominant cause of death. We report our experience using proton beam therapy and intensity modulated radiation therapy for reirradiation in such cases, focusing on patterns of failure, criteria for patient selection, and predictors of toxicity. Methods and Materials: A total of 102 patients underwent reirradiation for intrathoracic recurrent NSCLC at a single institution. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). All patients had received radiation therapy for NSCLC (median initial dose of 70 EQD2 Gy), with median interval to reirradiation of 17 months and median reirradiation dose of 60.48 EQD2 Gy. Median follow-up time was 6.5 months (range, 0-72 months). Results: Ninety-nine patients (97%) completed reirradiation. Median local failure-free survival, distant metastasis-free survival (DMFS), and overall survival times were 11.43 months (range, 8.6-22.66 months), 11.43 months (range, 6.83-23.84 months), and 14.71 (range, 10.34-20.56 months), respectively. Toxicity was acceptable, with rates of grade ≥3 esophageal toxicity of 7% and grade ≥3 pulmonary toxicity of 10%. Of the patients who developed local failure after reirradiation, 88% had failure in either the original or the reirradiation field. Poor local control was associated with T4 disease, squamous histology, and Eastern Cooperative Oncology Group performance status score >1. Concurrent chemotherapy improved DMFS, but T4 disease was associated with poor DMFS. Higher T status, Eastern Cooperative Oncology Group performance status ≥1, squamous histology, and larger reirradiation target volumes led to worse overall survival; receipt of concurrent chemotherapy and higher EQD2 were associated with improved OS. Conclusions: Intensity modulated radiation therapy and proton beam therapy are options for treating recurrent non-small cell lung cancer. However, rates of

Cd toxicity in Ash amended to plantations; the dilemma of different answers at different levels of description

DEFF Research Database (Denmark)

Christensen, Søren; Ekelund, Flemming; Kjøller, Rasmus

2018-01-01

. Other more abundant cations like Zn regulate Cd uptake. Mycorrhiza reduce Cd uptake in several plants. In barley Cd gradually decrease from root via stem to seeds. In conclusion for ash amounts up to 10 t/ha, we do not find metal toxicity of ash or evidence for bioaccumulation of metals in soil...... growth, equally because of the pH increase and the nutrients added. The pH increase stimulates decomposition activity. Soil carbon availability is not permanently increased with ash amendment, however, which may suggest that decomposition increase is coupled to primary production increase. Plantation....... Wood ash increase plantation soil Cd, and so did Cd in grass although at a very low level, Cd in lichens and Cd in the small biomass of earthworms. The toxicity of Cd is regulated by metal binding to soil being several orders of magnitude lower than in pure liquid. Ash is toxic towards microarthropods...

The pH sensitive properties of carboxymethyl chitosan nanoparticles cross-linked with calcium ions.

Science.gov (United States)

Kalliola, Simo; Repo, Eveliina; Srivastava, Varsha; Heiskanen, Juha P; Sirviö, Juho Antti; Liimatainen, Henrikki; Sillanpää, Mika

2017-05-01

In environmental applications the applied materials are required to be non-toxic and biodegradable. Carboxymethyl chitosan nanoparticles cross-linked with Ca 2+ ions (CMC-Ca) fulfill these requirements, and they are also renewable. These nanoparticles were applied to oil-spill treatment in our previous study and here we focused on enhancing their properties. It was found that while the divalent Ca 2+ ions are crucial for the formation of the CMC-Ca, the attractive interaction between NH 3 + and COO - groups contributed significantly to the formation and stability of the CMC-Ca. The stability decreased as a function of pH due to the deprotonation of the amino groups. Therefore, the nanoparticles were found to be fundamentally pH sensitive in solution, if the pH deviated from the pH (7-9) that was used in the synthesis of the nanoparticles. The pH sensitive CMC-Ca synthesized in pH 7 and 8 were most stable in the studied conditions and could find applications in oil-spill treatment or controlled-release of substances. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Interactive effects of pH, temperature and light during ammonia toxicity events in Elodea canadensis

NARCIS (Netherlands)

Netten, J.J.C.; Heide, van der T.; Smolders, A.J.P.

2013-01-01

Increased nutrient loading threatens many freshwater ecosystems. Elevated temperatures may increase the sensitivity to eutrophication in these ecosystems. Higher concentrations of possibly toxic reduced nitrogen (NHx) in the water layer may be expected as production and anaerobic breakdown rates

Preparation and characterization of nickel-spiked freshwater sediments for toxicity tests: toward more environmentally realistic nickel partitioning

Science.gov (United States)

Brumbaugh, William G.; Besser, John M.; Ingersoll, Christopher G.; May, Thomas W.; Ivey, Chris D.; Schlekat, Christian E.; Garman, Emily R.

2013-01-01

Two spiking methods were compared and nickel (Ni) partitioning was evaluated during a series of toxicity tests with 8 different freshwater sediments having a range of physicochemical characteristics. A 2-step spiking approach with immediate pH adjustment by addition of NaOH at a 2:1 molar ratio to the spiked Ni was effective in producing consistent pH and other chemical characteristics across a range of Ni spiking levels. When Ni was spiked into sediment having a high acid-volatile sulfide and organic matter content, a total equilibration period of at least 10 wk was needed to stabilize Ni partitioning. However, highest spiking levels evidently exceeded sediment binding capacities; therefore, a 7-d equilibration in toxicity test chambers and 8 volume-additions/d of aerobic overlying water were used to avoid unrealistic Ni partitioning during toxicity testing. The 7-d pretest equilibration allowed excess spiked Ni and other ions from pH adjustment to diffuse from sediment porewater and promoted development of an environmentally relevant, 0.5- to 1-cm oxic/suboxic sediment layer in the test chambers. Among the 8 different spiked sediments, the logarithm of sediment/porewater distribution coefficient values (log Kd) for Ni during the toxicity tests ranged from 3.5 to 4.5. These Kd values closely match the range of values reported for various field Ni-contaminated sediments, indicating that testing conditions with our spiked sediments were environmentally realistic.

Curcumin Attenuates Amyloid-β Aggregate Toxicity and Modulates Amyloid-β Aggregation Pathway.

Science.gov (United States)

Thapa, Arjun; Jett, Stephen D; Chi, Eva Y

2016-01-20

The abnormal misfolding and aggregation of amyloid-β (Aβ) peptides into β-sheet enriched insoluble deposits initiates a cascade of events leading to pathological processes and culminating in cognitive decline in Alzheimer's disease (AD). In particular, soluble oligomeric/prefibrillar Aβ have been shown to be potent neurotoxins. The naturally occurring polyphenol curcumin has been shown to exert a neuroprotective effect against age-related neurodegenerative diseases such as AD. However, its protective mechanism remains unclear. In this study, we investigated the effects of curcumin on the aggregation of Aβ40 as well as Aβ40 aggregate induced neurotoxicity. Our results show that the curcumin does not inhibit Aβ fibril formation, but rather enriches the population of "off-pathway" soluble oligomers and prefibrillar aggregates that were nontoxic. Curcumin also exerted a nonspecific neuroprotective effect, reducing toxicities induced by a range of Aβ conformers, including monomeric, oligomeric, prefibrillar, and fibrillar Aβ. The neuroprotective effect is possibly membrane-mediated, as curcumin reduced the extent of cell membrane permeabilization induced by Aβ aggregates. Taken together, our study shows that curcumin exerts its neuroprotective effect against Aβ induced toxicity through at least two concerted pathways, modifying the Aβ aggregation pathway toward the formation of nontoxic aggregates and ameliorating Aβ-induced toxicity possibly through a nonspecific pathway.

Vitamin E modulates reproductive toxicity of pyrethroid lambda-cyhalothrin in male rabbits.

Science.gov (United States)

Yousef, Mokhtar I

2010-05-01

The objective of the current study was to analyze the reproductive toxicity caused by lambda-cyhalothrin (LCT) in male rabbits, and to evaluate the possible protective effect of vitamin E (Vit. E) as antioxidant. Animals were orally administered their respective doses of LCT every other day and given drinking water supplemented with vitamin E for 16 weeks. Results showed that semen quality was deteriorated following treatment with LCT. Also, testosterone levels, body weight (BW), feed intake (FI), and relative testes (RTW) and epididymis (REW) weights were significantly decreased. Concentrations of thiobarbituric acid-reactive substances (TBARS) were significantly increased in seminal plasma of rabbits treated with LCT compared with control. While, activities of glutathione S-transferase (GST), transaminases and acid phosphatase (AcP) were significantly decreased. Vitamin E alone significantly increased testosterone levels, BW, FI, RTW, REW, semen characteristics and seminal plasma enzymes, and decreased the levels of TBARS. Also, the present study showed that vitamin E might be effective against LCT-induced reproductive toxicity. It was suggested that LCT exerted a significant adverse effect on reproductive performance of male rabbits. Furthermore, vitamin E antagonized the toxic effects of LCT and improved semen quality of male rabbit. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Biona-C Cell Culture pH Monitoring System

Science.gov (United States)

Friedericks, C.

1999-01-01

Sensors 2000! is developing a system to demonstrate the ability to perform accurate, real-time measurements of pH and CO2 in a cell culture media in Space. The BIONA-C Cell Culture pH Monitoring System consists of S2K! developed ion selective sensors and control electronics integrated with the fluidics of a cell culture system. The integrated system comprises a "rail" in the Cell Culture Module (CCM) of WRAIR (Space Biosciences of Walter Read Army Institute of Research). The CCM is a Space Shuttle mid-deck locker experiment payload. The BIONA-C is displayed along with associated graphics and text explanations. The presentation will stimulate interest in development of sensor technology for real-time cell culture measurements. The transfer of this technology to other applications will also be of interest. Additional information is contained in the original document.

Oxidation of indometacin by ferrate (VI): kinetics, degradation pathways, and toxicity assessment.

Science.gov (United States)

Huang, Junlei; Wang, Yahui; Liu, Guoguang; Chen, Ping; Wang, Fengliang; Ma, Jingshuai; Li, Fuhua; Liu, Haijin; Lv, Wenying

2017-04-01

The oxidation of indometacin (IDM) by ferrate(VI) (Fe(VI)) was investigated to determine the reaction kinetics, transformation products, and changes in toxicity. The reaction between IDM and Fe(VI) followed first-order kinetics with respect to each reactant. The apparent second-order rate constants (k app ) decreased from 9.35 to 6.52 M -1  s -1 , as the pH of the solution increased from 7.0 to 10.0. The pH dependence of k app might be well explained by considering the species-specific rate constants of the reactions of IDM with Fe(VI). Detailed product studies using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the oxidation products were primarily derived from the hydrolysis of amide linkages, the addition of hydroxyl groups, and electrophilic oxidation. The toxicity of the oxidation products was evaluated using the Microtox test, which indicated that transformation products exhibited less toxicity to the Vibrio fischeri bacteria. Quantitative structure-activity relationship (QSAR) analysis calculated by the ecological structure activity relationship (ECOSAR) revealed that all of the identified products exhibited lower acute and chronic toxicity than the parent pharmaceutical for fish, daphnid, and green algae. Furthermore, Fe(VI) was effective in the degradation IDM in water containing carbonate ions or fulvic acid (FA), and in lake water samples; however, higher Fe(VI) dosages would be required to completely remove IDM in lake water in contrast to deionized water.

Influence of fluoride on aluminum toxicity to Atlantic salmon (Salmo salar)

Science.gov (United States)

Hamilton, Steven J.; Haines, Terry A.

1995-01-01

Atlantic salmon (Salmo salar) alevins were exposed to various aluminum (0–4700 μg/L) and four fluoride (0–500 μg/L) concentrations at two pH values (5.5 and 6.5) for 4- and 30-d periods. In the 4-d tests, aluminum with fluoride was less toxic at pH 6.5 than at pH 5.5, whereas without fluoride, pH had no effect. In the 30-d test, mortality in all treatments was 17–21% at pH 5.5, but only 3–7% at pH 6.5. Fish length and weight after 30 d were reduced in all fluoride–aluminum treatments at pH 5.5, but only in the 200-μg/L aluminum without fluoride treatment at pH 6.5. At pH 5.5 and 6.5 without aluminum, histomorphological examinations revealed no abnormalities in gill tissue. However, in aluminum exposure with no fluoride, gill filaments and secondary lamellae were swollen and thickened. Addition of fluoride at pH 6.5 alleviated some gill damage. At pH 5.5 and 200 μg/L aluminum, addition of 100 μg/L fluoride reduced swelling of gill lamellae, but 200 μg/L fluoride did not reduce swelling. Low fluoride concentrations (fluoride concentrations (> 100 μg/L) may not reduce aluminum-induced effects.

pH gradients in the diffusive boundary layer of subarctic macrophytes

KAUST Repository

Hendriks, Iris E.; Duarte, Carlos M.; Marbà , Nú ria; Krause-Jensen, Dorte

2017-01-01

Highly productive macrophytes produce diurnal and seasonal cycles in CO concentrations modulated by metabolic activity, which cause discrepancies between pH in the bulk water and near seaweed blades, especially when entering the diffusion boundary layer (DBL). Calcifying epiphytic organisms living in this environment are therefore exposed to a different pH environment than that of the water column. To evaluate the actual pH environment on blade surfaces, we measured the thickness of the DBL and pH gradients within it for six subarctic macrophytes: Fucus vesiculosus, Ascophyllum nodosum, Ulva lactuca, Zostera marina, Saccharina longicruris, and Agarum clathratum. We measured pH under laboratory conditions at ambient temperatures (2–3 °C) and slow, stable flow over the blade surface at five light intensities (dark, 30, 50, 100 and 200 µmol photons m s). Boundary layer thickness ranged between 511 and 1632 µm, while the maximum difference in pH (∆pH) between the blade surface and the water column ranged between 0.4 ± 0.14 (average ± SE; Zostera) and 1.2 ± 0.13 (average ± SE; Ulva) pH units. These differences in pH are larger than predictions for pH changes in the bulk water by the end of the century. A simple quadratic model best described the relationship between light intensity and maximum ∆pH, pointing at relatively low optimum PAR of between 28 and 139 µmol photons m s to reach maximum ∆pH. Elevated pH at the blade surface may provide chemical “refugia” for calcifying epiphytic organisms, especially during summer at higher latitudes where photoperiods are long.

pH gradients in the diffusive boundary layer of subarctic macrophytes

KAUST Repository

Hendriks, Iris E.

2017-06-20

Highly productive macrophytes produce diurnal and seasonal cycles in CO concentrations modulated by metabolic activity, which cause discrepancies between pH in the bulk water and near seaweed blades, especially when entering the diffusion boundary layer (DBL). Calcifying epiphytic organisms living in this environment are therefore exposed to a different pH environment than that of the water column. To evaluate the actual pH environment on blade surfaces, we measured the thickness of the DBL and pH gradients within it for six subarctic macrophytes: Fucus vesiculosus, Ascophyllum nodosum, Ulva lactuca, Zostera marina, Saccharina longicruris, and Agarum clathratum. We measured pH under laboratory conditions at ambient temperatures (2–3 °C) and slow, stable flow over the blade surface at five light intensities (dark, 30, 50, 100 and 200 µmol photons m s). Boundary layer thickness ranged between 511 and 1632 µm, while the maximum difference in pH (∆pH) between the blade surface and the water column ranged between 0.4 ± 0.14 (average ± SE; Zostera) and 1.2 ± 0.13 (average ± SE; Ulva) pH units. These differences in pH are larger than predictions for pH changes in the bulk water by the end of the century. A simple quadratic model best described the relationship between light intensity and maximum ∆pH, pointing at relatively low optimum PAR of between 28 and 139 µmol photons m s to reach maximum ∆pH. Elevated pH at the blade surface may provide chemical “refugia” for calcifying epiphytic organisms, especially during summer at higher latitudes where photoperiods are long.

Influence of pH on the Transport of Silver Nanoparticles in Saturated Porous Media: Laboratory Experiments and Modeling

Science.gov (United States)

2012-03-01

the potential toxic effects of AgNPs (USEPA 2010). Recent in vitro and in vivo studies using various cell lines, algae , zooplankton, fish, rats and... TiO2 in Saturated Porous Media: Effects of pH, Surfactants and Flow Velocity.” Water Research, 45(2), 839-851. He, F., Zhang, M., Qian, T., and Zhao...of silver nanoparticles (AgNPs), the largest and fastest growing category of nanomaterials, and their potential for toxic effects to both humans

A novel "modularized" optical sensor for pH monitoring in biological matrixes.

Science.gov (United States)

Liu, Xun; Zhang, Shang-Qing; Wei, Xing; Yang, Ting; Chen, Ming-Li; Wang, Jian-Hua

2018-06-30

A novel core-shell structure optical pH sensor is developed with upconversion nanoparticles (UCNPs) serving as the core and silica as the shell, followed by grafting bovineserumalbumin (BSA) as another shell via glutaraldehyde cross-linking. The obtained core-shell-shell structure is shortly termed as UCNPs@SiO 2 @BSA, and its surface provides a platform for loading various pH sensitive dyes, which are alike "modules" to make it feasible for measuring pHs within different pH ranges by simply regulating the type of dyes. Generally, a single pH sensitive dye is adopted to respond within a certain pH range. This study employs bromothymol blue (BTB) and rhodamine B (RhB) to facilitate their responses to pH variations within two ranges, i.e., pH 5.99-8.09 and pH 4.98-6.40, respectively, with detection by ratio-fluorescence protocol. The core-shell-shell structure offers superior sensitivity, which is tens of times more sensitive than those achieved by ratio-fluorescence approaches based on various nanostructures, and favorable stability is achieved in high ionic strength medium. In addition, this sensor exhibits superior photostability under continuous excitation at 980 nm. Thanks to the near infrared excitation in the core-shell-shell structure, it effectively avoids the self-fluorescence from biological samples and thus facilitates accurate sensing of pH in various biological sample matrixes. Copyright © 2018 Elsevier B.V. All rights reserved.

Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

International Nuclear Information System (INIS)

Sveistrup, Joen; Rosenschöld, Per Munck af; Deasy, Joseph O; Oh, Jung Hun; Pommer, Tobias; Petersen, Peter Meidahl; Engelholm, Svend Aage

2014-01-01

Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction

Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs

International Nuclear Information System (INIS)

Yasuda, Shin; Idell, Steven; Fu Jian; Carter, Glendora; Snow, Rhodora; Liu, M.-C.

2007-01-01

The current study was designed to examine the role of sulfation in the metabolism of cigarette smoke toxicants and clarify whether these toxicants, by serving as substrates for the cytosolic sulfotransferases (SULTs), may interfere with the sulfation of key endogenous compounds. By metabolic labeling, [ 35 S]sulfated species were found to be generated and released into the media of HepG2 human hepatoma cells and primary human lung endothelial cells labeled with [ 35 S]sulfate in the presence of cigarette smoke extract (CSE). Concomitantly, several [ 35 S]sulfated metabolites observed in the medium in the absence of CSE either decreased or disappeared. Eleven previously prepared human cytosolic SULTs were tested for sulfating activity with CSE and known cigarette smoke toxicants as substrates. Activity data revealed SULT1A1, SULT1A2, SULT1A3, and SULT1C2 as major enzymes responsible for their sulfation. To examine their inhibitory effects on the sulfation of 17β-estradiol by SULT1A1, enzymatic assays were performed in the presence of three representative toxicant compounds, namely N-hydroxy-4-aminobiphenyl (N-OH-4-ABP), 4-aminobiphenyl (4-ABP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). IC 50 values determined for the sulfation of 17β-estradiol by SULT1A1 were 11.8 μM, 28.2 μM, and 500 μM, respectively, for N-OH-4-ABP, 4-ABP and PhIP. Kinetic analyses indicated that the mechanism underlying the inhibition of 17β-estradiol sulfation by these cigarette smoke toxicants is of a mixed competitive-noncompetitive type. Metabolic labeling experiments clearly showed inhibition of the production of [ 35 S]sulfated 17β-estradiol by N-OH-4-ABP in a concentration-dependent manner in HepG2 cells. Taken together, these results suggest that sulfation plays a significant role in the metabolism of cigarette smoke compounds. By serving as substrates for SULTs, cigarette smoke toxicants may interfere with the metabolism of 17β-estradiol and other endogenous

Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance.

Science.gov (United States)

Sveistrup, Joen; af Rosenschöld, Per Munck; Deasy, Joseph O; Oh, Jung Hun; Pommer, Tobias; Petersen, Peter Meidahl; Engelholm, Svend Aage

2014-02-04

Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1-2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5-7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction.

Keampferol-3-O-rhamnoside abrogates amyloid beta toxicity by modulating monomers and remodeling oligomers and fibrils to non-toxic aggregates

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Sharoar Md

2012-12-01

Full Text Available Abstract Background Aggregation of soluble, monomeric β- amyloid (Aβ to oligomeric and then insoluble fibrillar Aβ is a key pathogenic feature in development of Alzheimer’s disease (AD. Increasing evidence suggests that toxicity is linked to diffusible Aβ oligomers, rather than to insoluble fibrils. The use of naturally occurring small molecules for inhibition of Aβ aggregation has recently attracted significant interest for development of effective therapeutic strategies against the disease. A natural polyphenolic flavone, Kaempferol-3-O-rhamnoside (K-3-rh, was utilized to investigate its effects on aggregation and cytotoxic effects of Aβ42 peptide. Several biochemical techniques were used to determine the conformational changes and cytotoxic effect of the peptide in the presence and absence of K-3-rh. Results K-3-rh showed a dose-dependent effect against Aβ42 mediated cytotoxicity. Anti-amyloidogenic properties of K-3-rh were found to be efficient in inhibiting fibrilogenesis and secondary structural transformation of the peptide. The consequence of these inhibitions was the accumulation of oligomeric structural species. The accumulated aggregates were smaller, soluble, non-β-sheet and non-toxic aggregates, compared to preformed toxic Aβ oligomers. K-3-rh was also found to have the remodeling properties of preformed soluble oligomers and fibrils. Both of these conformers were found to remodel into non-toxic aggregates. The results showed that K-3-rh interacts with different Aβ conformers, which affects fibril formation, oligomeric maturation and fibrillar stabilization. Conclusion K-3-rh is an efficient molecule to hinder the self assembly and to abrogate the cytotoxic effects of Aβ42 peptide. Hence, K-3-rh and small molecules with similar structure might be considered for therapeutic development against AD.

Physiologic Conditions Affect Toxicity of Ingested Industrial Fluoride

OpenAIRE

Richard Sauerheber

2013-01-01

The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity ...

Ethanol Fermentation of Various Pretreated and Hydrolyzed Substrates at Low Initial pH

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Kádár, Zsófia; Maltha, San Feng; Szengyel, Zsolt; Réczey, Kati; de Laat, Wim

Lignocellulosic materials represent an abundant feedstock for bioethanol production. Because of their complex structure pretreatment is necessary to make it accessible for enzymatic attack. Steam pretreatment with or without acid catalysts seems to be one of the most promising techniques, which has already been applied for large variety of lignocellulosics in order to improve enzymatic digestibility. During this process a range of toxic compounds (lignin and sugar degradation products) are formed which inhibit ethanol fermentation. In this study, the toxicity of hemicellulose hydrolysates obtained in the steam pretreatment of spruce, willow, and corn stover were investigated in ethanol fermentation tests using a yeast strain, which has been previously reported to have a resistance to inhibitory compounds generated during steam pretreatment. To overcome bacterial contamination, fermentations were carried out at low initial pH. The fermentability of hemicellulose hydrolysates of pretreated lignocellulosic substrates at low pH gave promising results with the economically profitable final 5 vol% ethanol concentration corresponding to 85% of theoretical. Adaptation experiments have shown that inhibitor tolerance of yeast strain can be improved by subsequent transfer of the yeast to inhibitory medium.

Metal bioavailability and toxicity to fish in low-alkalinity lakes: A critical review

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Spry, D.J.; Wiener, James G.

1991-01-01

Fish in low-alkalinity lakes having pH of 6·0–6·5 or less often have higher body or tissue burdens of mercury, cadmium, and lead than do fish in nearby lakes with higher pH. The greater bioaccumulation of these metals in such waters seems to result partly from the greater aqueous abundances of biologically available forms (CH3 Hg+, Cd2+, and Pb2+) at low pH. In addition, the low concentrations of aqueous calcium in low-alkalinity lakes increase the permeability of biological membranes to these metals, which in fish may cause greater uptake from both water and food. Fish exposed to aqueous inorganic aluminum in the laboratory and field accumulate the metal in and on the epithelial cells of the gills; however, there is little accumulation of aluminum in the blood or internal organs. In low-pH water, both sublethal and lethal toxicity of aluminum has been clearly demonstrated in both laboratory and field studies at environmental concentrations. In contrast, recently measured aqueous concentrations of total mercury, methylmercury, cadmium, and lead in low-alkalinity lakes are much lower than the aqueous concentrations known to cause acute or chronic toxicity in fish, although the vast majority of toxicological research has involved waters with much higher ionic strength than that in low-alkalinity lakes. Additional work with fish is needed to better assess (1) the toxicity of aqueous metals in low-alkalinity waters, and (2) the toxicological significance of dietary methylmercury and cadmium.

Optical coherence tomography findings in methanol toxicity.

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Klein, Kendra A; Warren, Alexis K; Baumal, Caroline R; Hedges, Thomas R

2017-01-01

Methanol toxicity poses a significant public health problem in developing countries, and in Southeast Asia, where the most common source of poisoning is via adulterated liquor in local drinks. Methanol toxicity can have devastating visual consequences and retinal specialists should be aware of the features of this toxic optic neuropathy. The authors report a case of severe systemic methanol toxicity and relatively mild optic neuropathy demonstrating unique retinal changes on optical coherence tomography (OCT). A previously healthy student developed ataxia, difficulty breathing and loss of consciousness hours after drinking homemade alcohol while traveling in Indonesia. She was found to have a serum pH of 6.79 and elevated methanol levels. She was treated with intravenous ethanol, methylprednisolone and sodium bicarbonate. When she awoke she had bilateral central scotomas. At presentation, she had central depression on visual field testing. OCT of the retinal nerve fiber layer (RNFL) was normal but ganglion cell layer analysis (GCL) showed highly selective loss of the nasal fibers in both eyes. Further, OCT of the macula demonstrated inner nuclear layer (INL) microcysts in the corresponding area of selective GCL loss in both eyes. The selective involvement of the papillomacular bundle fibers is common in toxic optic neuropathies and represents damage to the small caliber axons rich in mitochondria. Despite severe systemic toxicity, the relative sparing of the optic nerve in this case enabled characterization of the evolution of methanol toxicity with segmental GCL involvement and preservation of the RNFL, corresponding to the papillomacular bundle. This is the first reported case of INL microcysts in methanol optic neuropathy and supports that they are a non-specific finding, and may represent preferential damage to the papillomacular bundle.

The toxicity of sulfolane and DIPA from sour gas plants to aquatic species

International Nuclear Information System (INIS)

Lintott, D.R.; Goudey, J.S.; Wilson, J.; Swanson, S.; Drury, C.

1997-01-01

The ecological effects of sulfolane and diisopropanolamine (DIPA), which are used to remove sulfur compounds from natural gas, were studied to establish risk-based cleanup criteria and to evaluate effective remedial measures. Toxicity tests were conducted on both the parent compounds and the thermal and biological degradation products. Toxicity testing focused on aquatic species because surface outlets, such as creeks, were found to be the major pathways for the water soluble DIPA and sulfolane chemicals. Sulfolane proved to be relatively non-toxic to aquatic species, with the exception of bacteria. DIPA was relatively toxic to algae at pH found in ground and surface waters. Aqueous and methanol reclaimer bottom extracts from five different gas plant sites were also tested using modified acute toxicity screening tests with different species. The reclaimer bottoms were found to be highly toxic to all species tested. DIPA and sulfolane did not entirely account for the toxicity of the reclaimer bottoms. Inorganic salts and metals present in reclaimer bottoms were found not to contribute to toxicity directly. The same was true for DIPA and sulfolane degradation products. 3 refs., 7 tabs., 8 figs

The toxicity of sulfolane and DIPA from sour gas plants to aquatic species

Energy Technology Data Exchange (ETDEWEB)

Lintott, D.R.; Goudey, J.S. [HydroQual Consultants, Inc., Calgary, AB (Canada); Wilson, J.; Swanson, S. [Golder Associates, Calgary, AB (Canada); Drury, C. [Shell Canada Ltd., Calgary, AB (Canada). Calgary Research Centre

1997-12-31

The ecological effects of sulfolane and diisopropanolamine (DIPA), which are used to remove sulfur compounds from natural gas, were studied to establish risk-based cleanup criteria and to evaluate effective remedial measures. Toxicity tests were conducted on both the parent compounds and the thermal and biological degradation products. Toxicity testing focused on aquatic species because surface outlets, such as creeks, were found to be the major pathways for the water soluble DIPA and sulfolane chemicals. Sulfolane proved to be relatively non-toxic to aquatic species, with the exception of bacteria. DIPA was relatively toxic to algae at pH found in ground and surface waters. Aqueous and methanol reclaimer bottom extracts from five different gas plant sites were also tested using modified acute toxicity screening tests with different species. The reclaimer bottoms were found to be highly toxic to all species tested. DIPA and sulfolane did not entirely account for the toxicity of the reclaimer bottoms. Inorganic salts and metals present in reclaimer bottoms were found not to contribute to toxicity directly. The same was true for DIPA and sulfolane degradation products. 3 refs., 7 tabs., 8 figs.

Identification of the cause of weak acute toxicity to rainbow trout at a petroleum refinery

International Nuclear Information System (INIS)

Arnold, W.R.; Zaleski, R.T.; Biddinger, G.R.

1995-01-01

The refinery in question performs flow through acute toxicity tests on its effluent four times per month using three fish species: fathead minnows (Pimephales promelas), threespine sticklebacks (Gasterosteus oculeatus) and rainbow trout (Oncorhynchus mykiss). Several months of monitoring data indicated a transient low level acute toxicity to rainbow trout. In most cases, several days were required for mortality to occur in the flow through tests and numerous attempts to reproduce toxicity in static and static renewal tests were unsuccessful. A decision was made to manipulate the effluent in an attempt to enhance the toxic effect in the static mode so that conventional methods could be used to identify the cause. these tests indicated that toxicity was pH dependent. Additional testing, using EPA's Phase 1 Toxicity Identification Evaluation methods suggested that the cause of toxicity was probably an organic acid. Experiments were subsequently begun to identify the specific cause and source of toxicity. This paper reviews the problems confronted during the various phases of the study and the decisions that were made that eventually led to an understanding of the basis of toxicity

Histone deacetylase-mediated regulation of endolysosomal pH.

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Prasad, Hari; Rao, Rajini

2018-05-04

The pH of the endolysosomal system is tightly regulated by a balance of proton pump and leak mechanisms that are critical for storage, recycling, turnover, and signaling functions in the cell. Dysregulation of endolysosomal pH has been linked to aging, amyloidogenesis, synaptic dysfunction, and various neurodegenerative disorders, including Alzheimer's disease. Therefore, understanding the mechanisms that regulate luminal pH may be key to identifying new targets for managing these disorders. Meta-analysis of yeast microarray databases revealed that nutrient-limiting conditions inhibited the histone deacetylase (HDAC) Rpd3 and thereby up-regulated transcription of the endosomal Na + /H + exchanger Nhx1, resulting in vacuolar alkalinization. Consistent with these findings, Rpd3 inhibition by the HDAC inhibitor and antifungal drug trichostatin A induced Nhx1 expression and vacuolar alkalinization. Bioinformatics analysis of Drosophila and mouse databases revealed that caloric control of the Nhx1 orthologs DmNHE3 and NHE6, respectively, is also mediated by HDACs. We show that NHE6 is a target of the transcription factor cAMP-response element-binding protein (CREB), a known regulator of cellular responses to low-nutrient conditions, providing a molecular mechanism for nutrient- and HDAC-dependent regulation of endosomal pH. Of note, pharmacological targeting of the CREB pathway to increase NHE6 expression helped regulate endosomal pH and correct defective clearance of amyloid Aβ in an apoE4 astrocyte model of Alzheimer's disease. These observations from yeast, fly, mouse, and cell culture models point to an evolutionarily conserved mechanism for HDAC-mediated regulation of endosomal NHE expression. Our insights offer new therapeutic strategies for modulation of endolysosomal pH in fungal infection and human disease. © 2018 Prasad and Rao.

Salivary pH as a marker of plasma adiponectin concentrations in Women

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Tremblay Monique

2012-02-01

Full Text Available Abstract Background Plasma adiponectin is a significant correlate of the pro-inflammatory cardiometabolic risk profile associated with obesity and type 2 diabetes. Salivary pH is influenced by several cardiometabolic risk components such as inflammation, oxidation and numerous oral and systemic health modulators, including the menopausal status. This study aimed to assess the association between plasma adiponectin concentrations and salivary pH in women according to the menopausal status. Method Unstimulated saliva collection was performed in 151 Caucasian women of French-Canadian origin (53 premenopausal women (PMW and 98 menopausal women (MW. Student's t test, ANOVA and linear regression models were used to assess the association between plasma adiponectin concentrations and salivary pH. Results Plasma adiponectin levels increased as a function of salivary pH in the whole sample and among MW (r = 0.29 and r = 0.36, p 2 was 10.8% (p Conclusions These results suggest that salivary pH is a significant correlate of plasma adiponectin levels in women. With the increasing prevalence of type 2 diabetes and obesity, new technologies should be developed to more easily monitor health status, disease onset and progression. Salivary pH, a simple, inexpensive and non-invasive measure, could be a very promising avenue.

Intracellular pH in increased after transformation of Chinese hamster embryo fibroblasts

International Nuclear Information System (INIS)

Ober, S.S.; Pardee, A.B.

1987-01-01

These studies reveal that a series of tumorigenic Chinese hamster embryo fibroblast (CHEF) cell lines maintain an internal pH (pH/sub i/) that is 0.12 +/- 0.04 pH unit above that of the nontumorigenic CHEF/18 parental line. pH measurements were made with [ 14 C]-benzoic acid. This increase of pH/sub i/ in the tumorigenic CHEF cells is not due to autocrine growth factor production or to the persistent activation of pathways previously shown to modulate Na + /H + -antiporter activity present in the CHEF/18 line. These findings suggest that the defect in pH/sub i/ regulation in the tumorigenic CHEF/18 derivatives lies in the Na + /H + antiporter itself. Further studies to determine the biological significance of an increased pH/sub i/ show that the external pH (pH 0 )-dependence curve for initiation of DNA synthesis in the tumorigenic CHEF lines is shifted by approximately 0.2 pH unit toward acidic values relative to that of the nontumorigenic CHEF/18 parent. These data show a critical role for pH/sub i/ in the regulation of DNA synthesis in Chinese hamster embryo fibroblasts and demonstrate that aberrations in pH/sub i/ can contribute to the acquisition of altered growth properties

Removal of toxic chemicals from water with activated carbon

Science.gov (United States)

Dawson, V.K.; Marking, L.L.; Bills, T.D.

1976-01-01

Activated carbon was effective in removing fish toxicants and anesthetics from water solutions. Its capacity to adsorb 3-trifluoromethyl-4-nitrophenol (TFM), antimycin, NoxfishA? (5% rotenone), Dibrorms, juglone, MSa??222, and benzocaine ranged from 0.1 to 64 mg per gram of carbon. The adsorptive capacity (end point considered as a significant discharge) of activated carbon for removal of TFM was determined at column depths of 15, 30, and 60 cm; temperatures of 7, 12, 17, and 22 C; pH's of 6.5, 7.5, 8.5, and 9.5; and flow rates of 50, 78, 100, 200, and 940 ml/min. Adsorptive capacity increased when the contact time was increased by reducing the flow rate or increasing the column depth. The adsorptive capacity was not significantly influenced by temperature but was substantially higher at pH 6.5 than at the other pH's tested. A practical and efficient filter for purifying chemically treated water was developed.

An ultrasensitive method of real time pH monitoring with complementary metal oxide semiconductor image sensor.

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Devadhasan, Jasmine Pramila; Kim, Sanghyo

2015-02-09

CMOS sensors are becoming a powerful tool in the biological and chemical field. In this work, we introduce a new approach on quantifying various pH solutions with a CMOS image sensor. The CMOS image sensor based pH measurement produces high-accuracy analysis, making it a truly portable and user friendly system. pH indicator blended hydrogel matrix was fabricated as a thin film to the accurate color development. A distinct color change of red, green and blue (RGB) develops in the hydrogel film by applying various pH solutions (pH 1-14). The semi-quantitative pH evolution was acquired by visual read out. Further, CMOS image sensor absorbs the RGB color intensity of the film and hue value converted into digital numbers with the aid of an analog-to-digital converter (ADC) to determine the pH ranges of solutions. Chromaticity diagram and Euclidean distance represent the RGB color space and differentiation of pH ranges, respectively. This technique is applicable to sense the various toxic chemicals and chemical vapors by situ sensing. Ultimately, the entire approach can be integrated into smartphone and operable with the user friendly manner. Copyright © 2014 Elsevier B.V. All rights reserved.

Manipulating and Monitoring On-Surface Biological Reactions by Light-Triggered Local pH Alterations.

Science.gov (United States)

Peretz-Soroka, Hagit; Pevzner, Alexander; Davidi, Guy; Naddaka, Vladimir; Kwiat, Moria; Huppert, Dan; Patolsky, Fernando

2015-07-08

Significant research efforts have been dedicated to the integration of biological species with electronic elements to yield smart bioelectronic devices. The integration of DNA, proteins, and whole living cells and tissues with electronic devices has been developed into numerous intriguing applications. In particular, the quantitative detection of biological species and monitoring of biological processes are both critical to numerous areas of medical and life sciences. Nevertheless, most current approaches merely focus on the "monitoring" of chemical processes taking place on the sensing surfaces, and little efforts have been invested in the conception of sensitive devices that can simultaneously "control" and "monitor" chemical and biological reactions by the application of on-surface reversible stimuli. Here, we demonstrate the light-controlled fine modulation of surface pH by the use of photoactive molecularly modified nanomaterials. Through the use of nanowire-based FET devices, we showed the capability of modulating the on-surface pH, by intensity-controlled light stimulus. This allowed us simultaneously and locally to control and monitor pH-sensitive biological reactions on the nanodevices surfaces, such as the local activation and inhibition of proteolytic enzymatic processes, as well as dissociation of antigen-antibody binding interactions. The demonstrated capability of locally modulating the on-surface effective pH, by a light stimuli, may be further applied in the local control of on-surface DNA hybridization/dehybridization processes, activation or inhibition of living cells processes, local switching of cellular function, local photoactivation of neuronal networks with single cell resolution and so forth.

Effect of long-term smoking on salivary flow rate and salivary pH

Directory of Open Access Journals (Sweden)

Mala Singh

2015-01-01

Full Text Available Introduction: Saliva is a complex and important body fluid which is very essential for oral health and it is the first biological fluid that is exposed to cigarette smoke, which contains numerous toxic compositions responsible for structural and functional changes in saliva. Aim: To evaluate the long-term effect of smoking on salivary flow rate (SFR and salivary pH. Materials and Methods: The subjects of the study were divided into smokers and nonsmokers. Each group comprised of 35 male adults. The saliva of each subject was collected under resting conditions. They were asked to spit in a graduated container at an interval of 60 s for 5 min. Salivary pH was measured immediately after measuring SFR using the (Indikrom Paper pH indicator and calibrated cylinder. Based on the color change of the indicator paper strip, the pH was assessed in comparison with a color chart. Data were analyzed by Student′s t-test using SPSS 15. Results: The mean (±standard deviation SFR and pH were 0.20 (±0.05 ml/min and 6.30 (±0.36 respectively in smokers while the mean SFR and pH were 0.36 (±0.06 ml/min and 7.10 (±0.24 in nonsmokers. The difference was statistically significant (P = 0.00. Conclusion: Long-term smoking significantly reduces the SFR and salivary pH.

Toxicity and dosimetric analysis of non-small cell lung cancer patients undergoing radiotherapy with 4DCT and image-guided intensity modulated radiotherapy: a regional centre's experience.

Science.gov (United States)

Livingston, Gareth C; Last, Andrew J; Shakespeare, Thomas P; Dwyer, Patrick M; Westhuyzen, Justin; McKay, Michael J; Connors, Lisa; Leader, Stephanie; Greenham, Stuart

2016-09-01

For patients receiving radiotherapy for locally advance non-small cell lung cancer (NSCLC), the probability of experiencing severe radiation pneumonitis (RP) appears to rise with an increase in radiation received by the lungs. Intensity modulated radiotherapy (IMRT) provides the ability to reduce planned doses to healthy organs at risk (OAR) and can potentially reduce treatment-related side effects. This study reports toxicity outcomes and provides a dosimetric comparison with three-dimensional conformal radiotherapy (3DCRT). Thirty curative NSCLC patients received radiotherapy using four-dimensional computed tomography and five-field IMRT. All were assessed for early and late toxicity using common terminology criteria for adverse events. All plans were subsequently re-planned using 3DCRT to the same standard as the clinical plans. Dosimetric parameters for lungs, oesophagus, heart and conformity were recorded for comparison between the two techniques. IMRT plans achieved improved high-dose conformity and reduced OAR doses including lung volumes irradiated to 5-20 Gy. One case each of oesophagitis and erythema (3%) were the only Grade 3 toxicities. Rates of Grade 2 oesophagitis were 40%. No cases of Grade 3 RP were recorded and Grade 2 RP rates were as low as 3%. IMRT provides a dosimetric benefit when compared to 3DCRT. While the clinical benefit appears to increase with increasing target size and increasing complexity, IMRT appears preferential to 3DCRT in the treatment of NSCLC.

Photosynthetic and cellular toxicity of cadmium in Chlorella vulgaris.

Science.gov (United States)

Ou-Yang, Hui-Ling; Kong, Xiang-Zhen; Lavoie, Michel; He, Wei; Qin, Ning; He, Qi-Shuang; Yang, Bin; Wang, Rong; Xu, Fu-Liu

2013-12-01

The toxic effects of cadmium (Cd) on the green alga Chlorella vulgaris were investigated by following the response to Cd of various toxicity endpoints (cell growth, cell size, photochemical efficiency of PSII in the light or Φ(PSII), maximal photochemical efficiency or Fv/Fm, chlorophyll a fluorescence, esterase activity, and cell viability). These toxicity endpoints were studied in laboratory batch cultures of C. vulgaris over a long-term 96-h exposure to different Cd concentrations using flow cytometry and pulse amplitude modulated fluorometry. The sequence of sensitivity of these toxicity endpoints was: cell yield > Φ(PSII) ≈ esterase activity > Fv/Fm > chlorophyll a fluorescence ≈ cell viability. It is shown that cell apoptosis or cell death only accounted for a minor part of the reduction in cell yield even at very high algistatic free Cd²⁺ concentrations, and other mechanisms such as blocked cell divisions are major contributors to cell yield inhibition. Furthermore, cadmium may affect both the electron donors and acceptors of the electron transport chain at high free Cd²⁺ concentration. Finally, the resistance of cells to cell death was size-dependent; medium-sized cells had the highest toxicity threshold. The present study brings new insights into the toxicity mechanisms of Cd in C. vulgaris and provides a detailed comparison of the sensitivity of various Cd toxicity endpoints. © 2013 SETAC.

Modulatory effects of Zn2+ ions on the toxicity of citrate- and PVP-capped gold nanoparticles towards freshwater algae, Scenedesmus obliquus.

Science.gov (United States)

Iswarya, V; Johnson, J B; Parashar, Abhinav; Pulimi, Mrudula; Chandrasekaran, N; Mukherjee, Amitava

2017-02-01

Gold nanoparticles (GNPs) are widely used for medical purposes, both in diagnostics as well as drug delivery, and hence are prone to release and distribution in the environment. Thus, we have explored the effects of GNPs with two distinct surface capping (citrate and PVP), and three different sizes (16, 27, and 37 nm) at 0.01-, 0.1-, and 1-mg L -1 concentrations on a predominant freshwater alga Scenedesmus obliquus in the sterile freshwater matrix. We have also investigated how an abundant metal ion from freshwater, i.e., Zn 2+ ions may modulate the effects of the selected GNPs (40 nm, citrate, and PVP capped). Preliminary toxicity results revealed that gold nanoparticles were highly toxic in comparison to zinc ions alone. A significant modulation in the toxicity of Zn ions was not noticed in the presence of GNPs. In contrast, zinc ions minimized the toxicity produced by GNPs (both CIT-37 and PVP-37), despite its individual toxicity. Approximately, about 42, 33, and 25% toxicity reduction was noted at 0.05-, 0.5-, and 5-mg L -1 Zn ions, respectively, for CIT-37 GNPs, while 31% (0.05 mg L -1 ), 24% (0.5 mg L -1 ), and 9% (5 mg L -1 ) of toxicity reduction were noted for PVP-37 GNPs. Maximum toxicity reduction was seen at 0.05 mg L -1 of Zn ions. Abbott modeling substantiated antagonistic effects offered by Zn 2+ ions on GNPs. Stability and sedimentation data revealed that the addition of zinc ions gradually induced the aggregation of NPs and in turn significantly reduced the toxicity of GNPs. Thus, the naturally existing ions like Zn 2+ have an ability to modulate the toxicity of GNPs in a real-world environment scenario.

Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells

International Nuclear Information System (INIS)

Reid, I.R.; Civitelli, R.; Avioli, L.V.; Hruska, K.A.

1988-01-01

It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pH i ) and there is some evidence that this in turn may influence cell growth. The authors have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5,(6)-carboxyfluorescein indicated that these cells regulate pH i by means of an amiloride-inhibitable Na + -H + exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pH i with a half-maximal effect at 10 -11 M. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pH i and [ 3 H]thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of [ 3 H]thymidine incorporation in the presence of amiloride, even though it did not affect pH i in these circumstances. It is concluded that PTH decreases pH i and growth in UMR 106 cells but that these changes can be dissociated. Depression of pH i may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment

Environment-friendly approach for the removal of toxic metals

International Nuclear Information System (INIS)

Zahra, N.; Mehmood, F.; Sheikh, S.T.; Javed, K.; Amin, A.

2006-01-01

Water pollution is serious economical problem and the presence of toxic metals like lead causes contamination of plants and then through nutritional chain it affects the health of humans and animals. This research work describes the removal of lead from wastewater using natural bentonites taken from various areas of Pakistan. The batch adsorption process was applied to remove this toxic metal. The quantities of lead metal before and after the treatment of standard solutions with different samples of bentonite were determined by atomic absorption spectroscopic method. The studies were carried out at room temperature, pH 7 and -200 mesh particle size using 50 ml of metal solutions. The time taken to maintain equilibrium was one hour. Then percentage adsorption was estimated on bentonite samples. (author)

Dimerization of Organic Dyes on Luminescent Gold Nanoparticles for Ratiometric pH Sensing.

Science.gov (United States)

Sun, Shasha; Ning, Xuhui; Zhang, Greg; Wang, Yen-Chung; Peng, Chuanqi; Zheng, Jie

2016-02-12

Synergistic effects arising from the conjugation of organic dyes onto non-luminescent metal nanoparticles (NPs) have greatly broadened their applications in both imaging and sensing. Herein, we report that conjugation of a well-known pH-insensitive dye, tetramethyl-rhodamine (TAMRA), to pH-insensitive luminescent gold nanoparticles (AuNPs) can lead to an ultrasmall nanoindicator that can fluorescently report local pH in a ratiometric way. Such synergy originated from the dimerization of TAMRA on AuNPs, of which geometry was very sensitive to surface charges of the AuNPs and can be reversely modulated through protonation of surrounding glutathione ligands. Not limited to pH-insensitive dyes, this pH-dependent dimerization can also enhance the pH sensitivity of fluorescein, a well-known pH-sensitive dye, within a larger pH range, opening up a new pathway to design ultrasmall fluorescent ratiometric nanoindicators with tunable wavelengths and pH response ranges. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lead toxicity thresholds in 17 Chinese soils based on substrate-induced nitrification assay.

Science.gov (United States)

Li, Ji; Huang, Yizong; Hu, Ying; Jin, Shulan; Bao, Qiongli; Wang, Fei; Xiang, Meng; Xie, Huiting

2016-06-01

The influence of soil properties on toxicity threshold values for Pb toward soil microbial processes is poorly recognized. The impact of leaching on the Pb threshold has not been assessed systematically. Lead toxicity was screened in 17 Chinese soils using a substrate-induced nitrification (SIN) assay under both leached and unleached conditions. The effective concentration of added Pb causing 50% inhibition (EC50) ranged from 185 to >2515mg/kg soil for leached soil and 130 to >2490mg/kg soil for unleached soil. These results represented >13- and >19-fold variations among leached and unleached soils, respectively. Leaching significantly reduced Pb toxicity for 70% of both alkaline and acidic soils tested, with an average leaching factor of 3.0. Soil pH and CEC were the two most useful predictors of Pb toxicity in soils, explaining over 90% of variance in the unleached EC50 value. The relationships established in the present study predicted Pb toxicity within a factor of two of measured values. These relationships between Pb toxicity and soil properties could be used to establish site-specific guidance on Pb toxicity thresholds. Copyright © 2016. Published by Elsevier B.V.

Algal and bacterial activities in acidic (pH 3) strip mine lakes

International Nuclear Information System (INIS)

Gyure, R.A.; Konopka, A.; Brooks, A.; Doemel, W.

1987-01-01

Reservoir 29 and Lake B are extremely acid lakes (epilimnion pHs of 2.7 and 3.2, respectively), because they receive acidic discharges from coal refuse piles. They differ in that the pH of profundal sediments in Reservoir 29 increased from 2.7 to 3.8 during the period of thermal stratification, whereas permanently anoxic sediments in Lake B had a pH of 6.2. The pH rise in Reservoir 29 sediments was correlated with a temporal increase in H 2 S concentration in the anaerobic hypolimnion from 0 to >1 mM. The chlorophyll a levels in the epilimnion of Reservoir 29 were low, and the rate of primary production was typical of an oligotrophic system. However, there was a dense 10-cm layer of algal biomass at the bottom of the metalimnion. Production by this layer was low owing to light limitation and possibly H 2 S toxicity. The specific photosynthetic rates of epilimnetic algae were low, which suggests that nutrient availability is more important than pH in limiting production. The highest photosynthetic rates were obtained in water samples incubated at pH 2.7 to 4. Heterotrophic bacterial activity (measured by [ 14 C]glucose metabolism) was greatest at the sediment/water interface. Bacterial production (assayed by thymidine incorporation) was as high in Reservoir 29 as in a nonacid mesotrophic Indiana lake

Silymarin protects PBMC against B(a)P induced toxicity by replenishing redox status and modulating glutathione metabolizing enzymes-An in vitro study

International Nuclear Information System (INIS)

Kiruthiga, P.V.; Pandian, S. Karutha; Devi, K. Pandima

2010-01-01

PAHs are a ubiquitous class of environmental contaminants that have a large number of hazardous consequences on human health. An important prototype of PAHs, B(a)P, is notable for being the first chemical carcinogen to be discovered and the one classified by EPA as a probable human carcinogen. It undergoes metabolic activation to QD, which generate ROS by redox cycling system in the body and oxidatively damage the macromolecules. Hence, a variety of antioxidants have been tested as possible protectors against B(a)P toxicity. Silymarin is one such compound, which has high human acceptance, used clinically and consumed as dietary supplement around the world for its strong anti-oxidant efficacy. Silymarin was employed as an alternative approach for treating B(a)P induced damage and oxidative stress in PBMC, with an emphasis to provide the molecular basis for the effect of silymarin against B(a)P induced toxicity. PBMC cells exposed to either benzopyrene (1 μM) or silymarin (2.4 mg/ml) or both was monitored for toxicity by assessing LPO, PO, redox status (GSH/GSSG ratio), glutathione metabolizing enzymes GR and GPx and antioxidant enzymes CAT and SOD. This study also investigated the protective effect of silymarin against B(a)P induced biochemical alteration at the molecular level by FT-IR spectroscopy. Our findings were quite striking that silymarin possesses substantial protective effect against B(a)P induced oxidative stress and biochemical changes by restoring redox status, modulating glutathione metabolizing enzymes, hindering the formation of protein oxidation products, inhibiting LPO and further reducing ROS mediated damages by changing the level of antioxidant enzymes. The results suggest that silymarin exhibits multiple protections and it should be considered as a potential protective agent for environmental contaminant induced immunotoxicity.

Temporal viscosity modulations driven by a pH sensitive polymer coupled to a pH-changing chemical reaction.

Science.gov (United States)

Escala, D M; Muñuzuri, A P; De Wit, A; Carballido-Landeira, J

2017-05-17

The Formaldehyde-Sulfite (FS) and the Formaldehyde-Sulfite-Gluconolactone (FSG) systems are examples of complex chemical reactions accompanied by well-controlled variations in pH. While the FS system exhibits a clock behavior, in the FSG reaction, this mechanism is coupled with the hydrolysis of the gluconolactone which gives the possibility to show large temporal oscillations of pH in an open reactor. In this work, we show how these reactive systems, due to their organic nature, can be coupled with pH sensitive polymers, particularly with polyacrylic acid (PAA) to trigger temporal changes of viscosity. We characterize this coupled reactive system showing the effects of changes in the initial concentrations of the polymer and in the chemical reagents on the induction time, the magnitude of the pH variations and the temporal modifications of the viscosity.

Resveratrol prevents ammonia toxicity in astroglial cells.

Directory of Open Access Journals (Sweden)

Larissa Daniele Bobermin

Full Text Available Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS. Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS, GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA and extracellular signal-regulated kinase (ERK pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity.

Resveratrol Prevents Ammonia Toxicity in Astroglial Cells

Science.gov (United States)

Guerra, Maria Cristina; Leite, Marina Concli; Souza, Diogo Onofre; Gonçalves, Carlos-Alberto; Gottfried, Carmem

2012-01-01

Ammonia is implicated as a neurotoxin in brain metabolic disorders associated with hyperammonemia. Acute ammonia toxicity can be mediated by an excitotoxic mechanism, oxidative stress and nitric oxide (NO) production. Astrocytes interact with neurons, providing metabolic support and protecting against oxidative stress and excitotoxicity. Astrocytes also convert excess ammonia and glutamate into glutamine via glutamine synthetase (GS). Resveratrol, a polyphenol found in grapes and red wines, exhibits antioxidant and anti-inflammatory properties and modulates glial functions, such as glutamate metabolism. We investigated the effect of resveratrol on the production of reactive oxygen species (ROS), GS activity, S100B secretion, TNF-α, IL-1β and IL-6 levels in astroglial cells exposed to ammonia. Ammonia induced oxidative stress, decreased GS activity and increased cytokines release, probably by a mechanism dependent on protein kinase A (PKA) and extracellular signal-regulated kinase (ERK) pathways. Resveratrol prevented ammonia toxicity by modulating oxidative stress, glial and inflammatory responses. The ERK and nuclear factor-κB (NF-κB) are involved in the protective effect of resveratrol on cytokines proinflammatory release. In contrast, other antioxidants (e.g., ascorbic acid and trolox) were not effective against hyperammonemia. Thus, resveratrol could be used to protect against ammonia-induced neurotoxicity. PMID:23284918

Critical Limits for Hg(II) in soils, derived from chronic toxicity data

International Nuclear Information System (INIS)

Tipping, E.; Lofts, S.; Hooper, H.; Frey, B.; Spurgeon, D.; Svendsen, C.

2010-01-01

Published chronic toxicity data for Hg(II) added to soils were assembled and evaluated to produce a data set comprising 52 chronic end-points, five each for plants and invertebrates and 42 for microbes. With end-points expressed in terms of added soil Hg(II) contents, Critical Limits were derived from the 5th percentiles of species sensitivity distributions, values of 0.13 μg (g soil) -1 and 3.3 μg (g soil organic matter) -1 being obtained. The latter value exceeds the currently recommended Critical Limit, used to determine Hg(II) Critical Loads in Europe, of 0.5 μg (g soil organic matter) -1 . We also applied the WHAM/Model VI chemical speciation model to estimate concentrations of Hg 2+ in soil solution, and derived an approximate Critical Limit Function (CLF) that includes pH; log [Hg 2+ ] crit = -2.15 pH -17.10. Because they take soil properties into account, the soil organic matter-based limit and the CLF provide the best assessment of toxic threat for different soils. For differing representative soils, each predicts a range of up to 100-fold in the dry weight-based content of mercury that corresponds to the Critical Limit. - Published laboratory toxicity data and chemical speciation modelling are used to derive Critical Limits expressed as either soil Hg(II) content or Hg 2+ concentration.

Quantifying Interfacial pH Variation at Molecular Length Scales Using a Concurrent Non-Faradaic Reaction.

Science.gov (United States)

Ryu, Jaeyune; Wuttig, Anna; Surendranath, Yogesh

2018-05-15

We quantify changes in the interfacial pH local to the electrochemical double layer during electrocatalysis, using a concurrent non-faradaic probe reaction. In the absence of electrocatalysis, nanostructured Pt/C surfaces mediate the reaction of H2 with cis-2-butene-1,4-diol to form a mixture of 1,4-butanediol and n-butanol with a selectivity that is linearly dependent on the bulk solution pH. We show that kinetic branching occurs from a common surface-bound intermediate, ensuring that this probe reaction is uniquely sensitive to the interfacial pH within molecular length scales of the surface. We use the pH-dependent selectivity of this reaction to track changes in interfacial pH during concurrent hydrogen oxidation electrocatalysis and find that the local pH can vary dramatically, > 3 units, relative to the bulk value even at modest current densities in well-buffered electrolytes. This work highlights the key role that interfacial pH variation plays in modulating inner-sphere electrocatalysis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway

Science.gov (United States)

Jung, Kwang-Woo; Strain, Anna K; Nielsen, Kirsten; Jung, Kwang-Hwan; Bahn, Yong-Sun

2012-01-01

Maintenance of cation homeostasis is essential for survival of all living organisms in their biological niches. It is also important for the survival of human pathogenic fungi in the host, where cation concentrations and pH will vary depending on different anatomical sites. However, the exact role of diverse cation transporters and ion channels in virulence of fungal pathogens remains elusive. In this study we functionally characterized ENA1 and NHA1, encoding a putative Na+/ATPase and Na+/H+ antiporter, respectively, in Cryptococcus neoformans, a basidiomycete fungal pathogen which causes fatal meningoencephalitis. Expression of NHA1 and ENA1 is induced in response to salt and osmotic shock mainly in a Hog1-dependent manner. Phenotypic analysis of the ena1, nha1, and ena1 nha1 mutants revealed that Ena1 controls cellular levels of toxic cations, such as Na+ and Li+ whereas both Ena1 and Nha1 are important for controlling less toxic K+ ions. Under alkaline conditions, Ena1 was highly induced and required for growth in the presence of low levels of Na+ or K+ salt and Nha1 played a role in survival under K+ stress. In contrast, Nha1, but not Ena1, was essential for survival at acidic conditions (pH 4.5) under high K+ stress. In addition, Ena1 and Nha1 were required for maintenance of plasma membrane potential and stability, which appeared to modulate antifungal drug susceptibility. Perturbation of ENA1 and NHA1 enhanced capsule production and melanin synthesis. However, Nha1 was dispensable for virulence of C. neoformans although Ena1 was essential. In conclusion, Ena1 and Nha1 play redundant and discrete roles in cation homeostasis, pH regulation, membrane potential, and virulence in C. neoformans, suggesting that these transporters could be novel antifungal drug targets for treatment of cryptococcosis. PMID:22343280

Scavenging of Toxic Acrolein by Resveratrol and Hesperetin and Identification of Adducts.

Science.gov (United States)

Wang, Weixin; Qi, Yajing; Rocca, James R; Sarnoski, Paul J; Jia, Aiqun; Gu, Liwei

2015-11-04

The objective of this study was to investigate the ability of resveratrol and hesperetin to scavenge acrolein at pH 7.4 and 37 °C. About 6.4 or 5.2% of acrolein remained after reaction with resveratrol or hesperetin for 12 h at equimolar concentrations. An acrolein-resveratrol adduct and two acrolein-hesperetin adducts were isolated. Their structures were elucidated using mass and NMR spectroscopy. Acrolein reacted with resveratrol at the C-2 and C-3 positions through nucleophilic addition and formed an additional heterocyclic ring. Two similar monoacrolein-conjugated adducts were identified for hesperetin. Spectroscopic data suggested each acrolein-hesperetin adduct was a mixture of four stereoisomers due to the existence of two chiral carbon atoms. Yield of adducts was low at pH 5.4 but increased at pH 7.4 and 8.4. Higher pH also promoted the formation of diacrolein adducts. Results suggest that resveratrol and hesperetin exert health benefits in part through neutralizing toxic acrolein in vivo.

Removal of toxic chromium from aqueous solution, wastewater and saline water by marine red alga Pterocladia capillacea and its activated carbon

Directory of Open Access Journals (Sweden)

Ahmed El Nemr

2015-01-01

Full Text Available Pterocladia capillacea, a red marine macroalgae, was tested for its ability to remove toxic hexavalent chromium from aqueous solution. A new activated carbon obtained from P. capillacea via acid dehydration was also investigated as an adsorbent for toxic chromium. The experiments were conducted to study the effect of important parameters such as pH, chromium concentration and adsorbent weight. Batch equilibrium tests at different pH conditions showed that at pH 1.0, a maximum chromium uptake was observed for both inactivated dried red alga P. capillacea and its activated carbon. The maximum sorption capacities for dried red alga and its activated carbon were about 12 and 66 mgg−1, respectively, as calculated by Langmuir model. The ability of inactivated red alga P. capillacea and developed activated carbon to remove chromium from synthetic sea water, natural sea water and wastewater was investigated as well. Different isotherm models were used to analyze the experimental data and the models parameters were evaluated. This study showed that the activated carbon developed from red alga P. capillacea is a promising activated carbon for removal of toxic chromium.

An intramolecular charge transfer process based fluorescent probe for monitoring subtle pH fluctuation in living cells.

Science.gov (United States)

Sun, Mingtai; Du, Libo; Yu, Huan; Zhang, Kui; Liu, Yang; Wang, Suhua

2017-01-01

It is crucial to monitor intracellular pH values and their fluctuation since the organelles of cells have different pH distribution. Herein we construct a new small molecule fluorescent probe HBT-O for monitoring the subtle pH values within the scope of neutral to acid in living cells. The probe exhibited good water solubility, a marked turquoise to olivine emission color change in response to pH, and tremendous fluorescence hypochromatic shift of ∼50nm (1718cm -1 ) as well as the increased fluorescence intensity when the pH value changed from neutral to acid. Thus, the probe HBT-O can distinguish the subtle changes in the range of normal pH values from neutral to acid with significant fluorescence changes. These properties can be attributed to the intramolecular charge transfer (ICT) process of the probe upon protonation in buffer solutions at varied pH values. Moreover, the probe was reversible and nearly non-toxic for living cells. Then the probe was successfully used to detect pH fluctuation in living cells by exhibiting different fluorescence colors and intensity. These findings demonstrate that the probe will find useful applications in biology and biomedical research. Copyright © 2016 Elsevier B.V. All rights reserved.

Biocompatibility Research of a Novel pH Sensitive Ion Exchange Resin Microsphere.

Science.gov (United States)

Liu, Hongfei; Shi, Shuangshuang; Pan, Weisan; Sun, Changshan; Zou, Xiaomian; Fu, Min; Feng, Yingshu; Ding, Hui

2014-01-01

The main objective of this study was to investigate biocompatibility and provide in-vivo pharmacological and toxicological evidence for further investigation of the possibility of pH sensitive ion exchange resin microsphere for clinical utilizations. Acute toxicity study and general pharmacological studies were conducted on the pH sensitive ion exchange resin microsphere we prepared. The general pharmacological studies consist of the effects of the pH sensitive ion exchange resin microsphere on the nervous system of mice, the functional coordination of mice, the hypnosis of mice treated with nembutal at subliminal dose, the autonomic activities of tested mice, and the heart rate, blood pressure, ECG and breathing of the anesthetic cats. The LD50 of pH sensitive ion exchange resin microsphere after oral administration was more than 18.84 g·Kg(-1). Mice were orally administered with 16 mg·Kg(-1), 32 mg·Kg(-1) and 64 mg·Kg(-1) of pH sensitive ion exchange resin microsphere and there was no significant influence on mice nervous system, general behavior, function coordination, hypnotic effect treated with nembutal at subliminal dose and frequency of autonomic activities. Within the 90 min after 5 mg·Kg(-1), 10 mg·Kg(-1), 20 mg·Kg(-1) pH sensitive ion exchange resin microsphere was injected to cat duodenum, the heart rate, blood pressure, breathing and ECG of the cats didn't make significant changes in each experimental group compared with the control group. The desirable pharmacological and toxicological behaviors of the pH sensitive ion exchange resin microsphere exhibited that it has safe biocompatibility and is possible for clinical use.

Comparison of mucous and cutaneous toxicity of IMRT and of conventional radiotherapy associated with cetuximab; Comparaison de la toxicite muqueuse et cutanee de la RCMI et de la radiotherapie classique associee au cetuximab

Energy Technology Data Exchange (ETDEWEB)

Kreps, S.; Tamby, E.; Dessard Diana, B.; Berges, O.; Botti, M.; Deberne, M.; Henni, M.; Durdux, C.; Housset, M.; Giraud, P. [Hopital europeen Georges-Pompidou, Paris (France)

2011-10-15

The authors report a retrospective assessment of acute, cutaneous and mucous toxicity resulting from an association of cetuximab and conventional conformational radiotherapy, and from an intensity-modulated conformational radiotherapy (IMRT). Seven patients presenting nasopharyngeal, oropharyngeal or hypopharyngeal tumours have been irradiated with intensity modulation, and seven without. It appears that the association of cetuximab and radiotherapy is not well tolerated and requires a close monitoring. Intensity-modulated radiotherapy allows a significant reduction of dose and of toxicity. However, mucous toxicity remains significant. Short communication

The challenge in treating locally recurrent T3-4 nasopharyngeal carcinoma: the survival benefit and severe late toxicities of re-irradiation with intensity-modulated radiotherapy.

Science.gov (United States)

Tian, Yun-Ming; Huang, Wei-Zeng; Yuan, Xia; Bai, Li; Zhao, Chong; Han, Fei

2017-06-27

Effective treatments for patients with advanced locally recurrent nasopharyngeal carcinoma (NPC) are limited. This investigation was to determine the potential benefits from re-irradiation by intensity-modulated radiotherapy (IMRT) on survival and the effects of severe late toxicities. A retrospective study was conducted in 245 patients diagnosed with locally recurrent T3-T4 NPC who had undergone re-irradiation with IMRT. Follow-up data was colletedand factors associated with survival and severe late toxicities were analyzed. The 5-year local-regional failure-free survival, distant failure-free survival and overall survival rates were 60.9%, 78.3% and 27.5%, respectively. The presence of severe late complications, recurrent T4 disease and gross tumor volume >30 cm3 were associated with poor survival. The incidences of mucosal necrosis, temporal lobe necrosis, cranial neuropathy and trismus were 22.0%, 14.6%, 27.0% and 14.6% respectively. Re-irradiation with IMRT is an effective choice in patients with locally recurrent T3-T4 NPC. However, the survival benefits can be partly offset by severe late complications and optimum treatments in these patients remain a challenge.

Digestibility and antigenicity of β-lactoglobulin as affected by heat, pH and applied shear.

Science.gov (United States)

Rahaman, Toheder; Vasiljevic, Todor; Ramchandran, Lata

2017-02-15

Processing induced conformational changes can modulate digestibility of food allergens and thereby their antigenicity. Effect of different pH (3, 5, 7), temperature (room temperature, 120°C) and shear (0s(-1), 1000s(-1)) on simulated gastrointestinal digestibility of β-lg and post digestion antigenic characteristics have been studied. At all pH levels unheated β-lg showed resistance to peptic digestion with high antigenic value while it was fairly susceptible to pancreatin with moderate reduction in antigenicity. Heating at 120°C significantly improved both peptic and pancreatic digestion attributed to structural alterations that resulted in much lower antigenicity; the level of reduction being pH dependant. The lowest antigenicity was recorded at pH 5. Shearing (1000s(-1)) had a minor impact reducing digestibility and thereby enhancing antigenicity of unheated β-lg at pH 5 and 7 slightly; however in conjunction with heating (120°C) it reduced antigenicity further irrespective of the pH. Overall, treatment at pH 5, 120°C and 1000s(-1) could potentially reduce post digestion antigenicity of β-lg. Copyright © 2016. Published by Elsevier Ltd.

A high-throughput method for assessing chemical toxicity using a Caenorhabditis elegans reproduction assay

International Nuclear Information System (INIS)

Boyd, Windy A.; McBride, Sandra J.; Rice, Julie R.; Snyder, Daniel W.; Freedman, Jonathan H.

2010-01-01

The National Research Council has outlined the need for non-mammalian toxicological models to test the potential health effects of a large number of chemicals while also reducing the use of traditional animal models. The nematode Caenorhabditis elegans is an attractive alternative model because of its well-characterized and evolutionarily conserved biology, low cost, and ability to be used in high-throughput screening. A high-throughput method is described for quantifying the reproductive capacity of C. elegans exposed to chemicals for 48 h from the last larval stage (L4) to adulthood using a COPAS Biosort. Initially, the effects of exposure conditions that could influence reproduction were defined. Concentrations of DMSO vehicle ≤ 1% did not affect reproduction. Previous studies indicated that C. elegans may be influenced by exposure to low pH conditions. At pHs greater than 4.5, C. elegans reproduction was not affected; however below this pH there was a significant decrease in the number of offspring. Cadmium chloride was chosen as a model toxicant to verify that automated measurements were comparable to those of traditional observational studies. EC 50 values for cadmium for automated measurements (176-192 μM) were comparable to those previously reported for a 72-h exposure using manual counting (151 μM). The toxicity of seven test toxicants on C. elegans reproduction was highly correlative with rodent lethality suggesting that this assay may be useful in predicting the potential toxicity of chemicals in other organisms.

External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor

Science.gov (United States)

Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K.; Shi, Yingtang; Wagner, Paul G.; Pivaroff-Ward, Kendra; Sassic, Jessica K.; Bayliss, Douglas A.

2013-01-01

The Ether-a-go-go (EAG) superfamily of voltage-gated K+ channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K+ currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K+ channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance–voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn2+. Low pH similarly reduces Mg2+ sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca2+. Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K+ currents observed in vivo. PMID:23712551

External pH modulates EAG superfamily K+ channels through EAG-specific acidic residues in the voltage sensor.

Science.gov (United States)

Kazmierczak, Marcin; Zhang, Xiaofei; Chen, Bihan; Mulkey, Daniel K; Shi, Yingtang; Wagner, Paul G; Pivaroff-Ward, Kendra; Sassic, Jessica K; Bayliss, Douglas A; Jegla, Timothy

2013-06-01

The Ether-a-go-go (EAG) superfamily of voltage-gated K(+) channels consists of three functionally distinct gene families (Eag, Elk, and Erg) encoding a diverse set of low-threshold K(+) currents that regulate excitability in neurons and muscle. Previous studies indicate that external acidification inhibits activation of three EAG superfamily K(+) channels, Kv10.1 (Eag1), Kv11.1 (Erg1), and Kv12.1 (Elk1). We show here that Kv10.2, Kv12.2, and Kv12.3 are similarly inhibited by external protons, suggesting that high sensitivity to physiological pH changes is a general property of EAG superfamily channels. External acidification depolarizes the conductance-voltage (GV) curves of these channels, reducing low threshold activation. We explored the mechanism of this high pH sensitivity in Kv12.1, Kv10.2, and Kv11.1. We first examined the role of acidic voltage sensor residues that mediate divalent cation block of voltage activation in EAG superfamily channels because protons reduce the sensitivity of Kv12.1 to Zn(2+). Low pH similarly reduces Mg(2+) sensitivity of Kv10.1, and we found that the pH sensitivity of Kv11.1 was greatly attenuated at 1 mM Ca(2+). Individual neutralizations of a pair of EAG-specific acidic residues that have previously been implicated in divalent block of diverse EAG superfamily channels greatly reduced the pH response in Kv12.1, Kv10.2, and Kv11.1. Our results therefore suggest a common mechanism for pH-sensitive voltage activation in EAG superfamily channels. The EAG-specific acidic residues may form the proton-binding site or alternatively are required to hold the voltage sensor in a pH-sensitive conformation. The high pH sensitivity of EAG superfamily channels suggests that they could contribute to pH-sensitive K(+) currents observed in vivo.

Effect of pH on the formation of disinfection byproducts in swimming pool water – Is less THM better?

DEFF Research Database (Denmark)

Hansen, Kamilla Marie Speht; Willach, Sarah; Antoniou, Maria

2012-01-01

This study investigated the formation and predicted toxicity of different groups of disinfection byproducts (DBPs) from human exudates in relation to chlorination of pool water at different pH values. Specifically, the formation of the DBP groups trihalomethanes (THMs), haloacetic acids (HAAs......), haloacetonitriles (HANs) and trichloramine (NCl3), resulting from the chlorination of body fluid analog, were investigated at 6.0 ≤ pH ≤ 8.0. Either the initial concentration of active chorine or free chlorine was kept constant in the tested pH range. THM formation was reduced by decreasing pH but HAN, and NCl3...... formation was investigated and found to follow the same pH dependency as without bromide present, with the overall DBP formation increasing, except for HAAs. Estimation of genotoxicity and cytotoxicity of the chlorinated human exudates showed that among the quantified DBP groups, HAN formation were...

Development of manganese toxicity in pasture legumes under extreme climatic conditions. [Trifolium subterraneum; Medicago sativa; Brassica campestris

Energy Technology Data Exchange (ETDEWEB)

Siman, A; Cradock, F W; Hudson, A W

1974-08-01

Manganese levels and pH in soil were measured on limed and unlimed plots at bi-monthly intervals for two years at five field sites with lucerne (Medicago sativa) and subterranean clover (Trifolium subterraneum) and related to rainfall and temperature. Pot experiments with lucerne, subterranean clover and rape (Brassica campestris) were used to confirm the results of the field experiments. Manganese toxicity developed in lucerne and subterranean clover under waterlogged conditions after heavy rain on the slightly acid soils (pH 4.7-5.5). Lucerne also showed manganese toxicity on the same soils in summer after extended hot, dry conditions. The maximum available manganese was 210 ..mu..g/g in the waterlogged soil (0-15 cm) the 128 ..mu..g/g in the heat affected soil. Lime treatment of 2240 kg/ha reduced the maximum available manganese to 148 ..mu..g/g in waterlogged plots and to 47 ..mu..g/g in the heat affected plots but failed to correct manganese toxicity. However, lime corrected toxicity symptoms under less severe conditions. In the pot experiments, available manganese reached 270 ..mu..g/g after 2 weeks artificial waterlogging and 68 ..mu..g/g after 2 weeks dry heat exposure. 12 references, 4 figures, 3 tables.

Extractability, plant yield and toxicity thresholds for boron in compost

Energy Technology Data Exchange (ETDEWEB)

Brinton, W.F.; Evans, E.; Blewett, C. [Woods End Labs Inc., Mt. Vernon, ME (United States)

2008-04-01

Boron (B) is a trace element essential to crop growth in small soil concentrations (0.2-1.5ppm), yet may produce plant toxicity symptoms readily as the amount in the soil solution increases over 2ppm. Our study examined commercial compost made with coal fly-ash used to prepare growing media for cultivars of varying sensitivity (corn, beans, cucumber, peas). We examined total vs. extractable boron content and relate final visual symptoms of B-toxicity to yields and tissue concentrations. Visual toxicity effects included tip burn (corn), leaf mottling and necrosis (beans and peas) and leaf mottling and cupping (cucumbers). Fly ash added to compost increased hot-water soluble (HWS) B in proportion to rate and in dependence on pH, with 30% and 10% of total-B expressed as HWS-B at a media pH of 6 and 7.5, respectively. Biomass for bean and cucumber was significantly reduced by 45 to 55%, respectively, by addition of 33% fly-ash compost to growing media (28ppm total-B) while plant tissue-B increased by 6- to 4-fold, respectively. Economic yield depressions in compost media are evident for all crops and appeared at levels of HWS-B in compost media exceeding 5 ppm. The study underscores the need for careful management of exogenous factors that may be present in composts and suggests detailed understanding of media-pH and cultivar preferences may be required in preparation of growing media in order to reduce potential negative growth effects.

Orthophosphate modulates the phytotoxicity of nano-ZnO to Lemna minor (L.).

Science.gov (United States)

Chen, Xiaolin; O'Halloran, John; Jansen, Marcel A K

2018-03-02

Because of their applications in large numbers of products, Zinc Oxide nanoparticles (nano-ZnO) will inevitably enter into the environment. Nano-ZnO released into the environment will be present in a complex matrix which can cause various chemical and physical transformations and modulate the biological reactivity of these particles. Due to their rapid growth and small size, Lemna minor is recommended by OECD for toxicological testing. Here, we tested how nano-ZnO reactivity is modulated by the suite of macro- and micronutrients that are present in Lemna minor growth media. Specifically, we measured ex situ Reactive Oxygen Species (ROS) formation by nano-ZnO, and subsequent in planta toxicity. The data show how orthophosphate can modulate both ex situ ROS formation, and in planta toxicity. This has ramifications for phytotoxicity testing, which is commonly performed under controlled conditions and on media containing orthophosphate.

Decreased extracellular pH inhibits osteogenesis through proton-sensing GPR4-mediated suppression of yes-associated protein.

Science.gov (United States)

Tao, Shi-Cong; Gao, You-Shui; Zhu, Hong-Yi; Yin, Jun-Hui; Chen, Yi-Xuan; Zhang, Yue-Lei; Guo, Shang-Chun; Zhang, Chang-Qing

2016-06-03

The pH of extracellular fluids is a basic property of the tissue microenvironment and is normally maintained at 7.40 ± 0.05 in humans. Many pathological circumstances, such as ischemia, inflammation, and tumorigenesis, result in the reduction of extracellular pH in the affected tissues. In this study, we reported that the osteogenic differentiation of BMSCs was significantly inhibited by decreases in the extracellular pH. Moreover, we demonstrated that proton-sensing GPR4 signaling mediated the proton-induced inhibitory effects on the osteogenesis of BMSCs. Additionally, we found that YAP was the downstream effector of GPR4 signaling. Our findings revealed that the extracellular pH modulates the osteogenic responses of BMSCs by regulating the proton-sensing GPR4-YAP pathway.

Toxicity Reduction of Reactive Red Dye-238 Using Advanced Oxidation Process by Solar Energy

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Riyad Al-Anbari

2017-09-01

Full Text Available Decolorization of red azo dye (Cibacron Red FN-R from synthetic wastewater has been investigated as a function of solar advanced oxidation process. The photocatalytic activity using ZnO as a photocatalysis has been estimated. Different parameters affected the removal efficiency, including pH of the solution, initial dye concentration and H2O2 concentration were evaluated to find out the optimum value of these parameters. The results proved that the optimal pH value was 8 and the most efficient H2O2 concentration was 100mg/L. Toxicity reduction percent for effluent solution was also monitored to assess the degradation process. This treatment method was able to strongly reduce the color and toxicity of reactive red dye-238 to about (99 and 80 % respectively. It can be concluded, from these experiments, that the using of ZnO as a photocatalysis was exhibited as economical and efficient treatment method to remove reactive red dye-238 from aqueous solution.

Oxygen limitation modulates pH regulation of catabolism and hydrogenases, multidrug transporters, and envelope composition in Escherichia coli K-12

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Radmacher Michael D

2006-10-01

Full Text Available Abstract Background In Escherichia coli, pH regulates genes for amino-acid and sugar catabolism, electron transport, oxidative stress, periplasmic and envelope proteins. Many pH-dependent genes are co-regulated by anaerobiosis, but the overall intersection of pH stress and oxygen limitation has not been investigated. Results The pH dependence of gene expression was analyzed in oxygen-limited cultures of E. coli K-12 strain W3110. E. coli K-12 strain W3110 was cultured in closed tubes containing LBK broth buffered at pH 5.7, pH 7.0, and pH 8.5. Affymetrix array hybridization revealed pH-dependent expression of 1,384 genes and 610 intergenic regions. A core group of 251 genes showed pH responses similar to those in a previous study of cultures grown with aeration. The highly acid-induced gene yagU was shown to be required for extreme-acid resistance (survival at pH 2. Acid also up-regulated fimbriae (fimAC, periplasmic chaperones (hdeAB, cyclopropane fatty acid synthase (cfa, and the "constitutive" Na+/H+ antiporter (nhaB. Base up-regulated core genes for maltodextrin transport (lamB, mal, ATP synthase (atp, and DNA repair (recA, mutL. Other genes showed opposite pH responses with or without aeration, for example ETS components (cyo,nuo, sdh and hydrogenases (hya, hyb, hyc, hyf, hyp. A hypF strain lacking all hydrogenase activity showed loss of extreme-acid resistance. Under oxygen limitation only, acid down-regulated ribosome synthesis (rpl,rpm, rps. Acid up-regulated the catabolism of sugar derivatives whose fermentation minimized acid production (gnd, gnt, srl, and also a cluster of 13 genes in the gadA region. Acid up-regulated drug transporters (mdtEF, mdtL, but down-regulated penicillin-binding proteins (dacACD, mreBC. Intergenic regions containing regulatory sRNAs were up-regulated by acid (ryeA, csrB, gadY, rybC. Conclusion pH regulates a core set of genes independently of oxygen, including yagU, fimbriae, periplasmic chaperones, and nha

Dynamic regulation of gastric surface pH by luminal pH

OpenAIRE

Chu, Shaoyou; Tanaka, Shin; Kaunitz, Jonathan D.; Montrose, Marshall H.

1999-01-01

In vivo confocal imaging of the mucosal surface of rat stomach was used to measure pH noninvasively under the mucus gel layer while simultaneously imaging mucus gel thickness and tissue architecture. When tissue was superfused at pH 3, the 25 μm adjacent to the epithelial surface was relatively alkaline (pH 4.1 ± 0.1), and surface alkalinity was enhanced by topical dimethyl prostaglandin E2 (pH 4.8 ± 0.2). Luminal pH was changed from pH 3 to pH 5 to mimic the fasted-to-fed transition in intra...

A ph sensor based on a flexible substrate

Science.gov (United States)

Huang, Wen-Ding

implanted inside the esophagus. Our pH electrode can monitor the pH changes of gastric juice in real time when the reflux happening in the esophagus. Our micro flexible pH sensor performed clear responses in each distinct pH reflux episode quickly and accurately comparing with the other commercial pH monitoring system. For the food freshness monitoring applications, we used the flexible pH sensor as a freshness indicator to monitor the pH changing profile during the food spoilage procedure. The sensor was then embedded with radio frequency identification (RFID) based passive telemetry enabling remote monitoring of food freshness. In the result, our pH-wireless RFID system presented 633Hz/pH of the sensitivity in the frequency calibration. The calibration of stability and dynamical response of the RFID system were also demonstrated before the test on food freshness monitoring. Finally, a white fish meat for long term spoilage procedure monitoring was applied and tested by using our wireless IrOx pH sensing system. Our RFID pH sensing module is able to monitor, collect and transmit the pH information continuously for 18 hours during the food spoilage procedure. In this dissertation, a micro size of IrOx/AgCl pH sensor was fabricated on a flexible substrate. The physical properties of the IrO x thin film was verified in the work. The different sensing capability such as the sensitivity, stability, reversibility, response time, repeatability, selectivity, and temperature dependence was then demonstrated in this work. After the different in-vitro tests, the pH sensor were embedded with our passive RFID circuitry for the in-vivo GERD diagnosis and food freshness monitoring application. Our wireless pH sensing system was able to deliver the accurate and quick pH sensing data wirelessly. In conclusion, our deformable IrOx pH electrodes have been demonstrated with the advantages of accommodating and conforming sensors in small spaces or curved surfaces. This miniature IrOx pH sensor

The potentiation effect makes the difference: Non-toxic concentrations of ZnO nanoparticles enhance Cu nanoparticle toxicity in vitro

Energy Technology Data Exchange (ETDEWEB)

Li, Lingxiangyu [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Fernández-Cruz, María Luisa; Connolly, Mona [Departamento de Medio Ambiente, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid 28040 (Spain); Conde, Estefanía; Fernández, Marta [Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid 28040 (Spain); Schuster, Michael [Department of Chemistry, Technische Universität München, Garching 85747 (Germany); Navas, José María, E-mail: jmnavas@inia.es [Departamento de Medio Ambiente, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid 28040 (Spain)

2015-02-01

Here we examined whether the addition of a non-toxic concentration (6.25 μg/mL) of zinc oxide nanoparticles (ZnONPs: 19, 35 and 57 nm, respectively) modulates the cytotoxicity of copper nanoparticles (CuNPs, 63 nm in size) in the human hepatoma cell line HepG2. The cytotoxic effect of CuNPs on HepG2 cells was markedly enhanced by the ZnONPs, the largest ZnONPs causing the highest increase in toxicity. However, CuNPs cytotoxicity was not affected by co-incubation with medium containing only zinc ions, indicating the increase in toxicity might be attributed to the particle form of ZnONPs. Transmission electron microscopy (TEM) revealed the presence of CuNPs and ZnONPs inside the cells co-exposed to both types of NP and outflow of cytoplasm through the damaged cell membrane. Inductively coupled plasma mass spectrometry (ICP-MS) determined an increase in the concentration of zinc and a decrease in that of copper in co-exposed cells. On the basis of these results, we propose that accumulation of large numbers of ZnONPs in the cells alters cellular membranes and the cytotoxicity of CuNPs is increased. - Highlights: • ZnONPs at non-toxic concentrations increased the toxicity of CuNPs in vitro. • ZnONPs of larger size provoked a stronger synergistic effect with CuNPs. • The synergistic effect was attributed to the particle fraction of ZnONPs.

Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

International Nuclear Information System (INIS)

Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan; Zheng Lan; Zhao Xia

2011-01-01

In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ∼ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

Energy Technology Data Exchange (ETDEWEB)

Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Zheng Lan; Zhao Xia, E-mail: anderson-qian@163.com [West China Second University Hospital, West China Women' s and Children' s Hospital, Sichuan University, Chengdu 610041 (China)

2011-03-04

In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly({epsilon}-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and {approx} 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

Fate of petroleum hydrocarbons and toxic organics in Louisiana coastal environments

International Nuclear Information System (INIS)

DeLaune, R.D.; Gambrell, R.P.; Pardue, J.H.; Patrick, W.H. Jr.

1991-01-01

Numerous potentially toxic compounds are entering Louisiana's inshore and nearshore coastal environments. To a large degree there is insufficient information for predicting the fate and effect of these materials in aquatic environments. Studies documenting the impact of petroleum hydrocarbons entering Louisiana coastal wetlands are summarized. Also included are research findings on factors affecting the persistence of petroleum hydrocarbons and other toxic organics (pentachlorophenol (PCP), 2,4-dichlorophenoxyacetic acid (2,4-D), creosote, etc.) in sediment-water systems. Sediment pH and redox conditions have been found to play an important role in the microbial degradation of toxic organics. Most of the hydrocarbons investigated degrade more rapidly under high redox (aerobic) conditions although there are exceptions (e.g., 1,1,1-trichloro-2,2-bis(4-chlorophenyl)(DDT) and polychlorobiphenyls (PCBs)). Some of these compounds, due to their slow degradation in anaerobic sediment, may persist in the system for decades

Potential enzyme toxicity of oxytetracycline to catalase

Energy Technology Data Exchange (ETDEWEB)

Zhenxing, Chi; Rutao, Liu; Zhang Hao, E-mail: Trutaoliu@sdu.edu.cn [School of Environmental Science and Engineering, Shandong University, China-America CRC for Environment and Health, Shandong Province, 27 Shanda South Road, Jinan 250100 (China)

2010-10-15

Oxytetracycline (OTC) is a kind of widely used veterinary drugs. The residue of OTC in the environment is potentially harmful. In the present work, the non-covalent toxic interaction of OTC with catalase was investigated by the fluorescence spectroscopy, UV-vis absorption and circular dichroism (CD) spectroscopy at physiological pH 7.4. OTC can interact with catalase to form a complex mainly by van der Waals' interactions and hydrogen bonds with one binding site. The association constants K were determined to be K{sub 293K} = 7.09 x 10{sup 4} L mol{sup -1} and K{sub 311K} = 3.31 x 10{sup 4} L mol{sup -1}. The thermodynamic parameters ({Delta}H{sup o}, {Delta}G{sup o} and {Delta}S{sup o}) of the interaction were calculated. Based on the Foerster theory of non-radiative energy transfer, the distance between bound OTC and the tryptophan residues of catalase was determined to be 6.48 nm. The binding of OTC can result in change of the micro-environment of the tryptophan residues and the secondary structure of catalase. The activity of catalase was also inhibited for the bound OTC. This work establishes a new strategy to probe the enzyme toxicity of veterinary drug residues and is helpful for clarifying the molecular toxic mechanism of OTC in vivo. The established strategy can be used to investigate the potential enzyme toxicity of other small organic pollutants and drugs.

Potential enzyme toxicity of oxytetracycline to catalase

International Nuclear Information System (INIS)

Chi Zhenxing; Liu Rutao; Zhang Hao

2010-01-01

Oxytetracycline (OTC) is a kind of widely used veterinary drugs. The residue of OTC in the environment is potentially harmful. In the present work, the non-covalent toxic interaction of OTC with catalase was investigated by the fluorescence spectroscopy, UV-vis absorption and circular dichroism (CD) spectroscopy at physiological pH 7.4. OTC can interact with catalase to form a complex mainly by van der Waals' interactions and hydrogen bonds with one binding site. The association constants K were determined to be K 293K = 7.09 x 10 4 L mol -1 and K 311K = 3.31 x 10 4 L mol -1 . The thermodynamic parameters (ΔH o , ΔG o and ΔS o ) of the interaction were calculated. Based on the Foerster theory of non-radiative energy transfer, the distance between bound OTC and the tryptophan residues of catalase was determined to be 6.48 nm. The binding of OTC can result in change of the micro-environment of the tryptophan residues and the secondary structure of catalase. The activity of catalase was also inhibited for the bound OTC. This work establishes a new strategy to probe the enzyme toxicity of veterinary drug residues and is helpful for clarifying the molecular toxic mechanism of OTC in vivo. The established strategy can be used to investigate the potential enzyme toxicity of other small organic pollutants and drugs.

Fermentation pH Modulates the Size Distributions and Functional Properties of Gluconobacter albidus TMW 2.1191 Levan

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Tharalinee Ua-Arak

2017-05-01

Full Text Available Bacterial levan has gained an increasing interest over the last decades due to its unique characteristics and multiple possible applications. Levan and other exopolysaccharides (EPSs production are usually optimized to obtain the highest concentration or yield while a possible change of the molecular size and mass during the production process is mostly neglected. In this study, the molar mass and radius of levan samples were monitored during fermentations with the food-grade, levan-producing acetic acid bacterium Gluconobacter (G. albidus TMW 2.1191 in shake flasks (without pH control and bioreactors (with pH control at 4.5, 5.5 and 6.5, respectively. In uncontrolled fermentations, the levan size/molar mass continuously decreased concomitantly with the continuous acidification of the nutrient medium. On the contrary, the amount, molar mass and size of levan could be directly influenced by controlling the pH during fermentation. Using equal initial substrate amounts, the largest weight average molar mass and geometric radius of levan were observed at constant pH 6.5, while the highest levan concentration was obtained at constant pH 4.5. Since there is a special demand to find suitable hydrocolloids from food-grade bacteria to develop novel gluten-free (GF products, these differently produced levans were used for baking of GF breads, and the best quality improvement was obtained by addition of levan with the highest mass and radius. This work, therefore, demonstrates for the first time that one bacterial strain can produce specific high molecular weight fractions of one EPS type, which differ in properties and sizes among each other in dependence of the controllable production conditions.

Toxicity and bioaccumulation of chlorophenols in earthworms, in relation to bioavailability in soil

Energy Technology Data Exchange (ETDEWEB)

van Gestel, C.A.; Ma, W.C.

1988-06-01

The acute toxicity of five chlorophenols for two earthworm species was determined in two sandy soils differing in organic matter content and the results were compared with adsorption data. Adsorption increased with increasing organic matter content of the soils, but for tetra- and pentachlorophenol was also influenced by soil pH. Earthworm toxicity was significantly higher in the soil with a low level of organic matter. This difference disappeared when LC50 values were recalculated to concentrations in soil solution using adsorption data. Eisenia fetida andrei showed LC50 values lower than those of Lumbricus rubellus although bioaccumulation was generally higher in the latter species. Toxicity and bioaccumulation based on soil solution concentrations increased with increasing lipophilicity of the chlorophenols. The present results indicate that the toxicity and bioaccumulation and therefore the bioavailability of chlorophenols in soil to earthworms are dependent on the concentration in soil solution and can be predicted on the basis of adsorption data. Both the toxicity of and bioaccumulation data on chlorophenols in earthworms demonstrated surprisingly good agreement with those on chlorophenols in fish.

Radiation degradation-adsorption treatment of some toxic dyes present in wastewater

International Nuclear Information System (INIS)

El-Kelesh, N.A.; Dessouki, A.M.; Amer, S.I.

2002-01-01

The radiolysis or three toxic dyes, viz. Reactive Yellow 3, Reactive Black 39, and Basic Blue 26, was investigated as a function of the dye concentration, pH, irradiation dose and dose rate. The radiolytic degradation was more pronounced with Reactive yellow 3 and Reactive Black 39 than with Basic Blue 26. The degree of degradation could be increased by combining the irradiation procedure with the conventional treatment, such as addition of oxygen or hydrogen peroxide; addition of nitrogen, on the other hand, resulted in no change. A pH drop was observed and tentatively attributed to the degradation of the dye molecules to lower molecular weight compounds such as organic acids. The primary radiolysis products as well as the secondary products are responsible for the degradation of the dye chromophore. Experiments with the adsorption or exchange of the dyes on GAC, some ion exchange resins and polymeric membranes were carried out to find that the polymeric membranes have the highest adsorption capacity for the pollutants except the basic dye. The combined treatment by irradiation and adsorption resulted in a complete removal of the toxic dyes in question

Role of diet in absorption and toxicity of oral cadmium- A review of ...

African Journals Online (AJOL)

The role of diet or its components in the absorption, distribution and toxicity of cadmium (Cd) has received attention in recent times. Experimental evidence in literature strongly suggests that the absorption of Cd is dependent on factors such as age, pH, diet and intestinal metallothionein (MT) production. The chemical forms ...

Morpho-physiological analysis of tolerance to aluminum toxicity in rice varieties of North East India.

Science.gov (United States)

Awasthi, Jay Prakash; Saha, Bedabrata; Regon, Preetom; Sahoo, Smita; Chowra, Umakanta; Pradhan, Amit; Roy, Anupam; Panda, Sanjib Kumar

2017-01-01

Aluminum (Al) is the third most abundant metal in earth crust, whose chemical form is mainly dependent on soil pH. The most toxic form of Al with respect to plants is Al3+, which exists in soil pH Eastern India 80% soil are acidic). Al3+ toxicity in plants ensues root growth inhibition leading to less nutrient and water uptake impacting crop productivity as a whole. Rice is one of the chief grains which constitutes the staple food of two-third of the world population including India and is not untouched by Al3+ toxicity. Al contamination is a critical constraint to plant production in agricultural soils of North East India. 24 indigenous Indica rice varieties (including Badshahbhog as tolerant check and Mashuri as sensitive check) were screened for Al stress tolerance in hydroponic plant growth system. Results show marked difference in growth parameters (relative growth rate, Root tolerance index, fresh and dry weight of root) of rice seedlings due to Al (100 μM) toxicity. Al3+ uptake and lipid peroxidation level also increased concomitantly under Al treatment. Histochemical assay were also performed to elucidate uptake of aluminum, loss of membrane integrity and lipid peroxidation, which were found to be more in sensitive genotypes at higher Al concentration. This study revealed that aluminum toxicity is a serious harmful problem for rice crop productivity in acid soil. Based on various parameters studied it's concluded that Disang is a comparatively tolerant variety whereas Joymati a sensitive variety. Western blot hybridization further strengthened the claim, as it demonstrated more accumulation of Glutathione reductase (GR) protein in Disang rice variety than Joymati under stressed condition. This study also observed that the emergence of lethal toxic symptoms occurs only after 48h irrespective of the dose used in the study.

Toxicity and metal speciation in acid mine drainage treated by passive bioreactors

Energy Technology Data Exchange (ETDEWEB)

Neculita, C.M.; Vigneaul, B.; Zagury, G.J. [Ecole Polytechnic, Montreal, PQ (Canada)

2008-08-15

Sulfate-reducing passive bioreactors treat acid mine drainage (AMD) by increasing its pH and alkalinity and by removing metals as metal sulfide precipitates. In addition to discharge limits based on physicochemical parameters, however, treated effluent is required to be nontoxic. Acute and sublethal toxicity was assessed for effluent from 3.5-L column bioreactors filled with mixtures of natural organic carbon sources and operated at different hydraulic retention times (HRTs) for the treatment of a highly contaminated AMD. Effluent was first tested for acute (Daphnia magna and Oncorhynchus mykiss) and sublethal (Pseudokirchneriella subcapitata, Ceriodaphnia dabia, and Lemna minor) toxicity. Acute toxicity was observed for D. magna, and a toxicity identification evaluation (TIE) procedure was then performed to identify potential toxicants. Finally, metal speciation in the effluent was determined using ultrafiltration and geochemical modeling for the interpretation of the toxicity results. The 10-d HRT effluent was nonacutely lethal for 0. mykiss but acutely lethal for D. magna. The toxicity to D. magna, however, was removed by 2 h of aeration, and the TIE procedure suggested iron as a cause of toxicity. Sublethal toxicity of the 10-d HRT effluent was observed for all test species, but it was reduced compared to the raw AMD and to a 7.3-d HRT effluent. Data regarding metal speciation indicated instability of both effluents during aeration and were consistent with the toxicity being caused by iron. Column bioreactors in operation for more than nine months efficiently improved the physicochemical quality of highly contaminated AMD at different HRTs.

Influence of global change-related impacts on the mercury toxicity of freshwater algal communities.

Science.gov (United States)

Val, Jonatan; Muñiz, Selene; Gomà, Joan; Navarro, Enrique

2016-01-01

The climatic-change related increase of temperatures, are expected to alter the distribution and survival of freshwater species, ecosystem functions, and also the effects of toxicants to aquatic biota. This study has thus assessed, as a first time, the modulating effect of climate-change drivers on the mercury (Hg) toxicity of freshwater algal photosynthesis. Natural benthic algal communities (periphyton) have been exposed to Hg under present and future temperature scenarios (rise of 5 °C). The modulating effect of other factors (also altered by global change), as the quality and amount of suspended and dissolved materials in the rivers, has been also assessed, exposing algae to Hg in natural river water or a synthetic medium. The EC50 values ranged from the 0.15-0.74 ppm for the most sensitive communities, to the 24-40 ppm for the most tolerant. The higher tolerance shown by communities exposed to higher Hg concentrations, as Jabarrella was in agreement with the Pollution Induced Community Tolerance concept. In other cases, the dominance of the invasive diatom Didymosphenia geminata explained the tolerance or sensitivity of the community to the Hg toxicity. Results shown that while increases in the suspended solids reduced Hg bioavailability, changes in the dissolved materials - such as organic carbon - may increase it and thus its toxic effects on biota. The impacts of the increase of temperatures on the toxicological behaviour of periphyton (combining both changes at species composition and physiological acclimation) would be certainly modulated by other effects at the land level (i.e., alterations in the amount and quality of dissolved and particulate substances arriving to the rivers). Copyright © 2015 Elsevier B.V. All rights reserved.

NIR Ratiometric Luminescence Detection of pH Fluctuation in Living Cells with Hemicyanine Derivative-Assembled Upconversion Nanophosphors.

Science.gov (United States)

Li, Haixia; Dong, Hao; Yu, Mingming; Liu, Chunxia; Li, Zhanxian; Wei, Liuhe; Sun, Ling-Dong; Zhang, Hongyan

2017-09-05

It is crucial for cell physiology to keep the homeostasis of pH, and it is highly demanded yet challenging to develop luminescence resonance energy transfer (LRET)-based near-infrared (NIR) ratiometric luminescent sensor for the detection of pH fluctuation with NIR excitation. As promising energy donors for LRET, upconversion nanoparticles (UCNPs) have been widely used to fabricate nanosensors, but the relatively low LRET efficiency limits their application in bioassay. To improve the LRET efficiency, core/shell/shell structured β-NaGdF 4 @NaYF 4 :Yb,Tm@NaYF 4 UCNPs were prepared and decorated with hemicyanine dyes as an LRET-based NIR ratiometric luminescent pH fluctuation-nanosensor for the first time. The as-developed nanosensor not only exhibits good antidisturbance ability, but it also can reversibly sense pH and linearly sense pH in a range of 6.0-9.0 and 6.8-9.0 from absorption and upconversion emission spectra, respectively. In addition, the nanosensor displays low dark toxicity under physiological temperature, indicating good biocompatibility. Furthermore, live cell imaging results revealed that the sensor can selectively monitor pH fluctuation via ratiometric upconversion luminescence behavior.

Comparative Studies on the pH Dependence of DOW of Microcystin-RR and -LR Using LC-MS

Directory of Open Access Journals (Sweden)

Gaodao Liang

2011-01-01

Full Text Available Microcystins (MCs are well known worldwide as hepatotoxins produced by cyanobacteria, but little is known about the physicochemical properties of these compounds. The dependence of the n-octanol/water distribution ratio (DOW of MC-RR and -LR to pH was measured by high-performance liquid chromatography combined with mass spectrometry (LC-MS. There was a remarkable difference in such relationships between MC-RR and -LR. The log DOW of MC-LR decreased from 1.63 at pH 1.0 to -1.26 at pH 6.5, and stabilized between -1.04 and -1.56 at a pH of 6.5~12.0; log DOW of MC-RR varied between -1.24 and -0.67 at a pH of 1.00~4.00, and stabilized between -1.20 and -1.54 at a pH of 4.00~12.00. The difference of hydrophobicity in acidic condition between MC-RR and -LR is important, not only for the analytical method of both toxins, but perhaps also for understanding the difference of toxicity to animals between the two toxins.

Deletion of thioredoxin reductase and effects of selenite and selenate toxicity in Caenorhabditis elegans.

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Christopher J Boehler

Full Text Available Thioredoxin reductase-1 (TRXR-1 is the sole selenoprotein in C. elegans, and selenite is a substrate for thioredoxin reductase, so TRXR-1 may play a role in metabolism of selenium (Se to toxic forms. To study the role of TRXR in Se toxicity, we cultured C. elegans with deletions of trxr-1, trxr-2, and both in axenic media with increasing concentrations of inorganic Se. Wild-type C. elegans cultured for 12 days in Se-deficient axenic media grow and reproduce equivalent to Se-supplemented media. Supplementation with 0-2 mM Se as selenite results in inverse, sigmoidal response curves with an LC50 of 0.20 mM Se, due to impaired growth rather than reproduction. Deletion of trxr-1, trxr-2 or both does not modulate growth or Se toxicity in C. elegans grown axenically, and (75Se labeling showed that TRXR-1 arises from the trxr-1 gene and not from bacterial genes. Se response curves for selenide (LC50 0.23 mM Se were identical to selenite, but selenate was 1/4(th as toxic (LC50 0.95 mM Se as selenite and not modulated by TRXR deletion. These nutritional and genetic studies in axenic media show that Se and TRXR are not essential for C. elegans, and that TRXR alone is not essential for metabolism of inorganic Se to toxic species.

Fixation by ion exchange of toxic materials in a glass matrix

International Nuclear Information System (INIS)

Simmons, C.J.; Simmons, J.H.; Macedo, P.B.; Litovitz, T.A.

1982-01-01

A process is reported for reacting a porous silicate or borosilicate glass or silica gel with alkali metal cations, Group lb cations and/or ammonium cations bonded to the silicon through divalent oxygen linkages on the internal surfaces of the pores. Ion exchange of the cations with toxic or radioactive cations was possible resulting in a distribution of internal silicon-bonded toxic cation oxide groups within the pores of the glass or silica gel. The ion exchange reaction may be done successfully with acidic, neutral or alkaline pH solutions. The aim of the immobilization is for permanent storage of hazardous materials such as Hg 2+ , Hg + , Cd 2+ , Tl + , Pb 2+ and radioactive cations

Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

International Nuclear Information System (INIS)

Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

2002-01-01

Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

Intensity-Modulated Whole Abdominal Radiotherapy After Surgery and Carboplatin/Taxane Chemotherapy for Advanced Ovarian Cancer: Phase I Study

International Nuclear Information System (INIS)

Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D.; Dinkel, Julien; Herfarth, Klaus K.; Schubert, Kai; Eichbaum, Michael H.; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

2010-01-01

Purpose: To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Methods and Materials: Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Results: Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. Conclusions: The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

Intensity-modulated whole abdominal radiotherapy after surgery and carboplatin/taxane chemotherapy for advanced ovarian cancer: phase I study.

Science.gov (United States)

Rochet, Nathalie; Sterzing, Florian; Jensen, Alexandra D; Dinkel, Julien; Herfarth, Klaus K; Schubert, Kai; Eichbaum, Michael H; Schneeweiss, Andreas; Sohn, Christof; Debus, Juergen; Harms, Wolfgang

2010-04-01

To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

The MDT-15 subunit of mediator interacts with dietary restriction to modulate longevity and fluoranthene toxicity in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Jennifer Schleit

Full Text Available Dietary restriction (DR, the limitation of calorie intake while maintaining proper nutrition, has been found to extend life span and delay the onset of age-associated disease in a wide range of species. Previous studies have suggested that DR can reduce the lethality of environmental toxins. To further examine the role of DR in toxin response, we measured life spans of the nematode Caenorhabditis elegans treated with the mutagenic polyaromatic hydrocarbon, fluoranthene (FLA. FLA is a direct byproduct of combustion, and is one of U.S. Environmental Protection Agency's sixteen priority environmental toxins. Treatment with 5 µg/ml FLA shortened the life spans of ad libitum fed nematodes, and DR resulted in increased sensitivity to FLA. To determine the role of detoxifying enzymes in the toxicity of FLA, we tested nematodes with mutations in the gene encoding the MDT-15 subunit of mediator, a transcriptional coactivator that regulates genes involved in fatty acid metabolism and detoxification. Mutation of mdt-15 increased the life span of FLA treated animals compared to wild-type animals with no difference observed between DR and ad libitum fed mdt-15 animals. We also examined mutants with altered insulin-IGF-1-like signaling (IIS, which is known to modulate life span and stress resistance in C. elegans independently of DR. Mutation of the genes coding for the insulin-like receptor DAF-2 or the FOXO-family transcription factor DAF16 did not alter the animals' susceptibility to FLA compared to wild type. Taken together, our results suggest that certain compounds have increased toxicity when combined with a DR regimen through increased metabolic activation. This increased metabolic activation appears to be mediated through the MDT-15 transcription factor and is independent of the IIS pathway.

Intensity Modulated Radiotherapy (IMRT) in locally advanced thyroid cancer: Acute toxicity results of a phase I study

International Nuclear Information System (INIS)

Urbano, Teresa Guerrero; Clark, Catharine H.; Hansen, Vibeke N.; Adams, Elizabeth J.; Miles, Elizabeth A.; Mc Nair, Helen; Bidmead, A. Margaret; Warrington, Jim; Dearnaley, David P.; Harmer, Clive; Harrington, Kevin J.; Nutting, Christopher M.

2007-01-01

Background and purpose: This phase 1 study was designed to determine the toxicity of accelerated fractionation IMRT in locally advanced thyroid cancer. Methods: Patients with high risk locally advanced thyroid cancer who required post-operative EBRT were recruited. A single-phase inverse-planned-simultaneous-boost was delivered by IMRT: 58.8 Gy/28F (daily) to the primary tumour and involved nodes and 50 Gy/28F to the elective nodes. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) was collected. Results: Thirteen patients were treated (7 medullary thyroid, 2 Hurthle cell and 4 well differentiated thyroid cancer). G3 and G2 radiation dermatitis rates were 38.5% and 31%; G3 and G2 mucositis rates 8% and 53% and G3 and G2 pain 23% and 54%. Thirty-one percentage required enteral feeding. G3 and G2 xerostomia rates were 0% and 31%. Recovery was seen, with 62% patients having dysphagia G ≤ 1 2 months after IMRT. Thirty percent of patients developed L'Hermitte's syndrome. No grade 4 toxicity was observed. No dose limiting toxicity was found. Conclusions: Accelerated fractionation IMRT in this group of patients is feasible and safe. The acute toxicity appeared acceptable and early indicators of late toxicity moderate and similar to what would be expected with conventional RT. Longer follow up is required to quantify late side effects

Alkali pH directly activates ATP-sensitive K+ channels and inhibits insulin secretion in beta-cells.

Science.gov (United States)

Manning Fox, Jocelyn E; Karaman, Gunce; Wheeler, Michael B

2006-11-17

Glucose stimulation of pancreatic beta-cells is reported to lead to sustained alkalization, while extracellular application of weak bases is reported to inhibit electrical activity and decrease insulin secretion. We hypothesize that beta-cell K(ATP) channel activity is modulated by alkaline pH. Using the excised patch-clamp technique, we demonstrate a direct stimulatory action of alkali pH on recombinant SUR1/Kir6.2 channels due to increased open probability. Bath application of alkali pH similarly activates native islet beta-cell K(ATP) channels, leading to an inhibition of action potentials, and hyperpolarization of membrane potential. In situ pancreatic perfusion confirms that these cellular effects of alkali pH are observable at a functional level, resulting in decreases in both phase 1 and phase 2 glucose-stimulated insulin secretion. Our data are the first to report a stimulatory effect of a range of alkali pH on K(ATP) channel activity and link this to downstream effects on islet beta-cell function.

Development of biotic ligand models for chronic manganese toxicity to fish, invertebrates, and algae.

Science.gov (United States)

Peters, Adam; Lofts, Stephen; Merrington, Graham; Brown, Bruce; Stubblefield, William; Harlow, Keven

2011-11-01

Ecotoxicity tests were performed with fish, invertebrates, and algae to investigate the effect of water quality parameters on Mn toxicity. Models were developed to describe the effects of Mn as a function of water quality. Calcium (Ca) has a protective effect on Mn toxicity for both fish and invertebrates, and magnesium (Mg) also provides a protective effect for invertebrates. Protons have a protective effect on Mn toxicity to algae. The models derived are consistent with models of the toxicity of other metals to aquatic organisms in that divalent cations can act as competitors to Mn toxicity in fish and invertebrates, and protons act as competitors to Mn toxicity in algae. The selected models are able to predict Mn toxicity to the test organisms to within a factor of 2 in most cases. Under low-pH conditions invertebrates are the most sensitive taxa, and under high-pH conditions algae are most sensitive. The point at which algae become more sensitive than invertebrates depends on the Ca concentration and occurs at higher pH when Ca concentrations are low, because of the sensitivity of invertebrates under these conditions. Dissolved organic carbon concentrations have very little effect on the toxicity of Mn to aquatic organisms. Copyright © 2011 SETAC.

Modeling pH variation in reverse osmosis.

Science.gov (United States)

Nir, Oded; Bishop, Noga Fridman; Lahav, Ori; Freger, Viatcheslav

2015-12-15

The transport of hydronium and hydroxide ions through reverse osmosis membranes constitutes a unique case of ionic species characterized by uncommonly high permeabilities. Combined with electromigration, this leads to complex behavior of permeate pH, e.g., negative rejection, as often observed for monovalent ions in nanofiltration of salt mixtures. In this work we employed a rigorous phenomenological approach combined with chemical equilibrium to describe the trans-membrane transport of hydronium and hydroxide ions along with salt transport and calculate the resulting permeate pH. Starting from the Nernst-Planck equation, a full non-linear transport equation was derived, for which an approximate solution was proposed based on the analytical solution previously developed for trace ions in a dominant salt. Using the developed approximate equation, transport coefficients were deduced from experimental results obtained using a spiral wound reverse osmosis module operated under varying permeate flux (2-11 μm/s), NaCl feed concentrations (0.04-0.18 M) and feed pH values (5.5-9.0). The approximate equation agreed well with the experimental results, corroborating the finding that diffusion and electromigration, rather than a priori neglected convection, were the major contributors to the transport of hydronium and hydroxide. The approach presented here has the potential to improve the predictive capacity of reverse osmosis transport models for acid-base species, thereby improving process design/control. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of the removal technology for toxic heavy metal ions by surface-modified activated carbon

International Nuclear Information System (INIS)

Park, Geun Il; Song, Kee Chan; Kim, Kwang Wook; Kim, In Tae; Cho, Il Hoon; Kim, Joon Hyung

2001-01-01

Adsorption capacities of both radionuclides(uranium, cobalt) and toxic heavy metals (lead, cadmium and chromium) using double surface-modified activated carbon in wide pH ranges are extensively evaluated. Surface-modified activated carbons are classified as AC(as-received carbon), OAC(single surface-modified carbon with nitric acid solution) and OAC-Na(double surface-modified carbon with various alkali solutions). It is established that optimal condition for the second surface modification of OAC is to use the mixed solution of both NaOH and NaCl with total concentration of 0.1 N based on adsorption efficiencies of uranium and cobalt. Variations of adsorption efficiencies in pH ranges of 2∼10 and the adsorption capacities in batch adsorber and fixed bed for removal of both radionuclides and toxic heavy metals using OAC-Na were shown to be superior to that of the AC and OAC even in a low pH range. Capacity factors of OAC-Na for the removal of various metal ions are also excellent to that of AC or OAC. Quantitative analysis of capacity factors for each ions showed that adsorption capacity of OAC-Na increased by 30 times for uranium, 60 times for cobalt, 9 times for lead, 30 times for cadmium, 3 times for chromium compared to that of AC at pH 5, respectively. Adsorption capacity of OAC-Na is comparable to that of XAD-16-TAR used as commercial ion exchange resin

Intensity-Modulated Radiotherapy for Sinonasal Cancer: Improved Outcome Compared to Conventional Radiotherapy

International Nuclear Information System (INIS)

Dirix, Piet; Vanstraelen, Bianca; Jorissen, Mark; Vander Poorten, Vincent; Nuyts, Sandra

2010-01-01

Purpose: To evaluate clinical outcome and toxicity of postoperative intensity-modulated radiotherapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: Between 2003 and 2008, 40 patients with cancer of the paranasal sinuses (n = 34) or nasal cavity (n = 6) received postoperative IMRT to a dose of 60 Gy (n = 21) or 66 Gy (n = 19). Treatment outcome and toxicity were retrospectively compared with that of a previous patient group (n = 41) who were also postoperatively treated to the same doses but with three-dimensional conformal radiotherapy without intensity modulation, from 1992 to 2002. Results: Median follow-up was 30 months (range, 4-74 months). Two-year local control, overall survival, and disease-free survival were 76%, 89%, and 72%, respectively. Compared to the three-dimensional conformal radiotherapy treatment, IMRT resulted in significantly improved disease-free survival (60% vs. 72%; p = 0.02). No grade 3 or 4 toxicity was reported in the IMRT group, either acute or chronic. The use of IMRT significantly reduced the incidence of acute as well as late side effects, especially regarding skin toxicity, mucositis, xerostomia, and dry-eye syndrome. Conclusions: Postoperative IMRT for sinonasal cancer significantly improves disease-free survival and reduces acute as well as late toxicity. Consequently, IMRT should be considered the standard treatment modality for malignancies of the nasal cavity and paranasal sinuses.

Modulating secretory pathway pH by proton channel co-expression can increase recombinant protein stability in plants.

Science.gov (United States)

Jutras, Philippe V; D'Aoust, Marc-André; Couture, Manon M-J; Vézina, Louis-Philippe; Goulet, Marie-Claire; Michaud, Dominique; Sainsbury, Frank

2015-09-01

Eukaryotic expression systems are used for the production of complex secreted proteins. However, recombinant proteins face considerable biochemical challenges along the secretory pathway, including proteolysis and pH variation between organelles. As the use of synthetic biology matures into solutions for protein production, various host-cell engineering approaches are being developed to ameliorate host-cell factors that can limit recombinant protein quality and yield. We report the potential of the influenza M2 ion channel as a novel tool to neutralize the pH in acidic subcellular compartments. Using transient expression in the plant host, Nicotiana benthamiana, we show that ion channel expression can significantly raise pH in the Golgi apparatus and that this can have a strong stabilizing effect on a fusion protein separated by an acid-susceptible linker peptide. We exemplify the utility of this effect in recombinant protein production using influenza hemagglutinin subtypes differentially stable at low pH; the expression of hemagglutinins prone to conformational change in mildly acidic conditions is considerably enhanced by M2 co-expression. The co-expression of a heterologous ion channel to stabilize acid-labile proteins and peptides represents a novel approach to increasing the yield and quality of secreted recombinant proteins in plants and, possibly, in other eukaryotic expression hosts. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Morpho-physiological analysis of tolerance to aluminum toxicity in rice varieties of North East India.

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Jay Prakash Awasthi

Full Text Available Aluminum (Al is the third most abundant metal in earth crust, whose chemical form is mainly dependent on soil pH. The most toxic form of Al with respect to plants is Al3+, which exists in soil pH <5. Acidic soil significantly limits crop production mainly due to Al3+ toxicity worldwide, impacting approximately 50% of the world's arable land (in North-Eastern India 80% soil are acidic. Al3+ toxicity in plants ensues root growth inhibition leading to less nutrient and water uptake impacting crop productivity as a whole. Rice is one of the chief grains which constitutes the staple food of two-third of the world population including India and is not untouched by Al3+ toxicity. Al contamination is a critical constraint to plant production in agricultural soils of North East India. 24 indigenous Indica rice varieties (including Badshahbhog as tolerant check and Mashuri as sensitive check were screened for Al stress tolerance in hydroponic plant growth system. Results show marked difference in growth parameters (relative growth rate, Root tolerance index, fresh and dry weight of root of rice seedlings due to Al (100 μM toxicity. Al3+ uptake and lipid peroxidation level also increased concomitantly under Al treatment. Histochemical assay were also performed to elucidate uptake of aluminum, loss of membrane integrity and lipid peroxidation, which were found to be more in sensitive genotypes at higher Al concentration. This study revealed that aluminum toxicity is a serious harmful problem for rice crop productivity in acid soil. Based on various parameters studied it's concluded that Disang is a comparatively tolerant variety whereas Joymati a sensitive variety. Western blot hybridization further strengthened the claim, as it demonstrated more accumulation of Glutathione reductase (GR protein in Disang rice variety than Joymati under stressed condition. This study also observed that the emergence of lethal toxic symptoms occurs only after 48h

Leaching characteristics of toxic constituents from coal fly ash mixed soils under the influence of pH

Energy Technology Data Exchange (ETDEWEB)

Komonweeraket, Kanokwan [Department of Civil and Environmental Engineering, University of Wisconsin, Madison, WI 53706 (United States); Cetin, Bora, E-mail: bora.cetin@sdsmt.edu [College of Engineering, University of Georgia, Athens, GA 30602 (United States); Benson, Craig H., E-mail: chbenson@wisc.edu [Department of Civil and Environmental Engineering, University of Wisconsin, Madison, WI 53706 (United States); Aydilek, Ahmet H., E-mail: aydilek@umd.edu [Department of Civil and Environmental Engineering, University of Maryland, College Park, MD 20742 (United States); Edil, Tuncer B., E-mail: edil@engr.wisc.edu [Department of Civil and Environmental Engineering, University of Wisconsin, Madison, WI 53706 (United States)

2015-04-15

Highlights: • The impact of pH on the leaching of elements and metals from fly ash mixed soils. • Generally Ca, Cd, Mg, and Sr follows a cationic leaching pattern. • The leaching of As and Se shows an oxyanionic leaching pattern. • The leaching behavior of elements does not change based on material type. • Different fly ash types show different abilities in immobilizing trace elements. - Abstract: Leaching behaviors of Arsenic (As), Barium (Ba), Calcium (Ca), Cadmium (Cd), Magnesium (Mg), Selenium (Se), and Strontium (Sr) from soil alone, coal fly ash alone, and soil-coal fly ash mixtures, were studied at a pH range of 2–14 via pH-dependent leaching tests. Seven different types of soils and coal fly ashes were tested. Results of this study indicated that Ca, Cd, Mg, and Sr showed cationic leaching pattern while As and Se generally follows an oxyanionic leaching pattern. On the other hand, leaching of Ba presented amphoteric-like leaching pattern but less pH-dependent. In spite of different types and composition of soil and coal fly ash investigated, the study reveals the similarity in leaching behavior as a function of pH for a given element from soil, coal fly ash, and soil-coal fly ash mixtures. The similarity is most likely due to similar controlling mechanisms (e.g., solubility, sorption, and solid-solution formation) and similar controlling factors (e.g., leachate pH and redox conditions). This offers the opportunity to transfer knowledge of coal fly ash that has been extensively characterized and studied to soil stabilized with coal fly ash. It is speculated that unburned carbon in off-specification coal fly ashes may provide sorption sites for Cd resulting in a reduction in concentration of these elements in leachate from soil-coal fly ash mixture. Class C fly ash provides sufficient CaO to initiate the pozzolanic reaction yielding hydrated cement products that oxyanions, including As and Se, can be incorporated into.

Alkaline cyanide degradation by Pseudomonas pseudoalcaligenes CECT5344 in a batch reactor. Influence of pH

International Nuclear Information System (INIS)

Huertas, M.J.; Saez, L.P.; Roldan, M.D.; Luque-Almagro, V.M.; Martinez-Luque, M.; Blasco, R.; Castillo, F.; Moreno-Vivian, C.; Garcia-Garcia, I.

2010-01-01

Water containing cyanide was biologically detoxified with the bacterial strain Pseudomonas pseudoalcaligenes CECT5344 in a batch reactor. Volatilization of toxic hydrogen cyanide (HCN) was avoided by using an alkaline medium for the treatment. The operational procedure was optimized to assess cyanide biodegradation at variable pH values and dissolved oxygen concentrations. Using an initial pH of 10 without subsequent adjustment allowed total cyanide to be consumed at a mean rate of approximately 2.81 mg CN - L -1 O.D. -1 h -1 ; however, these conditions posed a high risk of HCN formation. Cyanide consumption was found to be pH-dependent. Thus, no bacterial growth was observed with a controlled pH of 10; on the other hand, pH 9.5 allowed up to 2.31 mg CN - L -1 O.D. -1 h -1 to be converted. The combination of a high pH and a low dissolved oxygen saturation (10%) minimized the release of HCN. This study contributes new basic knowledge about this biological treatment, which constitutes an effective alternative to available physico-chemical methods for the purification of wastewater containing cyanide or cyano-metal complexes.

Critical Limits for Hg(II) in soils, derived from chronic toxicity data

Energy Technology Data Exchange (ETDEWEB)

Tipping, E., E-mail: et@ceh.ac.u [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Lofts, S. [Centre for Ecology and Hydrology, Lancaster Environment Centre, Library Avenue, Bailrigg, Lancaster LA1 4AP (United Kingdom); Hooper, H. [Centre for Ecology and Hydrology, Wallingford, OX10 8BB (United Kingdom); Frey, B. [Swiss Federal Research Institute WSL, 8903 Birmensdorf (Switzerland); Spurgeon, D.; Svendsen, C. [Centre for Ecology and Hydrology, Wallingford, OX10 8BB (United Kingdom)

2010-07-15

Published chronic toxicity data for Hg(II) added to soils were assembled and evaluated to produce a data set comprising 52 chronic end-points, five each for plants and invertebrates and 42 for microbes. With end-points expressed in terms of added soil Hg(II) contents, Critical Limits were derived from the 5th percentiles of species sensitivity distributions, values of 0.13 {mu}g (g soil){sup -1} and 3.3 {mu}g (g soil organic matter){sup -1} being obtained. The latter value exceeds the currently recommended Critical Limit, used to determine Hg(II) Critical Loads in Europe, of 0.5 {mu}g (g soil organic matter){sup -1}. We also applied the WHAM/Model VI chemical speciation model to estimate concentrations of Hg{sup 2+} in soil solution, and derived an approximate Critical Limit Function (CLF) that includes pH; log [Hg{sup 2+}]{sub crit} = -2.15 pH -17.10. Because they take soil properties into account, the soil organic matter-based limit and the CLF provide the best assessment of toxic threat for different soils. For differing representative soils, each predicts a range of up to 100-fold in the dry weight-based content of mercury that corresponds to the Critical Limit. - Published laboratory toxicity data and chemical speciation modelling are used to derive Critical Limits expressed as either soil Hg(II) content or Hg{sup 2+} concentration.

Optimization of urinary dipstick pH: Are multiple dipstick pH readings reliably comparable to commercial 24-hour urinary pH?

Science.gov (United States)

Abbott, Joel E; Miller, Daniel L; Shi, William; Wenzler, David; Elkhoury, Fuad F; Patel, Nishant D; Sur, Roger L

2017-09-01

Accurate measurement of pH is necessary to guide medical management of nephrolithiasis. Urinary dipsticks offer a convenient method to measure pH, but prior studies have only assessed the accuracy of a single, spot dipstick. Given the known diurnal variation in pH, a single dipstick pH is unlikely to reflect the average daily urinary pH. Our goal was to determine whether multiple dipstick pH readings would be reliably comparable to pH from a 24-hour urine analysis. Kidney stone patients undergoing a 24-hour urine collection were enrolled and took images of dipsticks from their first 3 voids concurrently with the 24-hour collection. Images were sent to and read by a study investigator. The individual and mean pH from the dipsticks were compared to the 24-hour urine pH and considered to be accurate if the dipstick readings were within 0.5 of the 24-hour urine pH. The Bland-Altman test of agreement was used to further compare dipstick pH relative to 24-hour urine pH. Fifty-nine percent of patients had mean urinary pH values within 0.5 pH units of their 24-hour urine pH. Bland-Altman analysis showed a mean difference between dipstick pH and 24-hour urine pH of -0.22, with an upper limit of agreement of 1.02 (95% confidence interval [CI], 0.45-1.59) and a lower limit of agreement of -1.47 (95% CI, -2.04 to -0.90). We concluded that urinary dipstick based pH measurement lacks the precision required to guide medical management of nephrolithiasis and physicians should use 24-hour urine analysis to base their metabolic therapy.

Application of bipolar electrodialysis to E.coli fermentation for simultaneous acetate removal and pH control

DEFF Research Database (Denmark)

Wong, M.; Woodley, John; Lye, G.J.

2010-01-01

The application of bipolar electrodialysis (BPED) for the simultaneous removal of inhibitory acetate and pH control during E. coli fermentation was investigated. A two cell pair electrodialysis module, consisting of cation exchange, anion exchange and bipolar membranes with working area of 100 cm2...

Transcriptomics-based identification of developmental toxicants through their interference with cardiomyocyte differentiation of embryonic stem cells

International Nuclear Information System (INIS)

Dartel, Dorien A.M. van; Pennings, Jeroen L.A.; Schooten, Frederik J. van; Piersma, Aldert H.

2010-01-01

The embryonic stem cell test (EST) predicts developmental toxicity based on the inhibition of cardiomyocyte differentiation of embryonic stem cells (ESC). The subjective endpoint, the long culture duration together with the undefined applicability domain and related predictivity need further improvement to facilitate implementation of the EST into regulatory strategies. These aspects may be improved by studying gene expression changes in the ESC differentiation cultures and their modulation by compound exposure using transcriptomics. Here, we tested the developmental toxicants monobutyl phthalate and 6-aminonicotinamide. ESC were allowed to differentiated, and cardiomyocyte differentiation was assessed after 10 days of culture. RNA of solvent controls was collected after 0, 24, 48, 72 and 96 h of exposure, and RNA of developmental-toxicant-exposed cultures was collected after 24 and 96 h. Samples were hybridized to DNA microarrays, and 1355 genes were found differentially expressed among the unexposed experimental groups. These regulated genes were involved in differentiation-related processes, and Principal Component Analysis (PCA) based on these genes showed that the unexposed experimental groups appeared in chronological order in the PCA, which can therefore be regarded as a continuous representation of the differentiation track. The developmental-toxicant-exposed cultures appeared to deviate significantly from this differentiation track, which confirms the compound-modulating effects on the differentiation process. The incorporation of transcriptomics in the EST is expected to provide a more informative and improved endpoint in the EST as compared with morphology, allowing early detection of differentiation modulation. Furthermore, this approach may improve the definition of the applicability domain and predictivity of the EST.

Thorium (IV) toxicity of green microalgae from Scenedesmus and Monoraphidium genera

International Nuclear Information System (INIS)

Queiroz, Juliana Cristina de

2009-01-01

The toxicity of thorium by two green microalgae species, Monoraphidium sp. and Scenedesmus sp was studied. During the toxicity tests, the microalgae cultures were inoculated in ASM-I culture medium in the presence and absence of thorium (cultures at pH 8.0 and 6.0 in the absence of thorium, - control - and at pH 6.0 for thorium concentrations ranging from 0.5 to 100.0 mg/L Th). Its effect was monitored by direct counting on Fuchs-Rosenthal chamber and with the help of software developed by the group during the experiments. The difference in pH value in the culture medium did not affect the growth of the microalgae, and pH 6.0 was chosen as a reference in order not to compromise solubility and speciation of thorium in solution. The toxicity of the metal over the species was observed just for thorium concentrations over 50.0 mg/L. A Monoraphidium sp. culture containing 6.25x10 5 microorganisms/mL reached a final concentration of 5.52x10 7 microorganisms/mL in the presence of thorium in the concentration of 10.0 mg/L. If we consider the 100.0 ppm thorium solution reached a final concentration of 8.57x10 6 microorganisms/mL. Control tests indicated a final concentration of 2.51x10 7 microorganisms/mL at the end of the growth. Scenedesmus sp. cells proved to be more resistant to the presence of thorium in solution. Low concentrations of the radionuclide favored the growth of these microalgae. A culture containing 7.65x10 5 microorganisms/mL reached a final concentration of 2.25x10 6 microorganisms/mL, in the absence of thorium in the medium. Toxicological tests indicated a final culture concentration of 5.87x10 6 microorganisms/mL in the presence of 0.5 mg/L thorium. The software used for comparison of direct count method proved to be very useful for the improvement of accuracy of the results obtained and a decrease in the uncertainty in counting. Beyond these advantages it also allowed recording of the data. From the present results one can conclude, that the presence

The antibacterial activity and toxicity of enrofloxacin are decreased by nanocellulose conjugated with aminobenzyl purin.

Science.gov (United States)

Yasini, Seyed Ali; Zadeh, Mohammad Hossein Balal; Shahdadi, Hossein

2015-11-01

The first aim of this study was to synthesize nanocellulose conjugated with aminobenzyl purin (NCABP), and the second aim was to evaluate the effect of NCABP on both toxicity and antibacterial activity of enrofloxacin. Here, the adsorption of enrofloxacin by NCABP was first modeled by molecular dynamic (MD) simulation. In the next step, NCABP was synthesized, and was exposed to enrofloxacin, 1000 μg mL(-1), at various conditions. Then, the quantity of adsorption and release was separately measured. Furthermore, both toxicity and antibacterial activity of NCABP, enrofloxacin, and (NCABP+enrofloxacin) were separately evaluated. In this study, MD simulation clearly showed the adsorption after 50 picoseconds. The adsorption tests revealed that the increase of incubation time and NCABP concentration, at range of 50-200 μg mL(-1), led to increase of adsorption. Moreover, the decrease of pH led to increase of adsorption. Interestingly, NCABP could adsorb enrofloxacin, up to 1000 μg mL(-1), in different types of meat. Moreover, the increase of incubation time and temperature did not release enrofloxacin, but the increase of pH increased release. This study showed that both toxicity and antibacterial activity of enrofloxacin were decreased when exposed together with NCABP. Copyright © 2015 Elsevier B.V. All rights reserved.

Standardized Total Average Toxicity Score: A Scale- and Grade-Independent Measure of Late Radiotherapy Toxicity to Facilitate Pooling of Data From Different Studies

Energy Technology Data Exchange (ETDEWEB)

Barnett, Gillian C., E-mail: gillbarnett@doctors.org.uk [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); West, Catharine M.L. [School of Cancer and Enabling Sciences, Manchester Academic Health Science Centre, University of Manchester, Christie Hospital, Manchester (United Kingdom); Coles, Charlotte E. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Pharoah, Paul D.P. [Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); Talbot, Christopher J. [Department of Genetics, University of Leicester, Leicester (United Kingdom); Elliott, Rebecca M. [School of Cancer and Enabling Sciences, Manchester Academic Health Science Centre, University of Manchester, Christie Hospital, Manchester (United Kingdom); Tanteles, George A. [Department of Clinical Genetics, University Hospitals of Leicester, Leicester (United Kingdom); Symonds, R. Paul [Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester, Leicester (United Kingdom); Wilkinson, Jennifer S. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Dunning, Alison M. [Cancer Research-UK Centre for Genetic Epidemiology and Department of Oncology, Strangeways Research Laboratories, Cambridge (United Kingdom); Burnet, Neil G. [University of Cambridge Department of Oncology, Oncology Centre, Cambridge (United Kingdom); Bentzen, Soren M. [University of Wisconsin, School of Medicine and Public Health, Department of Human Oncology, Madison, WI (United States)

2012-03-01

Purpose: The search for clinical and biologic biomarkers associated with late radiotherapy toxicity is hindered by the use of multiple and different endpoints from a variety of scoring systems, hampering comparisons across studies and pooling of data. We propose a novel metric, the Standardized Total Average Toxicity (STAT) score, to try to overcome these difficulties. Methods and Materials: STAT scores were derived for 1010 patients from the Cambridge breast intensity-modulated radiotherapy trial and 493 women from University Hospitals of Leicester. The sensitivity of the STAT score to detect differences between patient groups, stratified by factors known to influence late toxicity, was compared with that of individual endpoints. Analysis of residuals was used to quantify the effect of these covariates. Results: In the Cambridge cohort, STAT scores detected differences (p < 0.00005) between patients attributable to breast volume, surgical specimen weight, dosimetry, acute toxicity, radiation boost to tumor bed, postoperative infection, and smoking (p < 0.0002), with no loss of sensitivity over individual toxicity endpoints. Diabetes (p = 0.017), poor postoperative surgical cosmesis (p = 0.0036), use of chemotherapy (p = 0.0054), and increasing age (p = 0.041) were also associated with increased STAT score. When the Cambridge and Leicester datasets were combined, STAT was associated with smoking status (p < 0.00005), diabetes (p = 0.041), chemotherapy (p = 0.0008), and radiotherapy boost (p = 0.0001). STAT was independent of the toxicity scale used and was able to deal with missing data. There were correlations between residuals of the STAT score obtained using different toxicity scales (r > 0.86, p < 0.00005 for both datasets). Conclusions: The STAT score may be used to facilitate the analysis of overall late radiation toxicity, from multiple trials or centers, in studies of possible genetic and nongenetic determinants of radiotherapy toxicity.

Simulating CO₂ leakages from CCS to determine Zn toxicity using the marine microalgae Pleurochrysis roscoffensis.

Science.gov (United States)

Bautista-Chamizo, Esther; De Orte, Manoela Romanó; DelValls, Tomás Ángel; Riba, Inmaculada

2016-02-01

Due to the current climate change and ocean acidification, a new technology for CO2 mitigation has been proposed, the Carbon dioxide Capture and Storage (CCS). However, there is an ecological risk associated with potential CO2 leakages from the sub-seabed storages sites. To evaluate the effects related to CO2 leakages, laboratory-scales experiments were performed using the marine microalgae Pleurochrysis roscoffensis. Five Zn concentrations were tested at different pHs to study Zn toxicity under acidified conditions. Seawater was collected and submitted to acidification by means of CO2 injection and by HCl addition. Results showed differences between both acidification techniques: while microalgae growth was enhanced by CO2 supply, reaching the optimal growth at pH 6.5 and full inhibition at pH 5.5, HCl acidification growth was inhibited at pH 6.5. Although small concentrations of Zn were positive for P. roscoffensis growth, Zn toxicity increased at lower pHs, and more severely on samples acidified with HCl. The conclusions obtained in this work are useful to address the potential effects on the marine ecosystem related to changes in metal bioavailability during CO2 leakages scenarios. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ethanol potentiates the genotoxicity of the food-derived mammary carcinogen PhIP in human estrogen receptor-positive mammary cells: mechanistic support for lifestyle factors (cooked red meat and ethanol) associated with mammary cancer.

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Malik, Durr-E-Shahwar; David, Rhiannon M; Gooderham, Nigel J

2018-04-01

Consumption of cooked/processed meat and ethanol are lifestyle risk factors in the aetiology of breast cancer. Cooking meat generates heterocyclic amines such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Epidemiology, mechanistic and animal studies indicate that PhIP is a mammary carcinogen that could be causally linked to breast cancer incidence; PhIP is DNA damaging, mutagenic and oestrogenic. PhIP toxicity involves cytochrome P450 (CYP1 family)-mediated metabolic activation to DNA-damaging species, and transcriptional responses through Aryl hydrocarbon receptor (AhR) and estrogen-receptor-α (ER-α). Ethanol consumption is a modifiable lifestyle factor strongly associated with breast cancer risk. Ethanol toxicity involves alcohol dehydrogenase metabolism to reactive acetaldehyde, and is also a substrate for CYP2E1, which when uncoupled generates reactive oxygen species (ROS) and DNA damage. Here, using human mammary cells that differ in estrogen-receptor status, we explore genotoxicity of PhIP and ethanol and mechanisms behind this toxicity. Treatment with PhIP (10 -7 -10 -4 M) significantly induced genotoxicity (micronuclei formation) preferentially in ER-α positive human mammary cell lines (MCF-7, ER-α+) compared to MDA-MB-231 (ER-α-) cells. PhIP-induced CYP1A2 in both cell lines but CYP1B1 was selectively induced in ER-α(+) cells. ER-α inhibition in MCF-7 cells attenuated PhIP-mediated micronuclei formation and CYP1B1 induction. PhIP-induced CYP2E1 and ROS via ER-α-STAT-3 pathway, but only in ER-α (+) MCF-7 cells. Importantly, simultaneous treatments of physiological concentrations ethanol (10 -3 -10 -1 M) with PhIP (10 -7 -10 -4 M) increased oxidative stress and genotoxicity in MCF-7 cells, compared to the individual chemicals. Collectively, these data offer a mechanistic basis for the increased risk of breast cancer associated with dietary cooked meat and ethanol lifestyle choices.

Modulation of the toxicity and antitumour activity of alkylating drugs by steroids.

OpenAIRE

Shepherd, R.; Harrap, K. R.

1982-01-01

The steroids prednisolone and progesterone significantly altered the therapeutic indices of the alkylating agents, nitrogen mustard, melphalan, cyclophosphamide, phenyl acetic mustard and chlorambucil. For nitrogen mustard, chlorambucil and phenyl acetic mustard, prednisolone reduced host toxicity in the rat and enhanced the antitumour effectiveness against alkylating-agent-resistant strains of the Yoshida sarcoma and Walker carcinosarcoma. Progesterone also increased the therapeutic index of...

Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique.

Science.gov (United States)

Khan, Md Rajibur Rahaman; Kang, Shin-Won

2016-11-09

In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal's pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The sensitivity of the proposed pH sensor is 0.46 µs/pH, and the correlation coefficient R² is approximately 0.997. Additional advantages of the proposed optical-fiber PWM pH sensor include a short/fast response-time of about 8 s, good reproducibility properties with a relative standard deviation (RSD) of about 0.019, easy fabrication, low cost, small size, reusability of the optical-fiber sensing-element, and the capability of remote sensing. Finally, the performance of the proposed PWM pH sensor was compared with that of potentiometric, optical-fiber modal interferometer, and optical-fiber Fabry-Perot interferometer pH sensors with respect to dynamic range width, linearity as well as response and recovery times. We observed that the proposed sensing systems have better sensing abilities than the above-mentioned pH sensors.

Highly Sensitive and Wide-Dynamic-Range Multichannel Optical-Fiber pH Sensor Based on PWM Technique

Science.gov (United States)

Khan, Md. Rajibur Rahaman; Kang, Shin-Won

2016-01-01

In this study, we propose a highly sensitive multichannel pH sensor that is based on an optical-fiber pulse width modulation (PWM) technique. According to the optical-fiber PWM method, the received sensing signal’s pulse width changes when the optical-fiber pH sensing-element of the array comes into contact with pH buffer solutions. The proposed optical-fiber PWM pH-sensing system offers a linear sensing response over a wide range of pH values from 2 to 12, with a high pH-sensing ability. The sensitivity of the proposed pH sensor is 0.46 µs/pH, and the correlation coefficient R2 is approximately 0.997. Additional advantages of the proposed optical-fiber PWM pH sensor include a short/fast response-time of about 8 s, good reproducibility properties with a relative standard deviation (RSD) of about 0.019, easy fabrication, low cost, small size, reusability of the optical-fiber sensing-element, and the capability of remote sensing. Finally, the performance of the proposed PWM pH sensor was compared with that of potentiometric, optical-fiber modal interferometer, and optical-fiber Fabry–Perot interferometer pH sensors with respect to dynamic range width, linearity as well as response and recovery times. We observed that the proposed sensing systems have better sensing abilities than the above-mentioned pH sensors. PMID:27834865

Controllable synthesis of green and blue fluorescent carbon nanodots for pH and Cu(2+) sensing in living cells.

Science.gov (United States)

Shi, Lihong; Li, Yanyan; Li, Xiaofeng; Zhao, Bo; Wen, Xiangping; Zhang, Guomei; Dong, Chuan; Shuang, Shaomin

2016-03-15

We report a controllable strategy for fabrication of green and blue fluorescent carbon nanodots (CDs), and demonstrate their applications for pH and Cu(2+) sensing in living cells. Green and blue fluorescent CDs have been synthesized by hydrothermal method and pyrolysis of leeks, respectively, providing an easy way for the production of CDs without the request of tedious synthetic methodology or the use of toxic/expensive solvents and starting materials. Green fluorescent CDs (G-CDs) exhibit high tolerance to pH values and external cations. Blue fluorescent CDs (B-CDs) can be applied to pH and Cu(2+) sensing. The linear range of Cu(2+) detection is 0.01-10.00 μM and the detection limit is 0.05 μM. For pH detection, there is a good linearity in the pH range of 3.5-10.0. The linear and rapid response of B-CDs to Cu(2+) and pH is valuable for Cu(2+) and pH sensing in living cells. Confocal fluorescent imaging of human cervical carcinoma cells indicates that B-CDs could visualize Cu(2+) and pH fluctuations in living cells with negligible autofluorescence. Copyright © 2015 Elsevier B.V. All rights reserved.

Time-resolved studies define the nature of toxic IAPP intermediates, providing insight for anti-amyloidosis therapeutics

Science.gov (United States)

Abedini, Andisheh; Plesner, Annette; Cao, Ping; Ridgway, Zachary; Zhang, Jinghua; Tu, Ling-Hsien; Middleton, Chris T; Chao, Brian; Sartori, Daniel J; Meng, Fanling; Wang, Hui; Wong, Amy G; Zanni, Martin T; Verchere, C Bruce; Raleigh, Daniel P; Schmidt, Ann Marie

2016-01-01

Islet amyloidosis by IAPP contributes to pancreatic β-cell death in diabetes, but the nature of toxic IAPP species remains elusive. Using concurrent time-resolved biophysical and biological measurements, we define the toxic species produced during IAPP amyloid formation and link their properties to induction of rat INS-1 β-cell and murine islet toxicity. These globally flexible, low order oligomers upregulate pro-inflammatory markers and induce reactive oxygen species. They do not bind 1-anilnonaphthalene-8-sulphonic acid and lack extensive β-sheet structure. Aromatic interactions modulate, but are not required for toxicity. Not all IAPP oligomers are toxic; toxicity depends on their partially structured conformational states. Some anti-amyloid agents paradoxically prolong cytotoxicity by prolonging the lifetime of the toxic species. The data highlight the distinguishing properties of toxic IAPP oligomers and the common features that they share with toxic species reported for other amyloidogenic polypeptides, providing information for rational drug design to treat IAPP induced β-cell death. DOI: http://dx.doi.org/10.7554/eLife.12977.001 PMID:27213520