Pilot-scale UV/H2O2 advanced oxidation process for municipal reuse water: Assessing micropollutant degradation and estrogenic impacts on goldfish (Carassius auratus L.).

PubMed

Shu, Zengquan; Singh, Arvinder; Klamerth, Nikolaus; McPhedran, Kerry; Bolton, James R; Belosevic, Miodrag; Gamal El-Din, Mohamed

2016-09-15

Low concentrations (ng/L-μg/L) of emerging micropollutant contaminants in municipal wastewater treatment plant effluents affect the possibility to reuse these waters. Many of those micropollutants elicit endocrine disrupting effects in aquatic organisms resulting in an alteration of the endocrine system. A potential candidate for tertiary municipal wastewater treatment of these micropollutants is ultraviolet (UV)/hydrogen peroxide (H2O2) as an advanced oxidation process (AOP) which was currently applied to treat the secondary effluent of the Gold Bar Wastewater Treatment Plant (GBWWTP) in Edmonton, AB, Canada. A new approach is presented to predict the fluence-based degradation rate constants (kf') of environmentally occurring micropollutants including carbamazepine [(0.87-1.39) × 10(-3) cm(2)/mJ] and 2,4-Dichlorophenoxyacetic acid (2,4-D) [(0.60-0.91) × 10(-3) cm(2)/mJ for 2,4-D] in a medium pressure (MP) UV/H2O2 system based on a previous bench-scale investigation. Rather than using removal rates, this approach can be used to estimate the performance of the MP UV/H2O2 process for degrading trace contaminants of concern found in municipal wastewater. In addition to the ability to track contaminant removal/degradation, evaluation of the MP UV/H2O2 process was also accomplished by identifying critical ecotoxicological endpoints (i.e., estrogenicity) of the treated wastewater. Using quantitative PCR, mRNA levels of estrogen-responsive (ER) genes ERα1, ERα2, ERβ1, ERβ2 and NPR as well as two aromatase encoding genes (CYP19a and CYP19b) in goldfish (Carassius auratus L.) were measured during exposure to the GBWWTP effluent before and after MP UV/H2O2 treatment (a fluence of 1000 mJ/cm(2) and 20 mg/L of H2O2) in spring, summer and fall. Elevated expression of estrogen-responsive genes in goldfish exposed to UV/H2O2 treated effluent (a 7-day exposure) suggested that the UV/H2O2 process may induce acute estrogenic disruption to goldfish principally because of the possible formation of various oxidation by-products. However, prolonged exposure of goldfish (60 days) in UV/H2O2 treated effluent showed a restoration trend of ER gene expressions, especially in the summer. Collectively, our findings provide valuable indications regarding the long-term in vivo assessment of the MP UV/H2O2 process for removing/degrading endocrine disrupting compounds detected in the municipal wastewater effluents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Methylphenidate side effects in advanced cancer: a retrospective analysis.

PubMed

Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Davis, Mellar P; Rivera, Nilo; Khoshknabi, Dilara Seyidova

2010-02-01

Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults. To evaluate MP-associated symptoms or side effects (S/E). Data was collected from 2 published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All 3 reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 AM and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5, and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. 62 patients were enrolled. Fifty completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day. Most (96%) had improvement in depression and/or fatigue. Among the 62 patients, new symptom prevalence throughout the study was agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than 1 symptom simultaneously. Seven (11%) withdrew due to MP S/E. Some symptoms present before MP showed significant improvement during MP therapy. (1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated. (2) S/E symptoms with MP appeared to improve spontaneously despite continued MP therapy. (3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. (4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.

Sex Differences in the Physiological and Behavioral Effects of Chronic Oral Methylphenidate Treatment in Rats

PubMed Central

Robison, Lisa S.; Michaelos, Michalis; Gandhi, Jason; Fricke, Dennis; Miao, Erick; Lam, Chiu-Yim; Mauceri, Anthony; Vitale, Melissa; Lee, Junho; Paeng, Soyeh; Komatsu, David E.; Hadjiargyrou, Michael; Thanos, Panayotis K.

2017-01-01

Methylphenidate (MP) is a psychostimulant prescribed for Attention Deficit Hyperactivity Disorder. Previously, we developed a dual bottle 8-h-limited-access-drinking-paradigm for oral MP treatment of rats that mimics the pharmacokinetic profile of treated patients. This study assessed sex differences in response to this treatment. Male and female Sprague Dawley rats were assigned to one of three treatment groups at 4 weeks of age (n = 12/group): Control (water), low dose (LD) MP, and high dose (HD) MP. Rats drank 4 mg/kg MP (LD) or 30 mg/kg MP (HD) during the first hour, and 10 mg/kg (LD) or 60 mg/kg MP (HD) for the remaining 7 h each day. Throughout 3 months of treatment, rats were monitored for body weight, food intake, and fluid intake; as well as tested for open field behavior, circadian activity, novel object recognition, and social interaction. Chronic MP treated rats exhibited reduced fluid intake during distinct treatment weeks to a greater extent in males, and reduced total fluid intake in males only. HD MP treatment decreased body weight in both sexes, while HD MP increased total food intake in females only, likely to offset energy deficits resulting from MP-induced hyperactivity. LD and HD MP increased locomotor activity in the open field, particularly in females and during later treatment weeks. MP dose-dependently increased activity during the dark cycle of circadian testing in females, while in males hyperactivity was only exhibited by HD rats. HD MP increased center activity to a greater extent in males, while MP increased rearing behavior in females only. MP had no effect on social behavior or novel object recognition in either sex. This study concludes that chronic oral MP treatment at clinically-relevant dosages has significant effects on food intake, body weight, open field behavior, and wake cycle activity. Particularly marked sex differences were apparent for locomotor activity, with females being significantly more sensitive to the hyperactivating effects of the drug. These findings suggest that chronic MP exposure beginning in adolescence can have significant behavioral effects that are both dose- and sex-dependent, and raise concerns regarding the reversibility of these effects post-discontinuation of treatment. PMID:28400722

Characterization of a novel two dimensional diode array the "magic plate" as a radiation detector for radiation therapy treatment.

PubMed

Wong, J H D; Fuduli, I; Carolan, M; Petasecca, M; Lerch, M L F; Perevertaylo, V L; Metcalfe, P; Rosenfeld, A B

2012-05-01

Intensity modulated radiation therapy (IMRT) utilizes the technology of multileaf collimators to deliver highly modulated and complex radiation treatment. Dosimetric verification of the IMRT treatment requires the verification of the delivered dose distribution. Two dimensional ion chamber or diode arrays are gaining popularity as a dosimeter of choice due to their real time feedback compared to film dosimetry. This paper describes the characterization of a novel 2D diode array, which has been named the "magic plate" (MP). It was designed to function as a 2D transmission detector as well as a planar detector for dose distribution measurements in a solid water phantom for the dosimetric verification of IMRT treatment delivery. The prototype MP is an 11 × 11 detector array based on thin (50 μm) epitaxial diode technology mounted on a 0.6 mm thick Kapton substrate using a proprietary "drop-in" technology developed by the Centre for Medical Radiation Physics, University of Wollongong. A full characterization of the detector was performed, including radiation damage study, dose per pulse effect, percent depth dose comparison with CC13 ion chamber and build up characteristics with a parallel plane ion chamber measurements, dose linearity, energy response and angular response. Postirradiated magic plate diodes showed a reproducibility of 2.1%. The MP dose per pulse response decreased at higher dose rates while at lower dose rates the MP appears to be dose rate independent. The depth dose measurement of the MP agrees with ion chamber depth dose measurements to within 0.7% while dose linearity was excellent. MP showed angular response dependency due to the anisotropy of the silicon diode with the maximum variation in angular response of 10.8% at gantry angle 180°. Angular dependence was within 3.5% for the gantry angles ± 75°. The field size dependence of the MP at isocenter agrees with ion chamber measurement to within 1.1%. In the beam perturbation study, the surface dose increased by 12.1% for a 30 × 30 cm(2) field size at the source to detector distance (SDD) of 80 cm whilst the transmission for the MP was 99%. The radiation response of the magic plate was successfully characterized. The array of epitaxial silicon based detectors with "drop-in" packaging showed properties suitable to be used as a simplified multipurpose and nonperturbing 2D radiation detector for radiation therapy dosimetric verification.

Accurate tissue characterization in low-dose CT imaging with pure iterative reconstruction.

PubMed

Murphy, Kevin P; McLaughlin, Patrick D; Twomey, Maria; Chan, Vincent E; Moloney, Fiachra; Fung, Adrian J; Chan, Faimee E; Kao, Tafline; O'Neill, Siobhan B; Watson, Benjamin; O'Connor, Owen J; Maher, Michael M

2017-04-01

We assess the ability of low-dose hybrid iterative reconstruction (IR) and 'pure' model-based IR (MBIR) images to maintain accurate Hounsfield unit (HU)-determined tissue characterization. Standard-protocol (SP) and low-dose modified-protocol (MP) CTs were contemporaneously acquired in 34 Crohn's disease patients referred for CT. SP image reconstruction was via the manufacturer's recommendations (60% FBP, filtered back projection; 40% ASiR, Adaptive Statistical iterative Reconstruction; SP-ASiR40). MP data sets underwent four reconstructions (100% FBP; 40% ASiR; 70% ASiR; MBIR). Three observers measured tissue volumes using HU thresholds for fat, soft tissue and bone/contrast on each data set. Analysis was via SPSS. Inter-observer agreement was strong for 1530 datapoints (rs > 0.9). MP-MBIR tissue volume measurement was superior to other MP reconstructions and closely correlated with the reference SP-ASiR40 images for all tissue types. MP-MBIR superiority was most marked for fat volume calculation - close SP-ASiR40 and MP-MBIR Bland-Altman plot correlation was seen with the lowest average difference (336 cm 3 ) when compared with other MP reconstructions. Hounsfield unit-determined tissue volume calculations from MP-MBIR images resulted in values comparable to SP-ASiR40 calculations and values that are superior to MP-ASiR images. Accuracy of estimation of volume of tissues (e.g. fat) using segmentation software on low-dose CT images appears optimal when reconstructed with pure IR. © 2016 The Royal Australian and New Zealand College of Radiologists.

Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity

PubMed Central

Levinsen, Mette; Rosthøj, Susanne; Nygaard, Ulrikka; Heldrup, Jesper; Harila-Saari, Arja; Jonsson, Olafur G.; Bechensteen, Anne Grete; Abrahamsson, Jonas; Lausen, Birgitte; Frandsen, Thomas L.; Weinshilboum, Richard M.; Schmiegelow, Kjeld

2015-01-01

Purpose Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides (6TGN), the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMTIA) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Methods Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. Results The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However, since TPMTIA had lower blood counts at initiation of HD-MTX compared to TPMTHA patients (median WBC 2.8 vs. 3.3 ×109/L, P=0.01; median ANC 1.4 vs. 1.7 ×109/L, P=0.02), TPMTIA continued to have lower WBC and ANC levels compared to TPMTHA during all 28 days after HD-MTX (relative difference: 9% (95% CI: 2-17%), P=0.02 and 21% (95% CI: 6-39%), P=0.005). Still, the fractional decrease in WBC and ANC levels after HD-MTX did not differ between TPMTIA and TPMTHA patients (P=0.47 and P=0.38). The degree of leukopenia, neutropenia, thrombocytopenia and rise in aminotransferases were all significantly related to 6MP dose (P<0.001 for all analyses). Conclusion For both TPMTIA and TPMTHA patients dose of 6MP prior to HD-MTX should be guided by pre-HD-MTX blood counts, but not by TPMT activity. PMID:25347948

Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity.

PubMed

Levinsen, Mette; Rosthøj, Susanne; Nygaard, Ulrikka; Heldrup, Jesper; Harila-Saari, Arja; Jonsson, Olafur G; Bechensteen, Anne Grete; Abrahamsson, Jonas; Lausen, Birgitte; Frandsen, Thomas L; Weinshilboum, Richard M; Schmiegelow, Kjeld

2015-01-01

Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMT(IA)) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. The degree of myelosuppression following HD-MTX was similar for patients with TPMT(IA) and patients with high TPMT activity (TPMT(HA)), when HD-MTX started with same blood counts and 6MP doses. However, since TPMT(IA) had lower blood counts at initiation of HD-MTX compared with TPMT(HA) patients (median WBC 2.8 vs. 3.3 × 10⁹/L, P = 0.01; median ANC 1.4 vs. 1.7 × 10⁹/L, P = 0.02), TPMT(IA) continued to have lower WBC and ANC levels compared with TPMT(HA) during all 28 days after HD-MTX [relative difference 9 % (95 % CI 2-17), P = 0.02 and 21 % (95 % CI 6-39), P = 0.005]. Still, the fractional decrease in WBC and ANC levels after HD-MTX did not differ between TPMT(IA) and TPMT(HA) patients (P = 0.47; P = 0.38). The degree of leukopenia, neutropenia, thrombocytopenia and rise in aminotransferases were all significantly related to 6MP dose (P < 0.001 for all analyses). For both TPMT(IA) and TPMT(HA) patients, dose of 6MP prior to HD-MTX should be guided by pre-HD-MTX blood counts, but not by TPMT activity.

Preparation, characterization and binding behaviors of host-guest inclusion complexes of metoclopramide hydrochloride with α- and β-cyclodextrin molecules

NASA Astrophysics Data System (ADS)

Barman, Siti; Barman, Biraj Kumar; Roy, Mahendra Nath

2018-03-01

The supramolecular interaction of metoclopramide hydrochloride (MP) with α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) has been inspected by ultraviolet-visible (UV-vis) light, infra-red (IR) light, fluorescence and 1H NMR spectroscopy. The formation of an inclusion complex greatly affects the physical-chemical properties of the guest molecules, such as solubility, chemical reactivity and the spectroscopic and electrochemical properties. Thus the changes in the spectral properties and physico-chemical properties confirm the inclusion complex formation. Surface tension, conductivity studies and Job's plot indicate a 1: 1 stoichiometry of the MP:CD host-guest inclusion complexes. The binding/association constants have been evaluated by both UV-Vis and fluorescence spectroscopic study indicating a higher degree of encapsulation for β-cyclodextrin (β-CD). Furthermore, the negative value of thermodynamic parameter (ΔG°) of the host-guest system suggests that the inclusion process proceeded spontaneously at 298.15 K. Based on the NMR data, the plausible mode of interaction of MP:α-CD and MP:β-CD complexes were proposed, which suggested that lipophilic aromatic ring of the MP entered into the cavity of CDs from the wider side, with the amide (sbnd CONH) and methoxy (-OMe) residues inside the CD cavity.

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia

PubMed Central

Hawwa, Ahmed F; Collier, Paul S; Millership, Jeff S; McCarthy, Anthony; Dempsey, Sid; Cairns, Carole; McElnay, James C

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTThe cytotoxic effects of 6-mercaptopurine (6-MP) were found to be due to drug-derived intracellular metabolites (mainly 6-thioguanine nucleotides and to some extent 6-methylmercaptopurine nucleotides) rather than the drug itself.Current empirical dosing methods for oral 6-MP result in highly variable drug and metabolite concentrations and hence variability in treatment outcome. WHAT THIS STUDY ADDSThe first population pharmacokinetic model has been developed for 6-MP active metabolites in paediatric patients with acute lymphoblastic leukaemia and the potential demographic and genetically controlled factors that could lead to interpatient pharmacokinetic variability among this population have been assessed.The model shows a large reduction in interindividual variability of pharmacokinetic parameters when body surface area and thiopurine methyltransferase polymorphism are incorporated into the model as covariates.The developed model offers a more rational dosing approach for 6-MP than the traditional empirical method (based on body surface area) through combining it with pharmacogenetically guided dosing based on thiopurine methyltransferase genotype. AIMS To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m−2 day−1). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. CONCLUSIONS The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype. PMID:18823306

Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia: Clinical Facts and Fiction

PubMed Central

Nielsen, Stine N.; Frandsen, Thomas L.; Nersting, Jacob

2014-01-01

The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients’ ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments, extensive host genome profiling to understand diversity in treatment efficacy and toxicity, and alternative thiopurine dosing regimens to improve therapy for the individual patient. PMID:24936744

Emulsifying Properties of Oxidatively Stressed Myofibrillar Protein Emulsion Gels Prepared with (-)-Epigallocatechin-3-gallate and NaCl.

PubMed

Feng, Xianchao; Chen, Lin; Lei, Na; Wang, Shuangxi; Xu, Xinglian; Zhou, Guanghong; Li, Zhixi

2017-04-05

The dose-dependent effects of (-)-epigallocatechin-3-gallate (EGCG; 0, 100, or 1000 ppm) on the textural properties and stability of a myofibrillar protein (MP) emulsion gel were investigated. Addition of EGCG significantly inhibited formation of carbonyl but promoted the loss of both thiol and free amine groups. Addition of EGCG, particularly at 1000 ppm, initiated irreversible protein modifications, as evidenced by surface hydrophobicity changes, patterns in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and differential scanning calorimetry. These results indicated that MP was modified by additive reactions between the quinone of EGCG and thiols and free amines of proteins. These adducts increased cooking loss and destabilized the texture, especially with a large EGCG dose. Confocal laser scanning microscopy and scanning electron microscopy images clearly indicated the damage to the emulsifying properties and the collapse of the internal structure when the MP emulsion gel was treated with a large EGCG dose. A high concentration of NaCl (0.6 M) improved modification of MP and increased the rate of deterioration of the internal structure, especially with the large EGCG dose (1000 ppm), resulting in an MP emulsion gel with extremely unstable emulsifying properties.

6-mercaptopurine dosage and pharmacokinetics influence the degree of bone marrow toxicity following high-dose methotrexate in children with acute lymphoblastic leukemia.

PubMed

Schmiegelow, K; Bretton-Meyer, U

2001-01-01

Through inhibition of purine de novo synthesis and enhancement of 6-mercaptopurine (6MP) bioavailability high-dose methotrexate (HDM) may increase the incorporation into DNA of 6-thioguanine nucleotides (6TGN), the cytoxic metabolites of 6MP. Thus, coadministration of 6MP could increase myelotoxicity following HDM. Twenty-one children with standard risk (SR) and 25 with intermediate risk (IR) acute lymphoblastic leukemia (ALL) were studied. During consolidation therapy they received either three courses of HDM at 2 week intervals without concurrent oral 6MP (SR-ALL) or four courses of HDM given at 2 week intervals with 25 mg/m2 of oral 6MP daily (IR-ALL). During the first year of maintenance with oral 6MP (75 mg/m2/day) and oral MTX (20 mg/m2/week) they all received five courses of HDM at 8 week intervals. In all cases, HDM consisted of 5,000 mg of MTX/m2 given over 24 h with intraspinal MTX and leucovorin rescue. Erythrocyte levels of 6TGN (E-6TGN) and methotrexate (E-MTX) were, on average, measured every second week during maintenance therapy. When SR consolidation (6MP: 0 mg), IR consolidation (6MP: 25 mg/m2), and SR/IR maintenance therapy (6MP: 75 mg/m2) were compared, white cell and absolute neutrophil count (ANC) nadir, lymphocyte count nadir, thrombocyte count nadir, and hemoglobin nadir after HDM decreased significantly with increasing doses of oral 6MP. Three percent of the HDM courses given without oral 6MP (SR consolidation) were followed by an ANC nadir <0.5 x 10(9)/l compared to 50% of the HDM courses given during SR/IR maintenance therapy. Similarly, only 13% of the HDM courses given as SR-ALL consolidation induced a thrombocyte count nadir <100 x 10(9)/l compared to 58% of the HDM courses given during maintenance therapy. The best-fit model to predict the ANC nadir following HDM during maintenance therapy included the dose of 6MP prior to HDM (beta = -0.017, P= 0.001), the average ANC level during maintenance therapy (beta = 0.82, P = 0.004), and E-6TGN (beta = -0.0029, P= 0.02). The best-fit model to predict the thrombocyte nadir following HDM during maintenance therapy included only mPLATE (beta = 0.0057, P = 0.046). In conclusion, the study indicates that reductions of the dose of concurrently given oral 6MP could be one way of reducing the risk of significant myelotoxicity following HDM during maintenance therapy of childhood ALL.

Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed extract in rodent model of Parkinson's disease.

PubMed

Kasture, Sanjay; Pontis, Silvia; Pinna, Annalisa; Schintu, Nicoletta; Spina, Liliana; Longoni, Rosanna; Simola, Nicola; Ballero, Mauro; Morelli, Micaela

2009-02-01

Mucuna pruriens (MP) has long been used in Indian traditional medicine as support in the treatment of Parkinson's disease. However, no systematic preclinical studies that aimed at evaluating the efficacy of this substance are available to date. This study undertook an extensive evaluation of the antiparkinsonian effects of an extract of MP seeds known to contain, among other components, 12.5% L: -dihydroxyphenylalanine (L: -DOPA), as compared to equivalent doses of L: -DOPA. Moreover, the neuroprotective efficacy of MP and its potential rewarding effects were evaluated. The results obtained reveal how an acute administration of MP extract at a dose of 16 mg/kg (containing 2 mg/kg of L: -DOPA) consistently antagonized the deficit in latency of step initiation and adjusting step induced by a unilateral 6-hydroxydopamine lesion, whereas L: -DOPA was equally effective only at the doses of 6 mg/kg. At the same dosage, MP significantly improved the placement of the forelimb in vibrissae-evoked forelimb placing, suggesting a significant antagonistic activity on both motor and sensory-motor deficits. The effects of MP extract were moreover investigated by means of the turning behavior test and in the induction of abnormal involuntary movements (AIMs) after either acute or subchronic administration. MP extract acutely induced a significantly higher contralateral turning behavior than L: -DOPA (6 mg/kg) when administered at a dose of 48 mg/kg containing 6 mg/kg of L: -DOPA. On subchronic administration, both MP extract (48 mg/kg) and L: -DOPA (6 mg/kg) induced sensitization of contralateral turning behavior; however, L: -DOPA alone induced a concomitant sensitization in AIMs suggesting that the dyskinetic potential of MP is lower than that of L: -DOPA. MP (48 mg/kg) was also effective in antagonizing tremulous jaw movements induced by tacrine, a validated test reproducing parkinsonian tremor. Furthermore, MP induced no compartment preference in the place preference test, indicating the lack of components characterized by rewarding effects in the extract. Finally, in a subchronic mice model of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced dopamine neuron degeneration, MP extract did not prove capable of preventing either tyrosine hydroxylase decrease induced by MPTP or astroglial or microglial activation as assessed by means of GFAP and CD11b immunohistochemistry, supporting the absence of neuroprotective effects by MP. Characterization MP extract strongly supports its antiparkinsonian activity.

Nature and position of functional group on thiopurine substrates influence activity of xanthine oxidase--enzymatic reaction pathways of 6-mercaptopurine and 2-mercaptopurine are different.

PubMed

Tamta, Hemlata; Kalra, Sukirti; Thilagavathi, Ramasamy; Chakraborti, Asit K; Mukhopadhyay, Anup K

2007-02-01

Xanthine oxidase-catalyzed hydroxylation reactions of the anticancer drug 6-mercaptopurine (6-MP) and its analog 2-mercaptopurine (2-MP) as well as 6-thioxanthine (6-TX) and 2-thioxanthine (2-TX) have been studied using UV-spectroscopy, high pressure liquid chromatography, photodiode array, and liquid chromatography-based mass spectral analysis. It is shown that 6-MP and 2-MP are oxidatively hydroxylated through different pathways. Enzymatic hydroxylation of 6-MP forms 6-thiouric acid in two steps involving 6-TX as the intermediate, whereas 2-MP is converted to 8-hydroxy-2-mercaptopurine as the expected end product in one step. Surprisingly, in contrast to the other thiopurines, enzymatic hydroxylation of 2-MP showed a unique hyperchromic effect at 264 nm as the reaction proceeded. However, when 2-TX is used as the substrate, it is hydroxylated to 2-thiouric acid. The enzymatic hydroxylation of 2-MP is considerably faster than that of 6-MP, while 6-TX and 2-TX show similar rates under identical reaction conditions. The reason why 2-MP is a better substrate than 6-MP and how the chemical nature and position of the functional groups present on the thiopurine substrates influence xanthine oxidase activity are discussed.

Systemic Exposure to Thiopurines and Risk of Relapse in Children With Acute Lymphoblastic Leukemia: A Children's Oncology Group Study.

PubMed

Bhatia, Smita; Landier, Wendy; Hageman, Lindsey; Chen, Yanjun; Kim, Heeyoung; Sun, Can-Lan; Kornegay, Nancy; Evans, William E; Angiolillo, Anne L; Bostrom, Bruce; Casillas, Jacqueline; Lew, Glen; Maloney, Kelly W; Mascarenhas, Leo; Ritchey, A Kim; Termuhlen, Amanda M; Carroll, William L; Wong, F Lennie; Relling, Mary V

2015-06-01

Variability in prescribed doses of 6-mercaptopurine (6MP) and lack of adherence to a 6MP treatment regimen could result in intra-individual variability in systemic exposure to 6MP (measured as erythrocyte thioguanine nucleotide [TGN] levels) in children with acute lymphoblastic leukemia (ALL). The effect on relapse risk of this variability is unknown. To determine the effect of high intra-individual variability of 6MP systemic exposure on relapse risk in children with ALL. We used a prospective longitudinal design (Children's Oncology Group study [COG-AALL03N1]) to monitor 6MP and disease relapse in 742 children with ALL in ambulatory care settings of 94 participating institutions from May 30, 2005, to September 9, 2011. All participants met the following eligibility criteria: (1) diagnosis of ALL at 21 years or younger; (2) first continuous remission in progress at the time of study entry; (3) receiving self-, parent-, or caregiver-administered oral 6MP during maintenance therapy; and (4) completion of at least 6 months of maintenance therapy at the time of study enrollment. The median patient age at diagnosis was 5 years; 68% were boys; and 43% had National Cancer Institute-based high-risk disease. Daily 6MP regimen adherence was measured over 68 716 person-days using an electronic system that recorded the date and time of each 6MP bottle opening; adherence rate was defined as the ratio of days that a 6MP bottle was opened to days thata 6MP bottle was prescribed. Average monthly 6MP dose intensity was measured over 120 439 person-days by dividing the number of 6MP doses actually prescribed by the number of planned protocol doses (75 mg/m2/d). Monthly erythrocyte TGN levels (pmol/8 × 108 erythrocytes) were measured over 6 consecutive months per patient (n = 3944 measurements). Using intra-individual coefficients of variation (CV%), patients were classified as having stable (CV% <85th percentile) vs varying (CV% ≥85th percentile) indices. Median follow-up time was 6.7 years from the time of diagnosis. Adjusting for clinical prognosticators, we found that patients with 6MP nonadherence (mean adherence rate <95%) were at a 2.7-fold increased risk of relapse (95% CI, 1.3-5.6; P = .01) compared with patients with a mean adherence rate of 95% or greater. Among adherers, high intra-individual variability in TGN levels contributed to increased relapse risk (hazard ratio, 4.4; 95% CI, 1.2-15.7; P = .02). Furthermore, adherers with varying TGN levels had varying 6MP dose intensity (odds ratio [OR], 4.5; 95% CI, 1.5-13.4; P = .01) and 6MP drug interruptions (OR, 10.2; 95% CI, 2.2-48.3; P = .003). These findings emphasize the need to maximize 6MP regimen adherence and maintain steady thiopurine exposure to minimize relapse in children with ALL.

The evaluation of different treatment protocols for trauma-induced lung injury in rats

PubMed Central

Güzel, Aygül; Katı, Celal; Duran, Latif; Alaçam, Hasan; Gacar, Ayhan; Güvenç, Tolga; Murat, Naci; Şişman, Bülent

2014-01-01

Background Lung contusion is an important factor that affects mortality and morbidity of lung injury after blunt chest trauma (BCT). The present study aims to evaluate the effectiveness of different treatment regimens on BCT-induced lung injury. Methods A total of 35 Sprague Dawley rats were divided into five experimental groups (n=7): sham, control; BCT; BCT + MP, BCT group treated with methylprednisolone (MP; 30 mg/kg on first day and 3 mg/kg/d on the following days); BCT + Q, BCT group treated with quercetin (Q; 50 mg/kg/d for seven days); and BCT + MP + Q, BCT group treated with the same doses of MP and Q. Serum Clara Cell Protein-16 (CC-16), thiobarbituric acid reactive substances (TBARS), and superoxide dismutase (SOD) levels were analyzed to determine histopathological changes in the lung tissues. Results Elevated serum CC-16 and TBARS levels and reduced serum SOD levels were found in the BCT group compared to the Sham group. There was a significant change in the serum CC-16 levels in the BCT + MP group compared to the Sham group. Serum TBARS levels were significantly lower in the BCT + MP and BCT + Q group compared to the BCT group. The combined therapy regimen yielded significantly decreased CC-16 levels and increased serum SOD levels compared to the individual treatment groups. Serum TBARS levels did not significantly differ between the BCT + MP + Q group and the other treatment groups. Compared to the BCT + MP + Q group, the BCT + MP group showed significantly lower alveolar edema (AED) and alveolar exudate (AEX) scores, while the BCT + Q group showed significantly lower peribronchial inflammatory cell infiltration (PICI) and AED scores. Conclusions The combined usage of quercetin and low dose MP treatment after initial high dose MP at the early stage of lung injury after BCT is more effective. PMID:24605218

6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

PubMed

Agrawal, Vineet; Paul, Manash K; Mukhopadhyay, Anup K

2005-01-01

This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

The association between fasting hypoglycemia and methylated mercaptopurine metabolites in children with acute lymphoblastic leukemia.

PubMed

Melachuri, Samyuktha; Gandrud, Laura; Bostrom, Bruce

2014-06-01

Symptomatic fasting hypoglycemia has been reported as an unusual side effect in patients with acute lymphoblastic leukemia (ALL) on maintenance therapy. We evaluated the relation of the red cell 6-mercaptopurine (6-MP) metabolite 6-methyl-mercaptopurine (6MMP) with hypoglycemia. We retrospectively reviewed charts of three patients with ALL and symptomatic hypoglycemia while fasting who were noted to have high levels of 6MMP. All patients had an empiric trial of switching from evening to morning 6-MP administration, and two patients were subsequently switched to twice daily dosing. Patients also received complex carbohydrates at bedtime. Switching 6-MP from evening to morning administration reduced 6MMP levels yet preserved adequate levels of the active metabolite red cell 6-thioguanine nucleotide (6TGN). All patients had decreased hypoglycemic events when changed from evening to morning dosing. Two patients showed a rebound in 6MMP levels with return of hypoglycemic symptoms. Both were then switched to twice daily 6-MP dosing with one having a decrease in 6MMP and hypoglycemic symptoms. High levels of 6MMP are associated with symptomatic hypoglycemia which may be mitigated by switching to morning or twice daily 6-MP dose administration. © 2014 Wiley Periodicals, Inc.

IN VIVO EVALUATION OF SAFETY OF NANOPOROUS SILICON CARRIERS FOLLOWING SINGLE AND MULTIPLE DOSE INTRAVENOUS ADMINISTRATIONS IN MICE

PubMed Central

Tanaka, T.; Godin, B.; Bhavane, R.; Nieves-Alicea, R.; Gu, J.; Liu, X.; Chiappini, C.; Fakhoury, J. R.; Amra, S.; Ewing, A.; Li, Q.; Fidler, I.J.; Ferrari, M.

2010-01-01

Porous silicon (pSi) is being extensively studied as an emerging material for use in biomedical applications, including drug delivery, based on the biodegradability and versatile chemical and biophysical properties. We have recently introduced multistage nanoporous silicon microparticles (S1MP) designed as a cargo for nanocarrier drug delivery to enable the loaded therapeutics and diagnostics to sequential overcoming of the biological barriers to reach their target. In this first report on biocompatibility of intravenously administered pSi structures, we examined biocompatibility of negatively (−32.5±3.1mV) and positively (8.7±2.5mV) charged S1MP in acute single dose (107, 108, 5×108 S1MP/animal) and subchronic multiple dose (108 S1MP/animal/week for 4 weeks) administration schedules. Our data demonstrate that S1MP did not change plasma levels of renal (BUN and creatinine) and hepatic (LDH) biomarkers as well as23 plasma cytokines. LDH plasma levels of 145.2±23.6, 115.4±29.1 vs. 127.0±10.4; and 155.8±38.4, 135.5±52.3 vs. 178.4±74.6 were detected in mice treated with 108 negatively charged S1MP, 108 positively charged S1MP vs. saline control in single and multiple dose schedules, respectively. The S1MPs did not alter LDH levels in liver and spleen, nor lead to infiltration of leukocytes into the liver, spleen, kidney, lung, brain, heart, and thyroid. Collectively, these data provide evidence of a safe intravenous administration of S1MPs as a drug delivery carrier. PMID:20883755

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia.

PubMed

Hawwa, Ahmed F; Collier, Paul S; Millership, Jeff S; McCarthy, Anthony; Dempsey, Sid; Cairns, Carole; McElnay, James C

2008-12-01

To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m(-2) day(-1)). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.

A critical assessment of visual identification of marine microplastic using Raman spectroscopy for analysis improvement.

PubMed

Lenz, Robin; Enders, Kristina; Stedmon, Colin A; Mackenzie, David M A; Nielsen, Torkel Gissel

2015-11-15

Identification and characterisation of microplastic (MP) is a necessary step to evaluate their concentrations, chemical composition and interactions with biota. MP ≥10μm diameter filtered from below the sea surface in the European and subtropical North Atlantic were simultaneously identified by visual microscopy and Raman micro-spectroscopy. Visually identified particles below 100μm had a significantly lower percentage confirmed by Raman than larger ones indicating that visual identification alone is inappropriate for studies on small microplastics. Sixty-eight percent of visually counted MP (n=1279) were spectroscopically confirmed being plastic. The percentage varied with type, colour and size of the MP. Fibres had a higher success rate (75%) than particles (64%). We tested Raman micro-spectroscopy applicability for MP identification with respect to varying chemical composition (additives), degradation state and organic matter coating. Partially UV-degraded post-consumer plastics provided identifiable Raman spectra for polymers most common among marine MP, i.e. polyethylene and polypropylene. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phenothiazine-anthraquinone donor-acceptor molecules: synthesis, electronic properties and DFT-TDDFT computational study.

PubMed

Zhang, Wen-Wei; Mao, Wei-Li; Hu, Yun-Xia; Tian, Zi-Qi; Wang, Zhi-Lin; Meng, Qing-Jin

2009-09-17

Two donor-acceptor molecules with different pi-electron conjugative units, 1-((10-methyl-10H-phenothiazin-3-yl)ethynyl)anthracene-9,10-dione (AqMp) and 1,1'-(10-methyl-10H-phenothiazine-3,7-diyl)bis(ethyne-2,1-diyl)dianthracene-9,10-dione (Aq2Mp), have been synthesized and investigated for their photochemical and electrochemical properties. Density functional theory (DFT) calculations provide insights into their molecular geometry, electronic structures, and properties. These studies satisfactorily explain the electrochemistry of the two compounds and indicate that larger conjugative effect leads to smaller HOMO-LUMO gap (Eg) in Aq2Mp. Both compounds show ICT and pi --> pi* transitions in the UV-visible range in solution, and Aq2Mp has a bathochromic shift and shows higher oscillator strength of the absorption, which has been verified by time-dependent DFT (TDDFT) calculations. The differences between AqMp and Aq2Mp indicate that the structural and conjugative effects have great influence on the electronic properties of the molecules.

Evaluating UV-C LED disinfection performance and investigating potential dual-wavelength synergy.

PubMed

Beck, Sara E; Ryu, Hodon; Boczek, Laura A; Cashdollar, Jennifer L; Jeanis, Kaitlyn M; Rosenblum, James S; Lawal, Oliver R; Linden, Karl G

2017-02-01

A dual-wavelength UV-C LED unit, emitting at peaks of 260 nm, 280 nm, and the combination of 260|280 nm together was evaluated for its inactivation efficacy and energy efficiency at disinfecting Escherichia coli, MS2 coliphage, human adenovirus type 2 (HAdV2), and Bacillus pumilus spores, compared to conventional low-pressure and medium-pressure UV mercury vapor lamps. The dual-wavelength unit was also used to measure potential synergistic effects of multiple wavelengths on bacterial and viral inactivation and DNA and RNA damage. All five UV sources demonstrated similar inactivation of E. coli. For MS2, the 260 nm LED was most effective. For HAdV2 and B. pumilus, the MP UV lamp was most effective. When measuring electrical energy per order of reduction, the LP UV lamp was most efficient for inactivating E. coli and MS2; the LP UV and MP UV mercury lamps were equally efficient for HAdV2 and B. pumilus spores. Among the UV-C LEDs, there was no statistical difference in electrical efficiency for inactivating MS2, HAdV2, and B. pumilus spores. The 260 nm and 260|280 nm LEDs had a statistical energy advantage for E. coli inactivation. For UV-C LEDs to match the electrical efficiency per order of log reduction of conventional LP UV sources, they must reach efficiencies of 25-39% or be improved on by smart reactor design. No dual wavelength synergies were detected for bacterial and viral inactivation nor for DNA and RNA damage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neuroprotection and Acute Spinal Cord Injury: A Reappraisal

PubMed Central

Hall, Edward D.; Springer, Joe E.

2004-01-01

Summary: It has long been recognized that much of the post-traumatic degeneration of the spinal cord following injury is caused by a multi-factorial secondary injury process that occurs during the first minutes, hours, and days after spinal cord injury (SCI). A key biochemical event in that process is reactive oxygen-induced lipid peroxidation (LP). In 1990 the results of the Second National Acute Spinal Cord Injury Study (NASCIS II) were published, which showed that the administration of a high-dose regimen of the glucocorticoid steroid methylprednisolone (MP), which had been previously shown to inhibit post-traumatic LP in animal models of SCI, could improve neurological recovery in spinal-cord-injured humans. This resulted in the registration of high-dose MP for acute SCI in several countries, although not in the U.S. Nevertheless, this treatment quickly became the standard of care for acute SCI since the drug was already on the U.S. market for many other indications. Subsequently, it was demonstrated that the non-glucocorticoid 21-aminosteroid tirilazad could duplicate the antioxidant neuroprotective efficacy of MP in SCI models, and evidence of human efficacy was obtained in a third NASCIS trial (NASCIS III). In recent years, the use of high-dose MP in acute SCI has become controversial largely on the basis of the risk of serious adverse effects versus what is perceived to be on average a modest neurological benefit. The opiate receptor antagonist naloxone was also tested in NASCIS II based upon the demonstration of its beneficial effects in SCI models. Although it did not a significant overall effect, some evidence of efficacy was seen in incomplete (i.e., paretic) patients. The monosialoganglioside GM1 has also been examined in a recently completed clinical trial in which the patients first received high-dose MP treatment. However, GM1 failed to show any evidence of a significant enhancement in the extent of neurological recovery over the level afforded by MP therapy alone. The present paper reviews the past development of MP, naloxone, tirilazad, and GM1 for acute SCI, the ongoing MP-SCI controversy, identifies the regulatory complications involved in future SCI drug development, and suggests some promising neuroprotective approaches that could either replace or be used in combination with high-dose MP. PMID:15717009

Evaluating UV-C LED disinfection performance and ...

EPA Pesticide Factsheets

This study evaluated ultraviolet (UV) light emitting diodes (LEDs) emitting at 260 nm, 280 nm, and the combination of 260|280 nm together for their efficacy at inactivating Escherichia. coli, MS2 coliphage, human adenovirus type 2 (HAdV2), and Bacillus pumilus spores; research included an evaluation of genomic damage. Inactivation by the LEDs was compared with the efficacy of conventional UV sources, the low-pressure (LP) and medium-pressure (MP) mercury vapor lamps. The work also calculated the electrical energy per order of reduction of the microorganisms by the five UV sources.For E. coli, all five UV sources yielded similar inactivation rates. For MS2 coliphage, the 260 nm LED was most effective. For HAdV2 and B. pumilus, the MP UV lamp was significantly more effective than the LP UV and UVC LED sources. When considering electrical energy per order of reduction, the LP UV lamp was the most efficient for E. coli and MS2, and the MPUV and LPUV were equally efficient for HAdV2 and B. pumilus spores. Among the UVC LEDs, the 280 nm LED unit required the least energy per log reduction of E. coli and HAdV2. The 280 nm and 260|280 nm LED units were equally efficient per log reduction of B. pumilus spores, and the 260 nm LED unit required the lowest energy per order of reduction of MS2 coliphage. The combination of the 260 nm and 280 nm UV LED wavelengths was also evaluated for potential synergistic effects. No dual-wavelength synergy was detected for inactivation of

SLCO1B1 Polymorphisms are Associated With Drug Intolerance in Childhood Leukemia Maintenance Therapy.

PubMed

Eldem, İrem; Yavuz, Duygu; Cumaoğullari, Özge; İleri, Talia; Ünal İnce, Elif; Ertem, Mehmet; Doğanay Erdoğan, Beyza; Bindak, Recep; Özdağ, Hilal; Şatiroğlu-Tufan, N Lale; Uysal, L Zümrüt

2018-04-20

Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during maintenance therapy of childhood acute lymphoblastic leukemia (ALL). 6-MP/MTX intolerance in some of the patients cannot be explained by thiopurine S-methyl transferase (TPMT) gene variants. In this study, we aimed to investigate candidate pharmacogenetic determinants of 6-MP and MTX intolerance in Turkish ALL children. In total, 48 children with ALL who had completed or were receiving maintenance therapy according to Children's Oncology Group (COG) protocols were enrolled. Fifteen single-nucleotide polymorphisms in 8 candidate genes that were related to drug toxicity or had a role in the 6-MP/MTX metabolism (TPMT, ITPA, MTHFR, IMPDH2, PACSIN2, SLCO1B1, ABCC4, and PYGL) were genotyped by competitive allele-specific PCR (KASP). Drug doses during maintenance therapy were modified according to the protocol. The median drug dose intensity was 50% (28% to 92%) for 6-MP and 58% (27% to 99%) for MTX in the first year of maintenance therapy, which were lower than that scheduled in all patients. Among the analyzed polymorphisms, variant alleles in SLCO1B1 rs4149056 and rs11045879 were found to be associated with lower 6-MP/MTX tolerance. SLCO1B1 rs4149056 and rs11045879 polymorphisms may be important genetic markers to individualize 6-MP/MTX doses.

Formation and removal of genotoxic activity during UV/H(2)O(2)-GAC treatment of drinking water.

PubMed

Heringa, M B; Harmsen, D J H; Beerendonk, E F; Reus, A A; Krul, C A M; Metz, D H; Ijpelaar, G F

2011-01-01

The objective of this study was to determine the genotoxic activity of water after UV/H(2)O(2) oxidation and GAC filtration. Pre-treated surface water from three locations was treated with UV/H(2)O(2) with medium pressure (MP) lamps and passed through granulated activated carbon (GAC). Samples taken before and after each treatment step were extracted and concentrated by solid phase extraction (SPE) and analyzed for genotoxicity using the Comet assay with HepG2 cells and the Ames II assay. The Comet assay showed no genotoxic response in any of the samples. In the Ames II, no genotoxic response was obtained with the TAMix (a mix of six strains), but the TA98 strain showed an increase in genotoxic activity after MP-UV/H(2)O(2) for all three locations. GAC post treatment effectively reduced the activities to control levels at two of the three locations and to below the level of the pre-treated water at one site. The results indicate that UV/H(2)O(2) treatment may lead to the formation of genotoxic by-products, which can be removed by subsequent GAC filtration. Copyright © 2010 Elsevier Ltd. All rights reserved.

Development and validation of chemometrics-assisted spectrophotometric and liquid chromatographic methods for the simultaneous determination of two multicomponent mixtures containing bronchodilator drugs.

PubMed

El-Gindy, Alaa; Emara, Samy; Shaaban, Heba

2007-02-19

Three methods are developed for the determination of two multicomponent mixtures containing guaiphenesine (GU) with salbutamol sulfate (SL), methylparaben (MP) and propylparaben (PP) [mixture 1]; and acephylline piperazine (AC) with bromhexine hydrochloride (BX), methylparaben (MP) and propylparaben (PP) [mixture 2]. The resolution of the two multicomponent mixtures has been accomplished by using numerical spectrophotometric methods such as partial least squares (PLS-1) and principal component regression (PCR) applied to UV absorption spectra of the two mixtures. In addition HPLC method was developed using a RP 18 column at ambient temperature with mobile phase consisting of acetonitrile-0.05 M potassium dihydrogen phosphate, pH 4.3 (60:40, v/v), with UV detection at 243 nm for mixture 1, and mobile phase consisting of acetonitrile-0.05 M potassium dihydrogen phosphate, pH 3 (50:50, v/v), with UV detection at 245 nm for mixture 2. The methods were validated in terms of accuracy, specificity, precision and linearity in the range of 20-60 microg ml(-1) for GU, 1-3 microg ml(-1) for SL, 20-80 microg ml(-1) for AC, 0.2-1.8 microgml(-1) for PP and 1-5 microg ml(-1) for BX and MP. The proposed methods were successfully applied for the determination of the two multicomponent combinations in laboratory prepared mixtures and commercial syrups.

Testicular functions and serum titers of LH and testosterone in methyl parathion-fed roseringed parakeets.

PubMed

Maitra, Saumen Kumar; Mitra, Anindita

2008-09-01

Adult male roseringed parakeets were fed concentrations (0, 10 or 20 microg/100g body wt./day) of methyl parathion (MP) for 5 or 10 days. There were four sampling periods for each treatment group. The first two sampling periods were after 5 or 10 days of daily dosing. In two other sampling periods, birds were given daily doses for 10 days, and sampling occurred at 5 or 10 days after the end of treatment. A significant dose- and duration-dependent reduction in the paired testicular weight, seminiferous tubular diameters, the number of tubules with healthy germ cells, plasma acetylcholinesterase (AChE) activity and plasma levels of luteinizing hormone (LH) and testosterone occurred in MP-fed birds. The inhibitory influences of MP persisted till day-5 and followed by recovery from the gonado-suppressive effects of MP at day-10 after the end of last treatment for 10 days. These findings provide the first experimental evidence that MP-induced testicular dysfunctions in parakeets possibly results from an impaired activity of hypophysial-gonadal axis. Moreover, it is evident that the organophosphorous (OP)-induced changes in the avian testes are reversible.

The PDE10A inhibitor MP-10 and haloperidol produce distinct gene expression profiles in the striatum and influence cataleptic behavior in rodents.

PubMed

Gentzel, Renee C; Toolan, Dawn; Roberts, Rhonda; Koser, Amy Jo; Kandebo, Monika; Hershey, James; Renger, John J; Uslaner, Jason; Smith, Sean M

2015-12-01

Phosphodiesterase 10A (PDE10A) has garnered attention as a potential therapeutic target for schizophrenia due to its prominent striatal expression and ability to modulate striatal signaling. The present study used the selective PDE10A inhibitor MP-10 and the dopamine D2 antagonist haloperidol to compare effects of PDE10A inhibition and dopamine D2 blockade on striatopallidal (D2) and striatonigral (D1) pathway activation. Our studies confirmed that administration of MP-10 significantly elevates expression of the immediate early genes (IEG) c-fos, egr-1, and arc in rat striatum. Furthermore, we demonstrated that MP-10 induced egr-1 expression was distributed evenly between enkephalin-containing D2-neurons and substance P-containing D1-neurons. In contrast, haloperidol (3 mg/kg) selectively activated egr-1 expression in enkephalin neurons. Co-administration of MP-10 and haloperidol (0.5 mg/kg) increased IEG expression to a greater extent than either compound alone. Similarly, in a rat catalepsy assay, administration of haloperidol (0.5 mg/kg) or MP-10 (3-30 mg/kg) did not produce cataleptic behavior when dosed alone, but co-administration of haloperidol with MP-10 (3 and 10 mg/kg) induced cataleptic behaviors. Interestingly, co-administration of haloperidol with a high dose of MP-10 (30 mg/kg) failed to produce cataleptic behavior. These findings are important for understanding the neural circuits involved in catalepsy and suggest that the behavioral effects produced by PDE10A inhibitors may be influenced by concomitant medication and the level of PDE10A inhibition achieved by the dose of the inhibitor. Copyright © 2015. Published by Elsevier Ltd.

The Relationship of Genetics, Nursing Practice, and Informatics Tools in 6-Mercaptopurine Dosing in Pediatric Oncology [Formula: see text].

PubMed

Haylett, Wendy J

An antileukemic agent prescribed for pediatric oncology patients during the maintenance phase of therapy for acute lymphoblastic leukemia, 6-mercaptopurine (6-MP), is highly influenced by genetic variations in the thiopurine S-methyltransferase enzyme. As such, 6-MP must be dosed so that patients with 1 or 2 inactive thiopurine S-methyltransferase alleles will not incur an increased risk for myelosuppression or other toxicities. Informatics tools such as clinical decision support systems are useful for the application of this and similar pharmacogenetics information to the realm of nursing and clinical practice for safe and effective patient care. This article will discuss pharmacogenetics and the associated use of 6-MP; present implications for nursing practice; identify informatics tools such as clinical decision support systems, which can greatly enhance the care of patients whose treatment is based on critical genetic information; and examine the relationship of genetics, nursing practice, and informatics for 6-MP dosing in pediatric oncology.

Sun light mediated synthesis of gold nanoparticles as carrier for 6-mercaptopurine: Preparation, characterization and toxicity studies in zebrafish embryo model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganeshkumar, Moorthy; Sastry, Thotapalli Parvathaleswara; Sathish Kumar, Muniram

2012-09-15

Highlights: ► Gold nanoparticles prepared using eco-friendly method with good in vitro stability. ► Can be used as drug delivery system. ► Did not show any toxicity in zebrafish embryo. ► More toxic to cancer cells when compared to N-Au-Mp and Mp. -- Abstract: The objective of this study is to synthesize green chemistry based gold nanoparticles by sun light irradiation method. The prepared gold nanoparticles (AuNPs) were modified using folic acid and then coupled with 6-mercaptopurine. These modified nanoparticles were used as a tool for targeted drug delivery to treat laryngeal cancer. In the present study, novel bionanocomposites containingmore » nutrient agar coated gold nano particles (N-AuNPs) coupled with 6-mercaptopurine (drug) (N-AuNPs-Mp), folic acid (ligand) (N-AuNPs-Mp-Fa) and rhodamine (dye) (N-AuNPs-Rd), a fluorescent agent, were prepared and characterized by IR, UV, TEM, Particle size analysis and in vitro stability. The toxicity and fluorescence of N-Au was studied using zebrafish embryo model. The in vitro cytotoxicity of free Mp, N-Au-Mp and N-Au-Mp-Fa against HEp-2 cells was compared and found that the amount of Mp required to achieve 50% of growth of inhibition (IC{sub 50}) was much lower in N-Au-Mp-Fa than in free Mp and N-Au-Mp.« less

6-mercaptopurine (6-MP) entrapped stealth liposomes for improvement of leukemic treatment without hepatotoxicity and nephrotoxicity.

PubMed

Umrethia, Manish; Ghosh, Pradip Kumar; Majithya, Rita; Murthy, R S R

2007-03-01

6-mercaptopurine (6-MP) is a purine analogue used in childhood leukemia. Because of the oral bioavailability of 6-MP is low and highly variable, the aim of this study was to develop a new parenteral formulation that can prolong the biological half-life of the drug, improve its therapeutic efficacy, and its associated reduce side effects. Conventional and stealth 6-MP liposomes were prepared by a thin film hydration technique followed by a high-pressure homogenization process and characterized for percent entrapment efficiency (%EE), particle size, and stability in human plasma. Pharmacokinetic, tissue distribution, and biochemical analysis were performed after intravenous (IV) administration of all formulations of 6-MP on rats. The conventional liposomes were found less stable than stealth liposomes in human plasma at 37 degrees C. Stealth liposomes exhibited high peak plasma concentration (C(max)), and long circulating capacity in blood and biological half-life. The uptake of stealth liposomes by the liver and spleen and accumulation in the kidney were significantly less than that of conventional liposomes and the free drug. Serum urea, creatinine, GOT (Glutamic Oxaloacetic Transaminase), and GPT (Glutamic Pyruvic Transaminase) increased significantly in rats given an IV injection of conventional liposomes and the free drug, but not in those administered with the same dose of stealth liposomes. Stealth liposomes may help to increase therapeutic efficacy of 6-MP and to reduce total amount of dose as well as frequency of the dose. It also may reduce the possibility of the risk of toxicity to the liver and kidney generally associated with free 6-MP.

Susceptibility to 6-MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukaemia.

PubMed

Tanaka, Yoichi; Kato, Motohiro; Hasegawa, Daisuke; Urayama, Kevin Y; Nakadate, Hisaya; Kondoh, Kensuke; Nakamura, Kozue; Koh, Katsuyoshi; Komiyama, Takako; Manabe, Atsushi

2015-10-01

Genotyping of TPMT prior to 6-mercaptopurine (6-MP) administration in acute lymphoblastic leukaemia (ALL) patients has been integrated into clinical practice in some populations of European ancestry. However, the comparable rates of 6-MP myelotoxicity, but rarity of TPMT variants, in Asians suggest that major determinants have yet to be discovered in this population. We genotyped 92 Japanese paediatric ALL patients for NUDT15 rs116855232, a 6-MP toxicity-related locus discovered in Asians. Logistic regression and survival analysis were used to evaluate its association with leucopenia, hepatotoxicity, 6-MP dose reduction, therapy interruption and event-free survival. The allele frequency of rs116855232 was 0·16, and leucopenia was more common in carriers of the T allele (odds ratio, 7·20; 95% confidence interval, 2·49-20·80; P = 2·7 × 10(-4) ). As leucopenia results in 6-MP dose reduction, we observed average doses during maintenance therapy of 40·7, 29·3 and 8·8 mg/m(2) for patients with CC, CT and TT genotypes, respectively (P < 0·001). Hepatotoxicity was observed only in CC genotype patients. Event-free survival did not significantly differ by NUDT15 genotype. rs116855232 is an important determinant of 6-MP myelotoxicity in Japanese children with ALL and may represent the most robust toxicity-related locus in Asians to date. Considerations for clinical application may be warranted. © 2015 John Wiley & Sons Ltd.

Stabilization of gold nanoparticles by 6-mercaptopurine monolayers. Effects of the solvent properties.

PubMed

Viudez, Alfonso J; Madueño, Rafael; Pineda, Teresa; Blázquez, Manuel

2006-09-14

6-Mercaptopurine-coated gold nanoparticles (6MP-AuNPs) have been prepared by modification of the nanoparticle surface with 6MP upon displacement of the protective layer of citrate anions. The modification has been studied by UV-vis and FTIR spectroscopies. A study of the stability of these 6MP-AuNPs in aqueous solutions as a function of ionic strength and pH has shown the importance of the charges on the stabilization. The protonation of N9 of the 6MP molecules brings about a sudden flocculation phenomenon. However, the flocculation is reversible upon changing the pH to values where the molecules become newly charged. Evidence of the competence between the interaction of capping solvent molecules and the attractive forces between particles is also shown in this paper.

Ethnopharmacological analysis of medicinal plants used against non-communicable diseases in Rodrigues Island, Indian Ocean.

PubMed

Samoisy, Anne Kathie; Mahomoodally, M Fawzi

2015-09-15

Rodrigues is an autonomous outer island that form part of the Republic of Mauritius and one of three islands that constitute the Mascarene archipelago in the Indian Ocean. Though herbal medicine is in common use in Rodrigues, there has been no ethnopharmacological study to document quantitatively such traditional practise particularly against non-communicable diseases (NCD) which is currently a growing major health issue on the island. The aim of the present study was to collect, analyse and document traditionally used medicinal plants (MP) from key informants and traditional medicine practitioners (TMP) in the tropical island of Rodrigues to treat and/or manage common NCD. Data was collected via face-to-face interviews with MP users (n=113) and TMP (n=9). Seven quantitative ethnopharmacological indices, namely family use value (FUV), use value (UV), informant agreement ratio (IAR), relative frequency of citation (RFC), fidelity level (FL), relative importance (RI) and ethnobotanicity index (EI) were calculated. Hundred and three plants belonging to 55 families were recorded for the treatment and/or management of 27 different NCD. Three of the MP (Terminalia bentzoë (L.) L.F, Sarcostemma cf. adontolepis Balf.f. and Clerodendrum laciniatum Balf.f.) recorded are endemic to Rodrigues and 2 (Carissa xylopicron Thouars., Phyllanthus casticum Willemet f.) endemic to the Mascarene Islands. The most solicited MP family was Asteraceae with a total of 8 species. Citrus aurantifolia (Christm.) Swingle scored the highest RFC (RFC=1.02) value. Ten plants were found to score 100% FL and the highest IAR (0.98) was observed for the disease category of certain conditions originating in the perinatal period. Arecaceae scored the highest FUV value and Ayapana triplinervis (Vahl) R.M. King et H.Rob highest UV (UV= 2.72). Given the dearth of updated information on traditional medicine of Rodrigues, this study can provide an opportunity to establish valuable primary information on the different MP used by the local people and hence can open new perspectives for further pharmacological research. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration.

PubMed

Ding, Yu-Shin; Gatley, S John; Thanos, Panayotis K; Shea, Colleen; Garza, Victor; Xu, Youwen; Carter, Pauline; King, Payton; Warner, Don; Taintor, Nicholas B; Park, Daniel J; Pyatt, Bea; Fowler, Joanna S; Volkow, Nora D

2004-09-01

Methylphenidate (MP) (Ritalin) is widely used for the treatment of attention deficit hyperactivity disorder (ADHD). It is a chiral drug, marketed as the racemic mixture of d- and l-threo enantiomers. Our previous studies (PET and microdialysis) in humans, baboons, and rats confirm the notion that pharmacological specificity of MP resides predominantly in the d-isomer. A recent report that intraperitoneally (i.p.) administered l-threo-MP displayed potent, dose-dependent inhibition of cocaine- or apomorphine-induced locomotion in rats, raises the question of whether l-threo-MP has a similar effect when given orally. It has been speculated that l-threo-MP is poorly absorbed in humans when it is given orally because of rapid presystemic metabolism. To investigate whether l-threo-MP or its metabolites can be delivered to the brain when it is given orally, and whether l-threo-MP is pharmacologically active. PET and MicroPET studies were carried out in baboons and rats using orally delivered C-11-labeled d- and l-threo-MP ([methyl-(11)C]d-threo-MP and [methyl-(11)C]l-threo-MP). In addition, we assessed the effects of i.p. l-threo-MP on spontaneous and cocaine-stimulated locomotor activity in mice. There was a higher global uptake of carbon-11 in both baboon and rat brain for oral [(11)C]l-threo-MP than for oral [(11)C]d-threo-MP. Analysis of the chemical form of radioactivity in rat brain after [(11)C]d-threo-MP indicated mainly unchanged tracer, whereas with [(11)C]l-threo-MP, it was mainly a labeled metabolite. The possibility that this labeled metabolite might be [(11)C]methanol or [(11)C]CO(2), derived from demethylation, was excluded by ex vivo studies in rats. When l-threo-MP was given i.p. to mice at a dose of 3 mg/kg, it neither stimulated locomotor activity nor inhibited the increased locomotor activity due to cocaine administration. These results suggest that, in animal models, l-threo-MP or its metabolite(s) is (are) absorbed from the gastrointestinal tract and enters the brain after oral administration, but that l-threo-MP may not be pharmacologically active. These results are pertinent to the question of whether l-threo-MP contributes to the behavioral and side effect profile of MP during treatment of ADHD. Copyright 2004 Wiley-Liss, Inc.

The impact of high-dose methotrexate on intracellular 6-mercaptopurine disposition during interval therapy of childhood acute lymphoblastic leukemia.

PubMed

Adam de Beaumais, T; Dervieux, T; Fakhoury, M; Medard, Y; Azougagh, S; Zhang, D; Yakouben, K; Jacqz-Aigrain, E

2010-09-01

Low-dose methotrexate (MTX) therapy is the cornerstone treatment of acute lymphoblastic leukemia (ALL) and may enhance the activation of 6-mercaptopurine (6-MP) to 6-thioguanine nucleotides (6-TGN). Yet, data have established that high-dose MTX (HDMTX) hampers the accumulation of 6-TGN in red blood cells (RBC) and lymphoblasts. To clarify the pharmacokinetic interactions between these two antimetabolites, we serially measured RBC 6-TGN and MTX polyglutamates (MTXPG) levels following repeated courses of HDMTX (5 g/m(2) over 24 h) with daily oral 6-MP (25 mg/m(2)) during interval therapy in 20 children with ALL. HDMTX produced a rapid reduction in RBC 6-TGN 24 h after the start of MTX, and this effect was sustained at least by the third day (median decrease -21%; P < 0.001). However, a return to pre-infusion of 6-TGN levels was observed by the time of the following HDMTX course 14 days later (P < 0.001). RBC MTX polyglutamates accumulation followed Michaelis-Menten kinetics but was not associated with the change in pre-infusion 6-TGN levels which remained stable during the interval period. HDMTX does not appear to enhance 6-MP activation to 6-TGN. Moreover, given that the deleterious effect of HDMTX on intracellular 6-MP disposition has been shown to be several folds greater in lymphoblasts than in RBC. Our data warrant additional studies elucidating the optimal MTX dose synergizing with 6-MP.

Lanreotide autogel every 6 weeks compared with Lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a Phase III Study.

PubMed

Bajetta, Emilio; Procopio, Giuseppe; Catena, Laura; Martinetti, Antonia; De Dosso, Sara; Ricci, Sergio; Lecchi, Alberto S; Boscani, Paolo F; Iacobelli, Stefano; Carteni, Giacomo; De Braud, Filippo; Loli, Paola; Tartaglia, Andreas; Bajetta, Roberto; Ferrari, Leonardo

2006-11-15

The noninferiority of a 6-week dosing schedule of lanreotide Autogel (Lan ATG) at a dose of 120 mg compared with a 3-week dosing schedule of lanreotide microparticles (Lan MP) at a dose of 60 mg was investigated in patients with neuroendocrine tumors (NET). Patients who had sporadic, well differentiated NET with a low grade of malignancy were recruited for this open-label, Phase III, multicenter trial. Patients were randomized to receive either 3 deep subcutaneous injections of Lan ATG (120 mg, every 6 weeks) or 6 intramuscular injections of Lan MP (60 mg, every 3 weeks). Tumor markers, tumor size, and symptoms were assessed between baseline and Week 18. Success was classified as a response that ranged from disappearance to an increase <25% in tumor marker, tumor size, or symptom frequency. Sixty patients were randomized, and 46 patients completed the study. Both for tumor markers and for tumor size, Lan ATG was not inferior to Lan MP (55% and 59% of patients responded on tumor markers, respectively; 68% and 66% of patients responded on tumor size, respectively). There were too few symptomatic patients to compare carcinoid symptoms. Both treatments were tolerated well, and no safety concerns were identified. Lan ATG at a dose of 120 mg every 6 weeks was as effective for controlling NET as Lan MP at a dose of 60 mg every 3 weeks.

Safety and immunogenicity of a modified process hepatitis B vaccine in healthy neonates.

PubMed

Minervini, Gianmaria; McCarson, Barbara J; Reisinger, Keith S; Martin, Jason C; Stek, Jon E; Atkins, Barbara M; Nadig, Karin B; Liska, Vladimir; Schödel, Florian P; Bhuyan, Prakash K

2012-02-14

A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants. Healthy 1-10-day-old neonates (N=566) received 3 intramuscular doses (5μg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1-14. Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7mIU/mL for the mpHBV group and 670.1mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs. The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority. Copyright © 2012 Elsevier Ltd. All rights reserved.

Methyl parathion detection in vegetables and fruits using silver@graphene nanoribbons nanocomposite modified screen printed electrode

NASA Astrophysics Data System (ADS)

Govindasamy, Mani; Mani, Veerappan; Chen, Shen-Ming; Chen, Tse-Wei; Sundramoorthy, Ashok Kumar

2017-04-01

We have developed a sensitive electrochemical sensor for Organophosphorus pesticide methyl parathion (MP) using silver particles supported graphene nanoribbons (Ag@GNRs). The Ag@GNRs nanocomposite was prepared through facile wet chemical strategy and characterized by TEM, EDX, XRD, Raman, UV-visible, electrochemical and impedance spectroscopies. The Ag@GNRs film modified screen printed carbon electrode (SPCE) delivers excellent electrocatalytic ability to the reduction of MP. The Ag@GNRs/SPCE detects sub-nanomolar concentrations of MP with excellent selectivity. The synergic effects between special electrocatalytic ability of Ag and excellent physicochemical properties of GNRs (large surface area, high conductivity, high area-normalized edge-plane structures and abundant catalytic sites) make the composite highly suitable for MP sensing. Most importantly, the method is successfully demonstrated in vegetables and fruits which revealed its potential real-time applicability in food analysis.

Daily intake of Mucuna pruriens in advanced Parkinson's disease: A 16-week, noninferiority, randomized, crossover, pilot study.

PubMed

Cilia, Roberto; Laguna, Janeth; Cassani, Erica; Cereda, Emanuele; Raspini, Benedetta; Barichella, Michela; Pezzoli, Gianni

2018-04-01

Thousands of individuals with Parkinson's disease (PD) in low-income countries have limited access to marketed levodopa preparations. Mucuna pruriens (MP), a levodopa-containing leguminous plant growing in tropical areas, may be a sustainable alternative therapy for indigent patients. Single-dose intake of MP proved noninferior to marketed levodopa preparations. Fourteen PD patients with motor fluctuations and dyskinesias received MP powder (obtained from roasted seeds) and marketed levodopa/carbidopa (LD/CD) in a randomized order and crossover design over a 16-week period. Efficacy measures were changes in quality of life, motor and non-motor symptoms, and time with good mobility without troublesome dyskinesias. Safety measures included tolerability, frequency of adverse events, changes in laboratory indices and electrocardiogram. Daily intake of MP was associated with a variable clinical response, especially in terms of tolerability. Seven patients (50%) discontinued MP prematurely due to either gastrointestinal side-effects (n = 4) or progressive worsening of motor performance (n = 3), while nobody discontinued during the LD/CD phase. In those who tolerated MP, clinical response to MP was similar to LD/CD on all efficacy outcome measures. Patients who dropped out entered a study extension using MP supernatant water (median[IQR], 16 [7-20] weeks), which was well tolerated. The overall benefit provided by MP on the clinical outcome was limited by tolerability issues, as one could expect by the relatively rapid switch from LD/CD to levodopa alone in advanced PD. Larger parallel-group studies are needed to identify appropriate MP formulation (e.g. supernatant water), titration scheme and maintenance dose to minimize side-effects in the long-term. CLINICAL TRIALS. NCT02680977. Copyright © 2018 Elsevier Ltd. All rights reserved.

Alkylation of 6-mercaptopurine (6-MP) with N-alkyl-N-alkoxycarbonylaminomethyl chlorides: S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP prodrug structure effect on the dermal delivery of 6-MP.

PubMed

Siver, K G; Sloan, K B

1990-01-01

The S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP (6-CARB-6-MP) prodrugs 5-20 were synthesized from the reaction of 6-MP with N-alkyl-N-alkyoxycarbonylaminomethyl chlorides (4) in dimethyl sulfoxide in overall yields of 5-62%, depending on the N-alkyl and the alkoxy groups involved. The derivatives were fully characterized by spectral and microanalyses. The assignment of the substitution pattern as S6-alkyl was based on comparisons of the UV, 1H NMR and 13C NMR spectra with model compounds. A S6, 9-bis-alkyl derivative was obtained from the reaction of 2 equivalents of 4 with 6-MP but the product was unstable and decomposed on standing to a 9-alkyl derivative. The 6-CARB-6-MP prodrugs reverted to 6-MP in water by an SN1-type mechanism involving unimolecular charge separation in the transition state of the rate determining step. There was no effect of dermal enzymes on the rate of hydrolysis. The solubilities in isopropyl myristate (IPM) for all of the 6-CARB-6-MP prodrugs were significantly greater than the solubility of 6-MP in IPM but only one prodrug (5) was apparently even as soluble as 6-MP in water. Selected 6-CARB-6-MP prodrugs were examined in diffusion cell experiments. Only the N-methyl-N-methoxycarbonyl derivative 5 gave a steady-state rate of delivery of 6-MP from IPM that was significantly greater than the steady-state rate of delivery of 6-MP from 6-MP in IPM. All the other derivatives gave steady-state rates of delivery of 6-MP from IPM that were either not significantly different, or were significantly lower than the rate obtained from 6-MP in IPM. In all cases, the effect of the 6-CARB-6-MP:IPM suspensions on the permeability of the skin, as determined by the second application flux of theophylline:propylene glycol, was of the same magnitude as the effect of IPM alone.

Comparison of the effects of 2 doses of methylprednisolone on pain, swelling, and trismus after third molar surgery.

PubMed

UStün, Yakup; Erdogan, Ozgür; Esen, Emin; Karsli, Ebru Deniz

2003-11-01

The aim of this study was to compare the effects of intravenous administration of 1.5 mg/kg and 3 mg/kg of methylprednisolone sodium succinate (MP) on pain, swelling, and trismus after third molar surgery. Twenty-six healthy patients with symmetrically impacted mandibular third molars were included in this double-blind, cross-over study. Either 1.5 mg/kg or 3 mg/kg of MP was administered by intravenous route one hour prior to the first operation. At the second operation the other dose was applied. Trismus was determined by measuring maximum interincisal opening and facial swelling was evaluated using a tape measuring method. Pain was determined using visual analogue scale and recording the number of pain pills taken. There was no statistically significant difference in trismus, facial swelling, and pain between the two groups. No clinical benefit of the higher dose of MP was demonstrated.

Red blood cell hypoxanthine phosphoribosyltransferase activity measured using 6-mercaptopurine as a substrate: a population study in children with acute lymphoblastic leukaemia.

PubMed Central

Lennard, L; Hale, J P; Lilleyman, J S

1993-01-01

1. 6-Mercaptopurine (6-MP) is used in the continuing chemotherapy of childhood acute lymphoblastic leukaemia. The formation of red blood cell (RBC) 6-thioguanine nucleotide (6-TGN) active metabolites, not the dose of 6-MP, is related to cytotoxicity and prognosis. But there is an apparent sex difference in 6-MP metabolism. Boys require more 6-MP than girls to produce the same range of 6-TGN concentrations. Given the same dose, they experience fewer dose reductions because of cytotoxicity, and have a higher relapse rate. 2. The enzyme hypoxanthine phosphoribosyltransferase (HPRT) catalyses the initial activation step in the metabolism of 6-MP to 6-TGNs, a step that requires endogenous phosphoribosyl pyrophosphate (PRPP) as a cosubstrate. Both HPRT and the enzyme responsible for the formation of PRPP are X-linked. 3. RBC HPRT activity was measured in two populations, 86 control children and 63 children with acute lymphoblastic leukaemia. 6-MP was used as the substrate and the formation of the nucleotide product, 6-thioinosinic acid (TIA) was measured. RBC 6-TGN concentrations were measured in the leukaemic children at a standard dose of 6-MP. 4. There was a 1.3 to 1.7 fold range in HPRT activity when measured under optimal conditions. The leukaemic children had significantly higher HPRT activities than the controls (median difference 4.2 micromol TIA ml(-1) RBCs h(-1), 95% C.I. 3.7 to 4.7, P < 0.0001). In the leukaemic children HPRT activity (range 20.4 to 26.6 micromol TIA ml(-1) RBCs h(-1), median 23.6) was not related to the production of 6-TGNs (range 60 to 1,024 pmol 8 x 10(-8) RBCs, median 323). RBC HPRT was present at a high activity even in those children with low 6-TGN concentrations. 5. When HPRT is measured under optimal conditions it does not appear to be the metabolic step responsible for the observed sex difference in 6-MP metabolism. This may be because RBC HPRT activity is not representative of other tissues but it could equally be because other sex-linked factors are influencing substrate availability. PMID:12959304

Physiologically based pharmacokinetic modelling of methotrexate and 6-mercaptopurine in adults and children. Part 2: 6-mercaptopurine and its interaction with methotrexate.

PubMed

Ogungbenro, Kayode; Aarons, Leon

2014-04-01

6-mercaptopurine (6-MP) is a purine antimetabolite and prodrug that undergoes extensive intracellular metabolism to produce thionucleotides, active metabolites which have cytotoxic and immunosuppressive properties. Combination therapies involving 6-MP and methotrexate have shown remarkable results in the cure of childhood acute lymphoblastic leukaemia (ALL) in the last 30 years. 6-MP undergoes very extensive intestinal and hepatic metabolism following oral dosing due to the activity of xanthine oxidase leading to very low and highly variable bioavailability and methotrexate has been demonstrated as an inhibitor of xanthine oxidase. Despite the success recorded in the use of 6-MP in ALL, there is still lack of effect and life threatening toxicity in some patients due to variability in the pharmacokinetics of 6-MP. Also, dose adjustment during treatment is still based on toxicity. The aim of the current work was to develop a mechanistic model that can be used to simulate trial outcomes and help to improve dose individualisation and dosage regimen optimisation. A physiological based pharmacokinetic model was proposed for 6-MP, this model has compartments for stomach, gut lumen, enterocyte, gut tissue, spleen, liver vascular, liver tissue, kidney vascular, kidney tissue, skin, bone marrow, thymus, muscle, rest of body and red blood cells. The model was based on the assumption of the same elimination pathways in adults and children. Parameters of the model include physiological parameters and drug-specific parameter which were obtained from the literature or estimated using plasma and red blood cell concentration data. Age-dependent changes in parameters were implemented for scaling and variability was also introduced on the parameters for prediction. Inhibition of 6-MP first-pass effect by methotrexate was implemented to predict observed clinical interaction between the two drugs. The model was developed successfully and plasma and red blood cell concentrations were adequately predicted both in terms of mean prediction and variability. The predicted interaction between 6-MP and methotrexate was slightly lower than the reported clinical interaction between the two drugs. The model can be used to predict plasma and tissue concentration in adults and children following oral and intravenous dosing and may ultimately help to improve treatment outcome in childhood ALL patients.

Methylprednisolone does not inhibit the release of growth hormone after intravenous injection of a novel growth hormone secretagogue in rats.

PubMed

Malmlöf, K; Johansen, P B; Haahr, P M; Wilken, M; Oxlund, H

1999-12-01

The present study was undertaken to study the growth hormone-releasing properties and growth-promoting effect of a GH secretagogue ipamorelin (IPA) in rats given the synthetic glucocorticoid methylprednisolone (MP). In a first experiment, rats received either saline or MP (5.0 mg/kg) for 8 days. Treatment with MP significantly (P< 0.001) decreased body weight gain, but the acute response to either IPA or growth hormone releasing hormone (GHRH) in terms of plasma GH was not changed. In a second experiment, venous catheters were surgically implanted. On the next day, rats were randomly allocated to receive saline alone, MP alone (5.0 mg/kg) or MP plus IPA in doses of 0.4 or 1.6 mg/kg/day for 10 days. IPA was administered intravenously four times a day.MP treatment significantly (P< 0.05) retarded recovery from surgery in terms of body weight. Thus, saline treated animals lost 4.0 +/- 3.5 g over the entire experimental period, whereas animals receiving MP lost 13. 6 +/- 2.9 g. When IPA was given together with MP, losses in body weight were significantly (P< 0.05) reduced to 2.3 +/- 2.0 and 1.6 +/- 2.0 g in animals given the high and low dose of IPA, respectively. In parallel with this IGF-I levels increased. In conclusion, this work shows that MP does not disrupt the response of the GH-IGF-I axis to an exogenous stimulus like IPA, and repeated stimulation leads to increases in IGF-I and of body weight gain. Copyright 1999 Harcourt Publishers Ltd.

Renal damage induced by the pesticide methyl parathion in male Wistar rats.

PubMed

Fuentes-Delgado, Victor Hugo; Martínez-Saldaña, María Consolación; Rodríguez-Vázquez, María Luisa; Reyes-Romero, Miguel Arturo; Reyes-Sánchez, José Luis; Jaramillo-Juárez, Fernando

2018-01-01

Little information is apparently available regarding the nephrotoxic effects induced by pesticides. The aim of this study was to examine the influence of low doses of methyl parathion (MP) on the structure and function of the kidney of male Wistar rats. A corn oil (vehicle) was administered to control rats, whereas treated rats received MP at 0.56 mg/kg orally (1/25 of LD 50 ), every third day, for 8 weeks. At the end of each week following MP exposure, creatinine and glucose levels were measured in plasma, while glucose, inorganic phosphate, total proteins, albumin, and activity of γ-glutamyltranspeptidase (GGT) were determined in urine. Kidney histological study was also performed. Compared with control rats, MP significantly increased plasma glucose and creatinine levels accompanied by decreased urinary flow rate and elevated urinary excretion rates of glucose, phosphate, and albumin. Further, the activity of GGT in urine was increased significantly. The proximal cells exhibited cytoplasmic vacuolization, positive periodic acid Schiff inclusions, and brush border edge loss after 2 or 4 weeks following MP treatment. Finally, renal cortex samples were obtained at 2, 4, 6, and 8 weeks of MP treatment, and the concentrations of reduced glutathione (GSH) and glutathione peroxidase (GPx) activity were measured. The mRNA expression levels of BAX and tumor necrosis factor-α (TNF-α) were also determined (RT-PCR). MP significantly decreased renal GSH levels, increased GPx activity, as well as downregulated the mRNA expression of TNF-α and BAX. Densitometry analysis showed a significant reduction in TNF-α and BAX mRNA expression levels at 2 and 4 weeks following MP treatment. Low doses of MP produced structural and functional damage to the proximal tubules of male rat kidney.

Quantitation of intracellular metabolites of [35S]-6-mercaptopurine in L5178Y cells grown in time-course incubates.

PubMed

Breter, H J; Zahn, R K

1979-09-01

6-Mercaptopurine (6MP) metabolism was quantitatively determined in L5178Y murine lymphoma. Cells grown in time-course incubates with [35S]-6MP were extracted with cold perchloric acid, and the buffered extracts were subjected to high-performance liquid cation-exchange chromatography prior to and after hydrolysis with alkaline phosphatase. Free sulfate, 6-thiouric acid, 6-thioxanthosine, 6-thioguanosine, 6-thioinosine, free 6MP, and 6-methylthioinosine were separated from each other; identified in the radiochromatograms by elution volume, UV spectroscopic data, and enzymatic peak-shifting analyses with purine nucleoside phosphorylase; and quantitatively determined by means of 35S radioactivity. Gross intracellular 35S concentrations remained constant at 5 x 10(-5) M after 1 hr of incubation. 6MP metabolism in L5178Y cells was distinguished into an early phase (to 1 hr of incubation) in which 6MP was predominantly catabolized to 6-thiouric acid and free sulfate, into an intermediate phase (to 8 hr) in which substantial amounts of free 6MP and of ribonucleotides of 6-thioxanthosine and 6-thioguanosine were present while the concentrations of nonnucleotide oxidation products sharply decreased, and into a late phase (to 24 hr) in which the ribonucleotides of 6MP, of 6-thioguanosine and, in particular, of 6-methylthioinosine were the most abundant metabolites.

Ultra-low dose quantitative CT myocardial perfusion imaging with sparse-view dynamic acquisition and image reconstruction: A feasibility study.

PubMed

Enjilela, Esmaeil; Lee, Ting-Yim; Hsieh, Jiang; Wisenberg, Gerald; Teefy, Patrick; Yadegari, Andrew; Bagur, Rodrigo; Islam, Ali; Branch, Kelley; So, Aaron

2018-03-01

We implemented and validated a compressed sensing (CS) based algorithm for reconstructing dynamic contrast-enhanced (DCE) CT images of the heart from sparsely sampled X-ray projections. DCE CT imaging of the heart was performed on five normal and ischemic pigs after contrast injection. DCE images were reconstructed with filtered backprojection (FBP) and CS from all projections (984-view) and 1/3 of all projections (328-view), and with CS from 1/4 of all projections (246-view). Myocardial perfusion (MP) measurements with each protocol were compared to those with the reference 984-view FBP protocol. Both the 984-view CS and 328-view CS protocols were in good agreements with the reference protocol. The Pearson correlation coefficients of 984-view CS and 328-view CS determined from linear regression analyses were 0.98 and 0.99 respectively. The corresponding mean biases of MP measurement determined from Bland-Altman analyses were 2.7 and 1.2ml/min/100g. When only 328 projections were used for image reconstruction, CS was more accurate than FBP for MP measurement with respect to 984-view FBP. However, CS failed to generate MP maps comparable to those with 984-view FBP when only 246 projections were used for image reconstruction. DCE heart images reconstructed from one-third of a full projection set with CS were minimally affected by aliasing artifacts, leading to accurate MP measurements with the effective dose reduced to just 33% of conventional full-view FBP method. The proposed CS sparse-view image reconstruction method could facilitate the implementation of sparse-view dynamic acquisition for ultra-low dose CT MP imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of 6-mercaptopurine treatment after azathioprine hypersensitivity in inflammatory bowel disease

PubMed Central

Nagy, Ferenc; Molnár, Tamás; Szepes, Zoltán; Farkas, Klaudia; Nyári, Tibor; Lonovics, János

2008-01-01

AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indices (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA-intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients. PMID:18666323

Metabolomic Analysis of the Secretome of Human Embryonic Stem Cells Following Methyl Parathion and Methyl Paraoxon Exposure, Phase 1: Initial Nontargeted LC-MS

DTIC Science & Technology

2014-01-01

and threonine metabolism 6 40 0.006188 0.10 MP H hsa00260 Glycine, serine and threonine metabolism 3 40 0.010283 0.07 MP H hsa00280 Valine, leucine...hsa00770 Pantothenate and CoA biosynthesis 5 24 0.005066 0.07 MP M hsa04142 Lysosome 2 4 0.002426 0.10 MPO M hsa04930 Type II diabetes mellitus 3 5...of MPO and increased after exposure to all three dose levels of MP. The glycine, serine and threonine metabolism pathway is of interest because

New DNA-binding radioprotectors

NASA Astrophysics Data System (ADS)

Martin, Roger

The normal tissue damage associated with cancer radiotherapy has motivated the development at Peter Mac of a new class of DNA-binding radioprotecting drugs that could be applied top-ically to normal tissues at risk. Methylproamine (MP), the lead compound, reduces radiation induced cell kill at low concentrations. For example, experiments comparing the clonogenic survival of transformed human keratinocytes treated with 30 micromolar MP before and dur-ing various doses of ionising radiation, with the radiation dose response for untreated cells, indicate a dose reduction factor (DRF) of 2. Similar survival curve experiments using various concentrations of MP, with parallel measurements of uptake of MP into cell nuclei, have en-abled the relationship between drug uptake and extent of radioprotection to be established. Radioprotection has also been demonstrated after systemic administration to mice, for three different endpoints, namely lung, jejunum and bone marrow (survival at 30 days post-TBI). The results of pulse radiolysis studies indicated that the drugs act by reduction of transient radiation-induced oxidative species on DNA. This hypothesis was substantiated by the results of experiments in which MP radioprotection of radiation-induced DNA double-strand breaks, assessed as -H2AX foci, in the human keratinocyte cell line. For both endpoints, the extent of radioprotection increased with MP concentration up to a maximal value. These results are consistent with the hypothesis that radioprotection by MP is mediated by attenuation of the extent of initial DNA damage. However, although MP is a potent radioprotector, it becomes cytotoxic at higher concentrations. This limitation has been addressed in an extensive program of lead optimisation and some promising analogues have emerged from which the next lead will be selected. Given the clinical potential of topical radioprotection, the new analogues are being assessed in terms of delivery to mouse oral mucosa. This is facilitated by the fact that, like the parent minor groove-binding drug Hoechst 33342, DNA-bound MP (and its analogues) are fluorescent, enabling quantitative assessment of delivery of topically applied drug to basal cells in the mouse oral mucosa. Comparison with the data from prior in vitro experiments described above, indicate that topical delivery is sufficient to confer radioprotection. Although the primary motivation for this project relates to Radiation Oncology, the new ra-dioprotectors obviously have more general potential.

Reconstruction of the erythemal UV radiation data in Novi Sad (Serbia) using the NEOPLANTA parametric model

NASA Astrophysics Data System (ADS)

Malinovic-Milicevic, S.; Mihailovic, D. T.; Radovanovic, M. M.

2015-07-01

This paper focuses on the development and application of a technique for filling the daily erythemal UV dose data gaps and the reconstruction of the past daily erythemal UV doses in Novi Sad, Serbia. The technique implies developing the empirical equation for estimation of daily erythemal UV doses by means of relative daily sunshine duration under all sky conditions. A good agreement was found between modeled and measured values of erythemal UV doses. This technique was used for filling the short gaps in the erythemal UV dose measurement series (2003-2009) as well as for the reconstruction of the past time-series values (1981-2002). Statistically significant positive erythemal UV dose trend of 6.9 J m-2 per year was found during the period 1981-2009. In relation to the reference period 1981-1989, an increase in the erythemal UV dose of 6.92 % is visible in the period 1990-1999 and the increase of 9.67 % can be seen in the period 2000-2009. The strongest increase in erythemal UV doses has been found for winter and spring seasons.

ENHANCEMENT OF ANTIBODY SYNTHESIS BY 6-MERCAPTOPURINE

PubMed Central

Chanmougan, Devendrathan; Schwartz, Robert S.

1966-01-01

The administration of 6-MP to rabbits led to either suppression or enhancement of antibody production, depending on when the drug was given in relation to the antigenic challenge. Maximum enhancement of antibody synthesis was found when a small dose of BGG was administered 5 days after the last dose of a 1 wk course of 6-MP. There were no indications that the macrophage system or immunological memory was affected in animals with augmented antibody synthesis. It was proposed that enhancement of antibody production by 6-MP was due to nucleic acids released from cells killed or injured by the drug. It was suggested that lymphocytes incorporating these nucleic acids were transformed into specialized cells capable of direct and immediate stimulation by antigen and lacking immunological memory (hemocytoblasts). A relatively small dose of antigen was apparently capable of stimulating all the hemocytoblasts representing a given clone) with the result that large amounts of antibody rapidly appeared in the serum. PMID:4162484

Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation.

PubMed

Kingery, W S; Guo, T; Agashe, G S; Davies, M F; Clark, J D; Maze, M

2001-09-21

Sciatic nerve section in rats evokes chronic limb edema, pain behavior, and hindpaw hyperalgesia, a syndrome resembling the complex regional pain syndrome type II (CRPS II or causalgia) in man. Glucocorticoids such as methylprednisolone (MP) have been used as analgesic and anti-edematous agents in patients suffering from CRPS, and interestingly these therapeutic effects appear to persist in some patients after stopping the medication. Similar to the CRPS clinical response to glucocorticoids, we now demonstrate that chronic hindpaw edema in the sciatic transection CRPS model is reversed by a continuous infusion of MP (3 mg/kg/day over 21 days), and this anti-edematous effect persists for at least 1 week after discontinuing MP. Furthermore, there is a chronic increase in spontaneous protein extravasation in the hindpaw skin of rats after sciatic transection, similar to the increased protein extravasation observed in the edematous hands of CRPS patients. A 2-week infusion of MP (3 mg/kg/day) reduced spontaneous protein extravasation in the hindpaw skin by 80%. We postulated that increased spontaneous neurogenic extravasation resulted in development of limb edema in both the animal model and the CRPS patient, and that the anti-edematous effects of MP are due to an inhibition of spontaneous extravasation. Additional experiments examined the inhibitory effects of MP infusion on electrically-evoked neurogenic extravasation in the hindpaw skin of normal rats. MP inhibition was dose- and time-dependent, with an ED(50) of 1.2 mg/kg/day for a 14-day continuous infusion of MP, and a maximum inhibitory effect requiring 17 days of MP infusion (3 mg/kg/day). MP (3 mg/kg/day for 14 days) also blocked both capsaicin- and SP-evoked neurogenic extravasation, indicating a post-junctional inhibitory effect. Our interpretation is that increased spontaneous neurogenic extravasation in this CRPS model contributed to the development and maintenance of hindpaw edema, and that chronic MP administration dose- and time-dependently blocked neurogenic extravasation at a post-junctional level, thus reversing spontaneous extravasation and limb edema in this model.

[The determination of the discrepancy between the mathematically ascertained and experimentally provable efficiency of UV facilities for water disinfection].

PubMed

Leuker, G; Hingst, V

1992-10-01

Using three UV-plants of different technical designs for water disinfection, we studied the conformity between experimental germ reduction using standard test organisms and calculated UV-doses under various water flow conditions. Taking into consideration the style of construction of the UV-plants, the irradiation area and the layer thickness were used as constant parameters for dose calculations. This was also employed for the irradiation intensity, since the experiments were performed for a relatively short period compared of the life span of the UV-irradiators. Both exposure time and water transmission were employed as variable parameters in the dose calculations and experimental procedures respectively. The calculated UV-dose and experimentally obtained germ reduction values were comparatively the same for two of the three UV-plants studied. However, no correlation was observed between the reduction of E. coli and the corresponding calculated UV-dose values. Therefore, the calculated UV-dose values for any given UV-plant should be considered to be relative and by no means absolute values. We are of the opinion that within a certain range of water flow rate and transmission, antimicrobial effectiveness of different UV-plants should be demonstrated independent of dose values, technical and other construction characteristics. The applicability of the UV-plants studied is discussed.

Enhanced UV-B radiation during pupal stage reduce body mass and fat content, while increasing deformities, mortality and cell death in female adults of solitary bee Osmia bicornis.

PubMed

Wasielewski, Oskar; Wojciechowicz, Tatiana; Giejdasz, Karol; Krishnan, Natraj

2015-08-01

The effects of enhanced UV-B radiation on the oogenesis and morpho-anatomical characteristics of the European solitary red mason bee Osmia bicornis L. (Hymenoptera: Megachilidae) were tested under laboratory conditions. Cocooned females in the pupal stage were exposed directly to different doses (0, 9.24, 12.32, and 24.64 kJ/m(2) /d) of artificial UV-B. Our experiments revealed that enhanced UV-B radiation can reduce body mass and fat body content, cause deformities and increase mortality. Following UV exposure at all 3 different doses, the body mass of bees was all significantly reduced compared to the control, with the highest UV dose causing the largest reduction. Similarly, following UV-B radiation, in treated groups the fat body index decreased and the fat body index was the lowest in the group receiving the highest dose of UV radiation. Mortality and morphological deformities, between untreated and exposed females varied considerably and increased with the dose of UV-B radiation. Morphological deformities were mainly manifested in the wings and mouthparts, and occurred more frequently with an increased dose of UV. Cell death was quantified by the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (DNA fragmentation) during early stages of oogenesis of O. bicornis females. The bees, after UV-B exposure exhibited more germarium cells with fragmented DNA. The TUNEL test indicated that in germarium, low doses of UV-B poorly induced the cell death during early development. However, exposure to moderate UV-B dose increased programmed cell death. In females treated with the highest dose of UV-B the vast majority of germarium cells were TUNEL-positive. © 2014 Institute of Zoology, Chinese Academy of Sciences.

Methylprednisolone liver toxicity: A new case and a French regional pharmacovigilance survey.

PubMed

Dumortier, Jérôme; Cottin, Judith; Lavie, Caroline; Guillaud, Olivier; Hervieu, Valérie; Chambon-Augoyard, Christine; Scoazec, Jean-Yves; Vukusic, Sandra; Vial, Thierry

2017-09-01

Reported hepatotoxicity induced by corticosteroids is very rare, and the diagnosis is highly challenging in the context of auto-immune disease. We report here a case of high-dose methylprednisolone (MP)-induced acute hepatitis confirmed by liver histology in a patient with multiple sclerosis (MS) and a case series (n=4) notified to the French Pharmacovigilance center of Lyon. In all 5 cases, other common causes of hepatitis were excluded. The causal relationship with MP pulse therapy was supported by the fact that MP was the only culprit drug. In addition, 3 of these 5 patients underwent unintended single or multiple positive MP rechallenge. Our 5 patients scored a RUCAM score from 6 (probable) to 10 (highly probable). MP-induced liver injury is probably very rare, since only less than 30 cases have been reported in the literature. Nevertheless, our cases strongly illustrates that many cases could have been unrecognized; final diagnosis in 3 of 5 of our patients was made after the second or third episode of acute hepatitis. In conclusion, these cases we report here strongly illustrates that high-dose MP-induced liver injury can occur in patients treated for MS or auto-immune disorder. Unintended re-challenge can confirm the diagnosis and can help to distinguish it from autoimmune hepatitis. Performing liver function tests routinely both before and after MP administration would be beneficial, as the timely recognition of this complication and early drug withdrawal may prevent progression of severe necrosis hepatic injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study).

PubMed

Fritsch, K; Kasenda, B; Schorb, E; Hau, P; Bloehdorn, J; Möhle, R; Löw, S; Binder, M; Atta, J; Keller, U; Wolf, H-H; Krause, S W; Heß, G; Naumann, R; Sasse, S; Hirt, C; Lamprecht, M; Martens, U; Morgner, A; Panse, J; Frickhofen, N; Röth, A; Hader, C; Deckert, M; Fricker, H; Ihorst, G; Finke, J; Illerhaus, G

2017-04-01

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m 2 , days 1, 15, 29), high-dose methotrexate (3 g/m 2 days 2, 16, 30), procarbazine (60 mg/m 2 days 2-11) and lomustine (110 mg/m 2 , day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.

The excited-state decay of 1-methyl-2(1H)-pyrimidinone is an activated process.

PubMed

Ryseck, Gerald; Schmierer, Thomas; Haiser, Karin; Schreier, Wolfgang; Zinth, Wolfgang; Gilch, Peter

2011-07-11

The photophysics of 1-methyl-2(1H)-pyrimidinone (1MP) dissolved in water is investigated by steady-state and time-resolved fluorescence, UV/Vis absorption, and IR spectroscopy. In the experiments, excitation light is tuned to the lowest-energy absorption band of 1MP peaking at 302 nm. At room temperature (291 K) its fluorescence lifetime amounts to 450 ps. With increasing temperature this lifetime decreases and equals 160 ps at 338 K. Internal conversion (IC) repopulating the ground state and intersystem crossing (ISC) to a triplet state are the dominant decay channels of the excited singlet state. At room temperature both channels contribute equally to the decay, that is, the quantum yields of IC and ISC are both approximately 0.5. The temperature dependence of UV/Vis transient absorption signals shows that the activation energy of the IC process (2140 cm(-1)) is higher than that of the ISC process (640 cm(-1)). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus.

PubMed

Mathian, Alexis; Jouenne, Romain; Chader, Driss; Cohen-Aubart, Fleur; Haroche, Julien; Fadlallah, Jehane; Claër, Laetitia; Musset, Lucile; Gorochov, Guy; Amoura, Zahir; Miyara, Makoto

2015-01-01

A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE. We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA- cells; and (3) non-suppressive FoxP3lowCD45RA- cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score. Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53-8.43) at day 0 to 2.80% (0.83-14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50-12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02-20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20-17.70) at day 0 to 4.74% (1.03-9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2. IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE.

Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

PubMed Central

Chader, Driss; Cohen-Aubart, Fleur; Haroche, Julien; Fadlallah, Jehane; Claër, Laetitia; Musset, Lucile; Gorochov, Guy; Amoura, Zahir; Miyara, Makoto

2015-01-01

Background/Purpose A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE. Methods We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score. Results Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2. Conclusion IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE. PMID:26629828

Non-Invasive in vivo Mapping and Long-Term Monitoring of Magnetic Nanoparticles in Different Organs of Animals

NASA Astrophysics Data System (ADS)

Nikitin, Maxim; Yuriev, Mikhail; Brusentsov, Nikolai; Vetoshko, Petr; Nikitin, Petr

2010-12-01

Quantitative detection of magnetic nanoparticles (MP) in vivo is very important for various biomedical applications. Our original detection method based on non-linear MP magnetization has been modified for non-invasive in vivo mapping of the MP distribution among different organs of rats. A novel highly sensitive room-temperature device equipped with an external probe has been designed and tested for quantification of MP within 20-mm depth from the animal skin. Results obtained by external in vivo scanning of rats by the probe and ex vivo MP quantification in different organs of rats well correlated. The method allows long-term in vivo study of MP evolution, clearance and redistribution among different organs of the animal. Experiments showed that dynamics in vivo strongly depend on MP characteristics (size, material, coatings, etc.), site of injection and dose. The developed detection method combined with the magnetic nanolabels can substitute the radioactive labeling in many applications.

Determination of 6-mercaptopurine and azathioprine in plasma by high-performance liquid chromatography.

PubMed

Ding, T L; Benet, L Z

1979-07-21

Using 1-ml plasma samples, levels of 6-mercaptopurine (6MP) as low as 5 ng/ml and azathioprine (AZA) as low as 40 ng/ml can be detected using a high-performance liquid chromatography reversed-phase column procedure following extraction. Both compounds were stable in frozen plasma for seven weeks. AZA stability in blood was temperature dependent; the half-lives of AZA breakdown to 6MP at 37 degrees were 28 and 46 min in blood drawn from two rhesus monkeys. Plasma levels of 6MP were measured in a rhesus monkey following 6MP (1.47 mg/kg) and AZA (3 mg/kg) intravenous administration. 6MP levels were also measured in three renal transplant patients on daily 50- and 100-mg AZA doses. Peak levels (45-75 ng/ml) were reached within an hour and 6MP levels were detected for up to 7 h.

Effects of the hydroethanolic extract of Mucuna pruriens (L.) DC (Fabaceae) on haematological profile in normal and haloperidol treated rats.

PubMed

Akindele, Abidemi J; Busayo, Fadeyibi I

2011-01-01

Mucuna pruriens (L.) DC (Fabaceae) is a climbing plant claimed in traditional medicine to possess anti-anaemic effect. The study is to investigate the effects of the hydroethanolic extract of M. pruriens (MP) on haematological profile in normal and haloperidol treated rats. MP was administered p.o. at doses of 50, 100, 200, and 400 mg/kg to groups of rats daily for 28 days. Control animals received distilled water. Rats were sacrificed on the 28th day and blood samples collected for evaluation of haematological parameters and serum iron. Another set of animals received MP p.o. at same doses but along with haloperidol (0.2 mg/kg, i.p.) daily for 4 days. Three other groups of rats received distilled water, haloperidol, and MP at 400 mg/kg alone. Haematological parameters and serum iron were determined. Extract iron content, phytochemical analysis and acute toxicity studies were also carried out. MP administered to normal rats for 28 days significantly (p < 0.05) reduced the number of platelets and proportion of neutrophils. In haloperidol treated rats, MP significantly reversed the reduction in mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) values and increased the red blood cell (RBC) count and packed cell volume (PCV). MP also caused significant reduction in the number of platelets and proportion of neutrophils. Administered alone, MP caused a significant increase in the concentration of haemoglobin. The iron content of MP was found to be 61.20 mg/100 g and it was found to contain alkaloids, cardiac glycosides, saponins and tannins. Given up to 10 g/kg p.o., no deaths and visible signs of toxicity were observed while the LD50 for the i.p. route was estimated to be 1509.46 mg/kg. The findings in the study suggest that the hydroethanolic extract of Mucuna pruriens possibly possess beneficial effects in anaemic conditions especially associated with iron deficiency.

Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

PubMed Central

Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

2015-01-01

6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit.

PubMed

Stamenić, Tamara Timić; Poe, Michael M; Rehman, Sabah; Santrač, Anja; Divović, Branka; Scholze, Petra; Ernst, Margot; Cook, James M; Savić, Miroslav M

2016-11-15

We have synthesized and characterized MP-III-022 ((R)-8-ethynyl-6-(2-fluorophenyl)-N,4-dimethyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy-selective positive allosteric modulator of GABA A receptors containing the α5 subunit (α5GABA A Rs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 1-10mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of α5βγ2 GABA A receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2'F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200mg/kg), but at the price of activating non-α5 GABA A Rs as well as the desired α5GABA A Rs at the highest dose. At the dose of 10mg/kg, which elicits a strong positive modulation of α5GABA A Rs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABA A Rs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. Copyright © 2016 Elsevier B.V. All rights reserved.

Ester to amide substitution improves selectivity, efficacy and kinetic behavior of a benzodiazepine positive modulator of GABAA receptors containing the α5 subunit

PubMed Central

Stamenić, Tamara Timić; Poe, Michael M.; Rehman, Sabah; Santrač, Anja; Divović, Branka; Scholze, Petra; Ernst, Margot; Cook, James M.; Savić, Miroslav M.

2016-01-01

We have synthesized and characterized MP-III-022 ((R)-8-ethynyl-6-(2-fluorophenyl)-N,4-dimethyl-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxamide) in vitro and in vivo as a binding- and efficacy-selective positive allosteric modulator of GABAA receptors containing the α5 subunit (α5GABAARs). By approximation of the electrophysiological responses which the estimated free rat brain concentrations can induce, we demonstrated that convenient systemic administration of MP-III-022 in the dose range 1-10 mg/kg may result in a selective potentiation, over a wide range from mild to moderate to strong, of α5βγ2 GABAA receptors. For eliciting a comparable range of potentiation, the widely studied parent ligand SH-053-2′F-R-CH3 containing an ester moiety needs to be administered over a much wider dose range (10-200 mg/kg), but at the price of activating non-α5 GABAARs as well as the desired α5GABAARs at the highest dose. At the dose of 10 mg/kg, which elicits a strong positive modulation of α5GABAARs, MP-III-022 caused mild, but significant muscle relaxation, while at doses 1-10 mg/kg was devoid of ataxia, sedation or an influence on the anxiety level, characteristic for non-selective benzodiazepines. As an amide compound with improved stability and kinetic properties, MP-III-022 may represent an optimized tool to study the influence of α5GABAARs on the neuronal pathways related to CNS disorders such as schizophrenia, Alzheimer's disease, Down syndrome or autism. PMID:27639297

Methylprednisolone as a memory enhancer in rats: Effects on aversive memory, long-term potentiation and calcium influx.

PubMed

de Vargas, Liane da Silva; Gonçalves, Rithiele; Lara, Marcus Vinícius S; Costa-Ferro, Zaquer S M; Salamoni, Simone Denise; Domingues, Michelle Flores; Piovesan, Angela Regina; de Assis, Dênis Reis; Vinade, Lucia; Corrado, Alexandre P; Alves-Do-Prado, Wilson; Correia-de-Sá, Paulo; da Costa, Jaderson Costa; Izquierdo, Ivan; Dal Belo, Cháriston A; Mello-Carpes, Pâmela B

2017-09-01

It is well recognized that stress or glucocorticoids hormones treatment can modulate memory performance in both directions, either impairing or enhancing it. Despite the high number of studies aiming at explaining the effects of glucocorticoids on memory, this has not yet been completely elucidated. Here, we demonstrate that a low daily dose of methylprednisolone (MP, 5mg/kg, i.p.) administered for 10-days favors aversive memory persistence in adult rats, without any effect on the exploring behavior, locomotor activity, anxiety levels and pain perception. Enhanced performance on the inhibitory avoidance task was correlated with long-term potentiation (LTP), a phenomenon that was strengthen in hippocampal slices of rats injected with MP (5mg/kg) during 10days. Additionally, in vitro incubation with MP (30-300µM) concentration-dependently increased intracellular [Ca 2+ ] i in cultured hippocampal neurons depolarized by KCl (35mM). In conclusion, a low daily dose of MP for 10days may promote aversive memory persistence in rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of Levofloxacin inhalation solution to treat Pseudomonas aeruginosa in patients with cystic fibrosis

PubMed Central

Stockmann, Chris; Sherwin, Catherine M.T.; Ampofo, Krow; Spigarelli, Michael G.

2017-01-01

Inhaled therapies allow for the targeted delivery of antimicrobials directly into the lungs and have been widely used in the treatment of cystic fibrosis (CF) acute pulmonary exacerbations. Nebulized levofloxacin solution (MP-376) is a novel therapy that is currently being evaluated in phase I, II, and III clinical trials among patients with stable CF and recent isolation of Pseudomonas aeruginosa from sputum. Phase I studies have investigated the single and multiple-dose pharmacokinetics of MP-376 and shown that it is rapidly absorbed from the lungs and results in low systemic concentrations. A subsequent phase IB study found that MP-376 pharmacokinetics were comparable among adults and children 6–16 years of age. Further phase II studies reported that sputum P. aeruginosa density decreased in a dose-dependent manner among patients who were randomized to MP-376 when compared with patients who received placebo. Improvements in pulmonary function and a decrease in the need for other antipseudomonal antibiotics were also reported for patients who received inhaled levofloxacin. The most common adverse event was dysgeusia (abnormal taste sensation), which was reported by nearly half of the participants who received MP-376. No serious drug-related adverse events were reported. These findings are encouraging; however, data from the two ongoing phase III trials are needed to determine whether MP-376 demonstrates substantial evidence of safety and efficacy as a chronic CF maintenance therapy and therefore may be useful in routine clinical practice. PMID:24334337

Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes

PubMed Central

Wu, Lin; Chen, Mingyu; Mao, Huijuan; Wang, Ningning; Zhang, Bo; Zhao, Xiufen; Qian, Jun; Xing, Changying

2017-01-01

Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin-methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highly express the specific neonatal Fc receptor (FcRn) of albumin. Bovine serum albumin (BSA) was labeled with a fluorescent dye and linked with modified MP via an amide bond. The outcome nanoparticle named BSA633-MP showed a uniform size with a diameter of approximately 10 nm and contained 12 drug molecules on average. The nanoconjugates were found to be stable at pH 7.4 and acid-sensitive at pH 4.0, with approximately 72% release of the MP drug after 48 h of incubation. The nanoparticle demonstrated a 36-fold uptake in receptor-specific cellular delivery in the FcRn-expressing human podocytes compared to the uptake in the non-FcRn-expressing control cells. Co-localization further confirmed that uptake of the nanoconjugates involved receptor-mediated endocytosis followed by lysosome associated transportation. In vitro cellular experiments indicated that the BSA633-MP ameliorated puromycin aminonucleoside-induced podocyte apoptosis. Moreover, in vivo fluorescence molecular imaging showed that BSA633-MP was mainly accumulated in the liver and kidney after intravenous dosing for 24 h. Collectively, this study may provide an approach for the effective and safe therapy of nephrotic syndrome. PMID:28259932

Long-term erythemal UV doses at Sodankylä estimated using total ozone, sunshine duration and snow depth

NASA Astrophysics Data System (ADS)

Lindfors, A. V.; Arola, A.; Kaurola, J.; Taalas, P.; Svenøe, T.

2003-04-01

A method for estimating daily erythemal UV doses using total ozone, sunshine duration and snow depth has been developed. The method consists of three steps: (1) daily clear-sky UV doses were simulated using the UVSPEC radiative transfer program, with daily values of total ozone as input data, (2) an empirical relationship was sought between the simulated clear-sky UV doses, the measured UV doses and the duration of bright sunshine, (3) daily erythemal UV doses were estimated using this relationship. The method accounts for the varying surface albedo by dividing the period of interest into winter and summer days, depending on the snow depth. Using this method, the daily erythemal UV doses at Sodankylä were estimated for the period 1950--99. This was done using Tromsø's total ozone together with Sodankylä's own sunshine duration and snow depth as input data. Although the method is fairly simple, the results are in good agreement, even on the daily scale, with the UV radiation measured with the Brewer spectrophotometer at Sodankylä. Statistically significant increasing trends in erythemal UV doses of a few percents per decade over the period 1950--99 were found for March and April, suggesting a connection to the stratospheric ozone depletion. For July, on the other hand, a significant decreasing trend of about 3% per decade, supported by the changes in both total ozone and sunshine duration, was found. The produced data set of erythemal UV doses is the longest time series of estimated UV known to the authors.

Effects of 6-mercaptopurine treatment on sperm production and reproductive performance: a study in male mice.

PubMed

Ligumsky, Moshe; Badaan, Shadi; Lewis, Hadassa; Meirow, Dror

2005-04-01

Azathioprine and 6-mercaptopurine interact in purine metabolism and DNA synthesis, thus their potential mutagenic effects have been of concern in the management of inflammatory bowel disease (IBD), especially in patients of childbearing age. Although several clinical studies have indicated their safety in both reproduction and pregnancy, in a recent large epidemiological study concerns were raised about their adverse effects in pregnant patients with IBD, and experimental or basic data on this subject are limited. The aim of this study was to investigate sperm production, sperm quality, and reproductive outcome following prolonged 6-MP administration to male mice. Highly inbred Balb/c adult male mice were used. 6-MP at doses of 2, 5, and 8 mg/kg (n = 9 for each group) was given daily for 51 days and the treatment group was compared with controls. After 45 days of treatment, the mice were mated with females. Following 13 days of pregnancy, the products of conception were evaluated and live fetuses were examined for gross malformations. Sperm production and morphology were examined after 51 days of 6-MP administration. Treatment with 6-MP at all doses did not affect sperm morphology and sperm production in the testicular tubules, as compared with controls (70% normal sperm). However, pregnancy rates were inversely related to escalating doses of 6-MP: 55%, 41%, 28%, and 16% for control, 2, 5, and 8 mg/kg groups, respectively. Resorption rates (abortions) were 21% in the control group as compared with 45-50% in all the treatment groups, but the incidence of major congenital malformations was not increased. Long-term 6-MP treatment in male mice did not impair sperm production and sperm morphology. However, a significantly high rate of embryonic resorption indicated occult sperm damage. Thus, normal sperm analysis does not necessarily imply that sperm damage at genetic level did not occur. It is difficult to extrapolate from these results to the clinical use of 6-MP/azathioprine in IBD patients; however, further basic genetic testing for DNA damage and clinical follow-up are warranted.

A prospective evaluation of the impact of allopurinol in pediatric and adult IBD patients with preferential metabolism of 6-mercaptopurine to 6-methylmercaptopurine.

PubMed

Gerich, Mark E; Quiros, J Antonio; Marcin, James P; Tennyson, Linda; Henthorn, Maria; Prindiville, Thomas P

2010-11-01

6-mercaptopurine (6-MP) is used for the induction and maintenance of remission of inflammatory bowel disease (IBD). 6-MP is converted into 6-methylmercaptopurine (6-MMP) or 6-thioguanine nucleotides (6-TGN) intracellularly. Treatment response in IBD patients correlates with 6-TGN levels. This study prospectively evaluated the effect of allopurinol on 6-MP metabolites in adult and pediatric IBD patients. Additionally, we quantified the prevalence of preferential metabolism towards 6-MMP through a retrospective analysis of IBD patients. Twenty patients (10 adult; 10 pediatric) with evidence of preferential metabolism towards 6-MMP, (6-TGN<250 pmol/8×10⁸ RBCs and 6-MMP>5000 pmol/8×10⁸ RBCs) were prospectively treated with allopurinol 100 mg daily and up to 100 mg of 6-MP. 6-MP dose was adjusted after a 3-week metabolite measurement. The median dose of 6-MP for adults decreased from 100mg daily (range: 37.5-150 mg) to 25mg daily (range: 12.5-50 mg). The median dose of 6-MP for pediatric patients decreased from 50 mg (range: 25-50 mg) to 10.7 mg (range: 10.7 to 21.4 mg). Mean 6-TGN levels in all subjects increased from 197.4 (± 59) to 284.8 (± 107) pmol/8×10⁸ RBCs (p=0.0005). Mean 6-MMP levels in all subjects decreased from a mean of 7719.8 (± 4716) to 404.8 (± 332) pmol/8×10⁸ RBCs (p=0.0004). There were no complications associated with allopurinol therapy. Eighty-eight (30.9%) of 285 IBD patients had evidence of preferential metabolism towards 6-MMP. The proportion of preferential metabolism was equal in adults and pediatric patients. Our results indicate that the addition of allopurinol safely shifts metabolite production in both adult and pediatric IBD patients and that there is a high prevalence of preferential metabolism towards 6-MMP among IBD patients. Published by Elsevier B.V.

Tumor necrosis factor-inducing activities of Cryptococcus neoformans components.

PubMed Central

Delfino, D; Cianci, L; Migliardo, M; Mancuso, G; Cusumano, V; Corradini, C; Teti, G

1996-01-01

Cryptococcus neoformans-induced tumor necrosis factor alpha (TNF-alpha) production may lead to increased human immunodeficiency virus replication in patients with AIDS. In order to identify cryptococcal components that are predominantly responsible for stimulating TNF production, various concentrations of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), mannoproteins (MP), and alpha(1-3) [corrected] glucan were added to whole-blood cultures. All of the cryptococcal components tested, as well as whole heat-killed cryptococci, were capable of inducing TNF-alpha release in a dose-dependent manner. MP were significantly more potent than any of the other cryptococcal components tested or heat-killed cryptococci in stimulating TNF-alpha production (P < 0.05). GXM, in contrast, was significantly less potent in this activity than either GalXM or MP (P < 0.05). As little as 0.5 microg of MP per ml was sufficient to produce moderate but significant elevations of TNF-alpha release. Maximal MP-induced TNF-alpha levels were similar to those induced by Salmonella enteritidis lipopolysaccharide, our positive control. Further experiments using isolated leukocytes suggested that monocytes were the cell population mainly responsible for TNF-alpha production, although the participation of other cell types could not be excluded. The presence of complement-sufficient plasma was a necessary requirement for TNF-alpha induction by GXM, GalXM, and low doses of MP. High MP concentrations (100 microg/ml) were also capable of stimulating TNF-alpha production in the absence of plasma. These data indicate that soluble products released by C. neoformans are capable of inducing TNF-alpha secretion in human leukocytes. This may be clinically relevant, since high concentrations of such products are frequently found in the body fluids of AIDS patients infected with C. neoformans. PMID:8945566

Stents Eluting 6-Mercaptopurine Reduce Neointima Formation and Inflammation while Enhancing Strut Coverage in Rabbits

PubMed Central

Ruiter, Matthijs S.; van Tiel, Claudia M.; Doornbos, Albert; Marinković, Goran; Strang, Aart C.; Attevelt, Nico J. M.; de Waard, Vivian; de Winter, Robbert J.; Steendam, Rob; de Vries, Carlie J. M.

2015-01-01

Background The introduction of drug-eluting stents (DES) has dramatically reduced restenosis rates compared with bare metal stents, but in-stent thrombosis remains a safety concern, necessitating prolonged dual anti-platelet therapy. The drug 6-Mercaptopurine (6-MP) has been shown to have beneficial effects in a cell-specific fashion on smooth muscle cells (SMC), endothelial cells and macrophages. We generated and analyzed a novel bioresorbable polymer coated DES, releasing 6-MP into the vessel wall, to reduce restenosis by inhibiting SMC proliferation and decreasing inflammation, without negatively affecting endothelialization of the stent surface. Methods Stents spray-coated with a bioresorbable polymer containing 0, 30 or 300 μg 6-MP were implanted in the iliac arteries of 17 male New Zealand White rabbits. Animals were euthanized for stent harvest 1 week after implantation for evaluation of cellular stent coverage and after 4 weeks for morphometric analyses of the lesions. Results Four weeks after implantation, the high dose of 6-MP attenuated restenosis with 16% compared to controls. Reduced neointima formation could at least partly be explained by an almost 2-fold induction of the cell cycle inhibiting kinase p27Kip1. Additionally, inflammation score, the quantification of RAM11-positive cells in the vessel wall, was significantly reduced in the high dose group with 23% compared to the control group. Evaluation with scanning electron microscopy showed 6-MP did not inhibit strut coverage 1 week after implantation. Conclusion We demonstrate that novel stents coated with a bioresorbable polymer coating eluting 6-MP inhibit restenosis and attenuate inflammation, while stimulating endothelial coverage. The 6-MP-eluting stents demonstrate that inhibition of restenosis without leaving uncovered metal is feasible, bringing stents without risk of late thrombosis one step closer to the patient. PMID:26389595

Mucuna pruriens reduces inducible nitric oxide synthase expression in Parkinsonian mice model.

PubMed

Yadav, Satyndra Kumar; Rai, Sachchida Nand; Singh, Surya Pratap

2017-03-01

Parkinson's disease is one of the most common neurodegenerative disease found in aged peoples. Plentiful studies are being conducted to find a suitable and effective cure for this disease giving special impetus on use of herbal plants. The study aimed at investigating the effect of ethanolic extract of Mucuna pruriens (Mp) on level of nitric oxide (NO) in paraquat (PQ) induced Parkinson's disease (PD) mouse model and its subsequent contribution to lipid peroxidation. Twenty four Swiss albino mice were divided into three groups; Control, PQ and PQ+Mp. PQ doses were given intraperitoneally, twice in a week and oral dose of ethanolic extract of Mp seed was given for 9 weeks. Nitrite content and lipid peroxidation was measured in all treated groups along with respective controls. RNA was isolated from the nigrostriatal tissue of control and the treated mice and was reverse transcribed into cDNA. PCR was performed to amplify iNOS mRNA and western blot analysis was performed to check its protein level. We had also perfused the mice in all treated group and performed Tyrosine hydroxylase (TH) and iNOS immunoreactivity in substantia nigra region of mice brain. PQ-treatment increased nitrite content, expression of iNOS and lipid peroxidation compared to respective controls. Mp treatment resulted in a significant attenuation of iNOS expression, nitrite content and lipid peroxidation demonstrating that it reduces nitric oxide in PQ-induced Parkinson's disease. Interestingly; we also observed that mRNA, protein expression and immunoreactivity of iNOS was significantly decreased after Mp treatment and TH immunoreactivity was significantly improved after the treatment of Mp. Our results demonstrated that Mp protects the dopaminergic neurons from the NO injury in substantia nigra. Copyright © 2016 Elsevier B.V. All rights reserved.

Synthesis and Characterization of Liquid Crystalline Copolymethacrylates, Copolyacrylates and Copolysiloxanes Containing 4-Methoxy-4’-Hydroxy-alpha-Methylstilbene and 4-Hydroxy-4’-Methoxy-alpha-Methylstilbene Constitutional Isomers as Side Groups.

DTIC Science & Technology

1987-01-01

oven, LC-600 autosampler, and Sigma 15 data station. High pressure liquid chromatography ( HPLC ) determinations were performed with the same...white crystals of 99.0% purity as determined by HPLC . m.p.=184-186*C (lit. 25, m.p.=182-1830C). ’H-NMR (DMSO-de, TMS, 6, ppm): 2.2 (s, -CHa), 6.7 (s, =CH...is about 99% ( HPLC ). HPLC equipped with UV detector, can not discriminate between the two isomers of MHMS. 200 MHz 1H-NMR spectra of sample A and

2D mapping of the MV photon fluence and 3D dose reconstruction in real time for quality assurance during radiotherapy treatment

NASA Astrophysics Data System (ADS)

Alrowaili, Z. A.; Lerch, M. L. F.; Carolan, M.; Fuduli, I.; Porumb, C.; Petasecca, M.; Metcalfe, P.; Rosenfeld, A. B.

2015-09-01

Summary: the photon irradiation response of a 2D solid state transmission detector array mounted in a linac block tray is used to reconstruct the projected 2D dose map in a homogenous phantom along rays that diverge from the X-ray source and pass through each of the 121 detector elements. A unique diode response-to-dose scaling factor, applied to all detectors, is utilised in the reconstruction to demonstrate that real time QA during radiotherapy treatment is feasible. Purpose: to quantitatively demonstrate reconstruction of the real time radiation dose from the irradiation response of the 11×11 silicon Magic Plate (MP) detector array operated in Transmission Mode (MPTM). Methods and Materials: in transmission mode the MP is positioned in the block tray of a linac so that the central detector of the array lies on the central axis of the radiation beam. This central detector is used to determine the conversion factor from measured irradiation response to reconstructed dose at any point on the central axis within a homogenous solid water phantom. The same unique conversion factor is used for all MP detector elements lying within the irradiation field. Using the two sets of data, the 2D or 3D dose map is able to be reconstructed in the homogenous phantom. The technique we have developed is illustrated here for different depths and irradiation field sizes, (5 × 5 cm2 to 40 × 40 cm2) as well as a highly non uniform irradiation field. Results: we find that the MPTM response is proportional to the projected 2D dose map measured at a specific phantom depth, the "sweet depth". A single factor, for several irradiation field sizes and depths, is derived to reconstruct the dose in the phantom along rays projected from the photon source through each MPTM detector element. We demonstrate that for all field sizes using the above method, the 2D reconstructed and measured doses agree to within ± 2.48% (2 standard deviation) for all in-field MP detector elements. Conclusions: a 2D detector system and method to reconstruct the dose in a homogeneous phantom and in real time has been demonstrated. The success of this work is an exciting development toward real time QA during radiotherapy treatment.

Construction of 6-thioguanine and 6-mercaptopurine carriers based on βcyclodextrins and gold nanoparticles.

PubMed

Sierpe, R; Noyong, Michael; Simon, Ulrich; Aguayo, D; Huerta, J; Kogan, Marcelo J; Yutronic, N

2017-12-01

As a novel strategy to overcome some of the therapeutic disadvantages of 6-thioguanine (TG) and 6-mercaptopurine (MP), we propose the inclusion of these drugs in βcyclodextrin (βCD) to form the complexes βCD-TG and βCD-MP, followed by subsequent interaction with gold nanoparticles (AuNPs), generating the ternary systems: βCD-TG-AuNPs and βCD-MP-AuNPs. This modification increased their solubility and improved their stability, betting by a site-specific transport due to their nanometric dimensions, among other advantages. The formation of the complexes was confirmed using powder X-ray diffraction, thermogravimetric analysis and one and two-dimensional NMR. A theoretical study using DFT and molecular modelling was conducted to obtain the more stable tautomeric species of TG and MP in solution and confirm the proposed inclusion geometries. The deposition of AuNPs onto βCD-TG and βCD-MP via sputtering was confirmed by UV-vis spectroscopy. Subsequently, the ternary systems were characterized by TEM, FE-SEM and EDX to directly observe the deposited AuNPs and evaluate their sizes, size dispersion, and composition. Finally, the in vitro permeability of the ternary systems was studied using parallel artificial membrane permeability assay (PAMPA). Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiochromic film dosimetry for UV-C treatments of apple fruit

USDA-ARS?s Scientific Manuscript database

Radiochromic films were evaluated for their suitability to estimate UV-C doses and dose uniformity on apple fruit surface. Parameters investigated included film type, color changes of the films in response to different UV-C doses, color stability of films, UV-C light intensity, and temperature. In...

UV Disinfection System for Cabin Air

NASA Astrophysics Data System (ADS)

Lim, Soojung

Ultraviolet (UV) radiation is commonly used for disinfection of water. As a result of advancements made in the last 10-15 years, the analysis and design of UV disinfection systems for water is well developed. UV disinfection is also used for disinfection of air; however, despite the fact the UV-air systems have a longer record of application than UV-water systems, the methods used to analyze and design UV-air disinfection systems remain quite empirical. It is well-established that the effectiveness of UV-air systems is strongly affected by the type of microorganisms, the irradiation level/type (lamp power and wavelength), duration of irradiation (exposure time), air movement pattern (mixing degree), and relative humidity. This paper will describe ongoing efforts to evaluate, design and test a UV-air system based on first principles. Specific issues to be addressed in this work will include laboratory measurements of relevant kinetics (i.e., UV dose-response behavior) and numerical simulations designed to represent fluid mechanics and the radiation intensity field. UV dose-response behavior of test microorganism was measured using a laboratory (bench-scale) system. Target microorganisms (e.g., bacterial spores) were first applied to membrane filters at sub-monolayer coverage. The filters were then transferred to an environmental chamber at fixed relative humidity (RH) and allowed to equilibrate with their surroundings. Microorganisms were then subjected to UV exposure under a collimated beam. The experiment was repeated at RH values ranging from 20% to 100%. UV dose-response behavior was observed to vary with RH. For example, at 100% RH, a UV dose of 20 mJ/cm2 accomplished 90% (1 log10 units) of the B. subtilis spore inactivation, whereas 99 % (2 log10 units) inactivation was accomplished at this same UV dose under 20% RH conditions. However, at higher doses, the result was opposite of that in low dose. Reactor behavior is simulated using an integrated application of computational fluid dynamics (CFD) and radiation intensity field models. These simulations followed a Lagrangian approach, wherein the UV radiation intensity field was mapped onto simulated particle trajectories for prediction of the UV dose delivered to each particle. By repeating these calculations for a large number of simulated particle trajectories, an estimate of the UV dose distribution delivered by the reactor can be made. In turn, these dose distribution estimates are integrated with the UV dose-response behavior described above to yield an estimate of microbial inactivation accomplished by the reactor. This modeling approach has the advantage of allowing simulation of many reactor configurations in a relatively short period of time. Moreover, by following this approach of "numerical prototyping," it is possible to "build" and analyze several virtual reactors before the construction of a physical prototype. As such, this procedure allows effective development of efficient reactors.

Acceptability of minimally processed and irradiated pineapple and watermelon among Brazilian consumers

NASA Astrophysics Data System (ADS)

Martins, Cecília Geraldes; Aragon-Alegro, Lina Casale; Behrens, Jorge Herman; Oliveira Souza, Kátia Leani; Martins Vizeu, Dirceu; Hutzler, Beatriz Weltman; Teresa Destro, Maria; Landgraf, Mariza

2008-06-01

This study aimed at evaluating the acceptance of MP watermelon and pineapple exposed to 1.0 and 2.5 kGy compared to non-irradiated samples. No significant differences were observed in liking between irradiated and non-irradiated samples, and also between doses of 1.0 and 2.5 kGy. Significant differences in sourness (pineapple) or sweetness (watermelon) and between intention of purchase of irradiated and non-irradiated fruits were not observed as well. Results showed that MP watermelon and pineapple could be irradiated with doses up to 2.5 kGy without significant changes in acceptability.

Development of UV-B screening compounds in response to variation in ambient levels of UV-B radiation

NASA Astrophysics Data System (ADS)

Sullivan, Joe H.; Xu, Chenping; Gao, Wei; Slusser, James R.

2005-08-01

The induction of UV-B screening compounds in response to exposure to UV-B radiation is a commonly reported response and is generally considered to be an adaptive response of plants for protection from UVinduced damage. However, a number of questions remain to be answered including the importance of qualitative and localization differences among species in providing protection, indirect consequences of changes in leaf secondary chemistry on ecological processes and the dose response of metabolite accumulation. In this study we utilized UV monitoring data provided on site by the USDA UV-B Monitoring and Research Program to monitor the changes in UV-screening compounds in soybeans under a range of UV-B levels due to natural variation in ambient UV-B radiation. Soybean cultivars Essex, Clark and Clark-magenta, an isoline of Clark that produces minimal levels of flavonols, were grown beneath shelters covered either with polyester to block most UV-B radiation or teflon which is nearly transparent in the UV range and harvested at regular intervals for pigment and protein analysis. Daily levels of weighted UV-B varied from <1 to >7 kJ m-2. Increases in UV-screening compounds showed a positive dose response to UV-B radiation in all cultivars with Essex showing the steepest dose response. UV-A also induced screening compounds in all species The hydroxycinnimates of the magenta isoline showed a steep dose response to UV-A and a rather constant (non dose specific) but small additional increment in response to UV-B. The Clark isoline, which produced primarily the flavonol quercetin, showed a dose response to UV-B intermediate between that of Clark-magenta and Essex. All three cultivars show similar tolerance to UV-B in field conditions indicating that UV-induced pigment production is adequate to protect them from excessive UV-B damage.

Estimated ultraviolet radiation doses in wetlands in six national parks

USGS Publications Warehouse

Diamond, S.A.; Trenham, P.C.; Adams, Michael J.; Hossack, B.R.; Knapp, R.A.; Stark, L.; Bradford, D.; Corn, P.S.; Czarnowski, K.; Brooks, P.D.; Fagre, D.B.; Breen, B.; Dentenbeck, N.E.; Tonnessen, K.

2005-01-01

Ultraviolet-B radiation (UV-B, 280–320-nm wavelengths) doses were estimated for 1024 wetlands in six national parks: Acadia (Acadia), Glacier (Glacier), Great Smoky Mountains (Smoky), Olympic (Olympic), Rocky Mountain (Rocky), and Sequoia/Kings Canyon (Sequoia). Estimates were made using ground-based UV-B data (Brewer spectrophotometers), solar radiation models, GIS tools, field characterization of vegetative features, and quantification of DOC concentration and spectral absorbance. UV-B dose estimates were made for the summer solstice, at a depth of 1 cm in each wetland. The mean dose across all wetlands and parks was 19.3 W-h m−2 (range of 3.4–32.1 W-h m−2). The mean dose was lowest in Acadia (13.7 W-h m−2) and highest in Rocky (24.4 W-h m−2). Doses were significantly different among all parks. These wetland doses correspond to UV-B flux of 125.0 μW cm−2 (range 21.4–194.7 μW cm−2) based on a day length, averaged among all parks, of 15.5 h. Dissolved organic carbon (DOC), a key determinant of water-column UV-B flux, ranged from 0.6 (analytical detection limit) to 36.7 mg C L−1 over all wetlands and parks, and reduced potential maximal UV-B doses at 1-cm depth by 1%–87 %. DOC concentration, as well as its effect on dose, was lowest in Sequoia and highest in Acadia (DOC was equivalent in Acadia, Glacier, and Rocky). Landscape reduction of potential maximal UV-B doses ranged from zero to 77% and was lowest in Sequoia. These regional differences in UV-B wetland dose illustrate the importance of considering all aspects of exposure in evaluating the potential impact of UV-B on aquatic organisms.

Update 2014: advances to optimize 6-mercaptopurine and azathioprine to reduce toxicity and improve efficacy in the management of IBD.

PubMed

Amin, Jaimin; Huang, Brian; Yoon, Jessica; Shih, David Q

2015-02-01

The thiopurine drugs, 6-mercaptopurine (6-MP) and azathioprine (AZA), remain as a mainstay therapy in inflammatory bowel disease (IBD). Differences in metabolism of these drugs lead to individual variation in thiopurine metabolite levels that can determine its therapeutic efficacy and development of adverse reactions. In this update, we will review thiopurine metabolic pathway along with the up-to-date approaches in administering thiopurine medications based on the current literature. A search of the PubMed database by 2 independent reviewers identifying 98 articles evaluating thiopurine metabolism and IBD management. Monitoring thiopurine metabolites can assist physicians in optimizing 6-MP and AZA therapy in treating patients with IBD. Of the dosing strategies reviewed, we found evidence for monitoring thiopurine metabolite level, use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of AZA or 6-MP to optimize thiopurine therapy and minimize adverse effects in IBD. Based on the currently available literature, various dosing strategies to improve therapeutic response and reduce adverse reactions can be considered, including use of allopurinol with thiopurine, use of mesalamine with thiopurine, combination therapy with thiopurine and anti-tumor necrosis factor agents, and split dosing of thiopurine.

Actions of 2-methylpiperidine (MP) and its interactions with (-)-nicotine (N) in the dog and rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sloan, J.W.; Martin, W.R.; Bostwick, M.

1986-03-01

(+/-)-MP is a highly specific drug for enhancing the binding of (+/-)-(/sup 3/H)N in the rat brain P/sub 2/ preparation. Competition studies employing (+/-)-(/sup 3/H)N as the labelled ligand show that this activity resides in the (+) isomer. Saturation studies employing (+/-)-(/sup 3/H)MP indicate that it binds to a very high affinity site which is presumed to be an up-regulatory site. Studies were conducted where (+/-)-MP was injected through an implanted cannula into the 4th ventricle of intact beagle-type dogs. (+/-)-MP, like low doses of (+)-N, another drug which has specificity in enhancing the binding of (+/-)-, and (-)- andmore » (+)-(/sup 3/H)N, produced EEG synchronization and miosis. (-)-N produced analgesia where as (+/-)-MP produced hyperalgesia. In the urethane-pentobarbital anethetized rats, the i.v. infusion of (+)-MP (600 ..mu..g/kg/min for 10 min), had no effect on heart rate, blood pressure or respiration. Pretreatment with (+)-MP delayed and decreased the bradycardia, vasodepression, and enhanced tidal volume produced by (-)-N infusion (60 ..mu..g/kg/min). These data show that the pharmacologic actions of MP are different from (-)-N and hexamethonium and that MP, which enhances the binding of (+/-)- and (-)-(/sup 3/H)N at the high affinity site, appears to exert opposite effects to and antagonistic effects against (-)-N.« less

High-dose methylprednisolone treatment of laser-induced retinal injury exacerbates acute inflammation and long-term scarring

NASA Astrophysics Data System (ADS)

Schuschereba, Steven T.; Cross, Michael E.; Scales, David K.; Pizarro, Jose M.; Edsall, Peter R.; Stuck, Bruce E.; Marshall, John

1999-06-01

Purpose. To evaluate therapeutics for attenuating retinal laser injury. Methods. New Zealand Red rabbits (n=76) were pretreated (IV) with either a single dose of hydroxyethyl starch conjugated deferoxamine (HES-DFO, n=29) (6.1 ml/kg, 16.4 mg/ml) or methylprednisolone sodium succinate (MP, n=22) (30 mg/kg, followed by taper of 30, 20, 20, and 10 mg/kg/day for a total of 5d). Controls were untreated (n=25). Fifteen min later, animals were irradiated with a multiline cw argon laser (285 mW, 10 msec pulse durations, 16 lesions/eye). Funduscopy, fluorescein angiography, histology, and morphometry were performed at 10 min, 1h, 3h, 24h, 1 mo, and 6 mo after irradiation. Leukocytes were counted at lesion centers for retinal and choroidal compartments at 1, 3, and 24h. Results. At 3h, percent area incrase for the lesions was highest for MP (44%) and lowest for HES-DFO (16%)(p<0.05). In hemorrhagic lesions, MP treatment resulted in the highest increase of retinal neotrophils by 24h (p<0.05), and by 1 and 6 mo extensive chorio-retinal scarring occurred in nonhemorrhagic and hemorrhagic lesions. Also, no benefit was demonstrated on sparing of photoreceptors with MP treatment. Conclusions. Treatment of laser-induced retinal injury with methylprednisolone (MP) exacerbates acute inflammation and long-term chorio-retinal scarring; however, hydroxyethyl starch conjugated deferoxamine therapy ameliorates these aspects of injury. Data suggest caution in the use of MP therapy for laser injuries.

Urinary profile of methylprednisolone and its metabolites after oral and topical administrations.

PubMed

Matabosch, Xavier; Pozo, Oscar J; Monfort, Núria; Pérez-Mañá, Clara; Farré, Magi; Marcos, Josep; Segura, Jordi; Ventura, Rosa

2013-11-01

Methylprednisolone (MP) is prohibited in sports competitions when administered by systemic routes; however its use by topical administration is allowed. Therefore, analytical approaches to distinguish between these different administration pathways are required. A reporting level of 30ng/mL was established for this purpose. However, the suitability of that reporting level for MP is not known. In the present work, excretion profiles of MP and different metabolites after oral and topical administrations have been compared. A method for the quantification of MP and the qualitative detection of fifteen previously reported metabolites has been validated. The method involved an enzymatic hydrolysis, liquid-liquid extraction and analysis by liquid chromatography coupled to tandem mass spectrometry. The method was found to be linear, selective, precise and accurate. The high sensitivity (limit of detection 0.1ng/mL) and linear range (0.1-250ng/mL) achieved allowed for the quantification of MP at both the low concentrations present after topical administration and the high concentrations detected after oral intake. The method was applied to samples collected after oral (4 or 40mg) and topical administration (10mg of MP aceponate/day for 5 consecutive days) to healthy volunteers. After oral administration, MP and all metabolites were detected in urines collected up to at least 36h. Only MP and five metabolites were detected in samples obtained after topical treatment. As expected, concentrations of MP after topical administration were well below current reporting level (30ng/mL), however 3 out of 4 samples in range 8-24h after the low oral dose (4mg) were also below that concentration. Taking into account metabolites detected after both administration routes, metabolites 16β,17α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11,20-trione (M8) and 17α,20α,21-trihydroxy-6α-methylpregna-1,4-diene-3,11-dione (M11) are best markers to differentiate between topical and oral administrations. Their signals after topical administration were lower than those obtained in the first 48h after all oral doses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preferential inhibition of xanthine oxidase by 2-amino-6-hydroxy-8-mercaptopurine and 2-amino-6-purine thiol.

PubMed

Kalra, Sukirti; Jena, Gopabandhu; Tikoo, Kulbhushan; Mukhopadhyay, Anup Kumar

2007-05-18

The anticancer drug, 6-mercaptopurine (6MP) is subjected to metabolic clearance through xanthine oxidase (XOD) mediated hydroxylation, producing 6-thiouric acid (6TUA), which is excreted in urine. This reduces the effective amount of drug available for therapeutic efficacy. Co-administration of allopurinol, a suicide inhibitor of XOD, which blocks the hydroxylation of 6MP inadvertently enhances the 6MP blood level, counters this reduction. However, allopurinol also blocks the hydroxylation of hypoxanthine, xanthine (released from dead cancer cells) leading to their accumulation in the body causing biochemical complications such as xanthine nephropathy. This necessitates the use of a preferential XOD inhibitor that selectively inhibits 6MP transformation, but leaves xanthine metabolism unaffected. Here, we have characterized two such unique inhibitors namely, 2-amino-6-hydroxy-8-mercaptopurine (AHMP) and 2-amino-6-purinethiol (APT) on the basis of IC50 values, residual activity in bi-substrate simulative reaction and the kinetic parameters like Km, Ki, kcat. The IC50 values of AHMP for xanthine and 6MP as substrate are 17.71 +/- 0.29 microM and 0.54 +/- 0.01 microM, respectively and the IC50 values of APT for xanthine and 6MP as substrates are 16.38 +/- 0.21 microM and 2.57 +/- 0.08 microM, respectively. The Ki values of XOD using AHMP as inhibitor with xanthine and 6MP as substrate are 5.78 +/- 0.48 microM and 0.96 +/- 0.01 microM, respectively. The Ki values of XOD using APT as inhibitor with xanthine and 6MP as substrate are 6.61 +/- 0.28 microM and 1.30 +/- 0.09 microM. The corresponding Km values of XOD using xanthine and 6MP as substrate are 2.65 +/- 0.02 microM and 6.01 +/- 0.03 microM, respectively. The results suggest that the efficiency of substrate binding to XOD and its subsequent catalytic hydroxylation is much superior for xanthine in comparison to 6MP. In addition, the efficiency of the inhibitor binding to XOD is much more superior when 6MP is the substrate instead of xanthine. We further undertook the toxicological evaluation of these inhibitors in a single dose acute toxicity study in mice and our preliminary experimental results suggested that the inhibitors were equally non-toxic in the tested doses. We conclude that administration of either APT or AHMP along with the major anti-leukemic drug 6MP might serve as a good combination cancer chemotherapy regimen.

76 FR 35672 - Revised Effectiveness Determination; Sunscreen Drug Products for Over-the-Counter Human Use

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

... are given ultraviolet (UV) radiation doses produced by a solar simulator (i.e., a UV lamp). Under... increasingly higher UV doses produced by the solar simulator. However, because the solar simulator can produce far higher UV radiation doses than a consumer would ever receive even under the most severe sun...

TEMIS UV product validation using NILU-UV ground-based measurements in Thessaloniki, Greece

NASA Astrophysics Data System (ADS)

Zempila, Melina-Maria; van Geffen, Jos H. G. M.; Taylor, Michael; Fountoulakis, Ilias; Koukouli, Maria-Elissavet; van Weele, Michiel; van der A, Ronald J.; Bais, Alkiviadis; Meleti, Charikleia; Balis, Dimitrios

2017-06-01

This study aims to cross-validate ground-based and satellite-based models of three photobiological UV effective dose products: the Commission Internationale de l'Éclairage (CIE) erythemal UV, the production of vitamin D in the skin, and DNA damage, using high-temporal-resolution surface-based measurements of solar UV spectral irradiances from a synergy of instruments and models. The satellite-based Tropospheric Emission Monitoring Internet Service (TEMIS; version 1.4) UV daily dose data products were evaluated over the period 2009 to 2014 with ground-based data from a Norsk Institutt for Luftforskning (NILU)-UV multifilter radiometer located at the northern midlatitude super-site of the Laboratory of Atmospheric Physics, Aristotle University of Thessaloniki (LAP/AUTh), in Greece. For the NILU-UV effective dose rates retrieval algorithm, a neural network (NN) was trained to learn the nonlinear functional relation between NILU-UV irradiances and collocated Brewer-based photobiological effective dose products. Then the algorithm was subjected to sensitivity analysis and validation. The correlation of the NN estimates with target outputs was high (r = 0. 988 to 0.990) and with a very low bias (0.000 to 0.011 in absolute units) proving the robustness of the NN algorithm. For further evaluation of the NILU NN-derived products, retrievals of the vitamin D and DNA-damage effective doses from a collocated Yankee Environmental Systems (YES) UVB-1 pyranometer were used. For cloud-free days, differences in the derived UV doses are better than 2 % for all UV dose products, revealing the reference quality of the ground-based UV doses at Thessaloniki from the NILU-UV NN retrievals. The TEMIS UV doses used in this study are derived from ozone measurements by the SCIAMACHY/Envisat and GOME2/MetOp-A satellite instruments, over the European domain in combination with SEVIRI/Meteosat-based diurnal cycle of the cloud cover fraction per 0. 5° × 0. 5° (lat × long) grid cells. TEMIS UV doses were found to be ˜ 12.5 % higher than the NILU NN estimates but, despite the presence of a visually apparent seasonal pattern, the R2 values were found to be robustly high and equal to 0.92-0.93 for 1588 all-sky coincidences. These results significantly improve when limiting the dataset to cloud-free days with differences of 0.57 % for the erythemal doses, 1.22 % for the vitamin D doses, and 1.18 % for the DNA-damage doses, with standard deviations of the order of 11-13 %. The improvement of the comparative statistics under cloud-free cases further testifies to the importance of the appropriate consideration of the contribution of clouds in the UV radiation reaching the Earth's surface. For the urban area of Thessaloniki, with highly variable aerosol, the weakness of the implicit aerosol information introduced to the TEMIS UV dose algorithm was revealed by comparison of the datasets to aerosol optical depths at 340 nm as reported by a collocated CIMEL sun photometer, operating in Thessaloniki at LAP/AUTh as part of the NASA Aerosol Robotic Network.

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats

PubMed Central

2013-01-01

Introduction The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Methods Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. Results We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. Conclusions Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus. PMID:24131855

High Plasma Concentrations of Zidovudine (AZT) Do Not Parallel Intracellular Concentrations of AZT-Triphosphates in Infants During Prevention of Mother-to-Child HIV-1 Transmission.

PubMed

Kinai, Ei; Kato, Shingo; Hosokawa, Shinichi; Sadatsuki, Miyuki; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Lam, Nguyen Van; Ha, Do Quan; Kinh, Nguyen Van; Liem, Nguyen Thanh; Oka, Shinichi

2016-07-01

Zidovudine (AZT) is mainly used to prevent mother-to-child HIV-1 transmission (PMTCT). Despite serious concerns on AZT-associated toxicity, there is little information on pharmacokinetics of intracellular AZT metabolites in infants. We conducted a prospective study in 31 HIV-uninfected infants who received AZT for PMTCT. Blood samples were obtained from 14 infants on postdelivery days (PDD) 1, 7, 14, and 28 and from 17 infants at 0 and 4 hours after dosing on PDD-1. Plasma AZT concentrations (pAZT) and intracellular concentrations of AZT-monophosphate (icAZT-MP), diphosphate (icAZT-DP), and triphosphate (icAZT-TP) were determined. Plasma AZT and icAZT-MP concentrations were 2713 nmol/L and 79 fmol/10 cells in PDD-1, but decreased to 1437 nmol/L and 31 fmol/10 cells by PDD-28 (P = 0.02 and P = 0.07 for all PDDs, respectively), whereas those of icAZT-DP and icAZT-TP remained low throughout the sampling period (P = 0.29 and P = 0.61 for all PDDs, respectively) There were no differences in icAZT-TP between infants of the 2 mg/kg 4 times a day dose and 4 mg/kg twice daily dose (P = 0.25), whereas pAZT and icAZT-MP levels were higher in the latter (P < 0.01 and <0.01, respectively). The pAZT and icAZT-MP significantly increased from 0 to 4 hours after dosing (P < 0.001 and <0.001, respectively), whereas icAZT-DP, icAZT-TP levels were not changed (P = 0.41 and 0.33, respectively). The level of icAZT-TP did not change with age, time, or a single dose despite the wide range of pAZT concentration. A safer dosage needs to be determined because high pAZT levels do not parallel those of icAZT-TP.

Protective effects of systemic treatment with methylprednisolone in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION).

PubMed

Huang, Tzu-Lun; Huang, Shun-Ping; Chang, Chung-Hsing; Lin, Kung-Hung; Chang, Shu-Wen; Tsai, Rong-Kung

2015-02-01

This study investigated the protective effects of the administration of steroids on optic nerves (ON) and retinal ganglion cells (RGCs) in a rodent model of non-arteritic anterior ischemic optic neuropathy (rAION). We induced rAION using rose bengal and argon laser irradiation in a photodynamic procedure on the optic discs of rats. The treated groups received methylprednisolone (MP) via peritoneal injection for 2 weeks. The control group received intraperitoneal injections of phosphate-buffered saline (PBS) post-rAION. At the 4th week post-infarct, MP treatments significantly rescued the RGCs (mm(2)) in the central retinas (1920 ± 210, p < 0.001) and mid-peripheral retinas (950 ± 240, respectively, p = 0.018) compared with those of the PBS-treated rats (central: 900 ± 210 and mid-peripheral: 440 ± 180). Functional assessment with flash visual-evoked potentials demonstrated that P1 latency (ms) was shortened in the MP group compared to the PBS group (108 ± 14 and 147 ± 9, respectively, p < 0.001). In addition, the P1 amplitude (uV) was enhanced in the MP group compared to the PBS group (55 ± 12 and 41 ± 13, respectively, p < 0.05). TUNEL assays showed a decrease in the number of apoptotic cells in the RGC layers of MP-treated retinas compared to the PBS-treated group (p < 0.05). ED1 positive cells (/HPF) were significantly decreased in the ONs of the MP group compared to the PBS group (p < 0.001). In conclusion, systemic administration of MP had neuroprotective effects on RGC survival and ON function in the rAION animal model. Copyright © 2014 Elsevier Ltd. All rights reserved.

A cost effectiveness analysis of thiopurine methyltransferase testing for guiding 6-mercaptopurine dosing in children with acute lymphoblastic leukemia.

PubMed

Donnan, Jennifer R; Ungar, Wendy J; Mathews, Maria; Hancock-Howard, Rebecca L; Rahman, Proton

2011-08-01

An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more genetic testing for diagnosis and treatment. The objective was to assess the incremental cost-effectiveness per life-month gained of thiopurine methyltransferase (TPMT) genotyping to guide doses of 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL) compared to enzymatic testing and standard weight-based dosing. A cost-effectiveness analysis was conducted from a health care system perspective comparing costs and consequences over 3 months. Decision analysis was used to evaluate the impact of TPMT tests on preventing myelosuppression and improving survival in ALL patients receiving 6-MP. Direct medical costs included laboratory tests, medications, physician services, pharmacy and inpatient care. Probabilities were derived from published evidence. Survival was measured in life-months. The robustness of the results to variable uncertainty was tested in one-way sensitivity analyses. Probabilistic sensitivity analysis examined the impact of parameter uncertainty and generated confidence intervals around point estimates. Neither of the testing interventions showed a benefit in survival compared to weight-based dosing. Both test strategies were more costly compared to weight-based dosing. Incremental costs per child (95% confidence interval) were $277 ($112, $442) and $298 ($392, $421) for the genotyping and phenotyping strategies, respectively, compared to weight-based dosing. The present analysis suggests that screening for TPMT mutations using either genotype or enzymatic laboratory tests prior to the administration of 6-MP in pediatric ALL patients is not cost-effective. Copyright © 2011 Wiley-Liss, Inc.

Use of allopurinol with low-dose 6-mercaptopurine in inflammatory bowel disease to achieve optimal active metabolite levels: A review of four cases and the literature

PubMed Central

Witte, Todd N; Ginsberg, Allen L

2008-01-01

BACKGROUND: At least one-third of patients with inflammatory bowel disease do not respond or are intolerant to therapy with 6-mercaptopurine (6-MP). A subgroup fails to attain optimal levels of 6-thioguanine nucleotide (6-TGN) and instead shunts to 6-methylmercaptopurine nucleotide (6-MMPN). PATIENTS AND METHODS: A retrospective chart review was conducted, and four patients are described who had been previously unable to achieve optimal 6-TGN metabolite levels until allopurinol was added to their treatment. RESULTS: All four patients achieved optimal 6-TGN levels and undetectable 6-MMPN with a mean 6-MP dose of 0.49 mg/kg. Three achieved steroid-free clinical remission. Two of those three patients had normalization of liver enzymes; one patient had baseline normal liver enzymes despite an initial 6-MMPN level of 27,369 pmol/8×108 red blood cells. Two patients experienced reversible leukopenia. CONCLUSIONS: Combination allopurinol and low-dose 6-MP is an effective means to achieve optimal metabolite levels and steroid-free clinical remission in previously refractory patients. Caution is advised. PMID:18299738

Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity.

PubMed

Sakakura, Kenichi; Roth, Austin; Ladich, Elena; Shen, Kai; Coleman, Leslie; Joner, Michael; Virmani, Renu

2015-02-01

The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall. Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment. In the gel model, the peak temperature was highest in the low power-long duration (LP-LD) dose, followed by the mid-low power-mid duration (MLP-MD) dose and the mid-high power-short duration (MHP-SD) dose, and lowest in the mid power-short duration (MP-SD) dose and the high power-ultra short duration (HP-USD) dose. In the animal study, total ablation area was significantly greater in the LP-LD group, followed by the MLP-MD group, and it was least in the HP-USD, MP-SD and MHP-SD groups (p=0.02). Maximum distance was significantly greater in the LP-LD group, followed by the MLP-MD group, the MHP-SD group, and the HP-USD group, and shortest in the MP-SD group (p=0.007). The short spare distance was not different among the five groups (p=0.38). Renal artery damage was minimal, while preserving significant nerve damage in all groups. The Paradise Ultrasound Renal Denervation System is a controllable system where total ablation area and depth of ablation can be optimised by changing ultrasound power and duration while sparing renal arterial tissue damage but allowing sufficient peri-arterial nerve damage.

Relationship between high daily erythemal UV doses, total ozone, surface albedo and cloudiness: An analysis of 30 years of data from Switzerland and Austria

NASA Astrophysics Data System (ADS)

Rieder, H. E.; Staehelin, J.; Weihs, P.; Vuilleumier, L.; Maeder, J. A.; Holawe, F.; Blumthaler, M.; Lindfors, A.; Peter, T.; Simic, S.; Spichtinger, P.; Wagner, J. E.; Walker, D.; Ribatet, M.

2010-10-01

This work investigates the occurrence frequency of days with high erythemal UV doses at three stations in Switzerland and Austria (Davos, Hoher Sonnblick and Vienna) for the time period 1974-2003. While several earlier studies have reported on increases in erythemal UV dose up to 10% during the last decades, this study focuses on days with high erythemal UV dose, which is defined as a daily dose at least 15% higher than for 1950s clear-sky conditions (which represent preindustrial conditions with respect to anthropogenic chlorine). Furthermore, the influence of low column ozone, clear-sky/partly cloudy conditions and surface albedo on UV irradiance has been analyzed on annual and seasonal basis. The results of this study show that in the Central Alpine Region the number of days with high UV dose increased strongly in the early 1990s. A large fraction of all days with high UV dose occurring in the period 1974-2003 was found especially during the years 1994-2003, namely 40% at Davos, 54% at Hoher Sonnblick and 65% at Vienna. The importance of total ozone, clear-sky/partly cloudy conditions and surface albedo (e.g. in dependence of snow cover) varies strongly among the seasons. However, overall the interplay of low total ozone and clear-sky/partly cloudy conditions led to the largest fraction of days showing high erythemal UV dose. Furthermore, an analysis of the synoptic weather situation showed that days with high erythemal UV dose, low total ozone and high relative sunshine duration occur at all three stations more frequently during situations with low pressure gradients or southerly advection.

A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells.

PubMed

Chen, C; Yang, R L

2013-08-01

MP [4-(3',3'-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27(KIP1) protein and p21(CIP1) mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21(CIP1), p16(INK4a) and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer.

Long-term erythemal UV doses at Sodankylä estimated using total ozone, sunshine duration, and snow depth

NASA Astrophysics Data System (ADS)

Lindfors, A. V.; Arola, A.; Kaurola, J.; Taalas, P.; SvenøE, T.

2003-08-01

A method for estimating daily erythemal UV doses using total ozone, sunshine duration, and snow depth has been developed. The method consists of three steps: (1) daily clear-sky UV doses were simulated using the UVSPEC radiative transfer program, with daily values of total ozone as input data, (2) an empirical relationship was sought between the simulated clear-sky UV doses, the measured UV doses, and the duration of bright sunshine, and (3) daily erythemal UV doses were estimated using this relationship. The method accounts for the varying surface albedo by dividing the period of interest into winter and summer days, depending on the snow depth. Using this method, the daily erythemal UV doses at Sodankylä were estimated for the period 1950-1999. This was done using Tromsø's total ozone together with Sodankylä's own sunshine duration and snow depth as input data. Although the method is fairly simple, the results are in good agreement, even on the daily scale, with the UV radiation measured with the Brewer spectrophotometer at Sodankylä. Over the period 1950-1999 a statistically significant increasing trend of 3.9% per decade in erythemal UV doses was found for March. The fact that this trend is much more pronounced during the latter part of the period, which is also the case for April, suggests a connection to the stratospheric ozone depletion. For July, on the other hand, a significant decreasing trend of 3.3% per decade, supported by the changes in both total ozone and sunshine duration, was found.

Maintenance therapy of childhood acute lymphoblastic leukemia revisited-Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

PubMed

Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard; Heyman, Mats; Wesenberg, Finn; Kristinsson, Jon; Vettenranta, Kim; Schrøeder, Henrik; Weinshilboum, Richard; Jensen, Katrine Lykke; Grell, Kathrine; Rosthoej, Susanne

2016-12-01

6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose adjustment guidelines. To identify relapse predictors, we collected 28,255 data sets on drug doses and blood counts (median: 47/patient) and analyzed erythrocyte (Ery) levels of cytotoxic 6MP/MTX metabolites in 9,182 blood samples (median: 14 samples/patient) from 532 children on MTX/6MP maintenance therapy targeted to a white blood cell count (WBC) of 1.5-3.5 × 10 9 /l. After a median follow-up of 13.8 years for patients in remission, stepwise Cox regression analysis did not find age, average doses of 6MP and MTX, hemoglobin, absolute lymphocyte counts, thrombocyte counts, or Ery levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10 9 /l rise [1.00-1.09], P = 0.048), the absolute neutrophil count (ANC; HR = 1.7 per 10 9 /l rise [1.3-2.4], P = 0.0007), and Ery thiopurine methyltransferase activity (HR = 2.7 per IU/ml rise [1.1-6.7], P = 0.03). WBC was significantly related to ANC (Spearman correlation coefficient, r s  = 0.77; P < 0.001), and only a borderline significant risk factor for relapse (HR = 1.28 [95% CI: 1.00-1.64], P = 0.046) when ANC was excluded from the Cox model. This study indicates that a low neutrophil count is likely to be the best hematological target for dose adjustments of maintenance therapy. © 2016 Wiley Periodicals, Inc.

Pharmacokinetics of two 6-mercaptopurine liquid formulations in children with acute lymphoblastic leukemia.

PubMed

Tolbert, Jaszianne A; Bai, Shasha; Abdel-Rahman, Susan M; August, Keith J; Weir, Scott J; Kearns, Gregory L; Neville, Kathleen A

2017-08-01

A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts. Group 1 (n = 11; five males) received a 5 mg/ml liquid formulation and the marketed 50 mg 6-MP tablet on separate occasions, and Group 2 (n = 11; five males) received a 50 mg/ml liquid formulation and the marketed tablet. The usual prescribed 6-MP dose (25-115 mg/m 2 ) was given after an 8-hr fast. Serial blood samples were collected over 8 hr postdose. Plasma 6-MP concentrations were determined using a good laboratory practice (GLP)-validated liquid chromatography-tandem mass spectrometry method. PK parameters were calculated using noncompartmental analysis and compared within and between cohorts, and thiopurine methyltransferase (TPMT) genotype was analyzed. No patient had a TPMT genotype reflective of a poor metabolizer phenotype. Comparison of PK parameters between 5 and 50 mg/ml treatments revealed significant differences (P <0.05) in AUC N (where AUC is area under the curve), C maxN , and T max . Comparisons within each group revealed significant differences in AUC 0-∞ and T max in the 5 mg/ml group. Pharmacokinetic profiles of 6-MP established in healthy adults with the approved liquid formulation may not reflect the PK profile in children with ALL. Formulation-specific differences in PK may significantly impact the dose-exposure profile in these children and must be considered. © 2017 Wiley Periodicals, Inc.

21 CFR 352.72 - General testing procedures.

Code of Federal Regulations, 2010 CFR

2010-04-01

... administered the doses of UV radiation. After UV radiation exposure from the solar simulator is completed, all... specified dosage of UV radiation, in a series of UV radiation exposures, in which the test site area is... subsites should be exposed to the varying doses of UV radiation in a randomized manner. (f) Waiting period...

Determination of urinary 6-mercaptopurine and three of its metabolites by HPLC-UV coupled with the iodine-azide reaction.

PubMed

Zakrzewski, Robert; Borowczyk, Kamila; Łuczak, Adam; Młynarski, Wojciech; Trelińska, Joanna

2013-04-01

The presented method is able to determine 6-mercaptopurine (6-MP), 6-thioguanine, 6-mercaptopurine riboside and 6-thioguanine riboside in urine, and is thereby dedicated to control of thiopurine therapy of children with acute lymphoblastic leukemia. Good separation of the mentioned compounds was achieved on a C18 stationary phase with a sodium azide and sodium heptane sulfonate solution, acetonitrile and water at ratio of 50:1:49 (v/v/v). Coefficient of regression is >0.99 for all linearity ranges. LOD and LOQ are 0.3, 0.4, 0.3, 0.8 and 0.4, 0.6, 0.5 and 0.9 nmol/ml of urine for 6-MP, 6-thioguanine, 6-mercaptopurine riboside and 6-thioguanine riboside, respectively. Intra- and inter-day recovery and RSD are close to 100% and less than 10%, respectively, for all investigated thiopurines. The elaborated method was successfully applied for detection and quantitation of 6-MP and its selected metabolites in patients' urine samples.

Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study.

PubMed

Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov; Behrendtz, Mikael; Forestier, Erik; Hasle, Henrik; Heyman, Mats; Kristinsson, Jon; Nersting, Jacob; Nygaard, Randi; Svendsen, Anne Louise; Vettenranta, Kim; Weinshilboum, Richard

2009-06-11

Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16 acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P = .07) were related to increased risk of SMN. Thiopurine methyltransferase (TPMT) methylates 6MP and its metabolites, and thus reduces cellular levels of cytotoxic 6-thioguanine nucleotides. Of 524 patients who had erythrocyte TPMT activity measured, the median TPMT activity in 9 patients developing an SMN was significantly lower than in the 515 that did not develop an SMN (median, 12.1 vs 18.1 IU/mL; P = .02). Among 427 TPMT wild-type patients for whom the 6MP dose was registered, those who developed SMN received higher average 6MP doses than the remaining patients (69.7 vs 60.4 mg/m2; P = .03). This study indicates that the duration and intensity of 6MP/MTX maintenance therapy of childhood ALL may influence the risk of SMNs in childhood ALL.

Therapeutic Efficacy of the Novel Stimuli-Sensitive Nano-Ferritins Containing Doxorubicin in a Head and Neck Cancer Model.

PubMed

Damiani, Verena; Falvo, Elisabetta; Fracasso, Giulio; Federici, Luca; Pitea, Martina; De Laurenzi, Vincenzo; Sala, Gianluca; Ceci, Pierpaolo

2017-07-18

Doxorubicin is employed alone or in combination for the treatment of several hematological and solid malignancies; despite its efficacy, there are associated cardiotoxicity limits both in its application in patients with heart disease risk factors and also in its long-term use. HFt-MP-PAS40 is a genetically engineered human ferritin heavy chain (HFt)-based construct able to efficiently entrap and deliver doxorubicin to cancer cells. HF-MP-PAS contains a short motif sequence (defined as MP) responsive to proteolytic cleavage by tumor matrix metalloproteases (MMPs), located between each HFt subunit and a masking polypeptide sequence rich in proline (P), alanine (A), and serine (S) residues (PAS). This carrier displayed excellent therapeutic efficacy in a xenogenic pancreatic cancer model in vivo, leading to a significant increase in overall animal survival in treated mice. Herein, we describe the HFt-MP-PAS40-Dox efficacy against squamous cell carcinomas of the head and neck (HNSCC) with the goal of validating the application of our nano-drug for the treatment of different solid tumors. In addition, a tolerability study in healthy mice was also performed. The results indicate that HFt-MP-PAS40-Dox produced increased anti-tumor effects both in vitro and in vivo in comparison to the free drug in several HNSCC cell lines. In the acute toxicity studies, the maximum tolerated dose (MTD) of HFt-MP-PAS40-Dox was about 3.5 higher than the free drug: 25 mg/kg versus 7 mg/kg doxorubicin equivalents. Importantly, evaluation of heart tissues provided evidence that doxorubicin is less cardio-toxic when encapsulated inside the ferritin carrier. In conclusion, HFt-MP-PAS40-Dox may be administered safely at higher doses compared with the free drug, resulting in superior efficacy to control HNSCC malignancies.

[Analysis of the cumulative solar ultraviolet radiation in Mexico].

PubMed

Castanedo-Cázares, Juan Pablo; Torres-Álvarez, Bertha; Portales-González, Bárbara; Martínez-Rosales, Karla; Hernández-Blanco, Diana

2016-01-01

The incidence of skin cancer has increased in Mexico in recent years. Ultraviolet radiation is the main risk factor associated. Due to the need to develop strategies to prevent skin cancer, the aim of the study was to estimate the UV intensity in several representative regions of Mexico, the average annual UV dose of these populations, and the potential benefit of applying sunscreen at different ages. The intensity of UV radiation was quantified by remote and terrestrial radiometry. The dose of UV exposure was measured in minimal erythema doses using validated models for face and arms. The benefit of using a sunscreen was calculated with the use of a sunscreen with SPF 15 from birth to age 70. The UV radiation is lower in December and greater in the period from May to July. The region with a lower annual dose is Tijuana; and the higher annual dose is in the Mexico City area. The annual difference between these regions was 58 %. Through life, a low SPF sunscreen can reduce up to 66 % of the received UV dose. The geographical location is a risk factor for accumulation of UV radiation in Mexico. Since childhood, people receive high amounts of it; however, most of this dose can be reduced using any commercially available sunscreen, if applied strategically.

Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, P.K.; Thanos, P.K.; Bermeo, C.

Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with themore » therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs. Thus, individuals with D4 receptor polymorphisms might show enhanced reinforcing responses to MP and AMPH and attenuated locomotor response to AMPH.« less

Preferential inhibition of xanthine oxidase by 2-amino-6-hydroxy-8-mercaptopurine and 2-amino-6-purine thiol

PubMed Central

Kalra, Sukirti; Jena, Gopabandhu; Tikoo, Kulbhushan; Mukhopadhyay, Anup Kumar

2007-01-01

Background The anticancer drug, 6-mercaptopurine (6MP) is subjected to metabolic clearance through xanthine oxidase (XOD) mediated hydroxylation, producing 6-thiouric acid (6TUA), which is excreted in urine. This reduces the effective amount of drug available for therapeutic efficacy. Co-administration of allopurinol, a suicide inhibitor of XOD, which blocks the hydroxylation of 6MP inadvertently enhances the 6MP blood level, counters this reduction. However, allopurinol also blocks the hydroxylation of hypoxanthine, xanthine (released from dead cancer cells) leading to their accumulation in the body causing biochemical complications such as xanthine nephropathy. This necessitates the use of a preferential XOD inhibitor that selectively inhibits 6MP transformation, but leaves xanthine metabolism unaffected. Results Here, we have characterized two such unique inhibitors namely, 2-amino-6-hydroxy-8-mercaptopurine (AHMP) and 2-amino-6-purinethiol (APT) on the basis of IC50 values, residual activity in bi-substrate simulative reaction and the kinetic parameters like Km, Ki, kcat. The IC50 values of AHMP for xanthine and 6MP as substrate are 17.71 ± 0.29 μM and 0.54 ± 0.01 μM, respectively and the IC50 values of APT for xanthine and 6MP as substrates are 16.38 ± 0.21 μM and 2.57 ± 0.08 μM, respectively. The Ki values of XOD using AHMP as inhibitor with xanthine and 6MP as substrate are 5.78 ± 0.48 μM and 0.96 ± 0.01 μM, respectively. The Ki values of XOD using APT as inhibitor with xanthine and 6MP as substrate are 6.61 ± 0.28 μM and 1.30 ± 0.09 μM. The corresponding Km values of XOD using xanthine and 6MP as substrate are 2.65 ± 0.02 μM and 6.01 ± 0.03 μM, respectively. The results suggest that the efficiency of substrate binding to XOD and its subsequent catalytic hydroxylation is much superior for xanthine in comparison to 6MP. In addition, the efficiency of the inhibitor binding to XOD is much more superior when 6MP is the substrate instead of xanthine. We further undertook the toxicological evaluation of these inhibitors in a single dose acute toxicity study in mice and our preliminary experimental results suggested that the inhibitors were equally non-toxic in the tested doses. Conclusion We conclude that administration of either APT or AHMP along with the major anti-leukemic drug 6MP might serve as a good combination cancer chemotherapy regimen. PMID:17511860

Effects of UV-B irradiation on isoforms of antioxidant enzymes and their activities in red alga Grateloupia filicina (Rhodophyta)

NASA Astrophysics Data System (ADS)

Zhao, Jiqiang; Li, Lixia

2014-11-01

Macroalgae in a littoral zone are inevitably exposed to UV-B irradiance. We analyzed the effects of UV-B on isoenzyme patterns and activities of superoxide dismutase (SOD), peroxidase (POX), catalase (CAT), and ascorbate peroxidase (APX) of red algae Grateloupia filicina (Lamour.) C. Agardh. The activities of SOD, CAT, and APX changed in response to UV-B in a time- and dose-dependent manner. POX activity increased significantly under all three UV-B treatments. The enzymatic assay showed three distinct bands of SODI (Mn-SOD), SODII (Fe-SOD), and SODIII (CuZn-SOD) under a low (Luv) and medium (Muv) dose of UV-B irradiation, while SODI and SODIII activities decreased significantly when exposed to a high dose of UV-B irradiation (Huv). The activity of POX isoenzymes increased significantly after exposure to UV-B, which is consistent with the total activity. In addition, a clear decrease in activity of CATIV was detected in response to all the three doses of UV treatments. Some bands of APX isoenzyme were also clearly influenced by UV-B irradiation. Correspondingly, the daily growth rate declined under all the three exposure doses, and was especially significant under Muv and Huv treatments. These data suggest that, although the protection mechanisms of antioxidant defense system are partly inducible by UV-B to prevent the damage, G. filicina has incomplete tolerance to higher UV-B irradiation stress.

Abscisic acid induces biosynthesis of bisbibenzyls and tolerance to UV-C in the liverwort Marchantia polymorpha.

PubMed

Kageyama, Akito; Ishizaki, Kimitsune; Kohchi, Takayuki; Matsuura, Hideyuki; Takahashi, Kosaku

2015-09-01

Environmental stresses are effective triggers for the biosynthesis of various secondary metabolites in plants, and phytohormones such as jasmonic acid and abscisic acid are known to mediate such responses in flowering plants. However, the detailed mechanism underlying the regulation of secondary metabolism in bryophytes remains unclear. In this study, the induction mechanism of secondary metabolites in the model liverwort Marchantia polymorpha was investigated. Abscisic acid (ABA) and ultraviolet irradiation (UV-C) were found to induce the biosynthesis of isoriccardin C, marchantin C, and riccardin F, which are categorized as bisbibenzyls, characteristic metabolites of liverworts. UV-C led to the significant accumulation of ABA. Overexpression of MpABI1, which encodes protein phosphatase 2C (PP2C) as a negative regulator of ABA signaling, suppressed accumulation of bisbibenzyls in response to ABA and UV-C irradiation and conferred susceptibility to UV-C irradiation. These data show that ABA plays a significant role in the induction of bisbibenzyl biosynthesis, which might confer tolerance against UV-C irradiation in M. polymorpha. Copyright © 2015 Elsevier Ltd. All rights reserved.

Maternal blood, plasma, and breast milk lead: lactational transfer and contribution to infant exposure.

PubMed

Ettinger, Adrienne S; Roy, Ananya; Amarasiriwardena, Chitra J; Smith, Donald; Lupoli, Nicola; Mercado-García, Adriana; Lamadrid-Figueroa, Hector; Tellez-Rojo, Martha Maria; Hu, Howard; Hernández-Avila, Mauricio

2014-01-01

Human milk is a potential source of lead exposure. Yet lactational transfer of lead from maternal blood into breast milk and its contribution to infant lead burden remains poorly understood. We explored the dose-response relationships between maternal blood, plasma, and breast milk to better understand lactational transfer of lead from blood and plasma into milk and, ultimately, to the breastfeeding infant. We measured lead in 81 maternal blood, plasma, and breast milk samples at 1 month postpartum and in 60 infant blood samples at 3 months of age. Milk-to-plasma (M/P) lead ratios were calculated. Multivariate linear, piecewise, and generalized additive models were used to examine dose-response relationships between blood, plasma, and milk lead levels. Maternal lead levels (mean±SD) were as follows: blood: 7.7±4.0 μg/dL; plasma: 0.1±0.1 μg/L; milk: 0.8±0.7 μg/L. The average M/P lead ratio was 7.7 (range, 0.6-39.8) with 97% of the ratios being >1. The dose-response relationship between plasma lead and M/P ratio was nonlinear (empirical distribution function=6.5, p=0.0006) with the M/P ratio decreasing by 16.6 and 0.6 per 0.1 μg/L of plasma lead, respectively, below and above 0.1 μg/L plasma lead. Infant blood lead level (3.4±2.2 μg/dL) increased by 1.8 μg/dL per 1 μg/L milk lead (p<0.0001, R2=0.3). The M/P ratio for lead in humans is substantially higher than previously reported, and transfer of lead from plasma to milk may be higher at lower levels of plasma lead. Breast milk is an important determinant of lead burden among breastfeeding infants.

UV dose measurements of photosensitive dermatosis patients by polycrystalline GaN-based portable self-data-acquisition UV monitors.

PubMed

Yagi, Shigeru; Iwanaga, Takeshi; Kojima, Hiroshi; Shoji, Yoshio; Suzuki, Seiji; Seno, Kunihiro; Mori, Hisayoshi; Tokura, Yoshiki; Takigawa, Masahiro; Moriwaki, Shin-Ichi

2002-12-01

We have developed a UV monitor with polycrystalline (poly-) gallium nitride (GaN) UV sensors and evaluated its performance from the viewpoint of its effectiveness for use with photosensitive dermatosis patients. The poly-GaN UV sensor is sensitive to UV light from 280 to 410 nm even without optical filters. The UV monitor is a portable self-data-acquisition instrument with a minimum detection level (defined as average UV intensity over 290 to 400 nm) of 2 microW/cm2 and can store UV dose data for 128 days. It allows easy measurement of four orders of magnitude of ambient UV intensity and dose from indoor light to direct solar radiation in summer. Trial use of the UV monitor by five xeroderma pigmentosum patients started in June 2000 and was carried out for 1 year. It was demonstrated that the UV monitor was useful in improving their quality of life.

The ten-year single-center experience with 6-mercaptopurine in the treatment of inflammatory bowel disease.

PubMed

Glazier, Kenneth D; Palance, Adam L; Griffel, Louis H; Das, Kiron M

2005-01-01

To report the 10-year experience of a single center in treating patients with refractory inflammatory bowel disease (IBD) with relatively lower dose of 6-mercaptopurine (6-MP). The charts of 285 patients with IBD (Crohn's disease 160 and ulcerative colitis 125) receiving 6-MP were reviewed. Clinical response, subsequent breakthrough while taking 6-MP, and relapse rates when 6-MP was discontinued and side effects were assessed. Ninety-three percent of the patients were taking 50 to 75 mg/day of 6-MP. Complete remission was achieved in 62%, partial remission in 14.5%, and failure to achieve remission in 23.5% of the patients. Of complete responders, 27.5% had breakthrough while continuing 6-MP. Nine percent of those that achieved a complete remission experienced a relapse after 6-MP was discontinued. Side effects included leukopenia (11.2%), abnormal liver function tests (3.8%), various infections, including pneumonia (3.1%), pancreatitis (2.5%), nausea (2.1%), headache (2.8%), fever (1.4%), hair loss (1%), and rash (0.7%). Two cancers occurred while taking 6-MP: melanoma on the finger and a fatal colonic lymphoma. Four patients continued 6-MP throughout pregnancies and had normal outcomes. In our experience 6-MP is relatively safe and appears to be as effective at a lower dosage (0.84 mg/kg per day) compared with the recommended higher dosage (1-1.5 mg/kg per day), when leukopenia was more frequent. Serious side effects, although rare, need to be monitored.

Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4-methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi-organ carcinogenesis model.

PubMed

Hirose, M; Takesada, Y; Tanaka, H; Tamano, S; Kato, T; Shirai, T

1998-01-01

The carcinogenicity of low dietary levels of the antioxidants butylated hydroxyanisole (BHA), caffeic acid, sesamol, 4-methoxyphenol (4-MP) and catechol, known to target the forestomach or glandular stomach, were examined alone or in combination in a 2-year long-term experiment and their modifying effects assessed in a medium-term multiorgan model. In the carcinogenicity study, groups of 30-31 male F344 rats were treated with 0.4% BHA, 0.4% caffeic acid, 0.4% sesamol, 0.4% 4-MP and 0.16% catechol either alone or in combination for up to 104 weeks and then killed. In the medium-term multi-organ model, groups of 10 to 15 male F344 rats were given diethylnitrosamine (DEN), N-methylnitrosourea (MNU), 1,2-dimethylhydrazine (DMH), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) for a total multiple initiation period of 4 weeks (DMBDD treatment). BHA, caffeic acid, sesamol and 4-MP, each at doses of 0.4% or 0.08%, and catechol at doses of 0.16% or 0.032% were administered in the diet either alone or in combination after completion of the initiation regimen. All surviving animals were killed at the end of week 28, and major organs were examined histopathologically. In the carcinogenicity study, slightly increased incidences of forestomach papillomas were found in the sesamol- (15.8%), caffeic acid- (14.8%), catechol- (3%) and 4-MP- (11.5%) treated groups as compared with basal diet (0%), and a significant increase was observed with the five antioxidants in combination (42.9%, P < 0.001). In a medium-term multiorgan carcinogenesis model, incidences of forestomach papillomas and/or carcinomas were increased in each high dose group, but additive or synergistic effects were not found in the combination group. In the low dose case, the incidence of forestomach papillomas was significantly increased only in the combination group. With regard to other organs, the incidence of colon tumors was significantly decreased only in the high dose combination group. The results indicate that even at low dose levels phenolic compounds can exert additive/synergistic effect on carcinogenesis.

ESTIMATION OF UV-B EXPOSURE IN AMPHIBIAN AQUATIC ENVIRONMENTS

EPA Science Inventory

Estimation of ultraviolet radiation B (UV-B; 280 to 320 nm wavelenghts) dose is essential for determining whether UV-B contributes to amphibian population declines and malformations. UV-B dose in wetlands is effected by location, time of day and year, atmospheric levels of ozone,...

6-Mercaptopurine, an activator of Nur77, enhances transcriptional activity of HIF-1alpha resulting in new vessel formation.

PubMed

Yoo, Y-G; Na, T-Y; Yang, W-K; Kim, H-J; Lee, I-K; Kong, G; Chung, J-H; Lee, M-O

2007-05-31

Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in oxygen homeostasis. Previously, we reported that the orphan nuclear receptor Nur77 functions in stabilizing HIF-1alpha. Here, we demonstrate that 6-mercaptopurine (6-MP), an activator of the NR4A family members, enhances transcriptional activity of HIF-1. 6-MP enhanced the protein-level of HIF-1alpha as well as vascular endothelial growth factor (VEGF) in a dose- and time-dependent manner. The induction of HIF-1alpha was abolished by the transfection of either a dominant-negative Nur77 mutant or si-Nur77, indicating a critical role of Nur77 in the 6-MP action. The HIF-1alpha protein level remained up to 60 min in the presence of 6-MP when de novo protein synthesis was blocked by cycloheximide, suggesting that 6-MP induces stabilization of the HIF-1alpha protein. The fact that 6-MP decreased the association of HIF-1alpha with von Hippel-Lindau protein and the acetylation of HIF-1alpha, may explain how 6-MP induced stability of HIF-1alpha. Further, 6-MP induced the transactivation function of HIF-1alpha by recruiting co-activator cyclic-AMP-response-element-binding protein. Finally, 6-MP enhanced the expression of HIF-1alpha and VEGF, and the formation of capillary tubes in human umbilical vascular endothelial cells. Together, our results provide a new insight for 6-MP action in the stabilization of HIF-1alpha and imply a potential application of 6-MP in hypoxia-associated human vascular diseases.

Mucuna pruriens for Parkinson's disease: Low-cost preparation method, laboratory measures and pharmacokinetics profile.

PubMed

Cassani, Erica; Cilia, Roberto; Laguna, Janeth; Barichella, Michela; Contin, Manuela; Cereda, Emanuele; Isaias, Ioannis U; Sparvoli, Francesca; Akpalu, Albert; Budu, Kwabena Ofosu; Scarpa, Maria Teresa; Pezzoli, Gianni

2016-06-15

Parkinson's disease (PD) is a progressive neurological condition. Levodopa (LD) is the gold standard therapy for PD patients. Most PD patients in low-income areas cannot afford long-term daily Levodopa therapy. The aim of our study was to investigate if Mucuna pruriens (MP), a legume with high LD content that grows in tropical regions worldwide, might be potential alternative for poor PD patients. We analyzed 25 samples of MP from Africa, Latin America and Asia. We measured the content in LD in various MP preparations (dried, roasted, boiled). LD pharmacokinetics and motor response were recorded in four PD patients, comparing MP vs. LD+Dopa-Decarboxylase Inhibitor (DDCI) formulations. Median LD concentration in dried MP seeds was 5.29%; similar results were obtained in roasted powder samples (5.3%), while boiling reduced LD content up to 70%. Compared to LD+DDCI, MP extract at similar LD dose provided less clinical benefit, with a 3.5-fold lower median AUC. Considering the lack of a DDCI, MP therapy may provide clinical benefit only when content of LD is at least 3.5-fold the standard LD+DDCI. If long-term MP proves to be safe and effective in controlled clinical trials, it may be a sustainable alternative therapy for PD in low-income countries. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Memantine-derived drugs as potential antitumor agents for the treatment of glioblastoma.

PubMed

Cacciatore, Ivana; Fornasari, Erika; Marinelli, Lisa; Eusepi, Piera; Ciulla, Michele; Ozdemir, Ozlem; Tatar, Abdulgani; Turkez, Hasan; Di Stefano, Antonio

2017-11-15

Glioblastoma is one of the most aggressive malignant primary brain cancer in adults. To date, surgery, radiotherapy and current pharmacological treatments are not sufficient to manage this pathology that has a high mortality rate (median survival 12-15months). Recently, anticancer multi-targeted compounds have attracted much attention with the aim to obtain new drugs able to hit different biological targets that are involved in the onset and progression of the disease. Here, we report the synthesis of novel memantine-derived drugs (MP1-10) and their potential antitumor activities in human U87MG glioblastoma cell line. MP1-10 were synthetized joining memantine, which is a NMDA antagonist, to different histone deacetylase inhibitors to obtain one molecule with improved therapeutic efficacy. Biological results indicated that MP1 and MP2 possessed more potent anti-proliferative effects on U87MG cells than MP3-10 in a dose-dependent manner. MP1 and MP2 induced significant cell death by apoptosis characterized by apoptotic morphological changes in Hoechst staining. Both drugs also exhibited non-genotoxic and only mild cytotoxic effects in human whole blood cells. However, only MP1, showing good chemico-physical properties (solubility, LogP) and enzymatic stabilities in gastric and intestinal fluids, can be considered a suitable candidate for in vivo pharmacokinetic studies. Copyright © 2017 Elsevier B.V. All rights reserved.

UV EFFECTS IN TOOTH ENAMEL AND THEIR POSSIBLE APPLICATION IN EPR DOSIMETRY WITH FRONT TEETH

PubMed Central

Sholom, S.; Desrosiers, M.; Chumak, V.; Luckyanov, N.; Simon, S.L.; Bouville, A.

2009-01-01

The effects of ultraviolet (UV) radiation on ionizing radiation biodosimetry were studied in human tooth enamel samples using the technique of electron paramagnetic resonance (EPR) in X-band. For samples in the form of grains, UV-specific EPR spectra were spectrally distinct from that produced by exposure to gamma radiation. From larger enamel samples, the UV penetration depth was determined to be in the 60–120 μm range. The difference in EPR spectra from UV exposure and from exposure to gamma radiation samples was found to be a useful marker of UV equivalent dose (defined as the apparent contribution to the gamma dose in mGy that results from UV radiation absorption) in tooth enamel. This concept was preliminarily tested on front teeth from inhabitants of the region of the Semipalatinsk Nuclear Test Site (Kazakhstan) who might have received some exposure to gamma radiation from the nuclear tests conducted there as well as from normal UV radiation in sunlight. The technique developed here to quantify and subtract the UV contribution to the measured tooth is currently limited to cumulative dose measurements with a component of UV equivalent dose equal to or greater than 300 mGy. PMID:20065706

A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells

PubMed Central

Chen, C.; Yang, R.L.

2013-01-01

MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27KIP1 protein and p21CIP1 mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21CIP1, p16INK4a and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer. PMID:23903687

Ultraviolet radiation in the Atacama Desert.

PubMed

Cordero, R R; Damiani, A; Jorquera, J; Sepúlveda, E; Caballero, M; Fernandez, S; Feron, S; Llanillo, P J; Carrasco, J; Laroze, D; Labbe, F

2018-03-31

The world's highest levels of surface ultraviolet (UV) irradiance have been measured in the Atacama Desert. This area is characterized by its high altitude, prevalent cloudless conditions, and a relatively low total ozone column. In this paper, we provide estimates of the surface UV (monthly UV index at noon and annual doses of UV-B and UV-A) for all sky conditions in the Atacama Desert. We found that the UV index at noon during the austral summer is expected to be greater than 11 in the whole desert. The annual UV-B (UV-A) doses were found to range from about 3.5 kWh/m 2 (130 kWh/m 2 ) in coastal areas to 5 kWh/m 2 (160 kWh/m 2 ) on the Andean plateau. Our results confirm significant interhemispherical differences. Typical annual UV-B doses in the Atacama Desert are about 40% greater than typical annual UV-B doses in northern Africa. Mostly due to seasonal changes in the ozone, the differences between the Atacama Desert and northern Africa are expected to be about 60% in the case of peak UV-B levels (i.e. the UV-B irradiances at noon close to the summer solstice in each hemisphere). Interhemispherical differences in the UV-A are significantly lower since the effect of the ozone in this part of the spectrum is minor.

Pharyngeal and cervical cancer incidences significantly correlate with personal UV doses among whites in the United States.

PubMed

Godar, Dianne E; Tang, Rong; Merrill, Stephen J

2014-09-01

Because we found UV-exposed oral tissue cells have reduced DNA repair and apoptotic cell death compared with skin tissue cells, we asked if a correlation existed between personal UV dose and the incidences of oral and pharyngeal cancer in the United States. We analyzed the International Agency for Research on Cancer's incidence data for oral and pharyngeal cancers by race (white and black) and sex using each state's average annual personal UV dose. We refer to our data as 'white' rather than 'Caucasian,' which is a specific subgroup of whites, and 'black' rather than African-American because blacks from other countries around the world reside in the U.S. Most oropharyngeal carcinomas harboured human papilloma virus (HPV), so we included cervical cancer as a control for direct UV activation. We found significant correlations between increasing UV dose and pharyngeal cancer in white males (p=0.000808) and females (p=0.0031) but not in blacks. Shockingly, we also found cervical cancer in whites to significantly correlate with increasing UV dose (p=0.0154). Thus, because pharyngeal and cervical cancer correlate significantly with increasing personal UV dose in only the white population, both direct (DNA damage) and indirect (soluble factors) effects may increase the risk of HPV-associated cancer. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Structures, molecular orbitals and UV-vis spectra investigations on methyl 1-benzyl-1H-1,2,3-triazole-4-carboxylate: a computational study.

PubMed

Wang, Tsang-Hsiu; Chu, Hsing-Yu; Wang, I-Teng

2014-10-15

The methyl 1-benzyl-1H-1,2,3-triazole-4-carboxylate (C11H11N3O2) has been studied by theoretically methods. The structure of this compound is optimized by density functional theory (DFT), the second-order Møller-Plesset perturbation theory (MP2) and G3 theory (G3(MP2)) levels. Our calculation results are in very good agreement with experimental values. Compared to a perfect pentagonal structure, the geometrical structures of C11H11N3O2 show a little distortion of 1,2,3-triazole ring due to the highly electronegativity of substitution groups. In addition, dipole moment and frontier molecular orbitals (FMOs) of the C11H11N3O2 are calculated as well. Because of solvent effect, the HOMO-LUMO energy gap in methanol is predicted to be smaller than in gas phase by 0.367eV. The simulated UV-vis spectra are investigated by time-dependent density functional theory (TD-DFT), and two obviously absorption features have been predicted. These two absorption features are located between 170nm and 210nm, which is in ultraviolet C range. Moreover, the UV absorption features in methanol are predicted to be more intense than in gas phase; besides, the red shift is predicted in methanol as well. Copyright © 2014 Elsevier B.V. All rights reserved.

Distribution of boreal toad populations in relation to estimated UV-B dose in Glacier National Park, Montana, USA

USGS Publications Warehouse

Hossack, B.R.; Diamond, S.A.; Corn, P.S.

2006-01-01

A recent increase in ultraviolet B radiation is one hypothesis advanced to explain suspected or documented declines of the boreal toad (Bufo boreas Baird and Girard, 1852) across much of the western USA, where some experiments have shown ambient UV-B can reduce embryo survival. We examined B. boreas occupancy relative to daily UV-B dose at 172 potential breeding sites in Glacier National Park, Montana, to assess whether UV-B limits the distribution of toads. Dose estimates were based on ground-level UV-B data and the effects of elevation, local topographic and vegetative features, and attenuation in the water column. We also examined temporal trends in surface UV-B and spring snowpack to determine whether populations are likely to have experienced increased UV-B exposure in recent decades. We found no support for the hypothesis that UV-B limits the distribution of populations in the park, even when we analyzed high-elevation ponds separately. Instead, toads were more likely to breed in water bodies with higher estimated UV-B doses. The lack of a detectable trend in surface UV-B since 1979, combined with earlier snow melt in the region and increasing forest density at high elevations, suggests B. boreas embryos and larvae likely have not experienced increased UV-B.

Photodegradation of pharmaceuticals and personal care products during UV and UV/H2O2 treatments.

PubMed

Kim, Ilho; Yamashita, Naoyuki; Tanaka, Hiroaki

2009-10-01

Photodegradation characteristics of pharmaceuticals and personal care products (PPCPs) and the effectiveness of H(2)O(2) addition for PPCPs photodegradation during UV treatment were examined in this study. Average k (1st order rate constant) value for all the PPCPs investigated increased by a factor of 1.3 by H(2)O(2) addition during UV treatment using biologically treated water (TW) spiked with the 30 PPCPs. Therefore, the effectiveness of H(2)O(2) addition for PPCPs removal during UV treatment in real wastewater treatment process was expected. It could be also known that H(2)O(2) addition would improve photodegradation rates of PPCPs highly resistant for UV treatment such as DEET, ethenzamide and theophylline. UV dose required for 90% degradation of each PPCP was calculated from k values obtained in UV and UV/H(2)O(2) treatment experiments using TW spiked with 30 PPCPs. For UV treatment, UV dose required for degrading each PPCP by 90% of initial concentration ranged from 38 mJ cm(-2) to 5644 mJ cm(-2), indicating that most of PPCPs will not be removed sufficiently in UV disinfection process in wastewater treatment plant. For UV/H(2)O(2) treatment, all the PPCPs except seven PPCPs including cyclophosphamide and 2-QCA were degraded by more than 90% by UV irradiation for 30 min (UV dose: 691 mJ cm(-2)), indicating that H(2)O(2) addition during UV treatment will be highly effective for improving the degradation of PPCPs by UV, even though much higher UV dose is still necessary comparing to for UV disinfection.

Pre-harvest UV-C irradiation triggers VOCs accumulation with alteration of antioxidant enzymes and phytohormones in strawberry leaves.

PubMed

Xu, Yanqun; Luo, Zisheng; Charles, Marie Thérèse; Rolland, Daniel; Roussel, Dominique

2017-11-01

Recent studies have highlighted the biological and physiological effects of pre-harvest ultraviolet (UV)-C treatment on growing plants. However, little is known about the involvement of volatile organic compounds (VOCs) and their response to this treatment. In this study, strawberry plants were exposed to three different doses of UV-C radiation for seven weeks (a low dose: 9.6kJm -2 ; a medium dose: 15kJm -2 ; and a high-dose: 29.4kJm -2 ). Changes in VOC profiles were investigated and an attempt was made to identify factors that may be involved in the regulation of these alterations. Principle compounds analysis revealed that VOC profiles of UV-C treated samples were significantly altered with 26 VOCs being the major contributors to segregation. Among them, 18 fatty acid-derived VOCs accumulated in plants that received high and medium dose of UV-C treatments with higher lipoxygenase and alcohol dehydrogenase activities. In treated samples, the activity of the antioxidant enzymes catalase and peroxidase was inhibited, resulting in a reduced antioxidant capacity and higher lipid peroxidation. Simultaneously, jasmonic acid level was 74% higher in the high-dose group while abscisic acid content was more than 12% lower in both the medium and high-dose UV-C treated samples. These results indicated that pre-harvest UV-C treatment stimulated the biosynthesis of fatty acid-derived VOCs in strawberry leaf tissue by upregulating the activity of enzymes of the LOX biosynthetic pathway and downregulating antioxidant enzyme activities. It is further suggested that the mechanisms underlying fatty acid-derived VOCs biosynthesis in UV-C treated strawberry leaves are associated with UV-C-induced changes in phytohormone profiles. Crown Copyright © 2017. Published by Elsevier GmbH. All rights reserved.

Growth, yield and tuber quality of Solanum tuberosum L. under supplemental ultraviolet-B radiation at different NPK levels.

PubMed

Singh, S; Kumari, R; Agrawal, M; Agrawal, S B

2011-05-01

In many areas, decreases in the stratospheric ozone layer have resulted in an increase in ultraviolet-B (UV-B, 280-315 nm) radiation reaching the Earth's surface. The present study was conducted to evaluate the interactive effects of supplemental UV-B (sUV-B) and mineral nutrients on a tuber crop, potato (Solanum tuberosum L. var Kufri Badshah), under natural field conditions in a dry tropical environment. The nutrient treatments were the recommended dose of NPK (F(o)), 1.5 times the recommended dose of NPK (F(1)), 1.5 times the recommended dose of N (F(2)) and 1.5 times the recommended dose of K (F(3)). The response of potato plants to sUV-B varied with nutrient treatment and concentration. sUV-B adversely affected growth, yield and quality of tubers, causing an increase in reducing sugars in the tubers and thus reducing the economic value. Growth and fresh weight of tubers was maximal with sUV-B at 1.5 times recommended NPK, but the dry weight of tubers were highest with the recommended NPK dose. Reducing sugar content was lower in potato plants treated with sUV-B and the recommended NPK than with sUV-B and 1.5 times the recommended NPK. This study thus clearly shows that growing potato with 1.5 times the recommended NPK or 1.5 times the recommended dose of N/K does not alleviate the sUV-B induced changes in yield and quality of tubers compared to the recommended NPK dose. © 2010 German Botanical Society and The Royal Botanical Society of the Netherlands.

Cumulative effects from repeated exposures to ultraviolet radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaidbey, K.H.; Kligman, A.M.

Repeated exposures to subliminal doses of UVR, given at 24-hr intervals, resulted in a lowering of the erythema threshold dose. At erythemogenically equivalent doses, UV-A was the most effective and UV-C the least. A similar and more pronounced effect was observed following repeated exposures to subthreshold doses of UV-A and topically applied 8-methoxypsoralen. These findings provide quantitative evidence for the cumulative nature of acute UVR damage in human skin.

Comparison of UV-B measurements performed with a Brewer spectrophotometer and a new UVB-1 broad band detector

NASA Technical Reports Server (NTRS)

Bais, Alkiviadis F.; Zerefos, Christos S.; Meleti, Charicleia; Ziomas, Ioannis C.

1994-01-01

Measurements of the UV-B erythemal dose, based on solar spectra acquired with a Brewer spectrophotometer at Thessaloniki, Greece, are compared to measurements performed with the recently introduced, by the Yankee Environmental Systems, (Robertson type) broad band solar UV-B detector. The spectral response function of this detector, when applied to the Brewer spectral UV-B measurements, results in remarkably comparable estimates of the erythemal UV-B dose. The two instruments provide similar information on the UV-B dose when they are cross-examined under a variety of meteorological and atmospheric conditions and over the a large range of solar zenith angles and total ozone.

UV controlling factors and trends derived from the ground-based measurements taken at Belsk, Poland, 1976-1994

NASA Astrophysics Data System (ADS)

KrzyśCin, Janusz W.

1996-07-01

Monthly means of UV erythemal dose at ground level from the Robertson-Berger (RB) sunburn meter (1976-1992) and the UV-Biometer model 501 MED meter (1993-1994) located at Belsk (21°E, 52°N), Poland, are examined. The monthly means are calculated from all-sky daily means of UV erythemal dose. Ancillary measurements of column ozone (by Dobson spectrophotometer), sunshine duration (by Campbell-Stokes heliograph), and total (sun and sky) radiation (by a pyranometer) are considered to explain variations in the UV data. A multiple regression model is proposed to study trends in the UV data. The model accounts for the UV erythemal dose changes induced by total ozone, sunshine duration (surrogate for cloud cover variations), or total solar radiation (surrogate for combined cloud cover and atmospheric turbidity impact on the UV radiation), trends due to instrument drift, step changes in the data, and serial correlations. A strong relationship between monthly all-sky UV erythemal dose changes and total ozone (and total solar radiation) is found. Calculations show that an erythemal radiative amplification factor (RAF) due to ozone under all skies is close to its clear-sky value (about 1). However, the model gives evidence that the RAF due to ozone is smaller for cloudier (and/or more turbid) atmospheres than long-term reference. Total solar radiation change of 1% is associated with a change of 0.7% in the UV erythemal dose. Modeled trends in the Belsk's UV data, inferred from the model using ozone and total solar radiation as the UV forcing factors, are 2.3% ± 0.4% (1σ) per decade in the period 1976-1994. The large increase in the UV erythemal dose, of the order of 4% per decade due to ozone depletion (-3.2% per decade), is partially compensated by a decreasing tendency (-2.8% per decade) in total solar radiation. The model estimates the trend in the UV data of the order of 0.1% per decade (not statistically significant) due to superposition of the instrument drift and long-term effects related to other UV influencing factors (not parameterized by the model).

Daily Nutritional Dose Supplementation with Antioxidant Nutrients and Phytochemicals Improves DNA and LDL Stability: A Double-Blind, Randomized, and Placebo-Controlled Trial

PubMed Central

Kim, You Jin; Ahn, Yoon Hee; Lim, Yeni; Kim, Ji Yeon; Kim, Joohee; Kwon, Oran

2013-01-01

Reactive oxygen species are important risk factors for age-related diseases, but they also act as signaling factors for endogenous antioxidative defense. The hypothesis that a multi-micronutrient supplement with nutritional doses of antioxidant nutrients and phytochemicals (MP) may provide protection against oxidative damage and maintain the endogenous antioxidant defense capacity was assessed in subjects with a habitually low intake of fruits and vegetables. In a randomized, placebo-controlled, and parallel designed trial, 89 eligible subjects were assigned to either placebo or MP for eight weeks. Eighty subjects have completed the protocol and included for the analysis. MP treatment was superior at increasing serum folate (p < 0.0001) and resistance to DNA damage (p = 0.006, tail intensity; p = 0.030, tail moment by comet assay), and LDL oxidation (p = 0.009) compared with the placebo. Moreover, the endogenous oxidative defense capacity was not weakened after MP supplementation, as determined by the levels of glutathione peroxidase (p = 0.442), catalase (p = 0.686), and superoxide dismutase (p = 0.804). The serum folate level was negatively correlated with DNA damage (r = −0.376, p = 0.001 for tail density; r = −0.329, p = 0.003 for tail moment), but no correlation was found with LDL oxidation (r = −0.123, p = 0.275). These results suggest that MP use in healthy subjects with habitually low dietary fruit and vegetable intake may be beneficial in providing resistance to oxidative damage to DNA and LDL without suppressing the endogenous defense mechanisms. PMID:24352096

Dermal damage promoted by repeated low-level UV-A1 exposure despite tanning response in human skin.

PubMed

Wang, Frank; Smith, Noah R; Tran, Bao Anh Patrick; Kang, Sewon; Voorhees, John J; Fisher, Gary J

2014-04-01

Solar UV irradiation causes photoaging, characterized by fragmentation and reduced production of type I collagen fibrils that provide strength to skin. Exposure to UV-B irradiation (280-320 nm) causes these changes by inducing matrix metalloproteinase 1 and suppressing type I collagen synthesis. The role of UV-A irradiation (320-400 nm) in promoting similar molecular alterations is less clear yet important to consider because it is 10 to 100 times more abundant in natural sunlight than UV-B irradiation and penetrates deeper into the dermis than UV-B irradiation. Most (approximately 75%) of solar UV-A irradiation is composed of UV-A1 irradiation (340-400 nm), which is also the primary component of tanning beds. To evaluate the effects of low levels of UV-A1 irradiation, as might be encountered in daily life, on expression of matrix metalloproteinase 1 and type I procollagen (the precursor of type I collagen). In vivo biochemical analyses were conducted after UV-A1 irradiation of normal human skin at an academic referral center. Participants included 22 healthy individuals without skin disease. Skin pigmentation was measured by a color meter (chromometer) under the L* variable (luminescence), which ranges from 0 (black) to 100 (white). Gene expression in skin samples was assessed by real-time polymerase chain reaction. Lightly pigmented human skin (L* >65) was exposed up to 4 times (1 exposure/d) to UV-A1 irradiation at a low dose (20 J/cm2), mimicking UV-A levels from strong sun exposure lasting approximately 2 hours. A single exposure to low-dose UV-A1 irradiation darkened skin slightly and did not alter matrix metalloproteinase 1 or type I procollagen gene expression. With repeated low-dose UV-A1 irradiation, skin darkened incrementally with each exposure. Despite this darkening, 2 or more exposures to low-dose UV-A1 irradiation significantly induced matrix metalloproteinase 1 gene expression, which increased progressively with successive exposures. Repeated UV-A1 exposures did not suppress type I procollagen expression. A limited number of low-dose UV-A1 exposures, as commonly experienced in daily life, potentially promotes photoaging by affecting breakdown, rather than synthesis, of collagen. Progressive skin darkening in response to repeated low-dose UV-A1 exposures in lightly pigmented individuals does not prevent UV-A1-induced collagenolytic changes. Therefore, for optimal protection against skin damage, sunscreen formulations should filter all UV wavelengths, including UV-A1 irradiation.

Assessment of the risk of solar ultraviolet radiation to amphibians. III. Prediction of impacts in selected northern midwestern wetlands.

PubMed

Diamond, Stephen A; Peterson, Gregory S; Tietge, Joseph E; Ankley, Gerald T

2002-07-01

Solar ultraviolet radiation, especially UVB (280-320 nm), has been hypothesized to be at least partially responsible for adverse effects (e.g., declines and malformations) in amphibian species throughout the world. Evaluation of this hypothesis has been limited by the paucity of high-quality UV dose-response data and reliable estimates of typical UV doses that occur in amphibian habitats. In this preliminary risk assessment for effects of UV radiation on amphibians, dose-response relationships quantified in outdoor experiments were compared with UV exposure estimates for 26 wetlands in northern Minnesota and Wisconsin. A comparison of wetland doses, derived from model prediction, historical data, and dissolved organic carbon (DOC) characterization, with experimental effects levels for green (R. clamitans), northern leopard (R. pipiens), and mink (R. septentrionalis) frogs indicated that the risk of mortality and malformations due to UV exposure is low for the majority of wetlands evaluated. Wetland UV dose, averaged over the entire breeding season, exceeded effects doses for mortality for all three species in two of the 26 wetlands examined and for one species in an additional wetland. On the basis of evidence that shorter term doses caused mortality in amphibian larvae, 3-day doses were also evaluated. In three of the wetlands examined, 3-day doses in excess of 85% of full sunlight (the level that appeared to trigger effects in controlled experimentation) occurred at frequencies ranging 22-100% for all three species and at frequencies ranging from 15% to 58% for R. pipiens and R. septentrionalis in three additional wetlands. Risk of malformation in R. pipiens was apparent in five of the 26 wetlands evaluated. Overall, estimated UVB doses in 21 of the wetlands never exceeded experimental effects doses for mortality or malformations. These results suggest that most amphibians are not currently at significant risk for UVB effects in northern Minnesota and Wisconsin wetlands. However, continued reduction of ozone and other global climate change effects may increase UV doses in wetlands, suggesting that the risk of UV to amphibians should continue to be monitored and studied.

Minimal and maximal incidence rates of skin cancer in Caucasians estimated by use of sigmoidal UV dose-incidence curves.

PubMed

Juzeniene, Asta; Grigalavicius, Mantas; Baturaite, Zivile; Moan, Johan

2014-11-01

Sigmoidal (S-shaped) dose-cancer incidence relationships are often observed in animal bioassays for carcinogenicity. Ultraviolet (UV) radiation is an established skin carcinogen. The aim of this study is to examine if S-shaped curves describe the relationship between solar UV doses and skin cancer incidences, and if such relationships can be used to estimate threshold levels of non-carcinogenic UV exposure, as well as maximal incidence rates. We studied the incidence rate-annual erythema-effective UV dose relationship for squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and cutaneous melanoma (CM) among different Caucasian populations in Europe, Australia and New Zealand. Our analysis indicates that S-shaped associations describe the data well (P < 0.0001). The age-adjusted incidence rates for cases expected to be due to other causes than solar UV exposure (at zero UV dose) were found to be around 0.6, 9.7 and 4.0 per 100,000 for women in 1997-2007 for SCC, BCC and CM, respectively, and around 1.2, 14.3 and 2.6 per 100,000 for men. The analysis indicates that SCC, BCC and CM have maximal incidence of 361 ± 24, 1544 ± 49 and 36 ± 4 per 100,000 for women, and 592 ± 35, 2204 ± 109 and 50 ± 4 per 100,000 for men. Between 89 and 95% of the annual CM cases, around 99.8% SCC and 99.4% BCC cases are caused by solar UV exposure. The analysis did not identify any "safe" UV dose below which the risk for skin cancer was absent. Avoidance of UV radiation has a potential to reduce the incidence of skin cancer in fair-skinned population. Copyright © 2014 Elsevier GmbH. All rights reserved.

Evaluation of an Innovative Approach to Validation of ...

EPA Pesticide Factsheets

UV disinfection is an effective process for inactivating many microbial pathogens found in source waters with the potential as stand-alone treatment or in combination with other disinfectants. For surface and groundwater sourced drinking water applications, the U.S. Environmental Protection Agency (USEPA) provided guidance on the validation of UV reactors nearly a decade ago. The focus of the guidance was primarily for inactivation of Cryptosporidium and Giardia. Over the last ten years many lessons have been learned, validation practices have been modified, new science issues discovered, and changes in operation & monitoring of UV systems need to be addressed. Also, there remains no standard approach for validating UV reactors to meet a 4-log (99.99%) inactivation of viruses. USEPA in partnership with the Cadmus Group, Carollo Engineers, and other State & Industry collaborators, are evaluating new approaches for validating UV reactors to meet groundwater & surface water pathogen inactivation including viruses for low-pressure and medium-pressure UV systems. A particular challenge for medium-pressure UV is the monitoring of low-wavelength germicidal contributions for appropriate crediting of disinfection under varying reactor conditions of quartz sleeve fouling, lamp aging, and changes in UV absorbance of the water over time. In the current effort, bench and full-scale studies are being conducted on a low pressure (LP) UV reactor and a medium pressure (MP) UV re

Particle effects on ultraviolet disinfection of coliform bacteria in recycled water.

PubMed

Jolis, D; Lam, C; Pitt, P

2001-01-01

Pilot- and bench-scale coliform inactivation tests with UV irradiation were used to show how suspended solids remaining in filtered secondary effluent affect the efficiency of the UV disinfection process. Observed kinetic inactivation rates decreased with increasing suspended particle sizes of 7 microm or larger present in tertiary effluent. First-order inactivation rates estimated from collimated beam dose-response curves for discrete ranges of UV doses were substantially different, which should caution researchers not to compare inactivation data obtained with largely dissimilar UV doses or suspended particle distributions. A dose of approximately 800 J/m2 was identified as the minimum dose that will consistently meet the California wastewater reclamation coliform criterion when applied to in-line filtration effluent.

A search for the optimal duration of treatment with 6-mercaptopurine for ulcerative colitis.

PubMed

Lobel, Efrat Z; Korelitz, Burton I; Xuereb, Mark A; Panagopoulos, Georgia

2004-03-01

6-mercaptopurine has proven to be effective in the treatment and maintenance of remission of ulcerative colitis (UC). The optimal duration of treatment with 6-MP is unknown. The intention of this study was to determine the best duration of treatment with 6-MP in terms of maintenance efficacy once remission has been achieved. We reviewed the records from the inflammatory bowel disease (IBD) center at Lenox Hill Hospital and one large IBD practice in New York City of 334 patients treated with 6-MP for UC. These patients were followed from 4 months to 28.7 yr. Sixty-one patients were treated with 6-MP for at least 6 months and had at least a 3-month disease-free interval off steroids while on the medication. These patients were divided into two groups: Group 1 continued 6-MP and group 2 discontinued the drug at various times for reasons other than relapse. Time to relapse was calculated for both groups. A Kaplan-Meier survival analysis was employed and differences between the two groups were analyzed using the log-rank test. The median time to relapse in group 2 was 24 wk and in group 1 was 58 wk (p < 0.05). There were no significant differences between the two groups in age, gender, extent of disease, use of concomitant 5-ASA products, dose of 6-MP during remission, duration of UC, and duration of treatment with 6-MP before remission was achieved. Discontinuation of treatment with 6-MP while UC is in remission leads to a higher relapse rate than maintenance on 6-MP. Therefore, we favor the indefinite treatment with 6-MP in most patients.

Classification and discrimination of pediatric patients undergoing open heart surgery with and without methylprednisolone treatment by cytomics

NASA Astrophysics Data System (ADS)

Bocsi, Jozsef; Mittag, Anja; Pierzchalski, Arkadiusz; Osmancik, Pavel; Dähnert, Ingo; Tárnok, Attila

2011-02-01

Introduction: Methylprednisolone (MP) is frequently preoperatively administered in children undergoing open heart surgery. The aim of this medication is to inhibit overshooting immune responses. Earlier studies demonstrated cellular and humoral immunological changes in pediatric patients undergoing heart surgeries with and without MP administration. Here in a retrospective study we investigated the modulation of the cellular immune response by MP. The aim was to identify suitable parameters characterizing MP effects by cluster analysis. Methods: Blood samples were analysed from two aged matched groups with surgical correction of septum defects. Group without MP treatment consisted of 10 patients; MP was administered on 21 patients (median dose: 11mg/kg) before cardiopulmonary bypass (CPB). EDTA anticoagulated blood was obtained 24 h preoperatively, after anesthesia, at CPB begin and end (CPB2), 4h, 24h, 48h after surgery, at discharge and at out-patient followup (8.2; 3.3-12.2 month after surgery; median and IQR). Flow cytometry showed the biggest MP relevant changes at CPB2 and 4h postoperatively. They were used for clustering analysis. Classification was made by discriminant analysis and cluster analysis by means of Genes@work software. Results & conclusion: 146 parameters were obtained from analysis. Cross-validation revealed several parameters being able to discriminate between MP groups and to identify immune modulation. MP administration resulted in a delayed activation of monocytes, increased ratio of neutrophils, reduced T-lymphocytes counts. Cluster analysis demonstrated that classification of patients is possible based on the identified cytomics parameters. Further investigation of these parameters might help to understand the MP effects in pediatric open heart surgery.

The Effects of Mitiglinide and Repaglinide on Postprandial Hyperglycemia in Patients Undergoing Methylprednisolone Pulse Therapy.

PubMed

Tanaka, Kenichi; Okada, Yosuke; Mori, Hiroko; Torimoto, Keiichi; Arao, Tadashi; Tanaka, Yoshiya

2018-01-01

One adverse effect of methylprednisolone (MP) pulse therapy is an acute dose-dependent increase in the blood glucose level. Five patients with thyroid ophthalmopathy but normal glucose tolerance received MP pulse therapy (3 cycles, 3 days/week) and were assessed by continuous glucose monitoring. Steroid therapy increased the mean sensor glucose level, and all patients developed steroid-induced diabetes. The patients were treated alternately with mitiglinide (30 mg/day) and repaglinide (1.5 mg/day) during the second or third MP pulse therapy. The sensor glucose levels before lunch and dinner were more favorable during treatment with repaglinide than during treatment with mitiglinide. Repaglinide may be more clinically appropriate than mitiglinide.

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn’s disease with low rate of side effects: results of double blind Phase II clinical trial

PubMed Central

Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya’acov, A Ben; Shabbat, Y; Ilan, Y

2015-01-01

Therapy for Crohn’s disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn’s Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62+ expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. PMID:25846055

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

PubMed

Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya'acov, A Ben; Shabbat, Y; Ilan, Y

2015-08-01

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. © 2015 British Society for Immunology.

Analysis of Levodopa Content in Commercial Mucuna pruriens Products Using High-Performance Liquid Chromatography with Fluorescence Detection.

PubMed

Soumyanath, Amala; Denne, Tanya; Hiller, Amie; Ramachandran, Shaila; Shinto, Lynne

2018-02-01

Mucuna pruriens (MP) seeds contain levodopa (up to 2% by weight) and have been used in traditional Indian medicine to treat an illness named "Kampavata," now understood to be Parkinson's disease (PD). Studies have shown MP to be beneficial, and even superior, to levodopa alone in treating PD symptoms. Commercial products containing MP are readily available from online and retail sources to patients and physicians. Products often contain extracts of MP seeds, with significantly higher levodopa content than the seeds. However, MP products have limited regulatory controls with respect to quality and content of active ingredient. The aim of this study was to apply a quantitative method to determine levodopa content in readily available MP products that might be used by patients or in research studies. Levodopa present in six commercial MP products was quantified by solvent extraction followed by reversed-phase high-performance liquid chromatography (HPLC) coupled to fluorescence detection (FD). Certificates of analysis (COA) were obtained, from manufacturers of MP products, to assess the existence and implementation of specifications for levodopa content. HPLC-FD analysis revealed that the levodopa content of the six commercial MP products varied from 6% to 141% of individual label claims. No product contained levodopa within normal pharmacopeial limits of 90%-110% label claim. The maximum daily dose of levodopa delivered by the products varied from 14.4 to 720 mg/day. COAs were inconsistent in specifications for and verification of levodopa content. The commercial products tested varied widely in levodopa content, sometimes deviating widely from the label claim. These deficiencies could impact efficacy and safety of MP products used by PD patients and compromise the results of scientific studies on MP products. The HPLC-FD method described in this study could be utilized by both manufacturers and scientific researchers to verify levodopa content of MP products.

6-Mercaptopurine exerts an immunomodulatory and neuroprotective effect on permanent focal cerebral occlusion in rats.

PubMed

Chang, Chih-Zen; Kwan, Aij-Lie; Howng, Shen-Long

2010-08-01

A bursting cascade of inflammation imposes progressive neurological deterioration after experimental stroke has been demonstrated. In our study, 6-mercaptopurine (6-mp) has been successful in alleviating cerebral infarct in a rodent permanent middle cerebral artery occlusion (pMCAO) model. The present study was aimed to examine the effect of 6-mp on cytokine levels in experimental stroke. The rodent pMCAO model was employed. A dose of 2 mg/kg 6-mp or vehicle (0.1 mol/L PBS) was administered intraperitoneally 30 min after the induction of pMCAO. Neurological score, serum, and cerebrospinal fluid (CSF) cytokines such as IL-1beta, IL-6, and TNF-alpha and infarct volume were determined 48 h after pMCAO. Cerebral infarction volume was significantly decreased in animals treated with 6-mp (74.3%, p < 0.01), and the ratio of tissue edema was also decreased in 6-mp-treated groups (71%). Animals receiving 6-mp thus showed a significant decrease in IL-1 and TNF-alpha (18/43% and 48/64% in CSF/serum, respectively) when compared with the pMCAO groups (p < 0.01). This study demonstrates that 6-mp interposes the production of IL-1 and TNF-alpha in CSF and serum, attenuates ischemic brain injury, and thus alleviates neurological deficits in the pMCAO animals. These findings also offer first evidence that 6-mp may attenuate TNF-alpha-related neuron apoptosis and also support the notion that 6-mp and other anti-inflammatory agents could potentially have therapeutic uses in cases of cerebral infarct.

Double-stranded RNA delivery through soaking mediates silencing of the muscle protein 20 and increases mortality to the Asian citrus psyllid, Diaphorina citri.

PubMed

Yu, Xiudao; Gowda, Siddarame; Killiny, Nabil

2017-09-01

Asian citrus psyllid, Diaphorina citri Kuwayama, is the most important economic pest of citrus because it transmits Candidatus Liberibacter asiaticus (CLas), the causal agent of huanglongbing (HLB). Silencing genes by RNA interference (RNAi) is a promising approach for controlling D. citri. RNAi-based insect management strategies depend on the selection of suitable target genes. The muscle protein 20 gene DcMP20 was characterized from D. citri in an effort to impair proper muscle development through RNAi. Phylogenetic analysis showed that DcMP20 was more closely related to MP20 from Drosophila compared with its counterpart from other insect species. Developmental expression analysis revealed that transcription of DcMP20 was development dependent and reached a maximum level in the last instar (fourth-fifth) of the nymphal stage. The extent of RNAi in D. citri was dose dependent, with dsRNA-DcMP20 at 75 ng µL -1 being sufficient to knock down endogenous DcMP20 expression, which resulted in significant mortality and reduced body weight that positively correlated with the silencing of DcMP20. No effect was found when dsRNA-GFP or water was used, indicating the specific effect of dsRNA-DcMP20. Our results suggest that dsRNA can be delivered to D. citri through soaking, and DcMP20 is an effective RNAi target to be used in the management of D. citri. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

New apparatus with high radiation energy between 320 to 460 nm: physical description and dermatological applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mutzhas, M.F.; Holzle, E.; Hofmann, C.

1981-01-01

A new apparatus (UVASUN 5000) is presented with high radiation energy between 320 to 460 nm. The radiator is a specially developed source for high uv-A intensity, housing a quartz bulb with a mixture of argon, mercury and metal-halides. The uv-A energy in the range of 320 to 400 nm is about 84% of the total radiation energy. Effects of very high doses of uv-A on human skin were studied. Following single uv-A applications the minimal tanning dose uv-A (MTD) and the immediate pigment darkening (IPD) dose of uv-A were established. Repeated exposure to this uv-A delivering system yields longmore » lasting dark brown skin pigmentation without any clinical or histological signs of sunburn (uv-B) damage, epidermal hyperplasia or thickening of the stratum corneum. Minimal therapeutic results were seen in the phototherapy of vitiligo and inflammatory acne.« less

Yellow (577 nm) micropulse laser versus half-dose verteporfin photodynamic therapy in eyes with chronic central serous chorioretinopathy: results of the Pan-American Collaborative Retina Study (PACORES) Group.

PubMed

Roca, Jose A; Wu, Lihteh; Fromow-Guerra, Jans; Rodríguez, Francisco J; Berrocal, Maria H; Rojas, Sergio; Lima, Luiz H; Gallego-Pinazo, Roberto; Chhablani, Jay; Arevalo, J Fernando; Lozano-Rechy, David; Serrano, Martin

2018-02-08

To compare the functional and anatomical outcomes of eyes with chronic central serous chorioretinopathy treated with yellow micropulse (MP) laser versus half-dose verteporfin photodynamic therapy (PDT). This is a multicentre, retrospective comparative study of 92 eyes treated with yellow MP laser (duty cycle of 5%, zero spacing between spots, spot size varied from 100 to 200 µm, power varied from 320 to 660 mW, and the pulse burst duration was 200 ms) and 67 eyes treated with PDT (half-dose verteporfin (3 mg/m 2 ) infused over 10 min), followed by laser activation for 83 s. Spot sizes varied from 400 to 2000 µm. In the MP group, at 12 months of follow-up, the mean best corrected visual acuity (BCVA) improved from the logarithm of the minimum angle of resolution (logMAR) of 0.41±0.27 at baseline to 0.21±0.26 (P<0.0001), 48.9% (45/92) of eyes had an improvement of ≥3 lines of BCVA from baseline, 48.9% (45/92) of eyes remained within 2 lines of baseline BCVA, and only 2.2% (2/92) of eyes lost ≥3 lines of BCVA from baseline. In the PDT group, at 12 months of follow-up, the mean BCVA changed from logMAR of 0.50±0.34 at baseline to 0.47±0.34 (P=0.89), 19% (13/67) of eyes had an improvement of ≥3 lines of BCVA from baseline, 73% (49/67) of eyes remained within 2 lines of baseline BCVA, and 7% (5/67) of eyes lost ≥3 lines of BCVA from baseline. There were no adverse events attributable to the yellow MP laser treatment. One eye in the PDT group developed choroidal neovascularisation, which was treated with three intravitreal bevacizumab injections. Both PDT and MP are effective in restoring the macular anatomy. In places where PDT is not available, yellow MP laser may be an adequate treatment alternative. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Reversible Pharmacological Induction of Motor Symptoms in MPTP-Treated Mice at the Presymptomatic Stage of Parkinsonism: Potential Use for Early Diagnosis of Parkinson's Disease.

PubMed

Khakimova, Gulnara R; Kozina, Elena A; Kucheryanu, Valerian G; Ugrumov, Michael V

2017-07-01

A crucial event in the pathogenesis of Parkinson's disease is the death of dopaminergic neurons of the nigrostriatal system, which are responsible for the regulation of motor function. Motor symptoms first appear in patients 20-30 years after the onset of the neurodegeneration, when there has been a loss of an essential number of neurons and depletion of compensatory reserves of the brain, which explains the low efficiency of treatment. Therefore, the development of a technology for the diagnosing of Parkinson's disease at the preclinical stage is of a high priority in neurology. In this study, we have developed at an experimental model a fundamentally novel for neurology approach for diagnosis of Parkinson's disease at the preclinical stage. This methodology, widely used for the diagnosis of chronic diseases in the internal medicine, is based on the application of a challenge test that temporarily increases the latent failure of a specific functional system, thereby inducing the short-term appearance of clinical symptoms. The provocation test was developed by a systemic administration of α-methyl-p-tyrosine (αMpT), a reversible inhibitor of tyrosine hydroxylase to MPTP-treated mice at the presymptomatic stage of parkinsonism. For this, we first selected a minimum dose of αMpT, which caused a decrease of the dopamine level in the striatum of normal mice below the threshold at which motor dysfunctions appear. Then, we found the maximum dose of αMpT at which a loss of dopamine in the striatum of normal mice did not reach the threshold level, and motor behavior was not impaired. We showed that αMpT at this dose induced a decrease of the dopamine concentration in the striatum of MPTP-treated mice at the presymptomatic stage of parkinsonism below a threshold level that results in the impairment of motor behavior. Finally, we proved that αMpT exerts a temporal and reversible influence on the nigrostriatal dopaminergic system of MPTP-treated mice with no long-term side effects on other catecholaminergic systems. Thus, the above experimental data strongly suggest that αMpT-based challenge test might be considered as the provocation test for Parkinson's disease diagnosis at the preclinical stage in the future clinical trials.

Differential responses to high- and low-dose ultraviolet-B stress in tobacco Bright Yellow-2 cells

PubMed Central

Takahashi, Shinya; Kojo, Kei H.; Kutsuna, Natsumaro; Endo, Masaki; Toki, Seiichi; Isoda, Hiroko; Hasezawa, Seiichiro

2015-01-01

Ultraviolet (UV)-B irradiation leads to DNA damage, cell cycle arrest, growth inhibition, and cell death. To evaluate the UV-B stress–induced changes in plant cells, we developed a model system based on tobacco Bright Yellow-2 (BY-2) cells. Both low-dose UV-B (low UV-B: 740 J m−2) and high-dose UV-B (high UV-B: 2960 J m−2) inhibited cell proliferation and induced cell death; these effects were more pronounced at high UV-B. Flow cytometry showed cell cycle arrest within 1 day after UV-B irradiation; neither low- nor high-UV-B–irradiated cells entered mitosis within 12 h. Cell cycle progression was gradually restored in low-UV-B–irradiated cells but not in high-UV-B–irradiated cells. UV-A irradiation, which activates cyclobutane pyrimidine dimer (CPD) photolyase, reduced inhibition of cell proliferation by low but not high UV-B and suppressed high-UV-B–induced cell death. UV-B induced CPD formation in a dose-dependent manner. The amounts of CPDs decreased gradually within 3 days in low-UV-B–irradiated cells, but remained elevated after 3 days in high-UV-B–irradiated cells. Low UV-B slightly increased the number of DNA single-strand breaks detected by the comet assay at 1 day after irradiation, and then decreased at 2 and 3 days after irradiation. High UV-B increased DNA fragmentation detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay 1 and 3 days after irradiation. Caffeine, an inhibitor of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) checkpoint kinases, reduced the rate of cell death in high-UV-B–irradiated cells. Our data suggest that low-UV-B–induced CPDs and/or DNA strand-breaks inhibit DNA replication and proliferation of BY-2 cells, whereas larger contents of high-UV-B–induced CPDs and/or DNA strand-breaks lead to cell death. PMID:25954287

Beam perturbation characteristics of a 2D transmission silicon diode array, Magic Plate

PubMed Central

Alrowaili, Ziyad A.; Lerch, Michael L.F.; Petasecca, Marco; Carolan, Martin G.; Metcalfe, Peter E.

2016-01-01

The main objective of this study is to demonstrate the performance characteristics of the Magic Plate (MP) system when operated upstream of the patient in transmission mode (MPTM). The MPTM is an essential component of a real‐time QA system designed for operation during radiotherapy treatment. Of particular interest is a quantitative study into the influence of the MP on the radiation beam quality at several field sizes and linear accelerator potential differences. The impact is measured through beam perturbation effects such as changes in the skin dose and/or percentage depth dose (PDD) (both in and out of field). The MP was placed in the block tray of a Varian linac head operated at 6, 10 and 18 MV beam energy. To optimize the MPTM operational setup, two conditions were investigated and each setup was compared to the case where no MP is positioned in place (i.e., open field): (i) MPTM alone and (ii) MPTM with a thin passive contamination electron filter. The in‐field and out‐of‐field surface doses of a solid water phantom were investigated for both setups using a Markus plane parallel (Model N23343) and Attix parallel‐plate, MRI model 449 ionization chambers. In addition, the effect on the 2D dose distribution measured by the Delta4 QA system was also investigated. The transmission factor for both of these MPTM setups in the central axis was also investigated using a Farmer ionization chamber (Model 2571A) and an Attix ionization chamber. Measurements were performed for different irradiation field sizes of 5×5 cm2 and 10×10 cm2. The change in the surface dose relative to dmax was measured to be less than 0.5% for the 6 MV, 10 MV, and 18 MV energy beams. Transmission factors measured for both set ups (i & ii above) with 6 MV, 10 MV, and 18 MV at a depth of dmax and a depth of 10 cm were all within 1.6% of open field. The impact of both the bare MPTM and the MPTM with 1 mm buildup on 3D dose distribution in comparison to the open field investigated using the Delta4 system and both the MPTM versions passed standard clinical gamma analysis criteria. Two MPTM operational setups were studied and presented in this article. The results indicate that both versions may be suitable for the new real‐time megavoltage photon treatment delivery QA system under development. However, the bare MPTM appears to be slightly better suited of the two MP versions, as it minimally perturbs the radiation field and does not lead to any significant increase in skin dose to the patient. PACS number(s): 87.50.up, 87.53.Bn, 87.55.N, 87.55.Qr, 87.56.Fc. PMID:27074475

Sn-Mesoporphyrin interdiction of severe hyperbilirubinemia in Jehovah's Witness newborns as an alternative to exchange transfusion.

PubMed

Kappas, A; Drummond, G S; Munson, D P; Marshall, J R

2001-12-01

The religious convictions of parents who are Jehovah's Witness adherents lead them to reject the use of exchange transfusions as therapy for severe hyperbilirubinemia in newborns in whom intensive phototherapy has failed to control this problem. Consequently, physicians caring for such infants may be obliged to initiate legal action to compel use of the procedure when severe hyperbilirubinemia not sufficiently responsive to phototherapy warrants an exchange transfusion. Our goal was to determine if we could use the potent inhibitor of bilirubin production, Sn-Mesoporphyrin (SnMP), to resolve the troubling medical-legal issues in such situations in 2 infants with hemolytic disease of the newborn who required exchange transfusions for severe hyperbilirubinemia but whose Jehovah's Witness parents rejected the procedure. SnMP was administered in a single dose, as in previous studies, at the time when exchange transfusion would have been initiated and plasma bilirubin levels were monitored at close intervals thereafter. SnMP is a potent inhibitor of heme oxygenase, the rate-limiting enzyme in catabolism of heme to bilirubin. We found in earlier studies that in single doses of 6 micromol/kg birth weight, SnMP is extremely effective in moderating the course of hyperbilirubinemia and in eliminating the need for supplemental phototherapy in jaundiced newborns. In the 2 cases described, a single dose of SnMP (6 micromol/kg birth weight) was administered intramuscularly to severely jaundiced infants with immune hemolysis at a time when clinical circumstances dictated the need for exchange transfusion. CASE 1: This patient was a preterm male infant (gestational age: 35 5/7 weeks; birth weight: 2790 g) whose plasma bilirubin concentration (PBC) at 1 hour after birth was 5.0 mg/dL. Despite intensive phototherapy with 3 banks of lights and 1 biliblanket, the PBC increased steadily with no diminution in the rate of increase for 75 hours. In view of the problems of immune hemolysis, and prematurity, and the inability of phototherapy to stop progression of hyperbilirubinemia, a decision to carry out an exchange transfusion was made; the decision was, however, rejected by the Jehovah's Witness parents. Pending legal action to compel use of the procedure, a request to this (Rockefeller) laboratory for SnMP was made; its use was approved by the Food and Drug Administration; and the inhibitor was delivered to the physician-in-charge (D.P.M.) in Sioux Falls, South Dakota. The single dose of SnMP was administered to the infant at 75 hours after birth; the course of hyperbilirubinemia before and after the use of the inhibitor is shown in Fig 1. [figure: see text]. CASE 2: This female term infant (gestational age: 38-39 weeks; birth weight: 4140 g) with immune hemolysis was delivered by cesarean section and because of problems related to meconium aspiration required helicopter transfer to the Special Care Nursery in Abilene, Texas, where 10 hours after birth the first PBC was determined to be 18.0 mg/dL. Double-bank phototherapy plus a biliblanket was initiated; a third bank of lights was later ordered. The PBC fluctuated in the ensuing 2 days between 13.8 to 25.8 mg/dL during which suggestive clinical signs of possible bilirubin encephalopathy became manifest. In view of the clinical circumstances and the continued severe hyperbilirubinemia, permission for a double-exchange transfusion was requested. The parents, who were Jehovah's Witness adherents, refused the procedure. While preparing legal action to compel use of the exchange, a request was made to this (Rockefeller) laboratory for use of SnMP to attempt control of hyperbilirubinemia. With FDA approval, the SnMP was delivered to the attending neonatologist (J. R. M.) in Abilene and administered in a single dose (6 micromol/kg birth weight) at 56 hours after birth when the PBC was 19.5 mg/dL. The course of bilirubinemia before and after SnMP use is shown in Fig 2. [figure: see text]. The use of SnMP to moderate or prevent the development of severe hyperbilirubinemia in newborns (preterm, near-term, term with high PBCs [15-18 mg/dL], ABO-incompatibility; glucose-6-phosphate dehydrogenase deficiency) has been extensively studied in carefully conducted clinical trials the results of which have been reported earlier. This inhibitor of bilirubin production has demonstrated marked efficacy in moderating the course of hyperbilirubinemia in all diagnostic groups of unconjugated neonatal jaundice. The 2 cases described in this report confirmed the efficacy of SnMP in terminating progression of hyperbilirubinemia in infants in whom phototherapy had failed to sufficiently control the problem and whose parents, for religious reasons, would not permit exchange transfusions. Interdiction of severe hyperbilirubinemia by inhibiting the production of bilirubin with SnMP can be an effective alternative to the use of exchange transfusion in the management of severe newborn jaundice that has not responded sufficiently to light treatment to ease concern about the development of bilirubin encephalopathy.

Soft, stretchable, epidermal sensor with integrated electronics and photochemistry for measuring personal UV exposures.

PubMed

Shi, Yunzhou; Manco, Megan; Moyal, Dominique; Huppert, Gil; Araki, Hitoshi; Banks, Anthony; Joshi, Hemant; McKenzie, Richard; Seewald, Alex; Griffin, Guy; Sen-Gupta, Ellora; Wright, Donald; Bastien, Philippe; Valceschini, Florent; Seité, Sophie; Wright, John A; Ghaffari, Roozbeh; Rogers, John; Balooch, Guive; Pielak, Rafal M

2018-01-01

Excessive ultraviolet (UV) radiation induces acute and chronic effects on the skin, eye and immune system. Personalized monitoring of UV radiation is thus paramount to measure the extent of personal sun exposure, which could vary with environment, lifestyle, and sunscreen use. Here, we demonstrate an ultralow modulus, stretchable, skin-mounted UV patch that measures personal UV doses. The patch contains functional layers of ultrathin stretchable electronics and a photosensitive patterned dye that reacts to UV radiation. Color changes in the photosensitive dyes correspond to UV radiation intensity and are analyzed with a smartphone camera. A software application has feature recognition, lighting condition correction, and quantification algorithms that detect and quantify changes in color. These color changes are then correlated with corresponding shifts in UV dose, and compared to existing UV dose risk levels. The soft mechanics of the UV patch allow for multi-day wear in the presence of sunscreen and water. Two evaluation studies serve to demonstrate the utility of the UV patch during daily activities with and without sunscreen application.

Soft, stretchable, epidermal sensor with integrated electronics and photochemistry for measuring personal UV exposures

PubMed Central

Shi, Yunzhou; Manco, Megan; Moyal, Dominique; Huppert, Gil; Araki, Hitoshi; Banks, Anthony; Joshi, Hemant; McKenzie, Richard; Seewald, Alex; Griffin, Guy; Sen-Gupta, Ellora; Wright, Donald; Bastien, Philippe; Valceschini, Florent; Seité, Sophie; Wright, John A.; Ghaffari, Roozbeh; Rogers, John; Balooch, Guive

2018-01-01

Excessive ultraviolet (UV) radiation induces acute and chronic effects on the skin, eye and immune system. Personalized monitoring of UV radiation is thus paramount to measure the extent of personal sun exposure, which could vary with environment, lifestyle, and sunscreen use. Here, we demonstrate an ultralow modulus, stretchable, skin-mounted UV patch that measures personal UV doses. The patch contains functional layers of ultrathin stretchable electronics and a photosensitive patterned dye that reacts to UV radiation. Color changes in the photosensitive dyes correspond to UV radiation intensity and are analyzed with a smartphone camera. A software application has feature recognition, lighting condition correction, and quantification algorithms that detect and quantify changes in color. These color changes are then correlated with corresponding shifts in UV dose, and compared to existing UV dose risk levels. The soft mechanics of the UV patch allow for multi-day wear in the presence of sunscreen and water. Two evaluation studies serve to demonstrate the utility of the UV patch during daily activities with and without sunscreen application. PMID:29293664

How to select among available options for the treatment of multiple myeloma.

PubMed

Harousseau, J L

2012-09-01

The introduction of novel agents (thalidomide, bortezomib and lenalidomide) in the frontline therapy of multiple myeloma has markedly improved the outcome both in younger patients who are candidates for high-dose therapy plus autologous stem-cell transplantation (HDT/ASCT) and in elderly patients. In the HDT/ASCT paradigm, novel agents may be used as induction therapy or after HDT/ASCT as consolidation and/or maintenance therapy. It is now possible to achieve up to 70% complete plus very good partial remission after HDT/ASCT and 70% 3-year progression-free survival (PFS). However long-term non-intensive therapy may also yield high response rates and prolonged PFS. Randomized trials comparing these two strategies are underway. In elderly patients, six randomized studies show the benefit of adding thalidomide to melphalan-prednisone (MP). a large randomized trial has also shown that the combination of bortezomib-MP is superior to MP for all parameters measuring the response and outcome. Finally, the role of maintenance is currently evaluated and a randomized trial shows that low-dose lenalidomide maintenance prolongs PFS.

Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice

PubMed Central

Farook, Justin M.; Krazem, Ali; Littleton, John M.; Barron, Susan

2008-01-01

In the present study, we examined the effects of acamprosate for its ability to reduce handling induced convulsions (HICs) during alcohol withdrawal. Diazepam was used as a positive control. Swiss Webster male mice received three daily IP injections of alcohol (2.5 g/kg) or alcohol (2.5 g/kg) + methylpyrazole (4-MP) (9 mg/kg). (4-MP, being an alcohol dehydrogenase inhibitor slows down the breakdown of alcohol. 4-MP in combination with alcohol exhibits a dramatic increase in blood alcohol level compared to alcohol alone). Ten hours following the last alcohol injection, the mice were picked up by the tail and examined for their seizure susceptibility (HICs). Diazepam, a benzodiazepine known to reduce seizures during alcohol withdrawal, significantly reduced these HICs at doses of 0.25, 0.5 and 1mg/kg (p’s < 0.001). Acamprosate, an anti-relapse compound used clinically in newly abstinent alcoholics, also reduced these HICs at doses of 100, 200 and 300mg/kg (p’s < 0.05). This study supports the use of acamprosate during periods of alcohol withdrawal as well as during abstinence. PMID:18577392

Personalized cumulative UV tracking on mobiles & wearables.

PubMed

Dey, S; Sahoo, S; Agrawal, H; Mondal, A; Bhowmik, T; Tiwari, V N

2017-07-01

Maintaining a balanced Ultra Violet (UV) exposure level is vital for a healthy living as the excess of UV dose can lead to critical diseases such as skin cancer while the absence can cause vitamin D deficiency which has recently been linked to onset of cardiac abnormalities. Here, we propose a personalized cumulative UV dose (CUVD) estimation system for smartwatch and smartphone devices having the following novelty factors; (a) sensor orientation invariant measurement of UV exposure using a bootstrap resampling technique, (b) estimation of UV exposure using only light intensity (lux) sensor (c) optimal UV exposure dose estimation. Our proposed method will eliminate the need for a dedicated UV sensor thus widen the user base of the proposed solution, render it unobtrusive by eliminating the critical requirement of orienting the device in a direction facing the sun. The system is implemented on android mobile platform and validated on 1200 minutes of lux and UV index (UVI) data collected across several days covering morning to evening time frames. The result shows very impressive final UVI estimation accuracy. We believe our proposed solution will enable the future wearable and smartphone users to obtain a seamless personalized UV exposure dose across a day paving a way for simple yet very useful recommendations such as right skin protective measure for reducing risk factors of long term UV exposure related diseases like skin cancer and, cardiac abnormality.

Two brothers with skewed thiopurine metabolism in ulcerative colitis treated successfully with allopurinol and mercaptopurine dose reduction.

PubMed

Hoentjen, Frank; Hanauer, Stephen B; de Boer, Nanne K; Rubin, David T

2012-01-01

Thiopurine therapy effectively maintains remission in inflammatory bowel disease. However, many patients are unable to achieve optimum benefits from azathioprine or 6-mercaptopurine because of undesirable metabolism related to high thiopurine methyltransferase (TPMT) activity characterized by hepatic transaminitis secondary to increased 6-methylmercaptopurine (6-MMP) production and reduced levels of therapeutic 6-thioguanine nucleotide (6-TGN). Allopurinol can optimize this skewed metabolism. We discuss two brothers who were both diagnosed with ulcerative colitis (UC). Their disease remained active despite oral and topical mesalamines. Steroids followed by 6-mercaptopurine (MP) were unsuccessfully introduced for both patients and both were found to have high 6-MMP and low 6-TGN levels, despite normal TMPT enzyme activity, accompanied by transaminitis. Allopurinol was introduced in combination with MP dose reduction. For both brothers addition of allopurinol was associated with successful remission and optimized MP metabolites. These siblings with active UC illustrate that skewed thiopurine metabolism may occur despite normal TPMT enzyme activity and can lead to adverse events in the absence of disease control. We confirm previous data showing that addition of allopurinol can reverse this skewed metabolism, and reduce both hepatotoxicity and disease activity, but we now also introduce the concept of a family history of preferential MP metabolism as a clue to effective management for other family members.

Breast-feeding during maternal use of azathioprine.

PubMed

Moretti, Myla E; Verjee, Zul; Ito, Shinya; Koren, Gideon

2006-12-01

To report the clinical outcome of infants whose mothers were taking azathioprine while nursing and to quantify the transfer of 6-mercaptopurine (6-MP), its active metabolite, into breast milk. We report on a series of 4 patients treated with azathioprine while lactating. Breast milk samples were analyzed for 6-MP in 2 of the mothers. Several milk samples per patient were analyzed; levels of 6-MP were undetectable by high performance liquid chromatography (limit of detection 5 ng/mL). Therefore, the absolute relative infant dose would have been less than 0.09% of the maternal weight-adjusted dose. No adverse effects were encountered in any of the 4 infants. A large number of women of reproductive age are treated with azathioprine for a range of chronic conditions that require immunosuppression, such as systemic lupus erythematosus or solid organ transplants. Similar to other antimetabolites, the drug has generally been contraindicated for use during breast-feeding because of the theoretical concern for toxicity in the nursing infant. The available literature in this area is sparse and dated. The data presented here confirm published reports of minimal 6-MP excretion into milk, suggesting that significant systemic adverse effects in the infant are unlikely. Maternal azathioprine use during lactation does not appear to pose a significant immediate clinical risk to the suckling infant. Continued monitoring and long-term assessment of these infants are warranted.

Ultraviolet Radiation Dose National Standard of México

NASA Astrophysics Data System (ADS)

Cardoso, R.; Rosas, E.

2006-09-01

We present the Ultraviolet (UV) Radiation Dose National Standard for México. The establishment of this measurement reference at Centro Nacional de Metrología (CENAM) eliminates the need of contacting foreign suppliers in the search for traceability towards the SI units when calibrating instruments at 365 nm. Further more, the UV Radiation Dose National Standard constitutes a highly accurate and reliable source for the UV radiation dose measurements performed in medical and cosmetic treatments as in the the food and pharmaceutics disinfection processes, among other.

Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophinmore » (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA damage.« less

Long-term variations of the UV-B radiation over Central Europe since early 1960s, as revealed from the UV observations and reconstructed data

NASA Astrophysics Data System (ADS)

Krzyscin, J. W.

2003-04-01

A method of reconstruction of the UV variations for periods when UV-B measurements were not carried out is proposed. The reconstruction is based on observations of total (Sun+sky) radiation by a pyranometer, Dobson total ozone, sunshine duriation from the Campbel Stokes heliograph, and atmospheric column water content taken from NCEP/NOAA reanalysis. Modeled all-sky erythemaly weighted daily dose is calculated as a product of the cloud reduction factor (CRF) over UV range and clear-sky dose from a radiative transfer model. CRF over UV range is estimated from measured CRF for total solar radiation and the statistical dependence relating CRF over UV with that over whole solar spectrum. The measured daily UV doses and daily sum of total radiation taken at Belsk, Poland (52N, 21E) for the period 1976-2001 have been used to construct the regressions for various solar zenith angles. The time series of monthly means from the modeled daily UV doses follows the observed monthly means supporting the possibility of reconstruction of the UV time series for other periods. An inspection of the long-term stability of total radiation measurements is necessary to discuss trends in the reconstructed time series. We examine the data homogeneity analyzing the ratio of the observed to modeled total radiation for fully clear sky days that are selected from the daily values of sunshine duration measured by the Campbel-Stokes heliograph. Combining reconstructed and observed monthly means of the UV doses we found a positive trend in the UV radiation in the period 1980-1995 and almost constant UV level for other periods (early 60s up to 1980, and 1995-2001). The trend pattern suggests dominating role of the long-term total ozone forcing on the UV level with a small impact of the long-term changes in the cloud/aerosol properties.

The effects of grape seeds polyphenols on SKH-1 mice skin irradiated with multiple doses of UV-B.

PubMed

Filip, Adriana; Daicoviciu, Doina; Clichici, Simona; Bolfa, Pompei; Catoi, Cornel; Baldea, Ioana; Bolojan, Laura; Olteanu, Diana; Muresan, Adriana; Postescu, I D

2011-11-03

The study investigated the protective activity of red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on multiple doses of ultraviolet radiation (UV)-B-induced deleterious effects in SKH-1 mice skin. Eighty 8-weeks-old female SKH-1 mice were divided into 8 groups: control, vehicle, UV-B irradiated, vehicle+UV-B irradiated, BM 2.5mg polyphenols (PF)/cm(2)+UV-B irradiated, BM 4 mg PF/cm(2)+UV-B irradiated, UV-B+BM 2.5mg PF/cm(2), UV-B+BM 4 mg PF/cm(2). The extract was applied topically before or after each UV-B exposure (240 mJ/cm(2)), for 10 days consecutively. The antioxidant activity of BM extract is higher than gallic acid (k(BM)=0.017, k(gallic acid)=0.013). Multiple doses of UV-B generated the formation of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, increased glutathione peroxidase (GPx) and catalase (CAT) activities respectively glutathione (GSH) and IL-1β levels in skin. In group treated with 2.5mg PF/cm(2) before UV-B irradiation BM extract inhibited UV-B-induced sunburn cells, restored the superoxide dismutase (MnSOD) activity, increased insignificantly CAT and GPx activities and reduced IL-1β level. The BM 4.0 mg PF/cm(2) treatment decreased GSH level and reduced the percentage of CPDs positive cells in skin. Both doses of BM extract administered after UV-B irradiation increased the MnSOD and GPx activities and reduced the formation of sunburn cells in skin. Our results suggest that BM extract might be a potential chemo-preventive candidate in reducing the oxidative stress and apoptosis induced by multiple doses of UV-B in skin. Copyright © 2011 Elsevier B.V. All rights reserved.

Mitochondrial Uncoupler Prodrug of 2,4-Dinitrophenol, MP201, Prevents Neuronal Damage and Preserves Vision in Experimental Optic Neuritis

PubMed Central

Khan, Reas S.; Geisler, John G.

2017-01-01

The ability of novel mitochondrial uncoupler prodrug of 2,4-dinitrophenol (DNP), MP201, to prevent neuronal damage and preserve visual function in an experimental autoimmune encephalomyelitis (EAE) model of optic neuritis was evaluated. Optic nerve inflammation, demyelination, and axonal loss are prominent features of optic neuritis, an inflammatory optic neuropathy often associated with the central nervous system demyelinating disease multiple sclerosis. Currently, optic neuritis is frequently treated with high-dose corticosteroids, but treatment fails to prevent permanent neuronal damage and associated vision changes that occur as optic neuritis resolves, thus suggesting that additional therapies are required. MP201 administered orally, once per day, attenuated visual dysfunction, preserved retinal ganglion cells (RGCs), and reduced RGC axonal loss and demyelination in the optic nerves of EAE mice, with limited effects on inflammation. The prominent mild mitochondrial uncoupling properties of MP201, with slow elimination of DNP, may contribute to the neuroprotective effect by modulating the entire mitochondria's physiology directly. Results suggest that MP201 is a potential novel treatment for optic neuritis. PMID:28680531

Determination of minimal erythema dose and anomalous reactions to UVA radiation by skin phototype.

PubMed

Pérez Ferriols, A; Aguilera, J; Aguilera, P; de Argila, D; Barnadas, M A; de Cabo, X; Carrrascosa, J M; de Gálvez Aranda, M V; Gardeazábal, J; Giménez-Arnau, A; Lecha, M; Lorente, J; Martínez-Lozano, J A; Rodríguez Granados, M T; Sola, Y; Utrillas, M P

2014-10-01

Phototesting is a technique that assesses the skin's sensitivity to UV radiation by determining the smallest dose of radiation capable of inducing erythema (minimal erythema dose [MED]) and anomalous responses to UV-A radiation. No phototesting protocol guidelines have been published to date. This was a multicenter prospective cohort study in which 232 healthy volunteers were recruited at 9 hospitals. Phototests were carried out with solar simulators or fluorescent broadband UV-B lamps. Each individual received a total of 5 or 6 incremental doses of erythemal radiation and 4 doses of UV-A radiation. The results were read at 24hours. At hospitals where solar simulators were used, the mean (SD) MED values were 23 (8), 28 (4), 35 (4), and 51 (6) mJ/cm(2) for skin phototypes i to iv, respectively. At hospitals where broadband UV-B lamps were used, these values were 28 (5), 32 (3), and 34 (5) mJ/cm(2) for phototypes ii to iv, respectively. MED values lower than 7, 19, 27, and 38 mJ/cm(2) obtained with solar simulators were considered to indicate a pathologic response for phototypes I to IV, respectively. MED values lower than 18, 24, and 24mJ/cm(2) obtained with broadband UV-B lamps were considered to indicate a pathologic response for phototypes ii to iv, respectively. No anomalous responses were observed at UV-A radiation doses of up to 20J/cm(2). Results were homogeneous across centers, making it possible to standardize diagnostic phototesting for the various skin phototypes and establish threshold doses that define anomalous responses to UV radiation. Copyright © 2014 Elsevier España, S.L.U. y AEDV. All rights reserved.

Inferring ultraviolet anatomical exposure patterns while distinguishing the relative contribution of radiation components

NASA Astrophysics Data System (ADS)

Vuilleumier, Laurent; Milon, Antoine; Bulliard, Jean-Luc; Moccozet, Laurent; Vernez, David

2013-05-01

Exposure to solar ultraviolet (UV) radiation is the main causative factor for skin cancer. UV exposure depends on environmental and individual factors, but individual exposure data remain scarce. While ground UV irradiance is monitored via different techniques, it is difficult to translate such observations into human UV exposure or dose because of confounding factors. A multi-disciplinary collaboration developed a model predicting the dose and distribution of UV exposure on the basis of ground irradiation and morphological data. Standard 3D computer graphics techniques were adapted to develop a simulation tool that estimates solar exposure of a virtual manikin depicted as a triangle mesh surface. The amount of solar energy received by various body locations is computed for direct, diffuse and reflected radiation separately. Dosimetric measurements obtained in field conditions were used to assess the model performance. The model predicted exposure to solar UV adequately with a symmetric mean absolute percentage error of 13% and half of the predictions within 17% range of the measurements. Using this tool, solar UV exposure patterns were investigated with respect to the relative contribution of the direct, diffuse and reflected radiation. Exposure doses for various body parts and exposure scenarios of a standing individual were assessed using erythemally-weighted UV ground irradiance data measured in 2009 at Payerne, Switzerland as input. For most anatomical sites, mean daily doses were high (typically 6.2-14.6 Standard Erythemal Dose, SED) and exceeded recommended exposure values. Direct exposure was important during specific periods (e.g. midday during summer), but contributed moderately to the annual dose, ranging from 15 to 24% for vertical and horizontal body parts, respectively. Diffuse irradiation explained about 80% of the cumulative annual exposure dose.

Examples for the importance of radiophysical measurements in clinical phototherapy.

PubMed

Schneider, Lars Alexander; Wlaschek, Meinhard; Dissemond, Joachim; Scharffetter-Kochanek, Karin

2007-05-01

Optimal UV therapy requires regular surveillance of the variables that influence therapeutic success. In daily practice, phototherapy equipment is often operated with an attitude of "autocontrol." This implies that thorough control measurements of the emission spectra and calibration of UV fluences are not routinely performed. For both quality control and patient safety, it is essential to regularly check whether a UV source is providing the right target spectrum with the correct dose to the skin. We have exemplarily taken three UV sources currently used in clinical practice and performed radiophysical measurements, i. e. determined emission spectra, radiation output and correctness of dose calculation. All three sources revealed either a largely inhomogeneous distribution pattern of radiation intensity, variation of radiation intensity over time or insufficient filtering of the UV lamp emission spectrum. Furthermore the dose calculation procedures had to be revised because of significant differences between the estimated and the administered UV doses. Radiophysical measurement of all UV-equipment in clinical use is a simple and effective way to improve the safety and reliability of phototherapy. Such measurements help to uncover technical flaws in radiation sources and prevent unnecessary side effects and UV exposure risks for the patient.

Oxygen toxicity and antioxidative responses in arsenic stressed Helianthus annuus L. seedlings against UV-B.

PubMed

Yadav, Geeta; Srivastava, Prabhat Kumar; Parihar, Parul; Tiwari, Sanjesh; Prasad, Sheo Mohan

2016-12-01

In order to know the impact of elevated level of UV-B on arsenic stressed Helianthus annuus L. var. DRSF-113 plants, certain physiological (growth - root and shoot lengths, their fresh masses and leaf area; photosynthetic competence and respiration) and biochemical parameters (pigments - Chl a and b, Car, anthocyanin and flavonoids; reactive oxygen species - superoxide radicals, H 2 O 2 ; reactive carbonyl group, electrolyte leakage; antioxidants - superoxide dismutase, peroxidise, catalase, glutathione-S-transferase, proline) of their seedlings were analysed under the simultaneous exposures of two arsenic doses (6mgkg -1 soil, As 1 ; and 12mgkg -1 soil, As 2 ) and two UV-B doses (1.2kJm -2 d -1 , UV-B 1 ; and 3.6kJm -2 d -1 , UV-B 2 ). As 1 and As 2 alone declined all the studied growth parameters - along with photosynthetic pigments which were further aggravated after the simultaneous exposures of predefined levels of UV-B. Each As exposure was accompanied by significant accumulation of As in root, shoot and leaves and was substantiated by simultaneous exposures of UV-B doses which manifested into suppressed growth, decreased chlorophyll contents and photosynthesis. In similar conditions, other photo-shielding pigments, viz. carotenoids, anthocyanin and flavonoids along with respiration and oxidative stress markers such as O 2 • ¯, H 2 O 2 ; and indicators of cell membrane damage like MDA (malondialdehyde), RCG (reactive carbonyl group), electrolyte leakage were enhanced by As, and became more pronounced after the simultaneous exposures of UV-B doses. As doses stimulated the activities of SOD, POD, CAT, GST and Pro which got further accelerated after the simultaneous exposures of UV-B doses. Copyright © 2016 Elsevier B.V. All rights reserved.

Studies on the resistance/reactivation of Giardia muris cysts and Cryptosporidium parvum oocysts exposed to medium-pressure ultraviolet radiation.

PubMed

Belosevic, M; Craik, S A; Stafford, J L; Neumann, N F; Kruithof, J; Smith, D W

2001-10-16

The ex vivo and in vivo reactivation of Giardia muris cysts and Cryptosporidium parvum oocysts after exposure to different doses of ultraviolet (UV) radiation was determined using animal infectivity. The infectivity of UV-treated parasites stored for 1-4 days (G. muris) or 1-17 days (C. parvum) at room temperature in the dark was similar to that of organisms administered immediately after UV treatment, indicating that the parasites did not reactivate ex vivo. In contrast, we observed in vivo reactivation of G. muris in three of seven independent animal infectivity experiments, when parasites were treated with relatively low doses of medium-pressure UV (<25 mJ/cm(2)). Our observations indicate that G. muris cysts and C. parvum oocysts exposed to medium-pressure UV doses of 60 mJ/cm(2) or higher did not exhibit resistance to and/or reactivation following treatment. This suggests that when appropriate doses of UV are used, significant and permanent inactivation of these parasites may be achieved.

Time-course study of different innate immune mediators produced by UV-irradiated skin: comparative effects of short and daily versus a single harmful UV exposure.

PubMed

Cela, Eliana M; Friedrich, Adrian; Paz, Mariela L; Vanzulli, Silvia I; Leoni, Juliana; González Maglio, Daniel H

2015-05-01

The modulatory effects of solar UV radiation on the immune system have been widely studied. As the skin is the main target of UV radiation, our purpose was to compare the impact on skin innate immunity of two contrasting ways to be exposed to sunlight. Hairless mice were UV irradiated with a single high UV dose simulating a harmful exposure, or with repetitive low UV doses simulating short occasional daily exposures. Skin samples were taken at different times after UV irradiation to evaluate skin histology, inflammatory cell recruitment, epidermal T-cell population and the mitochondrial function of epidermal cells. The transcriptional profiles of pro-inflammatory cytokines, chemokines, antimicrobial peptides and Toll-like receptors were evaluated by RT-PCR and ELISA in tissue homogenates. Finally, a lymphangiography was performed to assess modification in the lymphatic vessel system. A single high UV dose produces a deep inflammatory state characterized by the production of pro-inflammatory cytokines and chemokines that, in turn, induces the recruitment of neutrophils and macrophages into the irradiated area. On the other hand, repetitive low UV doses drive the skin to a photo-induced alert state in which there is no sign of inflammation, but the epithelium undergoes changes in thickness, the lymphatic circulation increases, and the transcription of antimicrobial peptides is induced. © 2014 John Wiley & Sons Ltd.

Study of UV radiation dose received by the Spanish population.

PubMed

Gurrea, Gonzalo; Cañada, Javier

2007-01-01

Excess exposure to UV radiation can affect our health by causing sunburn, skin cancer, etc. It is therefore useful to determine the UV dosage received by people as a way of protecting them from the possible negative effects that this kind of radiation can cause. In this work, the personal outdoor percentage, which shows the time spent in outdoor activities, as well as personal UV doses, has been calculated by means of global UV radiation on a horizontal plane. A database of average daily UVB radiation on the horizontal plane given by the National Institute of Meteorology has been used. In this work we evaluate the standard erythema dose of the Spanish population throughout the year.

Conformational Effects of UV Light on DNA Origami.

PubMed

Chen, Haorong; Li, Ruixin; Li, Shiming; Andréasson, Joakim; Choi, Jong Hyun

2017-02-01

The responses of DNA origami conformation to UV radiation of different wavelengths and doses are investigated. Short- and medium-wavelength UV light can cause photo-lesions in DNA origami. At moderate doses, the lesions do not cause any visible defects in the origami, nor do they significantly affect the hybridization capability. Instead, they help relieve the internal stress in the origami structure and restore it to the designed conformation. At high doses, staple dissociation increases which causes structural disintegration. Long-wavelength UV does not show any effect on origami conformation by itself. We show that this UV range can be used in conjunction with photoactive molecules for photo-reconfiguration, while avoiding any damage to the DNA structures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, P.K.

The spontaneously hypertensive rat (SHR) is a widely accepted rodent model of Attention Deficit/Hyperactivity Disorder (ADHD), and methylphenidate (MP) is a central nervous systemstimulant that has been shown to have a dose-related positive effect on attention task performance in humans with ADHD. The current study was undertaken to compare SHR to its typical control strain, Wistar-Kyoto(WKY) rats, on the performance of a Visual Stimulus Position Discrimination Task (VSPDT) as well as of the responsiveness of the two rat strains to MP treatment. The rats were initially trained on the VSPDT, in which a light cue was presented randomly at threemore » different cue-light intervals (1 s, 300 ms and 100 ms) over one of two levers, and presses on the lever corresponding to the light cue were reinforced with a food pellet. Once rats reached stable performance, the treatment phase of the study began, during which they received daily intraperitoneal (IP) injections of saline, 2 mg/kg, 5 mg/kg, and 10 mg/kg of MP in a randomized order immediately prior to being tested on the VSPDT. Baseline performance accuracy on the VSPDT did not differ between the groups. Furthermore, a striking strain dissociation was evident in the response of the two strains to treatment; VSPDT performance was substantially disrupted by the 5 and 10 mg/kg dose in the WKY rats but only mildly in the SHR rats. Response omissions were also increased only in WKY rats. Finally, both strains had increased locomotor activity in the operant chamber following MP treatment. These findings point to an important difference in response tendency toMP in the two strains that supports a view that a critical difference between these strains may suggest neurochemical and neuroadaptive differences associated with the behavioral impairments of ADHD.« less

Is 6-thioguanine more appropriate than 6-mercaptopurine for children with acute lymphoblastic leukaemia?

PubMed Central

Lennard, L.; Davies, H. A.; Lilleyman, J. S.

1993-01-01

The cytotoxic activity of 6-mercaptopurine (6-MP) is affected by thiopurine methyltransferase (TPMT), a genetically regulated and variable intracellular enzyme. 6-Thioguanine (6-TG), a closely related thiopurine, is less affected by that enzyme and so it may be a more reliable drug-at least for patients with constitutionally high TPMT activity. We attempted to assess its suitability as an alternative by comparing the pharmacokinetics of both drugs in a small group of children with lymphoblastic leukaemia (ALL). Patients were included who were in their second or subsequent remission, who would otherwise have received 6-MP, and on whom pharmacokinetic data concerning 6-MP metabolism had been collected in a previous remission. Plasma 6-TG concentrations were assayed following an oral dose of 40 mg m-2, and the accumulation and fluctuation of intracellular (erythrocyte, RBC) 6-TG nucleotides (6-TGNs) were measured at regular intervals during daily oral therapy. Seven children were studied. Plasma 6-TG concentrations were low and cleared within 6 h of oral dosing. At 7 days, 6-TGN concentrations ranged from 959 to 2361 pmol 8 x 10(-8) RBCs, in all cases significantly higher (P = 0.002) than those produced by the same patients on 6-MP. After a total therapy time of 35 patient months, a modest rise of alanine aminotransferase was seen on one occasion, otherwise no toxicity apart from myelosuppression was encountered. In the context used, 6-TG appears well tolerated and produces higher concentrations of intracellular cytotoxic metabolites than 6-MP. For children constitutionally 'resistant' to the traditional drug, if not all, it may be a preferable alternative. PMID:8318412

The Impact of Peer Support and mp3 Messaging on Adherence to Inhaled Corticosteroids in Minority Adolescents with Asthma: A Randomized Controlled Trial

PubMed Central

Mosnaim, Giselle; Li, Hong; Martin, Molly; Richardson, DeJuran; Belice, Paula Jo; Avery, Elizabeth; Ryan, Norman; Bender, Bruce; Powell, Lynda

2013-01-01

Background Poor adherence to inhaled corticosteroids (ICS) is a critical risk factor contributing to asthma morbidity among low-income minority adolescents. Objective This trial tested whether peer support group meetings and peer asthma messages delivered via mp3 players improved adherence to ICS. Methods Low-income African American and/or Hispanic adolescents, ages 11–16, with persistent asthma, and poor (≤ 48%) adherence to prescription ICS during the 3-week run-in were randomized to intervention or attention control groups (ATG) for the 10-week treatment. During treatment, the intervention arm participated in weekly coping peer group support sessions and received mp3 peer-recorded asthma messages promoting adherence. The ATG participated in weekly meetings with a research assistant and received an equivalent number of mp3 doctor-recorded asthma messages. Adherence was measured using self-report and the DoserCT, (Meditrac, Inc.), an electronic dose counter. The primary outcome was the difference in adherence at 10 weeks between the two arms. Results Thirty-four subjects were randomized to each arm. At 10 weeks, no statistical difference in objectively measured adherence could be detected between the two arms adjusting for baseline adherence (P = 0.929). Adherence declined in both groups over the course of the active treatment period. Participants’ in both study arms self-reported adherence was significantly higher than their objectively measured adherence at week 10 (P < 0.0001). Conclusion Improving medication adherence in longitudinal studies is challenging. Peer support and mp3-delivered peer asthma messages may not be of sufficient dose to improve outcomes. PMID:24565620

The impact of peer support and mp3 messaging on adherence to inhaled corticosteroids in minority adolescents with asthma: a randomized, controlled trial.

PubMed

Mosnaim, Giselle; Li, Hong; Martin, Molly; Richardson, DeJuran; Belice, Paula Jo; Avery, Elizabeth; Ryan, Norman; Bender, Bruce; Powell, Lynda

2013-01-01

Poor adherence to inhaled corticosteroids (ICS) is a critical risk factor contributing to asthma morbidity among low-income minority adolescents. This trial tested whether peer support group meetings and peer asthma messages delivered via mp3 players improved adherence to ICS. Low-income African American and/or Hispanic adolescents, ages 11-16 years old, with persistent asthma, and poor (≤ 48%) adherence to prescription ICS during the 3-week run-in were randomized to intervention or attention control groups (ATG) for the 10-week treatment. During treatment, the intervention arm subjects participated in weekly coping peer group support sessions and received mp3 peer-recorded asthma messages that promoted adherence. The ATG participated in weekly meetings with a research assistant and received an equivalent number of mp3 physician-recorded asthma messages. Adherence was measured by using self-report and the Doser CT, an electronic dose counter. The primary outcome was the difference in adherence at 10 weeks between the 2 arms. Thirty-four subjects were randomized to each arm. At 10 weeks, no statistical difference in objectively measured adherence could be detected between the 2 arms when adjusting for baseline adherence (P = .929). Adherence declined in both groups over the course of the active treatment period. In both study arms, self-reported adherence by participants was significantly higher than their objectively measured adherence at week 10 (P < .0001). Improving medication adherence in longitudinal studies is challenging. Peer support and mp3-delivered peer asthma messages may not be of sufficient dose to improve outcomes. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Rift Valley Fever vaccines: An overview of the safety and efficacy of the live-attenuated MP-12 vaccine candidate

PubMed Central

Ikegami, Tetsuro

2017-01-01

Introduction Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Arabian Peninsula. High rates of abortion among infected ruminants and hemorrhagic fever in infected humans are major public health concerns. Commercially available veterinary RVF vaccines are important for preventing the spread of the Rift Valley fever virus (RVFV) in endemic countries; however, RVFV outbreaks continue to occur frequently in endemic countries in the 21st century. In the U.S., the live-attenuated MP-12 vaccine has been developed for both animal and human vaccination. This vaccine strain is well attenuated, and a single dose induces neutralizing antibodies in both ruminants and humans. Areas covered This review describes scientific evidences of MP-12 vaccine efficacy and safety, as well as MP-12 variants recently developed by reverse genetics, in comparison with other RVF vaccines. Expert commentary The containment of active RVF outbreaks and long-term protection from RVF exposure to infected mosquitoes are important goals for RVF vaccination. MP-12 vaccine will allow immediate vaccination of susceptible animals in case of an unexpected RVF outbreak in the U.S., whereas MP-12 vaccine may be also useful for the RVF control in endemic regions. PMID:28425834

Rift Valley fever vaccines: an overview of the safety and efficacy of the live-attenuated MP-12 vaccine candidate.

PubMed

Ikegami, Tetsuro

2017-06-01

Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Arabian Peninsula. High rates of abortion among infected ruminants and hemorrhagic fever in infected humans are major public health concerns. Commercially available veterinary RVF vaccines are important for preventing the spread of the Rift Valley fever virus (RVFV) in endemic countries; however, RVFV outbreaks continue to occur frequently in endemic countries in the 21st century. In the U.S., the live-attenuated MP-12 vaccine has been developed for both animal and human vaccination. This vaccine strain is well attenuated, and a single dose induces neutralizing antibodies in both ruminants and humans. Areas covered: This review describes scientific evidences of MP-12 vaccine efficacy and safety, as well as MP-12 variants recently developed by reverse genetics, in comparison with other RVF vaccines. Expert commentary: The containment of active RVF outbreaks and long-term protection from RVF exposure to infected mosquitoes are important goals for RVF vaccination. MP-12 vaccine will allow immediate vaccination of susceptible animals in case of an unexpected RVF outbreak in the U.S., whereas MP-12 vaccine may be also useful for the RVF control in endemic regions.

AVERAGE ANNUAL SOLAR UV DOSE OF THE CONTINENTAL US CITIZEN

EPA Science Inventory

The average annual solar UV dose of US citizens is not known, but is required for relative risk assessments of skin cancer from UV-emitting devices. We solved this problem using a novel approach. The EPA's "National Human Activity Pattern Survey" recorded the daily ou...

Pigmentation after single and multiple UV-exposures depending on UV-spectrum.

PubMed

Ravnbak, M H; Wulf, H C

2007-04-01

Minimal pigmentation dose (MMD) after a single UV-exposure is well investigated. Whereas only few studies have established MMD after multiple UV-exposures and mainly in fair-skinned persons. The purpose of this study was to establish MMD 1 week after, respectively, one and five UV-exposures in volunteers with a large variation in constitutive pigmentation. A total of 52 volunteers (skin Types II-V) had skin pigmentation quantified by reflectance spectroscopy. They were UV-exposed on the back for 1 and 5 days using a Solar Simulator, narrowband UVB, broadband UVA and UVA1. For all sources a higher dose was needed the more pigmented the skin, except for UVA1. After one UV-exposure, we found a significant positive linear correlation between UV-dose to one MMD, skin type and pre-exposure skin pigmentation. After five UV-exposures the positive linear correlation between UV-dose and MMD and skin type was only significant for narrow band UVB, pre-exposure skin pigmentation was significant also for Solar Simulator. For UVA and particularly UVA1 the MMD was independent of pre-exposure pigmentation. The number of SED to MMD is therefore almost the same for very fair-skinned and dark-skinned persons. Pre-exposure pigmentation was clearly more predictive of MMD than skin type. 50% of MMD equals a pigmentation increase of 1%. The shorter the wavelengths the higher the SED to produce MMD. Solar was the least melanogenic and UVA1 the most melanogenic. For the UVB-sources a higher dose was needed the more pigmented the skin. For UVA the MMD was independent of pre-exposure pigmentation.

Mutation induction in haploid yeast after split-dose radiation-exposure. I. Fractionated UV-irradiation.

PubMed

Schenk, K; Zölzer, F; Kiefer, J

1989-01-01

Mutation induction was investigated in wild-type haploid yeast Saccharomyces cerevisiae after split-dose UV-irradiation. Cells were exposed to fractionated 254 nm-UV-doses separated by intervals from 0 to 6 h with incubation either on non-nutrient or nutrient agar between. The test parameter was resistance to canavanine. If modifications of sensitivity due to incubation are appropriately taken into account there is no change of mutation frequency.

ULTRAVIOLET DISINFECTION OF A SECONDARY EFFLUENT: MEASUREMENT OF DOSE AND EFFECTS OF FILTRATION

EPA Science Inventory

Ultraviolet (UV) disinfection of wastewater secondary effluent was investigated in a two-phase study to develop methods for measuring UV dose and to determine the effects of filtration on UV disinfection. The first phase of this study involved a pilot plant study comparing filtra...

What happens with organic micropollutants during UV disinfection in WWTPs? A global perspective from laboratory to full-scale.

PubMed

Paredes, L; Omil, F; Lema, J M; Carballa, M

2018-01-15

The phototransformation of 18 organic micropollutants (OMPs) commonly detected in wastewater treatment plant (WWTP) effluents was examined attempting to explain their fate during UV disinfection in WWTPs. For this purpose, a lab-scale UV reactor (lamp emitting at 254nm) was used to study the influence of the operational conditions (UV dose, temperature and water matrix) on OMPs abatement and disinfection efficiency. Chemical properties of OMPs and the quality of treated effluent were identified as key factors affecting the phototransformation rate of these compounds. Sampling campaigns were carried out at the inlet and outlet of UV systems of three WWTPs, and the results evidenced that only the most photosensitive compounds, such as sulfamethoxazole and diclofenac, are eliminated. Therefore, despite UV treatment is an effective technology to phototransform OMPs, the UV doses typically applied for disinfection (10-50mJ/cm 2 ) are not sufficient to remove them. Consequently, small modifications (increase of UV dose, use of catalysts) should be applied in WWTPs to enhance the abatement of OMPs in UV systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Low-dose controlled release of mTOR inhibitors maintains T cell plasticity and promotes central memory T cells.

PubMed

Gammon, Joshua M; Gosselin, Emily A; Tostanoski, Lisa H; Chiu, Yu-Chieh; Zeng, Xiangbin; Zeng, Qin; Jewell, Christopher M

2017-10-10

An important goal for improving vaccine and immunotherapy technologies is the ability to provide further control over the specific phenotypes of T cells arising from these agents. Along these lines, frequent administration of rapamycin (Rapa), a small molecule inhibitor of the mammalian target of rapamycin (mTOR), exhibits a striking ability to polarize T cells toward central memory phenotypes (T CM ), or to suppress immune function, depending on the concentrations and other signals present during administration. T CM exhibit greater plasticity and proliferative capacity than effector memory T cells (T EFF ) and, therefore, polarizing vaccine-induced T cells toward T CM is an intriguing strategy to enhance T cell expansion and function against pathogens or tumors. Here we combined biodegradable microparticles encapsulating Rapa (Rapa MPs) with vaccines composed of soluble peptide antigens and molecular adjuvants to test if this approach allows polarization of differentiating T cells toward T CM . We show Rapa MPs modulate DC function, enhancing secretion of inflammatory cytokines at very low doses, and suppressing function at high doses. While Rapa MP treatment reduced - but did not stop - T cell proliferation in both CD4 + and CD8 + transgenic T cell co-cultures, the expanding CD8 + T cells differentiated to higher frequencies of T CM at low doses of MP Rapa MPs. Lastly, we show in mice that local delivery of Rapa MPs to lymph nodes during vaccination either suppresses or enhances T cell function in response to melanoma antigens, depending on the dose of drug in the depots. In particular, at low Rapa MP doses, vaccines increased antigen-specific T CM , resulting in enhanced T cell expansion measured during subsequent booster injections over at least 100days. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Can Carbamates Undergo Radical Oxidation in the Soil Environment? A Case Study on Carbaryl and Carbofuran.

PubMed

Ćwieląg-Piasecka, Irmina; Witwicki, Maciej; Jerzykiewicz, Maria; Jezierska, Julia

2017-12-19

Radical oxidation of carbamate insecticides, namely carbaryl and carbofuran, was investigated with spectroscopic (electron paramagnetic resonance [EPR] and UV-vis) and theoretical (density functional theory [DFT] and ab initio orbital-optimized spin-component scaled MP2 [OO-SCS-MP2]) methods. The two carbamates were subjected to reaction with • OH, persistent DPPH • and galvinoxyl radical, as well as indigenous radicals of humic acids. The influence of fulvic acids on carbamate oxidation was also tested. The results obtained with EPR and UV-vis spectroscopy indicate that carbamates can undergo direct reactions with various radical species, oxidizing themselves into radicals in the process. Hence, they are prone to participate in the prolongation step of the radical chain reactions occurring in the soil environment. Theoretical calculations revealed that from the thermodynamic point of view hydrogen atom transfer is the preferred mechanism in the reactions of the two carbamates with the radicals. The activity of carbofuran was determined experimentally (using pseudo-first-order kinetics) and theoretically to be noticeably higher in comparison with carbaryl and comparable with gallic acid. The findings of this study suggest that the radicals present in soil can play an important role in natural remediation mechanisms of carbamates.

Estimated UV doses to psoriasis patients during climate therapy at Gran Canaria in March 2006

NASA Astrophysics Data System (ADS)

Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.

2008-01-01

Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.

Changes in growth, leaf anatomy and pigment concentrations in pea under modulated UV-B field treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Day, T.A.; Howells, B.W.; Ruhland, C.T.

1995-06-01

In growth-chamber and greenhouse studies, garden pea is typically quite sensitive to enhanced UV-B radiation (280-320 nm). We assessed whether growth of pea was reduced under more ecologically relevant UV-B enhancements by employing modulated field lampbanks simulating 0, 16 or 24% ozone depletion. We also examined if these UV-B treatments altered leaf anatomy and concentrations of chlorophyll and UV-B-absorbing compounds, and whether this was dependent on leaf age. We used Pisum sativum mutant Argenteum which has an easily detachable epidermis that allowed us to compare concentrations in epidermal and mesophyll tissues. There were no significant UV-B effects on whole-plant growth.more » Of the 15 leaf-level parameters we examined, UV-B had a strong effect on only two parameters: the ratio of UV-B-absorbing compounds to chlorophyll (which increased with UV-B dose), and stomatal density of the adaxial surface (which decreased with UV-B dose). Chlorophyll concentrations tended to decrease, while the proportion of UV-B-absorbing compounds in the adaxial epidermis tended to increase with UV-B dose (p = 0.11 for both). In contrast to UV-B effects, we found strong leaf-age effects on nearly all parameters except the ratio of UV-B-absorbing compounds to chlorophyll, which remained relatively constant with leaf age.« less

Induction of homologous recombination in Saccharomyces cerevisiae.

PubMed

Simon, J R; Moore, P D

1988-09-01

We have investigated the effects of UV irradiation of Saccharomyces cerevisiae in order to distinguish whether UV-induced recombination results from the induction of enzymes required for homologous recombination, or the production of substrate sites for recombination containing regions of DNA damage. We utilized split-dose experiments to investigate the induction of proteins required for survival, gene conversion, and mutation in a diploid strain of S. cerevisiae. We demonstrate that inducing doses of UV irradiation followed by a 6 h period of incubation render the cells resistant to challenge doses of UV irradiation. The effects of inducing and challenge doses of UV irradiation upon interchromosomal gene conversion and mutation are strictly additive. Using the yeast URA3 gene cloned in non-replicating single- and double-stranded plasmid vectors that integrate into chromosomal genes upon transformation, we show that UV irradiation of haploid yeast cells and homologous plasmid DNA sequences each stimulate homologous recombination approximately two-fold, and that these effects are additive. Non-specific DNA damage has little effect on the stimulation of homologous recombination, as shown by studies in which UV-irradiated heterologous DNA was included in transformation/recombination experiments. We further demonstrate that the effect of competing single- and double-stranded heterologous DNA sequences differs in UV-irradiated and unirradiated cells, suggesting an induction of recombinational machinery in UV-irradiated S. cerevisiae cells.

The injury and cumulative effects on human skin by UV exposure from artificial fluorescence emission.

PubMed

Tian, Yan; Liu, Wei; Niu, TianHui; Dai, CaiHong; Li, Xiaoxin; Cui, Caijuan; Zhao, Xinyan; E, Yaping; Lu, Hui

2014-01-01

The injury and cumulative effects of UV emission from fluorescence lamp were studied. UV intensity from fluorescence lamp was measured, and human skin samples (hips, 10 volunteers) were exposed to low-dose UV irradiation (three times per week for 13 consecutive weeks). Three groups were examined: control group without UV radiation; low-dose group with a cumulative dose of 50 J cm(-2) which was equivalent to irradiation of the face during indoor work for 1.5 years; and high-dose group with 1000 J cm(-2) cumulative dose equivalent to irradiation of the face during outdoor activities for 1 year. Specific indicators were measured before and after UVA irradiation. The findings showed that extending the low-dose UVA exposure decreased the skin moisture content and increased the transepidermal water loss as well as induced skin color changes (decreased L* value, increased M index). Furthermore, irradiated skin showed an increased thickness of cuticle and epidermis, skin edema, light color and unclear staining collagen fibers in the dermis, and elastic fiber fragmentation. In addition, MMP-1, p53 and SIRT1 expression was also increased. Long-term exposure of low-dose UVA radiation enhanced skin photoaging. The safety of the fluorescent lamp needs our attention. © 2014 The American Society of Photobiology.

Low dose arsenite confers resistance to UV induced apoptosis via p53-MDM2 pathway in ketatinocytes

PubMed Central

Zhou, Y; Zeng, W; Qi, M; Duan, Y; Su, J; Zhao, S; Zhong, W; Gao, M; Li, F; He, Y; Hu, X; Xu, X; Chen, X; Peng, C; Zhang, J

2017-01-01

Chronic arsenite and ultraviolet (UV) exposure are associated with skin tumor. To investigate the details by low concentrations of arsenite and UV induced carcinogenesis in skin, hTERT-immortalized human keratinocytes were used as a cellular model with exposure to low concentrations of sodium arsenite and UV. The effect of NaAsO2 on UV treatment-induced apoptosis was measured by flow cytometry and Hoechst staining. We found that the cell apoptosis induced by UV exposure was significantly attenuated after exposure to low-dose arsenite, and knockdown of p53 could block UV-induced apoptosis indicating that this phenomenon depended on p53. Interestingly, the expression of murine double minute 2 (MDM2), including its protein and transcriptional levels, was remarkably high after exposure to low-dose arsenite. Moreover, low-dose arsenite treatment dramatically decreased the MDM2 gene promoter activity, suggesting that this effect has been mediated through transcription. In addition, treatment of PD98059 reversed low-dose arsenite-induced MDM2 expression, and the inhibition of ERK2 expression could significantly block MDM2 expression as a consequence, and p53 expression automatically was increased. To validate the role of p53 in exposure to low-dose arsenite, the expression of p53 was examined by immunohistochemistry in the skin of Sprague−Dawley rats model by chronic arsenite exposure for 6 months and in patients with arsenic keratosis, and the results showed that the expression of p53 was decreased in those samples. Taken together, our results demonstrated that low-dose arsenite-induced resistance to apoptosis through p53 mediated by MDM2 in keratinocytes. PMID:28785074

Potential Biomarker of Myofibrillar Protein Oxidation in Raw and Cooked Ham: 3-Nitrotyrosine Formed by Nitrosation.

PubMed

Feng, Xianchao; Li, Chenyi; Ullah, Niamat; Hackman, Robert M; Chen, Lin; Zhou, Guanghong

2015-12-30

The stability of cured meat products is increased by the protection of its proteins from oxidation by sodium nitrite (NaNO2) during processing. This study investigated the effects of NaNO2 (0, 50, 100, 200, and 400 mg/kg) on the physiochemical and structural characteristics of myofibrillar protein (MP) in raw and cooked ham. The NaNO2 showed a dose-dependent antioxidant effect, by inhibiting carbonyl formation, dityrosine formation, and denaturation of MP, and a nitrosative effect, through the formation of 3-Nitrotyrosine (3-NT). The 3-NT content within MP of raw ham had distinct negative correlations with sulfhydryl content and surface hydrophobicity. The 3-NT content within MP of cooked ham had significantly negative correlations with carbonyl, sulfhydryl content and turbidity and had significantly positive correlations with disulfide content. These results indicated that 3-NT may be a potential marker for protein oxidation in raw and cooked cured meat products.

Methylparaben induces malformations and alterations on apoptosis, oxidant-antioxidant status, ccnd1 and myca expressions in zebrafish embryos.

PubMed

Ateş, Perihan Seda; Ünal, İsmail; Üstündağ, Ünsal Veli; Alturfan, Ahmet Ata; Yiğitbaşı, Türkan; Emekli-Alturfan, Ebru

2018-03-01

Methylparabens (MP) are widely used as preservatives in cosmetics, pharmacy, and food industry. Although acute toxicity studies in animals indicated that parabens are not significantly toxic, the effects of chronic exposure under sublethal doses are still unknown and the number of related studies is limited. Our aim was to evaluate the effects of MP on the development of zebrafish embryos focusing on development, locomotor activity, oxidant-antioxidant status, apoptosis, and ccnd1 and myca expressions. The expressions of ccnd1 and myca were determined by RT-PCR. Lipid peroxidation (LPO), nitric oxide (NO), and glutathione-S-transferase (GST) activities were determined spectrophotometrically. Apoptosis was determined using acridine orange staining. Locomotor activity was measured using touch-evoked movement test. MP exposure increased malformations, LPO, apoptosis, ccnd1 and myca expressions, and decreased GST activities and NO levels compared with the control group. Our findings will lead to further understanding of the mechanism of MP toxicity, and merit further research. © 2018 Wiley Periodicals, Inc.

Rift Valley fever MP-12 vaccine Phase 2 clinical trial: Safety, immunogenicity, and genetic characterization of virus isolates.

PubMed

Pittman, Phillip R; Norris, Sarah L; Brown, Elizabeth S; Ranadive, Manmohan V; Schibly, Barbara A; Bettinger, George E; Lokugamage, Nandadeva; Korman, Lawrence; Morrill, John C; Peters, Clarence J

2016-01-20

An outbreak or deliberate release of Rift Valley fever (RVF) virus could have serious public health and socioeconomic consequences. A safe RVF vaccine capable of eliciting long-lasting immunity after a single injection is urgently needed. The live attenuated RVF MP-12 vaccine candidate has shown promise in Phase 1 clinical trials; no evidence of reversion to virulence has been identified in numerous animal studies. The objective of this Phase 2 clinical trial was to (a) further examine the safety and immunogenicity of RVF MP-12 in RVF virus-naïve humans and (b) characterize isolates of RVF MP-12 virus recovered from the blood of vaccinated subjects to evaluate the genetic stability of MP-12 attenuation. We found that RVF MP-12 was well tolerated, causing mostly mild reactions that resolved without sequelae. Of 19 subjects, 18 (95%) and 19 (100%) achieved, respectively, 80% and 50% plaque reduction neutralization titers (PRNT80 and PRNT50)≥1:20 by postvaccination day 28. All 18 PRNT80 responders maintained PRNT80 and PRNT50≥1:40 until at least postvaccination month 12. Viremia was undetectable in the plasma of any subject by direct plaque assay techniques. However, 5 of 19 vaccinees were positive for MP-12 isolates in plasma by blind passage of plasma on Vero cells. Vaccine virus was also recovered from buffy coat material from one of those vaccinees and from one additional vaccinee. Through RNA sequencing of MP-12 isolates, we found no reversions of amino acids to those of the parent virulent virus (strain ZH548). Five years after a single dose of RVF MP-12 vaccine, 8 of 9 vaccinees (89%) maintained a PRNT80≥1:20. These findings support the continued development of RVF MP-12 as a countermeasure against RVF virus in humans. Published by Elsevier Ltd.

Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference.

PubMed

Mu, Ying; Ren, Zhaoxiang; Jia, Jia; Gao, Bo; Zheng, Longtai; Wang, Guanghui; Friedman, Eitan; Zhen, Xuechu

2014-09-25

Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP). The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of morphine-induced CPP, but did accelerate the extinction of morphine-induced CPP. Additionally, chronic treatment with 2.5 mg/kg MP-10 decreased expression of phosphorylated CREB (pCREB), activated cAMP response element binding protein, in dorsomedial striatum, in shell of NAc, and in anterior cingulate cortex (ACC) as well as decreased expression of ΔFosB in the shell of NAc and ACC. The results suggest that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.

Effect of scattered electrons on the ‘Magic Plate’ transmission array detector response

NASA Astrophysics Data System (ADS)

Alrowaili, Z. A.; Lerch, M.; Petasecca, M.; Carolan, M.; Rosenfeld, A.

2017-02-01

Transmission type detectors can provide a measure of the energy fluence and if they are real-time systems that do not significantly attenuate the radiation beam have a distinct advantage over the current method as Quality Assurance (QA) could in principle be done during the actual patient treatment. The use of diode arrays in QA holds much promise due to real-time operation and feedback when compared to other methods e.g. films which are not real-time. The goal of this work is to describe the characterization of the radiation response of a silicon diode array called the Magic Plate (MP) when operated in transmission mode (MPTM). The response linearity of MPTM was excellent (R2=1). When the MP was placed in linac block tray position; the change in PDD at phantom surface (SSD 100 cm) for a 10 × 10 cm2 was -0.037 %, -0.178 % and -0.949 % for 6 MV, 10 MV and 18 MV beams. Therefore, MP does not provide a significant increase in skin dose to the patient and the percentage depth doses showed an excellent agreement with and without MPTM for 6 MV, 10 MV and 18 MV beams.

Focal dose escalation for prostate cancer using 68Ga-HBED-CC PSMA PET/CT and MRI: a planning study based on histology reference.

PubMed

Zamboglou, Constantinos; Thomann, Benedikt; Koubar, Khodor; Bronsert, Peter; Krauss, Tobias; Rischke, Hans C; Sachpazidis, Ilias; Drendel, Vanessa; Salman, Nasr; Reichel, Kathrin; Jilg, Cordula A; Werner, Martin; Meyer, Philipp T; Bock, Michael; Baltas, Dimos; Grosu, Anca L

2018-05-02

Focal radiation therapy has gained of interest in treatment of patients with primary prostate cancer (PCa). The question of how to define the intraprostatic boost volume is still open. Previous studies showed that multiparametric MRI (mpMRI) or PSMA PET alone could be used for boost volume definition. However, other studies proposed that the combined usage of both has the highest sensitivity in detection of intraprostatic lesions. The aim of this study was to demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of radiation therapy dose painting using 68 Ga-HBED-CC PSMA PET/CT, mpMRI or the combination of both in primary PCa. Ten patients underwent PSMA PET/CT and mpMRI followed by prostatectomy. Three gross tumour volumes (GTVs) were created based on PET (GTV-PET), mpMRI (GTV-MRI) and the union of both (GTV-union). Two plans were generated for each GTV. Plan95 consisted of whole-prostate IMRT to 77 Gy in 35 fractions and a simultaneous boost to 95 Gy (Plan95 PET /Plan95 MRI /Plan95 union ). Plan80 consisted of whole-prostate IMRT to 76 Gy in 38 fractions and a simultaneous boost to 80 Gy (Plan80 PET /Plan80 MRI /Plan80 union ). TCPs were calculated for GTV-histo (TCP-histo), which was delineated based on PCa distribution in co-registered histology slices. NTCPs were assessed for bladder and rectum. Dose constraints of published protocols were reached in every treatment plan. Mean TCP-histo were 99.7% (range: 97%-100%) and 75.5% (range: 33%-95%) for Plan95 union and Plan80 union , respectively. Plan95 union had significantly higher TCP-histo values than Plan95 MRI (p = 0.008) and Plan95 PET (p = 0.008). Plan80 union had significantly higher TCP-histo values than Plan80 MRI (p = 0.012), but not than Plan80 PET (p = 0.472). Plan95 MRI had significantly lower NTCP-rectum than Plan95 union (p = 0.012). No significant differences in NTCP-rectum and NTCP-bladder were observed for all other plans (p > 0.05). IMRT dose escalation on GTVs based on mpMRI, PSMA PET/CT and the combination of both was feasible. Boosting GTV-union resulted in significantly higher TCP-histo with no or minimal increase of NTCPs compared to the other plans.

Use of the dye stain assay and ultraviolet light test for assessing vaginal insertion of placebo-filled applicators before and after sex.

PubMed

Keller, Marla J; Buckley, Niall; Katzen, Lauren L; Walsh, Jennifer; Friedland, Barbara; Littlefield, Sarah; Lin, Juan; Xue, Xiaonan; Cornelison, Terri; Herold, Betsy C; Einstein, Mark H

2013-12-01

Applicator dye staining and ultraviolet (UV) light have been used in trials to measure adherence, but not in the setting of before and after sex gel dosing (BAT-24). This study was designed to determine if semen or presex gel dosing impacts the sensitivity and specificity of a dye stain assay (DSA) for measuring vaginal insertion of placebo-filled applicators with BAT-24 dosing. Healthy monogamous couples received Microlax-type applicators (Tectubes, Åstorp, Sweden) filled with hydroxyethylcelluose placebo gel. Women were instructed to vaginally insert 1 dose of gel before and a second dose after sex and to return applicators within 48 hours after sex. Applicators were stained to detect semen, followed by UV then DSA, and scored by 2 readers. Positive and negative controls were randomly included in applicator batches. Fifteen couples completed the study. Each woman returned at least 6 applicators over a 30-day period. The sensitivity for insertion of postsex applicators was higher for UV (97%) compared with DSA (90%), and the specificity was similar (≥96%). For presex applicators, the sensitivity and specificity were higher for DSA (100%) compared with UV testing (87% sensitivity, 96% specificity). Among returned postsex applicators, 95% tested positive by UV compared with 87% by DSA. Agreement between readers was significantly better on the presex applicators for DSA than for UV, and for postsex readings, agreement was less than half that for UV, although the results were not statistically significant. Applicator tests are feasible for measuring adherence in trials with gel dosing before and after sex.

UV-C Adaptation of Shigella: Morphological, Outer Membrane Proteins, Secreted Proteins, and Lipopolysaccharides Effects.

PubMed

Chourabi, Kalthoum; Campoy, Susana; Rodriguez, Jesus A; Kloula, Salma; Landoulsi, Ahmed; Chatti, Abdelwaheb

2017-11-01

Water UV disinfection remains extremely important, particularly in developing countries where drinking and reclaimed crop irrigation water may spread devastating infectious diseases. Enteric bacterial pathogens, among which Shigella, are possible contaminants of drinking and bathing water and foods. To study the effect of UV light on Shigella, four strains were exposed to different doses in a laboratory-made irradiation device, given that the ultraviolet radiation degree of inactivation is directly related to the UV dose applied to water. Our results showed that the UV-C rays are effective against all the tested Shigella strains. However, UV-C doses appeared as determinant factors for Shigella eradication. On the other hand, Shigella-survived strains changed their outer membrane protein profiles, secreted proteins, and lipopolysaccharides. Also, as shown by electron microscopy transmission, morphological alterations were manifested by an internal cytoplasm disorganized and membrane envelope breaks. Taken together, the focus of interest of our study is to know the adaptive mechanism of UV-C resistance of Shigella strains.

Effectiveness of two-sided UV-C treatments in inhibiting natural microflora and extending the shelf-life of minimally processed 'Red Oak Leaf' lettuce.

PubMed

Allende, Ana; McEvoy, James L; Luo, Yaguang; Artes, Francisco; Wang, Chien Y

2006-05-01

The use of UV-C radiation treatments to inhibit the microbial growth and extend the shelf-life of minimally processed 'Red Oak Leaf' lettuce was investigated. Initially, UV-C resistance of 20 bacterial strains from different genera often associated with fresh produce (Enterobacter, Erwinia, Escherichia, Leuconostoc, Pantoea, Pseudomonas, Rahnela, Salmonella, Serratia and Yersinia) were tested in vitro. Most of the bacterial strains were inhibited with the minimum dose (30 J m(-2)). Erwinia carotovora, Leuconostoc carnosum, Salmonella typhimurium, and Yersinia aldovae were the most resistant strains requiring a UV-C dose of 85 J m(-2) to completely inhibit growth. An in vivo study consisted of treating minimally processed 'Red Oak Leaf' lettuce (Lactuca sativa) with UV-C at three radiation doses (1.18, 2.37 and 7.11 kJ m(-2)) on each side of the leaves and storing the product under passive MAP conditions at 5 degrees C for up to 10 days. The gas composition inside packages varied significantly among the treatments, with CO2 concentrations positively and O2 concentrations negatively correlating with the radiation dose. All the radiation doses were effective in reducing the natural microflora of the product, although the highest doses showed the greatest microbial inhibitions. Taking into account the microbial limit set by Spanish legislation [Boletín Oficial del Estado (BOE), 2001. Normas de higiene para la elaboración, distribución y comercio de comidas preparadas, Madrid, Spain, Real Decreto 3484/2000, pp. 1435-1441], all UV-C treatments extended the shelf-life of the product. However, the 7.11 kJ m(-2) dose induced tissue softening and browning after 7 days of storage at 5 degrees C. Therefore, the use of two sided UV-C radiation, at the proper dose, is effective in reducing the natural microflora and extending the shelf-life of minimally processed 'Red Oak Leaf' lettuce.

Enhancement of SV40 transformation by treatment of C3H2K cells with uv light and caffeine. I. Combined effect of uv light and caffeine. [Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ide, T.; Anzai, K.; Andoh, T.

1975-08-01

Treatment of cultured mouse cells, C3H2K, with uv light and/or caffeine enhanced the frequency of SV40-induced transformation. This enhancement depends upon the doses of uv and caffeine and the mode of combination of these agents. Irradiation of cells with increasing doses of uv just before infection resulted in approximately 2-fold enhancement of the transformation frequency up to a dose of 90 ergs/mm/sup 2/ and 3.3-fold at 150 ergs/mm/sup 2/. Addition of 1 mM caffeine to the medium for 4 days subsequent to infection brought about a 2-fold enhancement. When cells were irradiated and treated with 1 mM caffeine, the enhancementmore » was approximately 4-fold up to a uv dose of 90 ergs/mm/sup 2/ and 5.9-fold at 150 ergs/mm/sup 2/. When 0.1 to 4 mM caffeine was added for 4 days postinfection, the absolute number of transformations increased, and an enhancement ratio of 1.3 to 6.8 resulted. After the addition of the same increasing doses of caffeine to uv-irradiated cells (75 ergs/mm/sup 2/), the enhancement of transformation frequency was even higher ranging 2.0 to 13.3. The transformation frequencies thus obtained by the double treatment were always higher than those predicted if uv and caffeine acted additively. The transformation frequency was little affected by the addition of dibutyrylcyclic AMP and theophylline.« less

Preoperative methylprednisolone does not reduce loss of knee-extension strength after total knee arthroplastyA randomized, double-blind, placebo-controlled trial of 61 patients.

PubMed

Lindberg-Larsen, Viktoria; Bandholm, Thomas Q; Zilmer, Camilla K; Bagger, Jens; Hornsleth, Mette; Kehlet, Henrik

2017-10-01

Background and purpose - Patients undergoing total knee arthroplasty (TKA) face challenges related to postoperative reduction in knee-extension strength. We evaluated whether inhibition of the inflammatory response by a single preoperative dose of methylprednisolone (MP) reduces the pronounced loss of knee-extension strength at discharge after fast-track TKA. Patients and methods - 70 patients undergoing elective unilateral TKA were randomized (1:1) to preoperative intravenous (IV) MP 125 mg (group MP) or isotonic saline IV (group C). All procedures were performed under spinal anesthesia without tourniquet, and with a standardized multimodal analgesic regime. The primary outcome was change in knee-extension strength from baseline to 48 hours postoperatively. Secondary outcomes were knee joint circumference, functional performance using the Timed Up and Go (TUG) test, pain during the aforementioned tests, rescue analgesic requirements, and plasma C-reactive protein (CRP) changes. Results - 61 patients completed the follow-up. The loss in quadriceps muscle strength was similar between groups; group MP 1.04 (0.22-1.91) Nm/kg (-89%) vs. group C 1.02 (0.22-1.57) Nm/kg (-88%). Also between-group differences were similar for knee circumference, TUG test, and pain scores. MP reduced the inflammatory response (CRP) at 24 hours postoperatively; group MP 33 (IQR 21-50) mg/L vs. group C 72 (IQR 58-92) mg/L (p < 0.001), and 48 hours postoperatively; group MP 83 (IQR 56-125) mg/L vs. group C 192 (IQR 147-265) mg/L (p < 0.001), respectively. Interpretation - Preoperative systemic administration of MP 125 mg did not reduce the pronounced loss of knee-extension strength or other functional outcomes at discharge after fast-track TKA despite a reduced systemic inflammatory response.

Preoperative methylprednisolone does not reduce loss of knee-extension strength after total knee arthroplasty

PubMed Central

Lindberg-Larsen, Viktoria; Bandholm, Thomas Q; Zilmer, Camilla K; Bagger, Jens; Hornsleth, Mette; Kehlet, Henrik

2017-01-01

Background and purpose Patients undergoing total knee arthroplasty (TKA) face challenges related to postoperative reduction in knee-extension strength. We evaluated whether inhibition of the inflammatory response by a single preoperative dose of methylprednisolone (MP) reduces the pronounced loss of knee-extension strength at discharge after fast-track TKA. Patients and methods 70 patients undergoing elective unilateral TKA were randomized (1:1) to preoperative intravenous (IV) MP 125 mg (group MP) or isotonic saline IV (group C). All procedures were performed under spinal anesthesia without tourniquet, and with a standardized multimodal analgesic regime. The primary outcome was change in knee-extension strength from baseline to 48 hours postoperatively. Secondary outcomes were knee joint circumference, functional performance using the Timed Up and Go (TUG) test, pain during the aforementioned tests, rescue analgesic requirements, and plasma C-reactive protein (CRP) changes. Results 61 patients completed the follow-up. The loss in quadriceps muscle strength was similar between groups; group MP 1.04 (0.22–1.91) Nm/kg (–89%) vs. group C 1.02 (0.22–1.57) Nm/kg (–88%). Also between-group differences were similar for knee circumference, TUG test, and pain scores. MP reduced the inflammatory response (CRP) at 24 hours postoperatively; group MP 33 (IQR 21–50) mg/L vs. group C 72 (IQR 58–92) mg/L (p < 0.001), and 48 hours postoperatively; group MP 83 (IQR 56–125) mg/L vs. group C 192 (IQR 147–265) mg/L (p < 0.001), respectively. Interpretation Preoperative systemic administration of MP 125 mg did not reduce the pronounced loss of knee-extension strength or other functional outcomes at discharge after fast-track TKA despite a reduced systemic inflammatory response. PMID:28657396

Azathioprine and 6-Mercaptopurine-induced Liver Injury: Clinical Features and Outcomes.

PubMed

Björnsson, Einar S; Gu, Jiezhun; Kleiner, David E; Chalasani, Naga; Hayashi, Paul H; Hoofnagle, Jay H

2017-01-01

The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%). Inflammatory bowel disease was the indication in 55%, and the median thiopurine dose was 150 (range, 25 to 300) mg daily. The median latency to onset was 75 (range, 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients, the median latency after dose increase being 44 (range, 3 to 254) days. At onset, the median alanine aminotransferase level was 210 U/L, alkaline phosphatase was 151 U/L, and bilirubin was 7.4 mg/dL (peak, 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had nonspecific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with preexisting cirrhosis required liver transplantation; all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset. Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with preexisting cirrhosis.

Azathioprine and 6-Mercaptopurine Induced Liver Injury: Clinical Features and Outcomes

PubMed Central

Björnsson, Einar S.; Gu, Jiezhun; Kleiner, David E.; Chalasani, Naga; Hayashi, Paul H.; Hoofnagle, Jay H.

2017-01-01

Goals To define the clinical, biochemical and histologic features of liver injury from thiopurines. Background Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury but no large series exist. Methods Clinical and laboratory data and 6-months outcomes were analyzed from patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study. Results 22 patients were identified, 12 due to Aza and 10 6-MP, with a median age of 55 years and the majority females (68%). Inflammatory bowel disease was the indication in 55%, and median thiopurine dose 150 (range 25–300) mg daily. The median latency to onset was 75 (range 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients; the median latency after dose increase being 44 (range 3 to 254) days. At onset, the median alanine aminotransferase was 210 U/L, alkaline phosphatase 151 U/L and bilirubin 7.4 mg/dL (peak 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had non-specific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced a cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with pre-existing cirrhosis required liver transplantation, all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset. Conclusions Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with pre-existing cirrhosis. PMID:27648552

Focal application of low-dose-rate brachytherapy for prostate cancer: a pilot study

PubMed Central

Spadinger, Ingrid T.; Salcudean, Septimiu E.; Kozlowski, Piotr; Chang, Silvia D.; Ng, Tony; Lobo, Julio; Nir, Guy; Moradi, Hamid; Peacock, Michael; Morris, W. James

2017-01-01

Purpose To evaluate the feasibility and to report the early outcomes of focal treatment of prostate cancer using low-dose-rate brachytherapy (LDR-PB). Material and methods Seventeen patients were screened with multi-parametric magnetic resonance imaging (mpMRI), 14 of whom proceeded to receive trans-perineal template mapping biopsy (TTMB). Focal LDR-PB was performed on five eligible patients using dual air kerma strength treatment plans based on planning target volumes derived from cancer locations and determined by TTMB. Patient follow-up includes prostate specific antigen (PSA) measurements, urinary and sexual function questionnaires, repeated imaging and TTMB at specific intervals post-treatment. Results Feasibility of focal LDR-PB was shown and short-term outcomes are promising. While the detection rate of tumors, a majority of which were low grade GS 3 + 3, was found to be low on mpMRI (sensitivity of 37.5%), our results suggest the potential of mpMRI in detecting the presence of higher grade (GS ≥ 3 + 4), and bilateral disease indicating its usefulness as a screening tool for focal LDR-PB. Conclusions Low-dose-rate brachytherapy is a favorable ablation option for focal treatment of prostate cancer, requiring minimal modification to the standard (whole gland) LDR-PB treatment, and appears to have a more favorable side effect profile. Further investigation, in the form of a larger study, is needed to assess the methods used and the long-term outcomes of focal LDR-PB. PMID:28725242

Photodetachment and UV-Vis spectral properties of Cl2rad -·nHO clusters: Extrapolation to bulk

NASA Astrophysics Data System (ADS)

Pathak, A. K.; Mukherjee, T.; Maity, D. K.

2008-03-01

Vertical detachment energy (VDE) and UV-Vis spectra of Cl2rad -·nHO clusters ( n = 1-11) are reported based on first principle electronic structure calculations. VDE of the hydrated clusters are calculated following second order Moller-Plesset perturbation (MP2) as well as coupled cluster theory with 6-311++G(d,p) set of basis function. The excess electron in these hydrated clusters is mainly localized over the solute Cl atoms. A linear relationship is obtained for VDE vs. ( n + 2.6) -1/3 and bulk VDE of Cl2rad - aqueous solution is calculated as 10.61 eV at CCSD(T) level of theory. UV-Vis spectra of these hydrated clusters are calculated applying CI with single electron (CIS) excitation procedure. Simulated UV-Vis spectra of Cl2rad -·10HO cluster is noted to be in excellent agreement with the reported spectra of Cl2rad - (aq) system, λmax for Cl2rad -·11HO system is calculated to be red shifted though.

An Ultraviolet Investigation of Activity on Exoplanet Host Stars

NASA Astrophysics Data System (ADS)

Shkolnik, Evgenya L.

2013-03-01

Using the far-UV (FUV) and near-UV (NUV) photometry from the NASA Galaxy Evolution Explorer (GALEX), we searched for evidence of increased stellar activity due to tidal and/or magnetic star-planet interactions (SPI) in the 272 known FGK planetary hosts observed by GALEX. With the increased sensitivity of GALEX, we are able probe systems with lower activity levels and at larger distances than what has been done to date with X-ray satellites. We compared samples of stars with close-in planets (a < 0.1 AU) to those with far-out planets (a > 0.5 AU) and looked for correlations of excess activity with other system parameters. This statistical investigation found no clear correlations with a, Mp , or Mp /a, in contrast to some X-ray and Ca II studies. However, there is tentative evidence (at a level of 1.8σ) that stars with radial-velocity-(RV)-detected close-in planets are more FUV-active than stars with far-out planets, in agreement with several published X-ray and Ca II results. The case is strengthened to a level of significance to 2.3σ when transit-detected close-in planets are included. This is most likely because the RV-selected sample of stars is significantly less active than the field population of comparable stars, while the transit-selected sample is similarly active. Given the factor of 2-3 scatter in fractional FUV luminosity for a given stellar effective temperature, it is necessary to conduct a time-resolved study of the planet hosts in order to better characterize their UV variability and generate a firmer statistical result. Based on observations made with the NASA Galaxy Evolution Explorer. GALEX is operated for NASA by the California Institute of Technology under NASA contract NAS5-98034.

CIE, Vitamin D and DNA Damage: A Synergetic Study in Thessaloniki, Greece

NASA Astrophysics Data System (ADS)

Zempila, Melina Maria; Taylor, Michael; Fountoulakis, Ilias; Koukouli, Maria Elissavet; Bais, Alkiviadis; Arola, Antii; van Geffen, Jos; van Weele, Michiel; van der A, Ronald; Kouremeti, Natalia; Kazadzis, Stelios; Meleti, Chariklia; Balis, Dimitrios

2016-08-01

The present study aims to validate different approaches for the estimation of three photobiological effective doses: the erythemal UV, the vitamin D and that for DNA damage, using high temporal resolution surface- based measurements of solar UV from 2005-2015. Data from a UV spectrophotometer, a multi-filter radiometer, and a UV radiation pyranometer that are located in Thessaloniki, Greece are used together with empirical relations, algorithms and models in order to calculate the desired quantities. In addition to the surface-based dose retrievals, OMI/Aura and the combined SCIAMACHY/Envisat and GOME/MetopA satellite products are also used in order to assess the accuracy of each method for deriving the photobiological doses.

The TROPOMI surface UV algorithm

NASA Astrophysics Data System (ADS)

Lindfors, Anders V.; Kujanpää, Jukka; Kalakoski, Niilo; Heikkilä, Anu; Lakkala, Kaisa; Mielonen, Tero; Sneep, Maarten; Krotkov, Nickolay A.; Arola, Antti; Tamminen, Johanna

2018-02-01

The TROPOspheric Monitoring Instrument (TROPOMI) is the only payload of the Sentinel-5 Precursor (S5P), which is a polar-orbiting satellite mission of the European Space Agency (ESA). TROPOMI is a nadir-viewing spectrometer measuring in the ultraviolet, visible, near-infrared, and the shortwave infrared that provides near-global daily coverage. Among other things, TROPOMI measurements will be used for calculating the UV radiation reaching the Earth's surface. Thus, the TROPOMI surface UV product will contribute to the monitoring of UV radiation by providing daily information on the prevailing UV conditions over the globe. The TROPOMI UV algorithm builds on the heritage of the Ozone Monitoring Instrument (OMI) and the Satellite Application Facility for Atmospheric Composition and UV Radiation (AC SAF) algorithms. This paper provides a description of the algorithm that will be used for estimating surface UV radiation from TROPOMI observations. The TROPOMI surface UV product includes the following UV quantities: the UV irradiance at 305, 310, 324, and 380 nm; the erythemally weighted UV; and the vitamin-D weighted UV. Each of these are available as (i) daily dose or daily accumulated irradiance, (ii) overpass dose rate or irradiance, and (iii) local noon dose rate or irradiance. In addition, all quantities are available corresponding to actual cloud conditions and as clear-sky values, which otherwise correspond to the same conditions but assume a cloud-free atmosphere. This yields 36 UV parameters altogether. The TROPOMI UV algorithm has been tested using input based on OMI and the Global Ozone Monitoring Experiment-2 (GOME-2) satellite measurements. These preliminary results indicate that the algorithm is functioning according to expectations.

Research and Operational Support for the Study of Militarily Relevant Infectious Diseases of Interest to the United States and Royal Thai Government

DTIC Science & Technology

2005-01-01

vaccine ( Varicella vaccine for dose 1 and Hemophilius B vaccine for dose 2). Fifty-one healthy male and female, flavivirus naive infants were enrolled...Bangkok, Thailand. 11th International Conference of Infectious Disease. Cancun, Mexico . 4-8 March 2004. 80. Zhang C, Klungthong C, Monkongdee P, Mammen MP

CYTOKINE PROFILING FOR CHEMICAL SENSITIZERS: APPLICATION OF THE RIBONUCLEASE PROTECTION ASSAY AND EFFECT OF DOSE

EPA Science Inventory

Cytokine Profiling for Chemical Sensitizers: Application of the Ribonuclease Protection Assay and Effect of Dose. L.M. Plitnick1, S.E. Loveless3, G.S. Ladics3, M.P. Holsapple4, M.J. Selgrade2, D.M. Sailstad2 and R.J. Smialowicz2. 1UNC, Curriculum in Toxicology, Chapel Hill, NC a...

Use of the Dye Stain Assay and Ultraviolet Light Test for Assessing Vaginal Insertion of Placebo-filled Applicators Before and After Sex

PubMed Central

Keller, Marla J.; Buckley, Niall; Katzen, Lauren L.; Walsh, Jennifer; Friedland, Barbara; Littlefield, Sarah; Lin, Juan; Xue, Xiaonan; Cornelison, Terri; Herold, Betsy C.; Einstein, Mark H.

2014-01-01

Background Applicator dye staining and ultraviolet (UV) light have been used in trials to measure adherence, but not in the setting of before and after sex gel dosing (BAT-24). This study was designed to determine if semen or pre-sex gel dosing impacts the sensitivity and specificity of a dye stain assay (DSA) for measuring vaginal insertion of placebo-filled applicators with BAT-24 dosing. Methods Healthy monogamous couples received Microlax®-type applicators filled with hydroxyethylcelluose placebo gel. Women were instructed to vaginally insert one dose of gel before and a second dose after sex and to return applicators within 48 hours after sex. Applicators were stained to detect semen followed by UV then DSA and scored by two readers. Positive and negative controls were randomly included in applicator batches. Results Fifteen couples completed the study. Each female returned at least six applicators over a 30-day period. The sensitivity for insertion of post-sex applicators was higher for UV (97%) compared to DSA (90%) and the specificity was similar (≥96%). For pre-sex applicators, the sensitivity and specificity were higher for DSA (100%) compared to UV testing (87% sensitivity, 96% specificity). Among returned post-sex applicators, 95% tested positive by UV compared to 87% by DSA. Agreement between readers was significantly better on the pre-sex applicators for DSA than for UV and for post-sex readings agreement was less than half that for UV, although the results were not statistically significant. Conclusions Applicator tests are feasible for measuring adherence in trials with gel dosing before and after sex. PMID:24220355

Remediation mechanisms of mercapto-grafted palygorskite for cadmium pollutant in paddy soil.

PubMed

Liang, Xuefeng; Qin, Xu; Huang, Qingqing; Huang, Rong; Yin, Xiuling; Cai, Yanming; Wang, Lin; Sun, Yuebing; Xu, Yingming

2017-10-01

The immobilization agent was the key factor that determined the success of remediation of heavy metal polluted soil. In this study, mercapto-grafted palygorskite (MP) as a novel and efficient immobilization agent was utilized for the remediation of Cd-polluted paddy soil in pot trials, and the remediation mechanisms were investigated in the aspect of soil chemistry and plant physiology with different rice cultivars as model plants. Mercapto-grafted palygorskite at applied doses of 0.1-0.3% could reduce Cd contents of brown rice and straws of different cultivars significantly. Both reduced DTPA-extractable Cd contents in rhizosphere and non-rhizosphere soil and decreasing Cd contents in iron plaques on rice root surfaces confirmed that MP was an efficient immobilization agent for Cd pollutant in paddy soil. In the aspect of soil chemistry, the pH values of rhizosphere and non-rhizosphere soils had no statistical changes in the MP treatment groups, but their zeta potentials decreased obviously, indicating that MP could enhance the fixation or sorption of Cd on soil compositions. In the aspect of antioxidant system, MP could increase POD activity of rice roots significantly to alleviate the stress of Cd to roots, and resulted in the decrease of T-AOC, SOD, and CAT activities of rice roots of the selected cultivars. MP had no inhabitation or enhancement effects on TSH of rice roots but enhance the contents of MTs and NPT to binding Cd to complete detoxification process. MP as a novel and efficient immobilization agent could complete the remediation effects through soil chemistry and plant physiological mechanisms.

De novo design, synthesis and characterisation of MP3, a new catalytic four-helix bundle hemeprotein.

PubMed

Faiella, Marina; Maglio, Ornella; Nastri, Flavia; Lombardi, Angela; Lista, Liliana; Hagen, Wilfred R; Pavone, Vincenzo

2012-12-07

A new artificial metalloenzyme, MP3 (MiniPeroxidase 3), designed by combining the excellent structural properties of four-helix bundle protein scaffolds with the activity of natural peroxidases, was synthesised and characterised. This new hemeprotein model was developed by covalently linking the deuteroporphyrin to two peptide chains of different compositions to obtain an asymmetric helix-loop-helix/heme/helix-loop-helix sandwich arrangement, characterised by 1) a His residue on one chain that acts as an axial ligand to the iron ion; 2) a vacant distal site that is able to accommodate exogenous ligands or substrates; and 3) an Arg residue in the distal site that should assist in hydrogen peroxide activation to give an HRP-like catalytic process. MP3 was synthesised and characterised as its iron complex. CD measurements revealed the high helix-forming propensity of the peptide, confirming the appropriateness of the model procedure; UV/Vis, MCD and EPR experiments gave insights into the coordination geometry and the spin state of the metal. Kinetic experiments showed that Fe(III)-MP3 possesses peroxidase-like activity comparable to R38A-hHRP, highlighting the possibility of mimicking the functional features of natural enzymes. The synergistic application of de novo design methods, synthetic procedures, and spectroscopic characterisation, described herein, demonstrates a method by which to implement and optimise catalytic activity for an enzyme mimetic. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of phenylenediamine isomers in hair dyes by coal cinders micro-column extraction and MEKC.

PubMed

Wu, Yiwei; Jiang, Feng; Chen, Lin; Zheng, Jing; Deng, Zhenli; Tao, Qing; Zhang, Jing; Han, Lijuan; Wei, Xiaoshu; Yu, Aimin; Zhang, Haili

2011-06-01

A new micellar electrokinetic chromatography (MEKC) method using beta-cyclodextrins (β-CDs) and 1-butyl-3-methylimidazolium hexafluorophosphates (ionic liquids) as additives was successfully developed for determination of para-, meta-, and ortho-phenylenediamines isomers (p-P, m-P, and o-P) in hair dyes. To improve the sensitivity of the MEKC-UV, a simple and cheap flow injection (FI) technique using a micro-column packed with coal cinders (the by-products from combustion in a boiler) as solid-phase extractant was also investigated. In the presence of 20 mmol L(-1) phosphates at pH 5.5, addition of 12 mmol L(-1) ionic liquids and 8 mmol L(-1) β-CDs greatly improved the separation efficiency. The three analytes could be quantitatively adsorbed by coal cinders, and desorbed readily with 0.15 mL of 0.01 mol L(-1) NaOH. Under the optimum conditions, an enrichment factor (EF) of 33.3 was obtained, and determination limits of p-P, m-P, and o-P were 1.97 × 10(-7), 0.99 × 10(-7), and 0.61 × 10(-7) mol L(-1), respectively. The adsorption capacities of the coal cinders micro-column for p-P, m-P, and o-P were all 1.20 mg g(-1). The presented procedure was successfully applied to the determination of p-P, m-P, and o-P in hair dyes with satisfactory results.

Ethnopharmacological appraisal of culturally important medicinal plants and polyherbal formulas used against communicable diseases in Rodrigues Island.

PubMed

Samoisy, Anne Kathie; Mahomoodally, Fawzi

2016-12-24

The tropical island of Rodrigues is one of three islands that constitute the Mascarene archipelago in the Indian Ocean. Currently considered as a biodiversity hotspot, the island has also a resilient history in the use of traditional medicine. However, there has been no ethnopharmacological study to document quantitatively such traditional practice against communicable diseases (CD), which currently accounts for 6.61% annual death and 30.7% attendances in public hospitals. The aim of the present study was to collect, analyse, and document traditionally used medicinal plants (MP) and polyherbal formulas from key informants and traditional medicine practitioners (TMP) in Rodrigues to treat and/or manage common CD. Data was collected via face-to-face interviews with MP users (n=113) and TMP (n=9) from 17 key sites. Seven quantitative ethnopharmacological indices, namely family use value (FUV), use value (UV), informant agreement ratio (IAR), relative frequency of citation (RFC), fidelity level (FL), relative importance (RI), and ethnobotanicity index (EI) were calculated. Ninety-seven plants belonging to 49 families were recorded to be in common use as monotherapy (80 plants) and/or as part of polyherbal preparation (23 plants) for the treatment and/or management of 16 different CD. Thirteen MPs were found to have a maximum FL of 100% for CD. The highest IAR (0.98) was observed for diseases of the eye and adnexa and skin and subcutaneous tissue. The highest FUV was for Arecaceae. Ayapana triplinervis (Vahl) R.M. king et H.Rob. scored the highest UV (UV=2.72). Seven endemic medicinal plants have been recorded to be employed in cultural rituals for the management of common CDs, whereas 14 polyherbal preparations were used to treat and/or manage 6 different types of CDs. Side effects were also reported following use of some these medicinal plants. Given the dearth of updated information on traditional medicine from Rodrigues, this work has provided an opportunity to establish valuable primary information on the different MP used by the local people. Further research is needed to probe into the possible active constituents that could open new perspectives for further pharmacological research and hence be the basis of an evidence-based investigation to discover new drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Different susceptibility of cells of porcine skin and internal organs to ultraviolet A-induced breaking of nuclear DNA.

PubMed

Brozyna, Anna; Chwirot, Barbara W

2005-01-01

There is a continuously growing interest in medical applications of ultraviolet radiation (UV-A and long-wavelength UV-B) especially for laser surgery, phototherapy and photodiagnostics of human internal organs. UV-B and UV-A radiation is potentially mutagenic, however, there has been very little information published to date concerning the significance of possible deleterious action of such photons on cells of internal tissues. The aim of this study is to compare the sensitivities of skin cells to those of internal organs upon exposure to UV-A. To assess this sensitivity we have determined the UV-A dose-dependent frequency of nuclear DNA breaks detected with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) technique. The materials for the study were macroscopic samples of porcine skin, colon and esophagus. The UV-A dose ranged from 0.1 to 1000 mJ/cm2, which is similar to doses received by cells in regions examined with laser-induced fluorescence or by cells surrounding areas subject to a laser ablation. To reduce the influence of DNA repair processes the tissue samples were kept at a low temperature during the irradiation and were deep frozen immediately after completing the irradiation procedure. The cells of the internal organs are much more susceptible to UV-A-induced breaking of DNA than the skin cells. The percentage fractions and the spatial distributions of the damaged cells and the characteristics of the UV-A dose dependence seem to vary by type of internal organ.

Hydromorphone transfer into breast milk after intranasal administration.

PubMed

Edwards, Jeffrey E; Rudy, Anita C; Wermeling, Daniel P; Desai, Nirmala; McNamara, Patrick J

2003-02-01

To determine the distribution of hydromorphone into breast milk and the potential exposure of the suckling infant, and whether the distribution of hydromorphone into milk can be predicted accurately by a passive diffusion model. Single-dose, pharmacokinetic study. University clinical research unit. Eight lactating, nonsmoking, healthy women aged 24-32 years. Hydromorphone HCl 2 mg was given intranasally to the women to characterize its pharmacokinetics and extent of its transfer into breast milk. Plasma and milk samples were analyzed using liquid chromatography with tandem mass spectrometry detection. The milk:plasma ratio (M:P) was calculated as the total area under the concentration-time curve (AUC) of the milk divided by the total AUC of the plasma. Predicted in vitro M:P ratios were calculated using a diffusion model. Protein binding in milk and plasma, partitioning into milk fat (whole milk:skim milk ratios), as well as pH partitioning between plasma and milk were incorporated in the model. Protein binding was determined by equilibrium dialysis. Protein binding was minimal in both milk and plasma, with unbound fractions of 1 and 0.84, respectively There was little partitioning into milk fat, as demonstrated by the whole milk:skim milk ratio of 0.98. The observed and predicted M:P ratios +/- SD for hydromorphone were 2.57 +/- 0.47 and 1.11 +/- 0.28, respectively. The 95% confidence interval for the observed M:P ratio overlapped the confidence interval of the predicted M:P ratio, a finding that supports a role for both passive diffusion and active transport as mechanisms of hydromorphone transfer into milk. Hydromorphone distributes rapidly from plasma into breast milk; however, the drug does not partition into fat. The suckling infant would receive approximately 0.67% of the maternal dose of hydromorphone (adjusted for body weight). As this is a limited exposure, further studies are needed to determine any potential impact to an infant who is fed breast milk from a mother treated with hydromorphone.

Intranasal immunization with a non-adjuvanted adhesive protein descended from Pasteurella pneumotropica and its preventive efficacy against opportunistic infection in mice.

PubMed

Sasaki, Hiraku; Ishikawa, Hiroki; Kojima, Ken; Itoh, Masahiro; Matsumoto, Tetsuya; Itoh, Takumi; Hosomi, Osamu; Kawamoto, Eiichi

2013-11-19

Intranasal vaccination is one of the most effective means of protecting against invading and colonizing pathogens because the vaccine elicits a mucosal immune response. The exploitation of vaccine adjuvants and delivery systems for intranasal vaccines is an important way to evoke antigen immunogenicity and elicit a better immune response at the mucosal sites. In the present study, we assessed the potential of intranasal immunization using a non-adjuvanted bacterial adhesive protein toward the host organs. We evaluated intranasal immunization with modified recombinant PnxIIIA (MP3) from Pasteurella pneumotropica and its preventive efficacy against opportunistic infection caused by P. pneumotropica, without using any adjuvants or delivery systems. The 100-kDa MP3 was confirmed to retain its immunogenicity and binding activity to collagen type I similar to the parent PnxIIIA. When MP3 was fused to green-fluorescent protein and inoculated into C57BL/6J mice intranasally, fluorescence intensity in the intranasal airway could be observed until 3 h after inoculation. Mice were intranasally immunized with MP3 at a maximum of 4 doses, with 7-day intervals. The antibody titer of serum IgG and IgA specific for MP3, as well as that of bronchoalveolar lavage fluid IgA, showed more than 9 (log₂) after 3 or 4 rounds of immunization. Experimentally infecting immunized mice with P. pneumotropica resulted in the inability to isolate the bacterium from the nasal cavity, trachea, conjunctiva, or cecum with more than 3 doses in the immunized mice. Although the detection in each organ seldom changed with less than 2 rounds of immunization, unlike that observed in the non-immunized mice, the detection remarkably decreased with 3 or more rounds of immunization. These results suggest that intranasal immunization with a non-adjuvanted adhesive protein could have preventive effects against opportunistic infection by P. pneumotropica. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inconstant sun: how solar evolution has affected cosmic and ultraviolet radiation exposure over the history of life on Earth.

PubMed

Karam, P Andrew

2003-03-01

Four billion years ago, sea-level UV exposure was more than 400 times as intense as today, the dose from solar cosmic rays was five times present levels, and galactic cosmic rays accounted for only about 10% their current contribution to sea-level radiation doses. Exposure to cosmic radiation accounts for about 10% of natural background radiation exposure today and includes dose from galactic cosmic rays and solar charged particles. There is little exposure to ionizing wavelengths of UV due to absorption by ozone. The sun has evolved significantly over its life; in the past there were higher levels of particulate radiation and lower UV emissions from the sun, and a stronger solar wind reduced radiation dose in the inner solar system from galactic cosmic rays. Finally, since the early atmosphere contained little to no oxygen, surface levels of UV radiation were far higher in the past.

Microbial inactivation and cytotoxicity evaluation of UV irradiated coconut water in a novel continuous flow spiral reactor.

PubMed

Bhullar, Manreet Singh; Patras, Ankit; Kilanzo-Nthenge, Agnes; Pokharel, Bharat; Yannam, Sudheer Kumar; Rakariyatham, Kanyasiri; Pan, Che; Xiao, Hang; Sasges, Michael

2018-01-01

A continuous-flow UV reactor operating at 254nm wave-length was used to investigate inactivation of microorganisms including bacteriophage in coconut water, a highly opaque liquid food. UV-C inactivation kinetics of two surrogate viruses (MS2, T1UV) and three bacteria (E. coli ATCC 25922, Salmonella Typhimurium ATCC 13311, Listeria monocytogenes ATCC 19115) in buffer and coconut water were investigated (D 10 values ranging from 2.82 to 4.54mJ·cm -2 ). A series of known UV-C doses were delivered to the samples. Inactivation levels of all organisms were linearly proportional to UV-C dose (r 2 >0.97). At the highest dose of 30mJ·cm -2 , the three pathogenic organisms were inactivated by >5 log 10 (p<0.05). Results clearly demonstrated that UV-C irradiation effectively inactivated bacteriophage and pathogenic microbes in coconut water. The inactivation kinetics of microorganisms were best described by log linear model with a low root mean square error (RMSE) and high coefficient of determination (r 2 >0.97). Models for predicting log reduction as a function of UV-C irradiation dose were found to be significant (p<0.05) with low RMSE and high r 2 . The irradiated coconut water showed no cytotoxic effects on normal human intestinal cells and normal mouse liver cells. Overall, these results indicated that UV-C treatment did not generate cytotoxic compounds in the coconut water. This study clearly demonstrated that high levels of inactivation of pathogens can be achieved in coconut water, and suggested potential method for UV-C treatment of other liquid foods. This research paper provides scientific evidence of the potential benefits of UV-C irradiation in inactivating bacterial and viral surrogates at commercially relevant doses of 0-120mJ·cm -2 . The irradiated coconut water showed no cytotoxic effects on normal intestinal and healthy mice liver cells. UV-C irradiation is an attractive food preservation technology and offers opportunities for horticultural and food processing industries to meet the growing demand from consumers for healthier and safe food products. This study would provide technical support for commercialization of UV-C treatment of beverages. Copyright © 2017 Elsevier Ltd. All rights reserved.

Apoptosome activation, an important molecular instigator in 6-mercaptopurine induced Leydig cell death

PubMed Central

Morgan, Jessica A.; Lynch, John; Panetta, John C.; Wang, Yao; Frase, Sharon; Bao, Ju; Zheng, Jie; Opferman, Joseph T.; Janke, Laura; Green, Daniel M.; Chemaitilly, Wassim; Schuetz, John D.

2015-01-01

Leydig cells are crucial to the production of testosterone in males. It is unknown if the cancer chemotherapeutic drug, 6-mercaptopurine (6 MP), produces Leydig cell failure among adult survivors of childhood acute lymphoblastic leukemia. Moreover, it is not known whether Leydig cell failure is due to either a loss of cells or an impairment in their function. Herein, we show, in a subset of childhood cancer survivors, that Leydig cell failure is related to the dose of 6 MP. This was extended, in a murine model, to demonstrate that 6 MP exposure induced caspase 3 activation, and the loss of Leydig cells was independent of Bak and Bax activation. The death of these non-proliferating cells was triggered by 6 MP metabolism, requiring formation of both cytosolic reactive oxygen species and thiopurine nucleotide triphosphates. The thiopurine nucleotide triphosphates (with physiological amounts of dATP) uniquely activated the apoptosome. An ABC transporter (Abcc4/Mrp4) reduced the amount of thiopurines, thereby providing protection for Leydig cells. The studies reported here demonstrate that the apoptosome is uniquely activated by thiopurine nucleotides and suggest that 6 MP induced Leydig cell death is likely a cause of Leydig cell failure in some survivors of childhood cancer. PMID:26576726

Apoptosome activation, an important molecular instigator in 6-mercaptopurine induced Leydig cell death.

PubMed

Morgan, Jessica A; Lynch, John; Panetta, John C; Wang, Yao; Frase, Sharon; Bao, Ju; Zheng, Jie; Opferman, Joseph T; Janke, Laura; Green, Daniel M; Chemaitilly, Wassim; Schuetz, John D

2015-11-18

Leydig cells are crucial to the production of testosterone in males. It is unknown if the cancer chemotherapeutic drug, 6-mercaptopurine (6 MP), produces Leydig cell failure among adult survivors of childhood acute lymphoblastic leukemia. Moreover, it is not known whether Leydig cell failure is due to either a loss of cells or an impairment in their function. Herein, we show, in a subset of childhood cancer survivors, that Leydig cell failure is related to the dose of 6 MP. This was extended, in a murine model, to demonstrate that 6 MP exposure induced caspase 3 activation, and the loss of Leydig cells was independent of Bak and Bax activation. The death of these non-proliferating cells was triggered by 6 MP metabolism, requiring formation of both cytosolic reactive oxygen species and thiopurine nucleotide triphosphates. The thiopurine nucleotide triphosphates (with physiological amounts of dATP) uniquely activated the apoptosome. An ABC transporter (Abcc4/Mrp4) reduced the amount of thiopurines, thereby providing protection for Leydig cells. The studies reported here demonstrate that the apoptosome is uniquely activated by thiopurine nucleotides and suggest that 6 MP induced Leydig cell death is likely a cause of Leydig cell failure in some survivors of childhood cancer.

Phosphodiesterase 10A inhibition attenuates sleep deprivation-induced deficits in long-term fear memory.

PubMed

Guo, Lengqiu; Guo, Zhuangli; Luo, Xiaoqing; Liang, Rui; Yang, Shui; Ren, Haigang; Wang, Guanghui; Zhen, Xuechu

2016-12-02

Sleep, particularly rapid eye movement (REM) sleep, is implicated in the consolidation of emotional memories. In the present study, we investigated the protective effects of a phosphodiesterase 10A (PDE10A) inhibitor MP-10 on deficits in long-term fear memory induced by REM sleep deprivation (REM-SD). REM-SD caused deficits in long-term fear memory, however, MP-10 administration ameliorated the deleterious effects of REM-SD on long term fear memory. Brain-derived neurotropic factor (BDNF) and phosphorylated cAMP response element-binding protein (pCREB) were altered in specific brain regions associated with learning and memory in REM-SD rats. Accordingly, REM-SD caused a significant decrease of pCREB in hippocampus and striatum and a significant decrease of BDNF in the hippocampus, striatum and amygdala, however, MP-10 reversed the effects of REM-SD in a dose-dependent manner. Our findings suggest that REM-SD disrupts the consolidation of long-term fear memory and that administration of MP-10 protects the REM-SD-induced deficits in fear memory, which may be due to the MP-10-induced expression of BDNF in the hippocampus, striatum and amygdala, and phosphorylation of CREB in the hippocampus and striatum. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hemato - Immunological and biochemical parameters, skin antibacterial activity, and survival in rainbow trout (Oncorhynchus mykiss) following the diet supplemented with Mentha piperita against Yersinia ruckeri.

PubMed

Adel, Milad; Pourgholam, Reza; Zorriehzahra, Jalil; Ghiasi, Maryam

2016-08-01

This study was aimed to assess the potential effects of Mentha piperita on the hemato - immunological and biochemical parameters, skin antibacterial activity and protection against Yersinia ruckeri infection in rainbow trout Oncorhynchus mykiss. Fish were divided into 4 groups before being fed diets supplemented with 0, 1, 2 and 3% of Mentha piperita (MP) plant extract for 8 weeks. Dose-dependent increases immune (both in skin mucus and blood serum) and hematological parameters (number of red and white cells, hematocrit and hemoglobin contents), as well as in respiratory burst activity, total protein, albumin, and neutrophil levels in fish fed supplemented diets compared to the control fish. Furthermore, dietary MP plant extract supplements have no significant effect on blood biochemical parameters and enzymatic activities of liver determined in serum of rainbow trout. After 8 weeks the cessation of feeding with MP plant extract, survival rates of 54.4%, 63.6% and 75.2% were recorded in groups which received 1, 2 and 3% of MP plant extract of feed, respectively, compared to 34.6% survivals in the control. This study underlying several positive effects of dietary administration of MP plant extract to farmed fish. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ultraviolet-C efficacy against a norovirus surrogate and hepatitis A virus on a stainless steel surface.

PubMed

Park, Shin Young; Kim, An-Na; Lee, Ki-Hoon; Ha, Sang-Do

2015-10-15

In this study, the effects of 10-300 mWs/cm(2) of ultraviolet radiation (UV-C) at 260 nm were investigated for the inactivation of two foodborne viruses: murine norovirus-1 (MNV-1; a human norovirus [NoV] surrogate) and hepatitis A virus (HAV). We used an experimentally contaminated stainless steel surface, a common food-contact surface, to examine the effects of low doses of UV-C radiation on MNV-1 and HAV titers. The modified Gompertz equation was used to generate non-linear survival curves and calculate dR-values as the UV-C dose of 90% reduction for MNV-1 (R(2)=0.95, RMSE=0.038) and HAV (R(2)=0.97, RMSE=0.016). Total MNV-1 and HAV titers significantly decreased (p<0.05) with higher doses of UV-C. MNV-1 and HAV were reduced to 0.0-4.4 and 0.0-2.6 log10PFU/ml, respectively, on the stainless steel surfaces by low-dose UV-C treatment. The dR-value, 33.3 mWs/cm(2) for MNV-1 was significantly (p<0.05) lower than 55.4 mWs/cm(2) of HAV. Therefore, the present study shows that HAV is more resistant to UV-C radiation than MNV-1. These data suggest that low doses of UV-C light on food contact surfaces could be effective to inactivate human NoV and HAV in restaurant, institutional, and industrial kitchens and facilities. Copyright © 2015 Elsevier B.V. All rights reserved.

Secondary formation of disinfection by-products by UV treatment of swimming pool water.

PubMed

Spiliotopoulou, Aikaterini; Hansen, Kamilla M S; Andersen, Henrik R

2015-07-01

Formation of disinfection by-products (DBPs) during experimental UV treatment of pool water has previously been reported with little concurrence between laboratory studies, field studies and research groups. In the current study, changes in concentration of seven out of eleven investigated volatile DBPs were observed in experiments using medium pressure UV treatment, with and without chlorine and after post-UV chlorination. Results showed that post-UV chlorine consumption increased, dose-dependently, with UV treatment dose. A clear absence of trihalomethane formation by UV and UV with chlorine was observed, while small yet statistically significant increases in dichloroacetonitrile and dichloropropanone concentrations were detected. Results indicate that post-UV chlorination clearly induced secondary formation of several DBPs. However, the formation of total trihalomethanes was no greater than what could be replicated by performing the DBP formation assay with higher chlorine concentrations to simulate extended chlorination. Post-UV chlorination of water from a swimming pool that continuously uses UV treatment to control combined chlorine could not induce secondary formation for most DBPs. Concurrence for induction of trihalomethanes was identified between post-UV chlorination treatments and simulated extended chlorination time treatment. Trihalomethanes could not be induced by UV treatment of water from a continuously UV treated pool. This indicates that literature reports of experimentally induced trihalomethane formation by UV may be a result of kinetic increase in formation by UV. However, this does not imply that higher trihalomethane concentrations would occur in pools that apply continuous UV treatment. The bromine fraction of halogens in formed trihalomethanes increased with UV dose. This indicates that UV removes bromine atoms from larger molecules that participate in trihalomethane production during post-UV chlorination. Additionally, no significant effect on DBP formation was observed due to photo-inducible radical forming molecules NO3- (potentially present in high concentrations in pool water) and H2O2 (added as part of commercially employed DBP reducing practices). Copyright © 2015 Elsevier B.V. All rights reserved.

Pulmonary emphysema induced by methylphenidate: experimental study.

PubMed

Rapello, Gabriel Victor Guimarães; Antoniolli, Andréia; Pereira, Daniel Martins; Facco, Gilberto; Pêgo-Fernandes, Paulo Manuel; Pazetti, Rogério

2015-01-01

Methylphenidate is the most widely used drug for treating attention deficit hyperactivity disorder. However, it has important side effects, such as abdominal pain, insomnia, anorexia and loss of appetite, and also some cases of early severe emphysema after drug abuse have been reported. Our aim was to investigate the development of pulmonary emphysema in rats that were subjected to different doses of methylphenidate. Experimental study carried out at the laboratory of a public university. Eighteen male Wistar rats were divided into three groups: control (0.9% saline solution); MP 0.8 (methylphenidate, 0.8 mg/kg); MP 1.2 (methylphenidate, 1.2 mg/kg). After 90 days of daily gavage, the animals were sacrificed and lung tissue samples were prepared for analysis on the mean alveolar diameter (Lm). The Lm was greater in MP 0.8 (47.91 ± 3.13; P < 0.01) and MP 1.2 (46.36 ± 4.39; P < 0.05) than in the control group (40.00 ± 3.48). Methylphenidate caused an increase in the alveolar diameter of rats, which was compatible with human pulmonary emphysema.

Controlled Cross-Linking with Glucose Oxidase for the Enhancement of Gelling Potential of Pork Myofibrillar Protein.

PubMed

Wang, Xu; Xiong, Youling L; Sato, Hiroaki; Kumazawa, Yoshiyuki

2016-12-21

Differential oxidative modifications of myofibrillar protein (MP) by hydroxyl radicals generated in an enzymatic system with glucose oxidase (GluOx) in the presence of glucose/FeSO 4 versus a Fenton system (H 2 O 2 /FeSO 4 ) were investigated. Pork MP was modified at 4 °C and pH 6.25 with hydroxyl radicals produced from 1 mg/mL glucose in the presence of 80, 160, or 320 μg/mL GluOx and 10 μM FeSO 4 . Total sulfhydryl content, solubility, cross-linking pattern, and gelation properties of MP were measured. H 2 O 2 production proceeded linearly with the concentration of GluOx and increased with reaction time. GluOx- and H 2 O 2 -dose-dependent protein polymerization, evidenced by faded myosin heavy chain and actin in SDS-PAGE as well as significant decreases in sulfhydryls, coincided with protein solubility loss. Firmer and more elastic MP gels were produced by GluOx than by the Fenton system at comparable H 2 O 2 levels due to an altered radical reaction pathway.

Antiradiation UV Vaccine: UV Radiation, Biological effects, lesions and medical management - immune-therapy and immune-protection.

NASA Astrophysics Data System (ADS)

Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

Key Words: Ultraviolet radiation,Standard Erythema Dose(SED), Minimal Erythema Dose(MED), Sun Burns, Solar Dermatitis, Sun Burned Disease, DNA Damage,Cell Damage, Antiradiation UV Vaccine, Immune-Prophylaxis of Sun Burned Diseases, Immune-Prophylaxis of Sun Burns, Immune-Therapy of Sun-Burned Disease and Sun Burns,Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), Toxic Epidermal Necrolysis(TEN). Introduction: High doses of UV generated by solar source and artificial sources create an exposure of mammals and other species which can lead to ultraviolet(UV)radiation- associated disease (including erythema, epilation, keratitis, etc.). UV radiation belongs to the non-ionizing part of the electromagnetic spectrum and ranges between 100 nm and 400 nm with 100 nm having been chosen arbitrarily as the boundary between non-ionizing and ionizing radiation, however EMR is a spectrum and UV can produce molecular ionization. UV radiation is conventionally categorized into 3 areas: UV-A (>315-400 nm),UV-B (>280-315 nm)and UV-C (>100-280 nm) [IARC,Working Group Reports,2005] An important consequence of stratospheric ozone depletion is the increased transmission of solar ultraviolet (UV)radiation to the Earth's lower atmosphere and surface. Stratospheric ozone levels have been falling, in certain areas, for the past several decades, so current surface ultraviolet-B (UV-B) radiation levels are thought to be close to their modern day maximum. [S.Madronich et al.1998] Overexposure of ultraviolet radiation a major cause of skin cancer including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) { collectively referred to as “non-melanoma" skin cancer (NMSC) and melanoma as well, with skin cancers being the most common cancer in North America. [Armstrong et al. 1993, Gallagher et al. 2005] Methods and Experimental Design: Our experiments and testing of a novel UV “Antiradiation Vaccine” have employed a wide variety of laboratory animals which include : Chinchilla rabbits, 11-12 months old, live weight 3.5-3.7 (n=11), Balb mice, 2-3 months old, live weight 20-22 g (n=33), Wistar rats, 3-4 months old, live weight 180-220 g(n=33). The studies were approved by the Animal Care and Use Committee for ethical animal research equivalent, at each institution. Seven rabbits, ten mice, eleven Wistar rats were vaccinated with a UV antiradiation vaccine. A second group of animals was used as biological control which received vaccine but no UV Radiation and a third group of animals was used as control without any interventions. Before and after UV Radiation, Vaccination with the UV antiradiation vaccine were provided 17 days prior to UV exposure. The animals were irradiated by a DRT-1 UV generator lamp. The dose of irradiation for laboratory, experimental animals was 10-12 * Standard Erythema Dose (SED) at L=283,7 Laboratory animals were placed in to the box with ventilation. Results: Ultraviolet irradiation of the skin was performed with high doses and causes an inflammation or erythema in all experimental animals. However the grade of skin damage and inflammation was significantly different between animals protected by vaccination and non-protected, non-vaccinated animals. Animals UV-irradiated, but who did not receive the antiradiation vaccine suffered from extensive UV skin burns of second or third degree (grade 2-3). However, animals protected with the UV antiradiation vaccine demonstrated much mild forms of skin cellular injury - mainly erythema, first degree skin burns and a few small patches with second degree skin burns (grade 1-2). Discussion: The severity of skin damage depended on area of exposed skin, time and dose of UV irradiation. Skin injury could be divided into 4 major grades: 1. Faint erythema with dry desquamation. 2. Moderate to severe erythema. 3. Severe erythema with blistering, moist desquamation. 4. Toxic epidermal necrolysis. Mild doses of UV radiation and ionizing radiation can induce cell death by apoptosis and moderate and high doses of UV and ionizing radiation induce cell death by necrosis and generate systemic inflammatory response syndrome (SIRS), toxic multiple organ injury (TMOI), toxic multiple organ dysfunction syndromes (TMODS),and finally, toxic multiple organ failure (TMOF). [D.Popov et al.2012, Fliedner T.et al. 2005, T. Azizova et al. 2004] UV-B is a complete carcinogen that is absorbed by DNA and directly damages DNA. DNA damage induced by UV-B irradiation typically includes the formation of cyclobutane pyrimidine dimmers (CPD) and 6-4 photoproducts (6-4P)[IARC, Working Group Reports, M.Saraiya et al. 2004]. The pre-vaccinated animals seem to have a blunted injury response relative to the unvaccinated animals, presumably by reduction in the inflammatory response and secondary injury effects. The mechanism of action of the antiradiation vaccine, needs further evaluation. Conclusion: A UV antiradiation vaccine appears to demonstrate efficacy as a prophylactic agent for acute solar burns and toxicity. An antiradiation UV vaccine could be used in conjunction with adjunctive measures, e.g. antioxidants and UV barriers to reduce UV radiation toxicity. The authors of this experiments would like to propose further development work of the antiradiation UV vaccine to enhance the armamentarium for prophylaxis and prevention of the various forms skin cancer.

Methylenetetrahydrofolate reductase gene haplotypes affect toxicity during maintenance therapy for childhood acute lymphoblastic leukemia in Japanese patients.

PubMed

Tanaka, Yoichi; Manabe, Atsushi; Nakadate, Hisaya; Kondoh, Kensuke; Nakamura, Kozue; Koh, Katsuyoshi; Kikuchi, Akira; Komiyama, Takako

2014-05-01

Abstract The aim of this study was to investigate the influence of daily 6-mercaptopurine (6-MP) and low-dose weekly methotrexate (MTX) combination treatment and methylenetetrahydrofolate reductase (MTHFR) haplotypes on toxicity during maintenance therapy in Japanese childhood acute lymphoblastic leukemia (ALL). We retrospectively analyzed the MTHFR C677T and A1298C polymorphisms and influence of haplotypes on toxicity in 73 patients. Patients with the MTHFR 677TT and 677CT + 1298AC were associated with severe liver toxicity (p = 0.014, odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.27-11.46) and more rapid onset of liver toxicity (p = 0.010). Patients with MTHFR 677TT and 677CT + 1298AC were associated with lower frequency of 6-MP and MTX dose reduction due to leukopenia (p < 0.05). No difference was observed in average drug doses in the MTHFR genotypes. In conclusion, the MTHFR C677T and A1298C haplotypes might be useful for monitoring adverse effects in childhood ALL maintenance therapy in Japanese patients.

Are current guidelines for sun protection optimal for health? Exploring the evidence.

PubMed

Lucas, Robyn M; Neale, Rachel E; Madronich, Sasha; McKenzie, Richard L

2018-06-15

Exposure of the skin to ultraviolet (UV) radiation is the main risk factor for skin cancer, and a major source of vitamin D, in many regions of the world. Sun protection messages to minimize skin cancer risks but avoid vitamin D deficiency are challenging, partly because levels of UV radiation vary by location, season, time of day, and atmospheric conditions. The UV Index provides information on levels of UV radiation and is a cornerstone of sun protection guidelines. Current guidelines from the World Health Organization are that sun protection is required only when the UV Index is 3 or greater. This advice is pragmatic rather than evidence based. The UV Index is a continuous scale; more comprehensive sun protection is required as the UV Index increases. In addition, a wide range of UVA doses is possible with a UVI of 3, from which there may be health consequences, while full sun protection when the UVI is "moderate" (between 3 and 5) may limit vitamin D production. Finally, the duration of time spent in the sun is an essential component of a public health message, in addition to the intensity of ambient UV radiation as measured by the UV Index. Together these provide the dose of UV radiation that is relevant to both skin cancer genesis and vitamin D production. Further education is required to increase the understanding of the UV Index; messages framed using the UV Index need to incorporate the importance of duration of exposure and increasing sun protection with increasing dose of UV radiation.

Individual variations in the correlation between erythemal threshold, UV-induced DNA damage and sun-burn cell formation.

PubMed

Heenen, M; Giacomoni, P U; Golstein, P

2001-10-01

A linear correlation between erythema intensity and DNA damage upon exposure to UV has not been firmly established. Many of the deleterious effects of UV exposure do occur after exposure to suberythemal doses. After DNA damage, cells undergo DNA repair. It is commonly accepted that when the burden of damage is beyond the repair capacities, the cell undergoes programmed cell death or apoptosis. The aim of this study is to quantify the amount of UV-induced DNA damage (estimated via the measurement of DNA repair or unscheduled DNA synthesis or UDS) and cellular damage (estimated via the determination of the density of sunburn cells or SBC). If DNA damage and erythema are correlated, similar intensity of UDS and similar density of SBC should be found in volunteers irradiated with a UV dose equal to two minimal erythema doses (MED). Our results show that in 15 different individuals the same relative dose (2 MEDs) provokes UDS values, which vary within a factor of 4. An even larger variability affects SBC counts after the same relative dose. When DNA damage or SBC are plotted versus the absolute dose (i.e. the dose expressed in J/m(2)), there is a rough correlation (with several exceptions) between dose and extent of UDS and SBC counts. It seems possible to divide the volunteers into two subpopulations with different susceptibilities to UV damage. It is well known that UDS and SBC measurements are often affected by large experimental indeterminacy, yet, the analysis of our results makes it plausible to suggest that for the triggering of erythema, a common threshold value for DNA damage or for SBC count are not to be found. In conclusion, the erythema response seems to be loosely correlated with DNA damage. This suggests that the protection offered by the sunscreens against DNA damage, the molecular basis of UV-induced mutagenesis, might not be related to the sun protection factor (SPF) indicated on the label of sunscreens, which is evaluated using the erythema as an endpoint.

Elimination of pharmaceutical residues in biologically pre-treated hospital wastewater using advanced UV irradiation technology: a comparative assessment.

PubMed

Köhler, C; Venditti, S; Igos, E; Klepiszewski, K; Benetto, E; Cornelissen, A

2012-11-15

UV irradiation technology as a membrane bioreactor (MBR) post-treatment was investigated and assessed. Both UV low pressure (LP) and medium pressure (MP) lamps were examined. The technology was installed in a pilot plant treating hospital wastewater to provide the study with adequate field data. The effect of the UV irradiation was enhanced with varying dosages of H2O2 to establish an advanced oxidation process (AOP). The efficiency of the pharmaceutical removal process was assessed by examining 14 micropollutants (antibiotics, analgesics, anticonvulsants, beta-blockers, cytostatics and X-ray contrast media) which are typically released by hospitals and detected with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS). While the MBR treatment generally showed only a low degradation capacity for persistent pharmaceuticals, much better degradation was obtained by applying UV irradiation and H2O2 as AOP. The "conventional" cost-benefit analysis of the different technology options taking into account both electrical energy consumption and pharmaceutical removal efficiency, revealed clearly better performance of low pressure UV lamps as AOP. However, a holistic comparison between the different scenarios was carried out by evaluating their environmental impacts using the life cycle assessment (LCA) methodology. Decisive advantages were highlighted to include this approach in the decision making process. Copyright © 2012 Elsevier B.V. All rights reserved.

Degradation and Byproduct Formation of Parathion in Aqueous Solutions by UV and UV/H2O2 Treatment

PubMed Central

Wu, Changlong; Linden, Karl G.

2013-01-01

The photodegradation of parathion, a US EPA Contaminant Candidate List pesticide, in aqueous solutions by UV and UV/H2O2 processes in batch reactors was evaluated. Direct photolysis of parathion both by LP (low pressure) and MP (medium pressure) lamps at pH 7 were very slow with quantum yields of 6.67 ± 0.33 ×10−4 and 6.00 ± 1.06 ×10−4 mol E−1, respectively. Hydrogen peroxide enhanced the photodegradation of parathion through the reaction between UV generated hydroxyl radical and parathion with a second-order reaction rate constant of 9.70 ± 0.45×109 M−1 s−1. However, addition of hydrogen peroxide did not result in a linear increase in the degradation rate. An optimum molar ratio between hydrogen peroxide and parathion was determined to be between 300 – 400. Photodegradation of parathion yielded several organic byproducts, of which the paraoxon, 4-nitrophenol, O,O,O-triethyl thiophosphate and O,O diethyl-methyl thiophosphate were quantified and their occurrence during UV/H2O2 processes were discussed. NO2−, PO43−, NO3− and SO42− were the major anionic byproducts of parathion photodegradation and their recover ratio were also discussed. A photodegradation mechanism scheme suggesting three simultaneous pathways was proposed in the study. PMID:18834610

Facile fabrication of redox-responsive thiol-containing drug delivery system via RAFT polymerization.

PubMed

Zhuang, Yuanyuan; Su, Yue; Peng, Yu; Wang, Dali; Deng, Hongping; Xi, Xiaodong; Zhu, Xinyuan; Lu, Yunfeng

2014-04-14

A novel kind of redox-responsive polymeric drug delivery system has been designed and prepared successfully through the coupling of the multithiol branched polymers and thiol-containing drugs. The branched poly((S-(4-vinyl) benzyl S'-propyltrithiocarbonate)-co-(poly(ethylene glycol) methacrylate)) (poly(VBPT-co-PEGMA)) was synthesized by one-pot reaction via reversible addition-fragmentation chain transfer (RAFT) copolymerization. Subsequently, the hydrophobic thiol-containing anticancer drug 6-mercaptopurine (MP) was conjugated to poly(VBPT-co-PEGMA) by thiol-disulfide exchange reaction, resulting in the formation of poly(VBPT-co-PEGMA)-S-S-MP conjugate. Due to its amphiphilicity, poly(VBPT-co-PEGMA)-S-S-MP conjugate self-assembled into amphiphilic micelles in aqueous solution. Under a reductive environment, the disassembly of polymeric micelles resulted in the MP release. Flow cytometry and confocal laser scanning microscopy (CLSM) measurements demonstrated that the poly(VBPT-co-PEGMA)-S-S-MP micelles could be taken up by Raji cells (a Burkitt lymphoma cell line). The viability of the Raji cells incubated with the glutathione (GSH) mediated poly(VBPT-co-PEGMA)-S-S-MP micelles was investigated by Cell Counting Kit-8 (CCK-8) assay. The experimental results showed that the viability of the glutathione monoester (GSH-OEt) pretreated cells was lower than that without pretreatment, while the viability of the buthionine sulfoximine (BSO) pretreated cells was higher than that without pretreatment. The poly(VBPT-co-PEGMA)-S-S-MP micelles could induce the apoptosis of Raji cells, and the apoptosis behavior was dose-dependent. This redox-responsive polymer-drug conjugate provides a promising platform for the delivery of thiol-containing biological molecules.

The effect of UV-B radiation on Bufo arenarum embryos survival and superoxide dismutase activity.

PubMed

Herkovits, J; D'Eramo, J L; Fridman, O

2006-03-01

The exposure of Bufo arenarum embryos to 300-310 nm UV-B at a dose of 4,104 Joule/m(2) resulted in 100% lethality within 24 hr while 820 Joule/m(2) was the NOEC value for short-term chronic (10 days) exposure. The dose response curves show that lethal effects are proportional with the dose and achieve its highest value within 48 hr post exposure. The superoxide dismutase (SOD) activity in amphibian embryos for sublethal UV-B exposures was evaluated by means of UV-B treatments with 273 (A), 820(B), 1368(C) and 1915(D) Joule/m(2) at 2 and 5 hours post irradiation. The SOD activity in units/mg protein in A, B, C and D at 2 hr after treatments were 80.72 +/- 14.29, 74.5 +/- 13.19, 39.5 +/- 6.99 and 10.7 +/- 1.89 respectively while for control embryos it was 10.88 +/- 1.31. At 5 hr after treatments the SOD values were similar to those found in control embryos. The results confirm the high susceptibility of amphibian embryos to UV-B and point out that the SOD activity is enhanced by low doses of UV-B irradiation achieving significantly higher values than in control embryos at 2 hr post exposure.

Transfer of parecoxib and its primary active metabolite valdecoxib via transitional breastmilk following intravenous parecoxib use after cesarean delivery: a comparison of naive pooled data analysis and nonlinear mixed-effects modeling.

PubMed

Paech, Michael J; Salman, Sam; Ilett, Kenneth F; O'Halloran, Sean J; Muchatuta, Neil A

2012-04-01

Multimodal analgesia, including nonopioid analgesics, is usually used for several days after cesarean delivery. Because the breastfed infant receives transitional milk during this same period, it is important to know how much of a maternal analgesic drug is received by the infant. We designed this study to estimate infant exposure to parecoxib and its active metabolite valdecoxib (a cyclooxygenase-2 inhibitor) after a single IV maternal dose of parecoxib after cesarean delivery. Forty women and their infants participated in the study. Parecoxib (40 mg) was administered IV at a mean of 41 hours after birth. Milk (4 samples) and plasma (1 sample) were collected from the women over the subsequent 24 hours and drug content was measured by liquid chromatography-tandem mass spectrometry. The infants were assessed the day after parecoxib dosing. Absolute (AID) and relative infant doses (RID) of both parecoxib and valdecoxib through milk were estimated by standard methods using the naïve pooled datasets, and where possible milk/plasma (M/P) concentration ratios were calculated. Nonlinear mixed-effects modeling was also used to fit the valdecoxib milk and plasma datasets to a compartmental model and to predict M/P, AID, and RID. M/P ratios (median [interquartile range; IQR]) were 0.5 (0.15 to 1.15) for parecoxib and 0.14 (0.11 to 0.18) for valdecoxib. Using the naïve pooled datasets, AID (drug concentration in milk×daily milk intake/kg) was 0.24 (0.05 to 1.85) μg/kg/day for parecoxib, and 1.82 (1.12 to 2.73) μg/kg/day, for valdecoxib. RID was 0.04 (0.01 to 0.43) % of the weight-adjusted maternal dose (one dose in 24 hours) for parecoxib and 0.47 (0.29 to 0.69) % for valdecoxib (as parecoxib equivalents). Compartmental modeling of valdecoxib alone produced a mean (interindividual variability) M/P of 0.149 (26%), median (IQR) AID of 1.47 (0.96 to 2.03) μg/kg/day, and median (IQR) RID of 0.39 (0.28 to 0.47) %. Neonatal neurologic and adaptive capacity scores (mean=34, 95% CI 33 to 35) were consistent with a normal expected score of 35. Both the naïve pooling of data and the modeling analyses gave similar results. The RID of both parecoxib and valdecoxib was low. We conclude that a single 40 mg IV dose of the cyclooxygenase-2 inhibitor parecoxib administered to lactating women after cesarean delivery is unlikely to cause adverse effects in breastfed infants.

Preharvest Ultraviolet C Irradiation Increased the Level of Polyphenol Accumulation and Flavonoid Pathway Gene Expression in Strawberry Fruit.

PubMed

Xu, Yanqun; Charles, Marie Thérèse; Luo, Zisheng; Mimee, Benjamin; Veronneau, Pierre-Yves; Rolland, Daniel; Roussel, Dominique

2017-11-22

Preharvest ultraviolet C (UV-C) irradiation is an innovative approach for increasing the bioactive phytochemical content of strawberries to increase the disease resistance and nutritional value. This study investigated the changes in individual flavonoids in strawberry developed with three different cumulative doses of preharvest UV-C treatment (low, 9.6 kJ m -2 ; middle, 15 kJ m -2 ; and high , 29.4 kJ m -2 ). Significant accumulation (p < 0.05) of phenolics (25-75% increase), namely, cyanidin 3-glucoside, pelargonidin 3-glucoside/rutinoside, glucoside and glucuronide of quercetin and kaempferol, and ellagic acid, was found in the fruit subjected to low and middle supplemental doses of UV-C radiation. The expression of the flavonoid pathway structural genes, i.e., FaCHS1, FaCHI, FaFHT, FaDFR, FaFLS, and FaFGT, was upregulated in the low- and middle-dose groups, while the early stage genes were not affected by the high dose. FaMYB1 was also relatively enhanced in the low- and middle-dose groups, while FaASR was upregulated in only the low-dose group. Hormetic preharvest UV-C dose ranges for enhancing the polyphenol content of strawberries were established for the first time.

Erythemal UV at Davos (Switzerland), 1926-2003, estimated using total ozone, sunshine duration, and snow depth

NASA Astrophysics Data System (ADS)

Lindfors, Anders; Vuilleumier, Laurent

2005-01-01

A method previously developed for reconstructing daily erythemal UV doses at Sodankylä, northern Finland, was adjusted to the local conditions at Davos, Switzerland, and used for estimating the erythemal UV doses there over the period 1926-2003. The method uses total ozone, sunshine duration, and snow depth as input, and is based on the empirical relationship between relative sunshine duration and relative UV doses. In order to examine how the method behaves in different environments, the relationships found for Davos and Sodankylä were compared. This revealed that the surface albedo and the cloud climate have a comparable influence on the relationship found. Although the method is fairly simple, it accounts for the most important factors affecting the amount of UV radiation reaching the Earth's surface. A comparison between estimated UV doses and the corresponding observations with a broadband biometer at Davos demonstrated the good performance of the method. The correlation coefficient for daily values varies between 0.95 and 0.98 depending on time of year, and the corresponding root mean square error is typically of the order of 20%. The monthly mean values show considerably less scatter around the regression line with a root mean square error of 4%. The time series of estimated UV shows that the UV level at Davos has varied considerably throughout the period of this study, with high values in the middle of the 1940s, in the early 1960s, and in the 1990s. Variations in the estimated UV doses prior to 1980, e.g., a steady decrease from the early 1960s to the late 1970s, were found to be caused primarily by changes in sunshine duration. Since 1980, on the other hand, there has been a distinct increase in the UV level caused mainly by the diminution of total ozone. This increase is most clearly seen during winter and spring, while the decrease from the early 1960s to the late 1970s is most pronounced during summer.

Ultraviolet-B radiation induces modulation of antigen presentation of herpes simplex virus by human epidermal cells.

PubMed

van der Molen, R G; Out-Luiting, C; Claas, F H; Norval, M; Koerten, H K; Mommaas, A M

2001-06-01

Although ultraviolet (UV) B radiation is known to be immunosuppressive, there is little information regarding a relevant immunological endpoint to assess human subjects in vivo. Therefore, we have examined the effect of in vivo UV radiation on the ability of human epidermal cells (EC) to present herpes simplex virus (HSV) antigens to memory T cells. Human volunteers, who were seropositive for HSV, were exposed to one minimal erythemal dose (MED) for four consecutive days. EC, prepared from suction blister roofs, were co-cultured with autologous T cells in the presence of HSV. HSV antigen presentation by UV-exposed EC was increased compared with control, nonexposed EC. This up-regulation correlated with an influx of macrophages into the epidermis, which are considered to be associated with UV-induced tolerance. Altering the UV protocol to a sub-erythemal UV dose for four consecutive days or to a single high dose of 2 MED, resulted in suppressed HSV antigen presentation, without the influx of the UV-macrophages. One of the goals of the present study was to eventually use this HSV system to investigate sunscreen immunoprotection. A pilot study with a TiO2-containing sunscreen suggested that the endpoint for UV-induced immunosuppression presented here is promising to be used for human in vivo sunscreen immunoprotection studies.

Impact of UV irradiation on multiwall carbon nanotubes in nanocomposites: formation of entangled surface layer and mechanisms of release resistance

PubMed Central

Nguyen, Tinh; Petersen, Elijah J.; Pellegrin, Bastien; Gorham, Justin M.; Lam, Thomas; Zhao, Minhua; Sung, Lipiin

2017-01-01

Multiwall carbon nanotubes (MWCNTs) are nanofillers used in consumer and structural polymeric products to enhance a variety of properties. Under weathering, the polymer matrix will degrade and the nanofillers may be released from the products potentially impacting ecological or human health. In this study, we investigated the degradation of a 0.72 % (by mass) MWCNT/amine-cured epoxy nanocomposite irradiated with high intensity ultraviolet (UV) light at various doses, the effects of UV exposure on the surface accumulation and potential release of MWCNTs, and possible mechanisms for the release resistance of the MWCNT surface layer formed on nanocomposites by UV irradiation. Irradiated samples were characterized for chemical degradation, mass loss, surface morphological changes, and MWCNT release using a variety of analytical techniques. Under 295 nm to 400 nm UV radiation up to a dose of 4865 MJ/m2, the nanocomposite matrix underwent photodegradation, resulting in formation of a dense, entangled MWCNT network structure on the surface. However, no MWCNT release was detected, even at very high UV doses, suggesting that the MWCNT surface layer formed from UV irradiation of polymer nanocomposites resist release. Four possible release resistance mechanisms of the UV-induced MWCNT surface layer are presented and discussed. PMID:28603293

Response of biological uv dosimeters to the simulated extraterrestrial uv radiation

NASA Astrophysics Data System (ADS)

Bérces, A.; Rontó, G.; Kerékgyártó, T.; Kovács, G.; Lammer, H.

In the Laboratory polycrystalline uracil thin layer and bacteriophage T7 detectors have been developed for UV dosimetry on the EarthSs surface. Exponential response of the uracil polycrystal has been detected both by absorption spectroscopy and measurements of the refractive index under the influence of terrestrial solar radiation or using UV-C sources. In UV biological dosimetry the UV dose scale is additive starting at a value of zero according to the definition of CIE (Technical Report TC-6-18). The biological dose can be defined by a measured end-effect. In our dosimeters (phage T7 and uracil dosimeter) exposed to natural (terrestrial) UV radiation the proportion of pyrimidin photoproducts among the total photoproducts is smaller than 0.1 and the linear correlation between the biological and physical dose is higher than 0.9. According to the experimental data this linear relationship is often not valid. We observed that UV radiation did not only induce dimerisation but shorter wavelengths caused monomerisation of pyrimidin dimers. Performing the irradiation in oxygen free environment and using a Deuterium lamp as UV source, we could increase monomerisation against dimerisation thus the DNA-based dosimetrySs additivity rule is not fulfilled in these conditions. In this study we will demonstrate those non-linear experiments which constitute the basis of our biological experiments on the International Space Station.

Evaluating the combined effects of pretilachlor and UV-B on two Azolla species.

PubMed

Prasad, Sheo Mohan; Kumar, Sushil; Parihar, Parul; Singh, Anita; Singh, Rachana

2016-03-01

The present study assessed the comparative responses of two agronomic species of Azolla (A.microphylla and A. pinnata) exposed to man-made and natural stressors by evaluating biomass accumulation, pigments (chlorophyll a and b and carotenoid contents), photosynthetic activity and nitrogen metabolism. The study was carried out in field where two species of Azolla were cultured and treated with various concentrations (5, 10 and 20 μg ml(-1)) of herbicide; pretilachlor [2-chloro-2,6-diethyl-N-(2-propoxyethyl) acetanilide] and enhanced levels (UV-B1: ambient +2.2 kJ m(-2) day(-1) and UV-B2: ambient +4.4 kJ m(-2) day(-1)) of UV-B, alone as well as in combination. Biomass accumulation, photosynthetic pigments; chlorophyll a, b and carotenoids, photosynthetic oxygen yield and photosynthetic electron transport activities i.e. photosystem II (PS II) and photosystem I (PS I) in both the species declined with the increasing doses of pretilachlor and UV-B radiation, which further declined when applied in combination. The lower doses (5 and 10 μg ml(-1)) of pretilachlor and UV-B (UV-B1 and UV-B2) alone, damaged mainly the oxidation side of PS II, whereas higher dose (20 μg ml(-1)) of pretilachlor alone and in combination with UV-B1 and UV-B2 caused damage to PS II reaction centre and beyond this towards the reduction side. A significant enhancement in respiration was also noticed in fronds of both the Azolla species following pretilachlor and UV-B treatment, hence indicating strong damaging effect. The nitrate assimilating enzymes - nitrate reductase and nitrite reductase and ammonium assimilating enzymes - glutamine synthetase and glutamate synthase were also severely affected when treated either with pretilachlor and/or UV-B while glutamate dehydrogenase exhibited a stimulatory response. The study suggests that both the species of Azolla showed considerable damage under pretilachlor and UV-B treatments alone, however, in combination the effect was more intense. Further, in comparison to A. pinnata, A. microphylla exhibited greater resistance against tested doses of both the stresses, either alone or in combination. Copyright © 2015 Elsevier Inc. All rights reserved.

A Contribution Toward Understanding the Biospherical Significance of Antarctic Ozone Depletion

NASA Astrophysics Data System (ADS)

Lubin, Dan; Mitchell, B. Greg; Frederick, John E.; Alberts, Amy D.; Booth, C. R.; Lucas, Timothy; Neuschuler, David

1992-05-01

Measurements of biologically active UV radiation made by the National Science Foundation (NSF) scanning spectroradiometer (UV-monitor) at Palmer Station, Antarctica, during the Austral springs of 1988, 1989, and 1990 are presented and compared. Column ozone abundance above Palmer Station is computed from these measurements using a multiple wavelength algorithm. Two contrasting action spectra (biological weighting functions) are used to estimate the biologically relevant dose from the spectral measurements: a standard weighting function for damage to DNA, and a new action spectrum representing the potential for photosynthesis inhibition in Antarctic phytoplankton. The former weights only UV-B wavelengths (280-320 nm) and gives the most weight to wavelengths shorter than 300 nm, while the latter includes large contributions out to 355 nm. The latter is the result of recent Antarctic field work and is relevant in that phytoplankton constitute the base of the Antarctic food web. The modest ozone hole of 1988, in which the ozone abundance above Palmer Station never fell below 200 Dobson units (DU), brought about summerlike doses of DNA-effective UV radiation 2 months early, but UV doses which could inhibit photosynthesis in phytoplankton did not exceed a clear-sky "maximum normal" dose for that time of year. The severe ozone holes of 1989 and 1990, in which the ozone abundance regularly fell below 200 DU, brought about increases in UV surface irradiance weighted by either action spectrum. Ozone abundances and dose-weighted irradiances provided by the NSF UV-monitor are used to derive the radiation amplification factors (RAFs) for both DNA-effective irradiance and phytoplankton-effective irradiance. The RAF for DNA-effective irradiance is nonlinear in ozone abundance and is in excess of the popular "two for one" rule, while the RAF for phytoplankton-effective irradiance approximately follows a "one for one" rule.

The effect of UV light on the inactivation of Giardia lamblia and Giardia muris cysts as determined by animal infectivity assay (P-2951-01).

PubMed

Mofidi, Alexander A; Meyer, Ernest A; Wallis, Peter M; Chou, Connie I; Meyer, Barbara P; Ramalingam, Shivaji; Coffey, Bradley M

2002-04-01

This study measured the effect of germicidal ultraviolet (UV) light on Giardia lamblia and Giardia muris cysts, as determined by their infectivity in Mongolian gerbils and CD-1 mice, respectively. Reduction of cyst infectivity due to UV exposure was quantified by applying most probable number techniques. Controlled bench-scale, collimated-beam tests exposed cysts suspended in filtered natural water to light from a low-pressure UV lamp. Both G. lamblia and G. muris cysts showed similar sensitivity to UV light. At 3 mJ/cm2, a dose 10-fold lower than what large-scale UV reactors may be designed to provide, > 2-log10 (99 percent) inactivation was observed. These results, combined with previously published data showing other protozoa and bacteria have similar, high sensitivity to UV light, establish that UV disinfection of drinking water is controlled by viruses which may require over 10-fold more UV dose for the same level of control.

Study of The Non-linear Uv Dosimetry In Simulated Extraterrestrial Conditions

NASA Astrophysics Data System (ADS)

Berces, A.; Kerekgyarto, T.; Ronto, G.; Lammer, H.; Kargl, G.; Komle, N. I.

In UV biological dosimetry the UV dose scale is additive starting at a value of zero ac- cording to the definition of CIE (Technical Report TC-6-18). The biological dose can be defined by a measured end-effect. In our dosimeters (phage T7 and uracil dosime- ter) exposed to natural (terrestrial) UV radiation the proportion of pyrimidin photo- products among the total photoproducts is smaller than 10 and the linear correlation between the biological and physical dose is higher than 0.9. According to the experi- mental data this linear relationship is often not valid. We observed that UV radiation did not only induce dimerisation but shorter wavelengths caused monomerisation of pyrimidin dimers. Performing the irradiation in oxygen free environment and using a Deuterium lamp as UV source, we could increase monomerisation against dimerisa- tion thus the DNA-based dosimetrySs additivity rule is not fulfilled in these conditions. In this study we will demonstrate those non-linear experiments which constitute the basis of our biological experiments on the International Space Station.

Influence of UV dose on the UV/H2O2 process for the degradation of carbamazepine in wastewater.

PubMed

Somathilake, Purnima; Dominic, John Albino; Achari, Gopal; Langford, Cooper H; Tay, Joo-Hwa

2018-05-02

This study evaluates the influence of UV dose on degradation of carbamazepine (CBZ) in wastewater under UV-C (λ = 254 nm) photolysis with and without H 2 O 2 . The rate of degradation of CBZ exhibited a direct dependence on the intensity of incident UV irradiation as the rate of degradation was observed to increase linearly (R 2  = 0.98) with UV intensity between 1.67 and 8.95 × 10 17 photons/s. More than 95% of the CBZ that spiked in wastewater rapidly degraded within 4 min with a first-order rate constant of 1.2 min -1 for an optimum H 2 O 2 dose of 100 mg/L. Bench-scale continuous flow reactor experiments also showed that CBZ degraded with first-order kinetics at a rate constant of 1.02 min -1 . The kinetic parameters obtained for a continuous bench-scale reactor were in good agreement with the relationships developed through batch experiments with only a marginal deviation of ± 6.5%. The relationship between UV intensity and CBZ degradation rate obtained in this study was extrapolated to the UV disinfection unit of a wastewater treatment plant to predict possible degradation of CBZ during UV disinfection. The addition of 100 mg/L of H 2 O 2 to the secondary-treated effluent entering the UV disinfection unit is predicted to achieve over 60% degradation of CBZ.

Evaluation of a pediatric liquid formulation to improve 6-mercaptopurine therapy in children.

PubMed

Tiphaine, Adam de Beaumais; Hjalgrim, Lisa Lynqsie; Nersting, Jacob; Breitkreutz, Joerg; Nelken, Brigitte; Schrappe, Martin; Stanulla, Martin; Thomas, Caroline; Bertrand, Yves; Leverger, Guy; Baruchel, André; Schmiegelow, Kjeld; Jacqz-Aigrain, Evelyne

2016-02-15

6-mercaptopurine (6-MP), a key drug for treatment of acute lymphoblastic leukemia (ALL), has until recently had no adequate formulation for pediatric patients. Several approaches have been taken but the only oral paraben-free 6-MP liquid formulation named Loulla was developed and evaluated in the target population. Preclinical and clinical evaluations were performed according to a Pediatric Investigation Plan, in order to apply for a Pediatric Use Marketing Authorization. The pre-clinical study assessed the maximum tolerated dosage-volume and evaluated local mucosal toxicity of 28 daily administrations in treated compared to controls gold hamsters. The multi-centre clinical study was single-dose, open-label, crossover trial, conducted in 15 ALL children during maintenance therapy. The bioavailability and palatability of a single 50mg fixed dose of Loulla compared to 50mg registered tablets were evaluated in a random order on two consecutive days. Seven blood samples over 9h were obtained each day to determine 6-MP pharmacokinetic parameters, including Tmax, Cmax, AUC0-9 and AUC0-∞. A questionnaire adapted to children testing Loulla palatability and preference for either Loulla or the usual 6-MP tablet was completed. Occurrence of adverse events was determined at study visits by vital sign measurements, patient's spontaneous reporting, investigator's questioning and clinical examination. The preclinical study in gold hamsters showed that dosage-volume of 75 mg/kg/day was well tolerated. The relative bioavailability of liquid Loulla formulation compared to the reference presentation is 76% for AUC0-9 and AUC0-∞ and 80% for Cmax. The taste of Loulla and the mouth feeling after ingestion compare favorably to the tablet. No adverse event occurred. Pharmacokinetic, palatability and safety data support the use of Loulla in children. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparing the effect of preoperative administration of methylprednisolone and its administration before and during surgery on the clinical outcome in pediatric open heart surgeries.

PubMed

Soltani, Ghasem; Abbasi Tashnizi, Mohammad; Moeinipour, Ali Asghar; Ganjifard, Mahmoud; Esfahanizadeh, Jamil; Sepehri Shamloo, Alireza; Purafzali Firuzabadi, Seyed Javad; Zirak, Nahid

2013-06-01

Cardiac surgery under Cardiopulmonary bypass causes a systemic inflammatory response with a multifactorial etiology including direct tissue damage, ischemia and stimulation of immune system induced by cardiopulmonary bypass. This study was designed due to the high prevalence and complications of this stimulated immune system in mortality, morbidity, length of ICU stay, and mechanical ventilation. This study was aimed to compare preoperative and intraoperative methylprednisolone (MP) to intraoperative MP alone with respect to postbypass inflammation and clinical outcome. Sixty pediatric patients (age < 5years) undergoing cardiopulmonary bypass surgery between September 2011-2012 at Imam Reza hospital-Mashhad were randomly assigned to receive preoperative and intraoperative MP (group 1: 30 mg/kg, 4 hours before bypass and in bypass prime, n = 30) or intraoperative MP only (group 2: 30 mg/kg, n = 30). Postoperative temperature (peak temperature and average temperature during the first 24 hours), amount of inotropic, duration of mechanical ventilation, ICU stay, WBC, BUN, creatinine, and CRP were recorded and compared in both groups. Data were analyzed with SPSS version 13 by T-test, Mann-Whitney test if necessary, and Chi-squared distribution. Patient characteristics including age, weight, gender, and duration of bypass were almost similar in both groups (P > 0.05). No significant difference in amount of inotropic medications used for hemodynamic supports, duration of mechanical ventilation, peak and average temperature and length of ICU stay was observed. Among the laboratory tests (WBC, BUN, creatinine, CRP) only WBC counts raised more in group 2 when compared to group 1(P < 0.05). There was no difference in clinical outcome after cardiac surgery when we administered an additional dose of methylprednisolone compared to a single dose of methylprednisolone.

Comparing the Effect of Preoperative Administration of Methylprednisolone and its Administration Before and During Surgery on the Clinical Outcome in Pediatric Open Heart Surgeries

PubMed Central

Soltani, Ghasem; Abbasi Tashnizi, Mohammad; Moeinipour, Ali Asghar; Ganjifard, Mahmoud; Esfahanizadeh, Jamil; Sepehri Shamloo, Alireza; Purafzali Firuzabadi, Seyed Javad; Zirak, Nahid

2013-01-01

Background Cardiac surgery under Cardiopulmonary bypass causes a systemic inflammatory response with a multifactorial etiology including direct tissue damage, ischemia and stimulation of immune system induced by cardiopulmonary bypass. This study was designed due to the high prevalence and complications of this stimulated immune system in mortality, morbidity, length of ICU stay, and mechanical ventilation. Objectives This study was aimed to compare preoperative and intraoperative methylprednisolone (MP) to intraoperative MP alone with respect to postbypass inflammation and clinical outcome. Patients and Methods Sixty pediatric patients (age < 5years) undergoing cardiopulmonary bypass surgery between September 2011-2012 at Imam Reza hospital-Mashhad were randomly assigned to receive preoperative and intraoperative MP (group 1: 30 mg/kg, 4 hours before bypass and in bypass prime, n = 30) or intraoperative MP only (group 2: 30 mg/kg, n = 30). Postoperative temperature (peak temperature and average temperature during the first 24 hours), amount of inotropic, duration of mechanical ventilation, ICU stay, WBC, BUN, creatinine, and CRP were recorded and compared in both groups. Data were analyzed with SPSS version 13 by T-test, Mann-Whitney test if necessary, and Chi-squared distribution. Results Patient characteristics including age, weight, gender, and duration of bypass were almost similar in both groups (P > 0.05). No significant difference in amount of inotropic medications used for hemodynamic supports, duration of mechanical ventilation, peak and average temperature and length of ICU stay was observed. Among the laboratory tests (WBC, BUN, creatinine, CRP) only WBC counts raised more in group 2 when compared to group 1(P < 0.05). Conclusions There was no difference in clinical outcome after cardiac surgery when we administered an additional dose of methylprednisolone compared to a single dose of methylprednisolone. PMID:24349746

Neutrophils Generate Microparticles during Exposure to Inert Gases Due to Cytoskeletal Oxidative Stress*

PubMed Central

Thom, Stephen R.; Bhopale, Veena M.; Yang, Ming

2014-01-01

This investigation was to elucidate the mechanism for microparticle (MP) formation triggered by exposures to high pressure inert gases. Human neutrophils generate MPs at a threshold of ∼186 kilopascals with exposures of 30 min or more. Murine cells are similar, but MP production occurs at a slower rate and continues for ∼4 h, whether or not cells remain under pressure. Neutrophils exposed to elevated gas but not hydrostatic pressure produce MPs according to the potency series: argon ≃ nitrogen > helium. Following a similar pattern, gases activate type-2 nitric-oxide synthase (NOS-2) and NADPH oxidase (NOX). MP production does not occur with neutrophils exposed to a NOX inhibitor (Nox2ds) or a NOS-2 inhibitor (1400W) or with cells from mice lacking NOS-2. Reactive species cause S-nitrosylation of cytosolic actin that enhances actin polymerization. Protein cross-linking and immunoprecipitation studies indicate that increased polymerization occurs because of associations involving vasodilator-stimulated phosphoprotein, focal adhesion kinase, the H+/K+ ATPase β (flippase), the hematopoietic cell multidrug resistance protein ABC transporter (floppase), and protein-disulfide isomerase in proximity to short actin filaments. Using chemical inhibitors or reducing cell concentrations of any of these proteins with small inhibitory RNA abrogates NOS-2 activation, reactive species generation, actin polymerization, and MP production. These effects were also inhibited in cells exposed to UV light, which photoreverses S-nitrosylated cysteine residues and by co-incubations with the antioxidant ebselen or cytochalasin D. The autocatalytic cycle of protein activation is initiated by inert gas-mediated singlet O2 production. PMID:24867949

Egg hatching response to a range of ultraviolet-B (UV-B) radiation doses for four predatory mites and the herbivorous spider mite Tetranychus urticae.

PubMed

Koveos, Dimitrios S; Suzuki, Takeshi; Terzidou, Anastasia; Kokkari, Anastasia; Floros, George; Damos, Petros; Kouloussis, Nikos A

2017-01-01

Egg hatchability of four predatory mites-Phytoseiulus persimilis Athias-Henriot, Iphiseius [Amblyseius] degenerans Berlese, Amblyseius swirskii Athias-Henriot, and Euseius finlandicus Oudemans (Acari: Phytoseiidae)-and the spider mite Tetranychus urticae Koch (Acari: Tetranychidae) was determined under various UV-B doses either in constant darkness (DD) or with simultaneous irradiation using white light. Under UV-B irradiation and DD or simultaneous irradiation with white light, the predator's eggs hatched in significantly lower percentages than in the control non-exposed eggs, which indicates deleterious effects of UV-B on embryonic development. In addition, higher hatchability percentages were observed under UV-B irradiation and DD in eggs of the predatory mites than in eggs of T. urticae. This might be caused by a higher involvement of an antioxidant system, shield effects by pigments or a mere shorter duration of embryonic development in predatory mites than in T. urticae, thus avoiding accumulative effects of UV-B. Although no eggs of T. urticae hatched under UV-B irradiation and DD, variable hatchability percentages were observed under simultaneous irradiation with white light, which suggests the involvement of a photoreactivation system that reduces UV-B damages. Under the same doses with simultaneous irradiation with white light, eggs of T. urticae displayed higher photoreactivation and were more tolerant to UV-B than eggs of the predatory mites. Among predators variation regarding the tolerance to UV-B effects was observed, with eggs of P. persimilis and I. degenerans being more tolerant to UV-B radiation than eggs of A. swirskii and E. finlandicus.

Tertiary treatment using microfiltration and UV disinfection for water reclamation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jolis, D.; Hirano, R.; Pitt, P.

Microfiltration and UV disinfection are two alternative technologies for water reclamation. The results of a pilot study combining these two processes are presented. In addition to producing filtrate turbidites averaging 0.06 nephelometric turbidity units, microfiltration was an effective barrier to pathogens, demonstrating average log reductions of 4.5 for total coliforms and 2.9 for MS2 bacteriophage. Ultraviolet disinfection following microfiltration reliably met the California Wastewater Reclamation Criteria (Title 22) total coliform standard of 2.2 colony-forming units/100 mL at a UV dose of 450 J/m{sup 2}. The MS2 bacteriophage standard, which requires a 5-log reduction, was achieved by microfiltration and a UVmore » dose of 880 J/m{sup 2}. A model of the kinetics of inactivation of MS2 bacteriophage was used in further analysis of disinfection data. The model indicated that considerable backmixing occurred in the pilot UV disinfection unit, and observed UV doses could be reduced with improved hydraulics.« less

Olfactory and behavioural responses of tabanid horseflies to octenol, phenols and aged horse urine.

PubMed

Baldacchino, F; Manon, S; Puech, L; Buatois, B; Dormont, L; Jay-Robert, P

2014-06-01

Electrophysiological and behavioural responses of females of two tabanid species, Tabanus bromius L. and Atylotus quadrifarius (Loew) (Diptera: Tabanidae), to ammonia, octenol (1-octen-3-ol), phenols and aged horse urine were compared. Electroantennogram (EAG) responses in both species to octenol, 4-methylphenol (4MP), 3-propylphenol (3PP) and a phenol mixture (4MP and 3PP at a ratio of 16 : 1) increased in a dose-dependent fashion. The most effective stimulus was 4MP and synergism between the two phenols may exist. Aged horse urine also elicited strong EAG responses in both species. Using gas chromatography-mass spectrometry (GC-MS) analysis, we identified 29 compounds in horse urine, which included, in particular, ketones, fatty alcohols and phenols, among which 4MP was the most abundant component (~ 80%). Trapping experiments were carried out using Nzi traps baited with various odours. Octenol and the phenol mixture in combination with ammonia increased catches of tabanids by 1.8-2.8 times relative to ammonia alone. Aged horse urine increased catches of T. bromius and A. quadrifarius by 2.2 and 4.1 times, respectively. The high attractiveness of aged horse urine, especially for A. quadrifarius, is not likely to derive from 4MP alone, but from the mixture of various active compounds used in host location. © 2013 The Royal Entomological Society.

Acute lymphoblastic leukemia: are Egyptian children adherent to maintenance therapy?

PubMed

Khalek, Elhamy Rifky Abdel; Sherif, Laila M; Kamal, Naglaa Mohamed; Gharib, Amal F; Shawky, H M

2015-01-01

BACKGROUND, AIMS, SETTINGS AND DESIGN: Poor adherence to oral maintenance chemotherapy can cause relapse of acute lymphoblastic leukemia (ALL). A multicenter study for the evaluation of adherence to oral 6-mercaptopurine (6-MP) maintenance chemotherapy for childhood ALL in Egypt to identify contributing factors and possible steps to promote adherence. The study included 129 children with ALL in complete remission receiving 6-MP single daily oral dose in the evening. Evaluation was done through specific questionnaires for the patients as well as serum 6-MP measurements. Nonadherence was detected in around 56% by questionnaires and around 50% by serum 6-MP level measurement. There was a highly significant correlation between nonadherence as found by the questionnaire and 6-MP level (P - 0.001). Nonadherence was significantly associated with low socioeconomic standard, noneducation and low educational level and large family size by both methods. High cost to come for follow-up visits was significant by questionnaire but not by 6-MP measurement. Adolescent age, the higher number of siblings, lack of written instructions, long time spent per visit, were all associated with higher rates of nonadherence, although none reached statistical significance. Nonadherence is a real problem in pediatric patients. Specific questionnaires can be an excellent reliable method for the routine follow-up of these children, and drug level assay can be requested only for confirmation. This protocol is especially effective in developing countries where financial resources may be limited. Every effort should be made to uncover its true incidence, contributing factors, and best methods of intervention.

Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial

PubMed Central

Matloub, Yousif; Broxson, Emmett; La, Mei; Yanofsky, Rochelle; Sather, Harland; Hutchinson, Ray; Heerema, Nyla A.; Sorrell, April D.; Masterson, Margaret; Bleyer, Archie; Gaynon, Paul S.

2010-01-01

The Children's Cancer Group 1952 (CCG-1952) clinical trial studied the substitution of oral 6-thioguanine (TG) for 6-mercaptopurine (MP) and triple intrathecal therapy (ITT) for intrathecal methotrexate (IT-MTX) in the treatment of standard-risk acute lymphoblastic leukemia. After remission induction, 2027 patients were randomized to receive MP (n = 1010) or TG (n = 1017) and IT-MTX (n = 1018) or ITT (n = 1009). The results of the thiopurine comparison are as follows. The estimated 7-year event-free survival (EFS) for subjects randomized to TG was 84.1% (± 1.8%) and to MP was 79.0% (± 2.1%; P = .004 log rank), although overall survival was 91.9% (± 1.4%) and 91.2% (± 1.5%), respectively (P = .6 log rank). The TG starting dose was reduced from 60 to 50 mg/m2 per day after recognition of hepatic veno-occlusive disease (VOD). A total of 257 patients on TG (25%) developed VOD or disproportionate thrombocytopenia and switched to MP. Once portal hypertension occurred, all subjects on TG were changed to MP. The benefit of randomization to TG over MP, as measured by EFS, was evident primarily in boys who began TG at 60 mg/m2 (relative hazard rate [RHR] 0.65, P = .002). The toxicities of TG preclude its protracted use as given in this study. This study is registered at http://clinicaltrials.gov as NCT00002744. PMID:20124218

Evaluation of tourists' UV exposure in Paris.

PubMed

Mahé, E; Corrêa, M P; Godin-Beekmann, S; Haeffelin, M; Jégou, F; Saiag, P; Beauchet, A

2013-03-01

Ultraviolet (UV) exposure is one of the most important risk factor for skin cancers. If UV hazard has been evaluated in tropical countries or in some population - children, outdoor activities - little information is available about UV hazard in high latitude towns like Paris, considered as the most 'charismatic city' in the world. To evaluate UV exposure in Paris in spring, in sun and shade, in real life conditions. We evaluated erythemal UV exposure, during four sunny days in May-June in eight Paris touristic sites during peak hours (2 days), and during two walks in touristic downtown of Paris. Measures were performed in sun and shade. UV radiation exposure was evaluated with UV index performed with a 'Solarmeter ultraviolet index (UVI)' and UV dose with 'standard erythema dose' (SED) and 'minimal erythema dose' (MED) calculations. Despite 'average' UVI in sunny conditions, a 4-h sun exposure reaches 13-20 SED and 3-10 MED according to phototype. Clouds were inefficient to protect against UV. Shade of places reduces moderately UVI (50-60%) in forecourts. Exposure during 1-h walk reach at least one MED in real life conditions for skin phototypes I-IV. UV risk for tourist is quite high in spring in Paris. UVI remains high despite high cloud fraction. Shade reduces UVI, but UV protection factor is only 2-3 in large places such as Place Notre Dame and Place Charles de Gaulle. So sun protection campaigns should be proposed, and sun protective strategies could be integrated in urban planning. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

The damaging effect of UV-C irradiation on lens alpha-crystallin.

PubMed

Fujii, Noriko; Uchida, Hiroki; Saito, Takeshi

2004-11-02

To evaluate the effect of UV-C irradiation on the structural properties of alpha-crystallin and its chaperone activity. alpha- and betaL-crystallins were isolated from bovine lenses using gel chromatography. The purified alpha-crystallin was subjected to UV-C irradiation (254 nm; 1, 2, 5, 10, 20, 50 J/cm2). We measured the tryptophan fluorescence, circular dichroism (CD) spectroscopy in the far UV, and the chaperone activity of both irradiated and non-irradiated alpha-crystallin. The tryptophan fluorescence of alpha-crystallin decreased, whereas the N-formylkynurenine fluorescence increased markedly with increasing doses of UV-C irradiation. Both the oxidation of Met1 and the racemization of Asp151 of alphaA-crystallin increased at a dose of 1-2 J/cm2 and then gradually decreased. The CD spectrum showed that the secondary structure of alpha-crystallin altered with increasing radiation dose, and almost all of the beta-sheet structure was lost at doses above 50 J/cm2. The chaperone activity of alpha-crystallin irradiated with doses under 5 J/cm2 remained intact. However, it was reduced to only 40% after irradiation at 10 J/cm2. Our study suggests that photo-oxidation of tryptophan residues in alpha-crystallin may be one of the events that affects the three-dimensional packing array and chaperone activity of this lens protein.

Development of action levels for MED/MPD skin-testing units in ultraviolet phototherapy

NASA Astrophysics Data System (ADS)

O'Connor, Una M.; O'Hare, Neil J.

2003-03-01

Ultraviolet (UV) Phototherapy is commonly used for treatment of skin diseases such as psoriasis and eczema. Treatment is carried out using UV phototherapy units, exposing all or part of the body for a certain exposure time. Prior to exposure in treatment units, an unaffected area of skin may be tested using UV skin-testing units in order to determine a suitable treatment regime. The exposure time at which barely perceptible erythema has developed is known as the Minimal Erythemal Dose (MED) for UVB therapy and Minimal Phototoxic Dose (MPD) for UVA therapy. This is used to determine the starting dose in the treatment regime. The presence of 'hotspots' and 'coldspots' in UV skin-testing units can result in inaccurate determination of MED/MPD. This could give rise to severe burns during treatment, or in a sub-optimal dose regime being used. Quality assurance protocols for UV phototherapy equipment have recently been developed and these protocols have highlighted the need for action levels for skin-testing units. An action level is a reference value, which is used to determine whether the difference in irradiance output level across a UV unit is acceptable. Current methodologies for skin-testing in Ireland have been characterised and errors introduced during testing have been estimated. Action levels have been developed based on analysis of errors and requirements of skin-testing.

The Effect of UV-B Radiation on Bufo arenarum Embryos Survival and Superoxide Dismutase Activity

PubMed Central

Herkovits, J.; D’Eramo, J. L.; Fridman, O.

2006-01-01

The exposure of Bufo arenarum embryos to 300–310 nm UV-B at a dose of 4,104 Joule/m2 resulted in 100% lethality within 24 hr while 820 Joule/m2 was the NOEC value for short-term chronic (10 days) exposure. The dose response curves show that lethal effects are proportional with the dose and achieve its highest value within 48 hr post exposure. The superoxide dismutase (SOD) activity in amphibian embryos for sublethal UV-B exposures was evaluated by means of UV-B treatments with 273 (A), 820(B), 1368(C) and 1915(D) Joule/m2 at 2 and 5 hours post irradiation. The SOD activity in units/mg protein in A, B, C and D at 2 hr after treatments were 80.72 ± 14.29, 74.5 ± 13.19, 39.5 ± 6.99 and 10.7 ± 1.89 respectively while for control embryos it was 10.88 ± 1.31. At 5 hr after treatments the SOD values were similar to those found in control embryos. The results confirm the high susceptibility of amphibian embryos to UV-B and point out that the SOD activity is enhanced by low doses of UV-B irradiation achieving significantly higher values than in control embryos at 2 hr post exposure. PMID:16823076

Mechanism of antihypertensive effect of Mucuna pruriens L. seed extract and its isolated compounds.

PubMed

Khan, Mohammad Yaseen; Kumar, Vimal

2017-06-21

Background In the search of safe and effective lead molecules from natural sources, Mucuna pruriens (MP) L. (Fabaceae) seeds were utilized for exploring the antihypertensive potential. Traditionally, it is used as diuretic and hypotensive. Methods Bioassay-guided fractions were utilized for the isolation of active compounds by column chromatography. IC50 value, enzyme kinetics and inhibition mechanism were determined. In vivo time and dose-dependent hypotensive study followed by changes in mean arterial pressure (MAP) induced by angiotensin I (3 nmol/kg), angiotensin II (3 nmol/kg), and bradykinin (10 nmol/kg) in anesthetized rats was done. Plasma and tissue angiotensin I-converting enzyme (ACE) activities were also determined. Results Phytochemical analysis by spectroscopic techniques revealed the presence of known compounds like genistein, ursolic acid and L-DOPA from the ethyl acetate and water fraction, respectively. In vitro study revealed MP ethyl acetate (MPEA) fraction and genistein as the most active fraction (IC50 156.45 µg/mL) and compound (IC50 253.81 µM), respectively. Lineweaver-Burk plots revealed a non-competitive mode of inhibition. ACE protein precipitation was the suggested mechanism for inhibition. The extract showed a time- and dose-dependent decrease in MAP. Genistein was able to dose-dependently reduce the MAP, up to 53±1.5 mmHg (40 mg/kg, i.v.). As compared to control, it showed a dose-dependent decrease in plasma ACE activity of 40.61 % and 54.76 % at 10 mg/kg and 20 mg/kg, respectively. It also decreased the ACE activity in the aorta (107.67nM/ml min at 10 mg, p<0.001; 95.33nM/ml min at 20 mg p<0.001). Captopril was used as a standard for various in vitro and in vivo assays. Conclusions The study revealed the antihypertensive potential of MP seed compounds via ACE inhibition.

Plasma Membrane Permeabilization by 60- and 600-ns Electric Pulses Is Determined by the Absorbed Dose

PubMed Central

Ibey, Bennett L.; Xiao, Shu; Schoenbach, Karl H.; Murphy, Michael R.; Pakhomov, Andrei G.

2008-01-01

We explored how the effect of plasma membrane permeabilization by nanosecond-duration electric pulses (nsEP) depends on the physical characteristics of exposure. The resting membrane resistance (Rm) and membrane potential (MP) were measured in cultured GH3 and CHO cells by conventional whole-cell patch-clamp technique. Intact cells were exposed to a single nsEP (60 or 600 ns duration, 0-22 kV/cm), followed by patch-clamp measurements after a 2-3 min delay. Consistent with earlier findings, nsEP caused long-lasting Rm decrease, accompanied by the loss of MP. The threshold for these effects was about 6 kV/cm for 60 ns pulses, and about 1 kV/cm for 600 ns pulses. Further analysis established that it was neither pulse duration nor the E-field amplitude per se, but the absorbed dose that determined the magnitude of the biological effect. In other words, exposure to nsEP at either pulse duration caused equal effects if the absorbed doses were equal. The threshold absorbed dose to produce plasma membrane effects in either GH3 or CHO cells at either pulse duration was found to be at or below 10 mJ/g. Despite being determined by the dose, the nsEP effect clearly is not thermal, as the maximum heating at the threshold dose is less than 0.01 °C. The use of the absorbed dose as a universal exposure metric may help to compare and quantify nsEP sensitivity of different cell types and of cells in different physiological conditions. The absorbed dose may also prove to be a more useful metric than the incident E-field in determining safety limits for high peak, lowaverage power EMF emissions. PMID:18839412

6-Mercaptopurine reverses experimental vasospasm and alleviates the production of endothelins in NO-independent mechanism-a laboratory study.

PubMed

Chang, Chih-Zen; Wu, Shu-Chuan; Kwan, Aij-Lie; Lin, Chih-Long; Hwang, Shiuh-Lin

2011-04-01

Increased endothelin-1 (ET-1) production and diminished nitric oxide synthase (NOS) bioavailability has been observed in aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) is effective in preventing and reversing arterial narrowing in a rodent SAH model. This present study is of interest to examine the effect of 6-mp on ET-1/endothelial nitric oxide synthase (eNOS) in this animal model. A rodent double hemorrhage SAH model was employed. Animals were randomly assigned to six groups (sham, SAH only, vehicle, 0.5, 1.0 and 2 mg kg(-1) day(-1) 6-mp treatment). Monoclonal CD45 immunostaining was utilized to evaluate monocytes and microglia. The level of pro-inflammatory cytokines, such as IL-1, IL-6 and TNF-α(RT-PCR), and ET-1 (ELISA) was measured. The basilar arteries (BAs) were harvested and sliced, and their cross-sectional areas were determined. Radiolabeled NOS assay kit was applied to detect eNOS. Morphologically, convolution of internal elastic lamina, endothelial cells distortion, and necrotic smooth muscle were prevalently present in the basilar artery of SAH groups, which was absent in the 1 and 2 mg kg(-1) day(-1) 6-mp plus SAH group or the healthy controls. Significant vasospasm was noted in the vehicle group (lumen patency, 54.6%, p ≤ 0.01 compared with the sham group), but it was less prominent in the 2 mg kg(-1) day(-1) 6-mp treatment group (lumen patency, 87.6%, p < 0.05). In addition, administration with 2 mg kg(-1) day(-1) 6-mp reduced cytokine levels by 11%, 47%, and 34% for IL-1, IL-6, and TNF-α, respectively, and increased ET-1 levels were found in all the animals subject to SAH (SAH only, SAH plus vehicle, SAH plus 0.5 and 1.0 mg kg(-1) day(-1) 6-mp) except in the 2 mg kg(-1) day(-1) 6-mp SAH group, when compared with the healthy controls (no SAH). Meanwhile, treatment with 6-mp did not induce the levels of expressed eNOS in BAs in the 6-mp groups (0.5, 1.0, and 2 mg kg(-1) day(-1) 6-mp plus SAH) when compared with that in the SAH groups (p > 0.1). In summary, treatment with 6-mp decreased the release of pro-inflammatory cytokines and diminished experimental vasospasm. This study offered first evidence that 6-mp dose-dependently reduces the level of ET-1 in a NO-independent mechanism, which corresponds to its antivasospastic effect in the condition of chronic vasospasm.

Potential link between fruit yield, quality parameters and phytohormonal changes in preharvest UV-C treated strawberry.

PubMed

Xu, Yanqun; Charles, Marie Thérèse; Luo, Zisheng; Roussel, Dominique; Rolland, Daniel

2017-07-01

Preharvest ultraviolet-C (UV-C) treatment of strawberry is a very new approach, and little information is available on the effect of this treatment on plant growth regulators. In this study, the effect of preharvest UV-C irradiations at three different doses on strawberry yield, fruit quality parameters and endogenous phytohormones was investigated simultaneously. The overall marketable yield of strawberry was not affected by the preharvest UV-C treatments, although more aborted and misshapen fruits were found in UV-C treated groups than in the untreated control. The fruits in the high dose group were firmer and had approximately 20% higher sucrose content and 15% higher ascorbic acid content than the control, while fruits from the middle and low dose groups showed no significant changes in these parameters. The lower abscisic acid (ABA) content found in the fruits in the high UV-C group may be associated with those quality changes. The citric acid content decreased only in the low dose group (reduction of 5.8%), with a concomitant 37% reduction in jasmonic acid (JA) content, compared to the control. The antioxidant status of fruits that received preharvest UV-C treatment was considered enhanced based on their oxygen radical absorbance capacity (ORAC) and malondialdehyde (MDA) content. In terms of aroma, three volatile alcohols differed significantly among the various treatments with obvious activation of alcohol acyltransferase (AAT) activity. The observed synchronous influence on physiological indexes and related phytohormones suggests that preharvest UV-C might affect fruit quality via the action of plant hormones. Crown Copyright © 2017. Published by Elsevier Masson SAS. All rights reserved.

Structural analysis and anti-obesity effect of a pectic polysaccharide isolated from Korean mulberry fruit Oddi (Morus alba L.).

PubMed

Choi, Ji Won; Synytsya, Andriy; Capek, Peter; Bleha, Roman; Pohl, Radek; Park, Yong Il

2016-08-01

A water-soluble polysaccharide JS-MP-1 was isolated from Korean mulberry fruits Oddi (Morus alba L.). Sugar linkage analysis and NMR data confirmed that it is a rhamnogalacturonan type I (RG I) polymer carrying arabinan and arabinogalactan (AG II) side chains. JS-MP-1 reduced dose-dependently the viability of 3T3-L1 pre-adipocyte cells, significantly stimulated the cleavage of caspases 9 and 3 and poly (ADP-ribose) polymerase (PARP) and decreased the ratio of Bcl-2 to Bax expression level that led to mitochondrial dysfunction and apoptosis in pre-adipocyte cells. The apoptotic death was mediated by stimulation of MAPKs (ERK and p38) signalling pathway. These results suggest that JS-MP-1 is able to reduce the number of fat cells and the mass of adipose tissue via inhibition of pre-adipocyte proliferation and thus JS-MP-1 itself or a crude aqueous Oddi extract containing this polysaccharide can be used as functional ingredient of health-beneficial food supplements for the treatment or prevention of obesity disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reconstruction of erythemal UV irradiance at Hohenpeissenberg (1968-2001) considering trends of total ozone, cloudiness, and turbidity

NASA Astrophysics Data System (ADS)

Trepte, S.; Winkler, P.

2003-04-01

The global mean total column ozone amount for the period 1997-2001 was approximately 3% below the 1964-1980 average. The largest ozone decreases in the northern hemisphere midlatitudes are observed during winter-spring (˜4%), with summer-autumn decreases approximately half as large. Total ozone measured at Hohenpeissenberg, Germany (48^oN, 11^oE) shows a strong decrease by about 10% since 1968, representing the long-term downward trend over Central Europe. The main consequence of this phenomenon is the expected increase of solar ultraviolet irradiation (UV-B) reaching the Earth's surface with the known harmful effects on the biosphere. Global data records of reliable routine observations of UV irradiance are still too short for accurate estimation of long-term UV variations and trends. While direct UV mesaurements at Hohenpeissenberg are available only since 1990, the long-term development of UV-B have to be reconstructed. Besides on the amount of total ozone the UV irradiation at the ground depends also on atmospheric turbidity and cloudiness. The reconstruction method is based on statistical correlations of measured UV-B data with the influencing parameters total ozone, turbidity and cloud modification factors derived from eye-observations in connection with total solar irradiance data. These observed data allow a realistic reconstruction of the UV-B time series, since no assumption on these influencing data have to be made. A model is presented, using hourly observed spectral UV-B irradiance (1990-1998), total solar irradiance, total ozone amount (daily mean) and clouds to derive erythemal UV irradiance and daily doses at Hohenpeissenberg in the period 1968-2001. A comparison with recorded UV data shows good agreement. Due to long-term total ozone loss, peak values of erythemal UV irradiance in spring and summer at clear-sky conditions have strongly increased (+4.2%/decade in June). Mean daily doses have also increased in this season (+5.4%/decade in May) but meteorological changes like reduced sunshine duration and increased cloudiness lead to a partly compensation of the ozone-loss effect in spring and to an overcompensation in autumn, where we found a long-term decrease of the daily dose (-3.0%/decade in September). Model calculations also demonstrate large year-to-year fluctuations of UV doses induced by meteorological variability, which exceed the long-term trend of the various months significantly. Nevertheless, this investigation has shown that on a long-term time scale the daily doses develop in a different way as compared to the peak values because the reasons for ozone decline (anthropogenic CFC's) and the cloud cover (hydrological cycle changes due to greenhouse effect) are caused by different phenomena.

Photolytic removal of DBPs by medium pressure UV in swimming pool water.

PubMed

Hansen, Kamilla M S; Zortea, Raissa; Piketty, Aurelia; Vega, Sergio Rodriguez; Andersen, Henrik Rasmus

2013-01-15

Medium pressure UV is used for controlling the concentration of combined chlorine (chloramines) in many public swimming pools. Little is known about the fate of other disinfection by-products (DBPs) in UV treatment. Photolysis by medium pressure UV treatment was investigated for 12 DBPs reported to be found in swimming pool water: chloroform, bromodichloromethane, dibromochloromethane, bromoform, dichloroacetonitrile, bromochloroacetonitrile, dibromoacetronitrile, trichloroacetonitrile, trichloronitromethane, dichloropropanone, trichloropropanone, and chloral hydrate. First order photolysis constants ranged 26-fold from 0.020 min(-1) for chloroform to 0.523 min(-1) for trichloronitromethane. The rate constants generally increased with bromine substitution. Using the UV removal of combined chlorine as an actinometer, the rate constants were recalculated to actual treatment doses of UV applied in a swimming pool. In an investigated public pool the UV dose was equivalent to an applied electrical energy of 1.34 kWh m(-3) d(-1) and the UV dose required to removed 90% of trichloronitromethane was 0.4 kWh m(-3) d(-1), while 2.6 kWh m(-3) d(-1) was required for chloral hydrate and the bromine containing haloacetonitriles and trihalomethanes ranged from 0.6 to 3.1 kWh m(-3) d(-1). It was predicted thus that a beneficial side-effect of applying UV for removing combined chlorine from the pool water could be a significant removal of trichloronitromethane, chloral hydrate and the bromine containing haloacetonitriles and trihalomethanes. Copyright © 2012 Elsevier B.V. All rights reserved.

New apparatus with high radiation energy between 320-460 nm: physical description and dermatological applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mutzhas, M.F.; Holzle, E.; Hofmann, C.

1981-01-01

A new apparatus (UVASUN 5000) is presented with high-radiation energy between 320 to 460 nm. The measureable energy below 320 nm was shown to be many orders of magnitude too low to produce erythema. The radiator is a specially developed source for high uv-A intensity, housing a quartz bulb with a mixture of argon, mercury and metal-halides. At a skin-target distance of 0.2 m the size of the irradiated area is 0.35 x 0.35 m, and the measured mean uv-A intensity is about 1400 W. m-2 (140 mW . cm-2). The uv-A energy in the range of 320 to 400more » nm is about 84% of the total radiation energy. Effects of very high doses of uv-A on human skin were studied. Following single uv-a applications the minimal tanning dose uv-A (MTD) and the immediate pigment darkening (IPD) dose of uv-A were established. The calculated IPD threshold time was 1.8 min at 0.2 m. Repeated exposure to this uv-A delivering system yields long lasting dark brown skin pigmentation without any clinical or histological signs of sunburn (uv-B) damage, epidermal hyperplasia or thickening of the stratum corneum. The instrument was also successfully used for photo-patch testing and reproduction of skin lesions of polymorphous light eruption. Minimal therapeutic results were seen in the phototherapy of vitiligo and inflammatory acne.« less

UV Disinfection of Wastewater and Combined Sewer Overflows.

PubMed

Gibson, John; Drake, Jennifer; Karney, Bryan

2017-01-01

Municipal wastewater contains bacteria, viruses, and other pathogens that adversely affect the environment, human health, and economic activity. One way to mitigate these effects is a final disinfection step using ultraviolet light (UVL). The advantages of UVL disinfection, when compared to the more traditional chlorine, include no chlorinated by-products, no chemical residual, and relatively compact size. The design of most UV reactors is complex. It involves lamp selection, power supply design, optics, and hydraulics. In general, medium pressure lamps are more compact, powerful, and emit over a wider range of light than the more traditional low pressure lamps. Low pressure lamps, however, may be electrically more efficient. In UV disinfection, the fraction of surviving organisms (e.g. E. coli) will decrease exponentially with increasing UV dose. However, the level of disinfection that can be achieved is often limited by particle-associated organisms. Efforts to remove or reduce the effects of wastewater particles will often improve UV disinfection effectiveness. Regrowth, photoreactivation, or dark repair after UV exposure are sometimes cited as disadvantages of UV disinfection. Research is continuing in this area, however there is little evidence that human pathogens can photoreactivate in environmental conditions, at doses used in wastewater treatment. The UV disinfection of combined sewer overflows, a form of wet weather pollution, is challenging and remains largely at the research phase. Pre-treatment of combined sewer overflows (CSOs) with a cationic polymer to induce fast settling, and a low dose of alum to increase UV transmittance, has shown promise at the bench scale.

Selection of process conditions by risk assessment for apple juice pasteurization by UV-heat treatments at moderate temperatures.

PubMed

Gayán, E; Torres, J A; Alvarez, I; Condón, S

2014-02-01

The effect of bactericidal UV-C treatments (254 nm) on Escherichia coli O157:H7 suspended in apple juice increased synergistically with temperature up to a threshold value. The optimum UV-C treatment temperature was 55 °C, yielding a 58.9% synergistic lethal effect. Under these treatment conditions, the UV-heat (UV-H55 °C) lethal variability achieving 5-log reductions had a logistic distribution (α = 37.92, β = 1.10). Using this distribution, UV-H55 °C doses to achieve the required juice safety goal with 95, 99, and 99.9% confidence were 41.17, 42.97, and 46.00 J/ml, respectively, i.e., doses higher than the 37.58 J/ml estimated by a deterministic procedure. The public health impact of these results is that the larger UV-H55 °C dose required for achieving 5-log reductions with 95, 99, and 99.9% confidence would reduce the probability of hemolytic uremic syndrome in children by 76.3, 88.6, and 96.9%, respectively. This study illustrates the importance of including the effect of data variability when selecting operational parameters for novel and conventional preservation processes to achieve high food safety standards with the desired confidence level.

Experimental ultraviolet photocarcinogenesis: wavelength interactions and time-dose relationships.

PubMed

Forbes, P D; Davies, R E; Urbach, F

1978-12-01

Tumors were induced in the skin of SKH hairless mice by exposure to fluorescent FS sun lamps or to a long-arc xenon solar simulator. Tumores developed about equally well with varying amounts of UV-A radiation (lambda greater than 320 nm) given simultaneously. In contrast, incremental changes in the UV-B region (lambda less than 320 nm) led to substantial increases in carcinogenic effectiveness. A tumor-"initiating" dose of UV-B (4-10 wk of daily FS lamp exposures) was rendered less effective by subsequent exposures of the mice to UV-A (6 hr/day, F-40 T12BL lamps). The mechanism for this effect is not known. Most tumors induced by a short course (10 wk) of FS lamp exposure grew slowly or regressed, whereas mice exposed for a longer period (30 wk) developed more tumors, and many of those that appeared early grew aggressively. Effects of daily dose fractionation were less clear, and the subject requires further study. These and other variables are being tested in a program designed to yield useful information on the effects of changing spectrum, dose, and dose delivery rates on sunlight-induced cancer.

A Survey of Blast Injury across the Full Landscape of Military Science (Etude d’ensemble des blessures dues aux explosions a travers le panorama complet de la science militaire)

DTIC Science & Technology

2011-04-01

Military Science (RTO-MP-HFM-207) Executive Summary Blast injury is a significant source of casualties in current NATO operations. The term “blast...toxicologique du souffle incluant les mécanismes de dose (par exemple, normes d’exposition à un tube à choc ), la description des points limites dose

Acute Phencyclidine Alters Neural Oscillations Evoked by Tones in the Auditory Cortex of Rats.

PubMed

Schnakenberg Martin, Ashley M; OʼDonnell, Brian F; Millward, James B; Vohs, Jenifer L; Leishman, Emma; Bolbecker, Amanda R; Rass, Olga; Morzorati, Sandra L

2017-01-01

The onset response to a single tone as measured by electroencephalography (EEG) is diminished in power and synchrony in schizophrenia. Because neural synchrony, particularly at gamma frequencies (30-80 Hz), is hypothesized to be supported by the N-methyl-D-aspartate receptor (NMDAr) system, we tested whether phencyclidine (PCP), an NMDAr antagonist, produced similar deficits to tone stimuli in rats. Experiment 1 tested the effect of a PCP dose (1.0, 2.5, and 4.5 mg/kg) on response to single tones on intracranial EEG recorded over the auditory cortex in rats. Experiment 2 evaluated the effect of PCP after acute administration of saline or PCP (5 mg/kg), after continuous subchronic administration of saline or PCP (5 mg/kg/day), and after a week of drug cessation. In both experiments, a time-frequency analysis quantified mean power (MP) and phase locking factor (PLF) between 1 and 80 Hz. Event-related potentials (ERPs) were also measured to tones, and EEG spectral power in the absence of auditory stimuli. Acute PCP increased PLF and MP between 10 and 30 Hz, while decreasing MP and PLF between approximately 50 and 70 Hz. Acute PCP produced a dose-dependent broad-band increase in EEG power that extended into gamma range frequencies. There were no consistent effects of subchronic administration on gamma range activity. Acute PCP increased ERP amplitudes for the P16 and N70 components. Findings suggest that acute PCP-induced NMDAr hypofunction has differential effects on neural power and synchrony which vary with dose, time course of administration and EEG frequency. EEG synchrony and power appear to be sensitive translational biomarkers for disrupted NMDAr function, which may contribute to the pathophysiology of schizophrenia and other neuropsychiatric disorders. © 2017 S. Karger AG, Basel.

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors.

PubMed

Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

2015-01-01

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection.

Chemoprevention of azoxymethane-induced colon cancer by ascorbylpalmitate, carbenoxolone, dimethylfumarate and p-methoxyphenol in male F344 rats.

PubMed

Rao, C V; Rivenson, A; Kelloff, G J; Reddy, B S

1995-01-01

The chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of ascorbylpalmitate (AP), carbenoxolone (CBX), dimethylfumarate (DMF) and p-methoxyphenol (p-MP) administrated in the diet before and during initiation and postinitiation phases of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD levels of AP, CBX, DMF and p-MP were determined in male F344 rats and found to be 5000 1500, 1000 and 1000 ppm, respectively, in modified AIN-76A diet. Based on these MTD values, 40 and 80% MTD levels of each agent was tested for their efficacy in color carcinogenesis. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A diet or diets containing 40 and 80% MTD levels of each AP, CBX, DMF and p-MP. At 7 weeks of age, all animals, except those in the vehicle (normal saline)-treated groups, were given two weekly s.c. injections of AOM at a dose rate of 15 mg/kg body weight/week. All groups were continued on their respective dietary regimen until the termination of the experiment 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. The results indicate that dietary administration of 40% MTD of AP significantly inhibited multiplicities (tumor/animal) of noninvasive and total (invasive plus noninvasive) adenocarcinoma of the colon (P < 0.05) and 80% MTD of AP significantly inhibited the incidence (% animals with tumors) and the multiplicities of invasive and total adenocarcinomas of the colon (P < 0.01). Dietary CBX at 40 and 80% MTD levels suppressed the incidence and multiplicities of invasive and total adenocarcinomas (P < 0.05 to 0.001) whereas 40 and 80% MTD of DMF and p-MP had significantly inhibited invasive adenocarcinoma incidence and multiplicity (P < 0.05 to 0.001). However, DMF and p-MP had no significant effect on noninvasive and total adenocarcinoma incidence and multiplicity (P > 0.05). These results suggest that AP and CBX possess potential chemopreventive properties against colon cancer.

Post-treatment of refinery wastewater effluent using a combination of AOPs (H2O2 photolysis and catalytic wet peroxide oxidation) for possible water reuse. Comparison of low and medium pressure lamp performance.

PubMed

Rueda-Márquez, J J; Levchuk, I; Salcedo, I; Acevedo-Merino, A; Manzano, M A

2016-03-15

The main aim of this work was to study the feasibility of multi-barrier treatment (MBT) consisting of filtration, hydrogen peroxide photolysis (H2O2/UVC) and catalytic wet peroxide oxidation (CWPO) for post-treatment of petroleum refinery effluent. Also the possibility of water reuse or safe discharge was considered. The performance of MBT using medium (MP) and low (LP) pressure lamps was compared as well as operation and maintenance (O&M) cost. Decomposition of organic compounds was followed by means of gas chromatography-mass spectrometry (GC-MS), total organic carbon (TOC) and chemical oxygen demand (COD) analysis. After filtration step (25 μm) turbidity and concentration of suspended solids decreased by 92% and 80%, respectively. During H2O2/UVC process with LP lamp at optimal conditions (H2O2:TOC ratio 8 and UVC dose received by water 5.28 WUVC s cm(-2)) removal of phenolic compounds, TOC and COD was 100%, 52.3% and 84.3%, respectively. Complete elimination of phenolic compounds, 47.6% of TOC and 91% of COD was achieved during H2O2/UVC process with MP lamp at optimal conditions (H2O2:TOC ratio 5, UVC dose received by water 6.57 WUVC s cm(-2)). In order to compare performance of H2O2/UVC treatment with different experimental set up, the UVC dose required for removal of mg L(-1) of COD was suggested as a parameter and successfully applied. The hydrophilicity of H2O2/UVC effluent significantly increased which in turn enhanced the oxidation of organic compounds during CWPO step. After H2O2/UVC treatment with LP and MP lamps residual H2O2 concentration was 160 mg L(-1) and 96.5 mg L(-1), respectively. Remaining H2O2 was fully consumed during subsequent CWPO step (6 and 3.5 min of contact time for LP and MP, respectively). Total TOC and COD removal after MBT was 94.7% and 92.2% (using LP lamp) and 89.6% and 95%, (using MP lamp), respectively. The O&M cost for MBT with LP lamp was estimated to be 0.44 € m(-3) while with MP lamp it was nearly five times higher. Toxicity assessment was performed using two marine species (Vibrio fischeri and Paracentrotus lividus sea-urchin) after each treatment step. The highest toxicity was attributed to H2O2/UVC effluent for both tested species. After MBT a drastic decrease of toxicity was achieved. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bone marrow necrosis in a patient with acute promyelocytic leukemia during re-induction therapy with arsenic trioxide.

PubMed

Ishitsuka, Kenji; Shirahashi, Akihiko; Iwao, Yasuhiro; Shishime, Mikiko; Takamatsu, Yasushi; Takatsuka, Yoshifusa; Utsunomiya, Atae; Suzumiya, Junji; Hara, Syuji; Tamura, Kazuo

2004-04-01

Arsenic trioxide (As2O3) therapy at a daily dose of 0.15 mg/kg was given to a 60-yr-old Japanese male with refractory acute promyelocytic leukemia. White blood cell (WBC) of 6.6 x 10(3)/microl increased to 134 x 10(3)/microl following the administration of As2O3. Daily hydroxyurea (HU), and 6-mercaptopurine (6-MP) were added on days 7 and 19, respectively. Both HU and 6-MP were discontinued on day 28, when WBC declined to 54.0 x 10(3)/microl. He developed unexplained fever and profound cytopenia requiring multiple blood products transfusions. Bone marrow examination on day 42 revealed massive necrosis. Pharmacokinetics confirmed a mean maximum plasma arsenic concentration (Cpmax) and a half-life time (t1/2) of 6.9 microm and 3.2 h, respectively, in the therapeutic range. This is the first case of bone marrow necrosis after standard-dose As2O3 therapy.

VIIRS VisNIR/SMWIR end of life sensitivity predictions

NASA Astrophysics Data System (ADS)

Murgai, Vijay; Nelson, Neil; Johnson, Eric; Yokoyama, Karen

2012-09-01

The Visible/Infrared Imaging Radiometer Suite (VIIRS) is a key sensor on the Suomi National Polar-orbiting Partnership (NPP) satellite launched on October 28, 2011 into a polar orbit of 824 km nominal altitude. VIIRS collects radiometric and imagery data of the Earth's atmosphere, oceans, and land surfaces in 22 spectral bands spanning the visible and infrared spectrum from 0.4 to 12.5 μm. The radiometric response for VIIRS spectral bands in the 600 - 2300 nm wavelength range (I1, M5, M6, M7 / I2, M8, M9, M10 / I3, M11), which started with significant signal to noise ratio margin at beginning of life, has shown some degradation on orbit. This degradation has been correlated with UV exposure of the VIIRS optics. UV exposure of witness samples from the Rotating Telescope Assembly (RTA) mirrors by Aerospace Corporation showed reflectance loss with the same spectral signature as the response degradation observed for VIIRS. The investigation and root cause determination for the VIIRS response degradation are discussed in separate papers. A model of VIIRS throughput degradation has been developed from witness sample UV exposure test results made by Aerospace. A direct relationship is assumed between UV dose (fluence) and the reflectance degradation of the RTA mirrors. The UV dose on orbit for the primary mirror is proportional to the incident earthshine and its solid angle of view. For subsequent mirrors the UV dose is weighted by solid angle and preceding mirror UV reflectance. UV dose is converted to reflectance change based on witness sample exposure measurements. The change in VIIRS throughput is calculated by multiplying the reflectance of the four RTA mirrors and agrees with the on-orbit measured response changes as a function of UV exposure time. Model predictions of the radiometric sensitivity for the affected VIIRS bands show positive margin at end of life for all affected bands.

Effects of photoperiod regimes and ultraviolet-C radiations on biosynthesis of industrially important lignans and neolignans in cell cultures of Linum usitatissimum L. (Flax).

PubMed

Anjum, Sumaira; Abbasi, Bilal Haider; Doussot, Joël; Favre-Réguillon, Alain; Hano, Christophe

2017-02-01

Lignans and neolignans are principal bioactive components of Linum usitatissimum L. (Flax), having multiple pharmacological activities. In present study, we are reporting an authoritative abiotic elicitation strategy of photoperiod regimes along with UV-C radiations. Cell cultures were grown in different photoperiod regimes (24h-dark, 24h-light and 16L/8D h photoperiod) either alone or in combination with various doses (1.8-10.8kJ/m 2 ) of ultraviolet-C (UV-C) radiations. Secoisolariciresinol diglucoside (SDG), lariciresinol diglucoside (LDG), dehydrodiconiferyl alcohol glucoside (DCG), and guaiacylglycerol-β-coniferyl alcohol ether glucoside (GGCG) were quantified by using reverse phase-high performance liquid chromatography (RP-HPLC). Results showed that the cultures exposed to UV-C radiations, accumulated higher levels of lignans, neolignans and other biochemical markers than cultures grown under different photoperiod regimes. 3.6kJ/m 2 dose of UV-C radiations resulted in 1.86-fold (7.1mg/g DW) increase in accumulation of SDG, 2.25-fold (21.6mg/g DW) in LDG, and 1.33-fold (9.2mg/g DW) in GGCG in cell cultures grown under UV+photoperiod than their respective controls. Furthermore, cell cultures grown under UV+dark showed 1.36-fold (60.0mg/g DW) increase in accumulation of DCG in response to 1.8kJ/m 2 dose of UV-C radiations. Smilar trends were observed in productivity of SDG, LDG and GGCG. Additionally, 3.6kJ/m 2 dose of UV-C radiations also resulted in 2.82-fold (195.65mg/l) increase in total phenolic production, 2.94-fold (98.9mg/l) in total flavonoid production and 1.04-fold (95%) in antioxidant activity of cell cultures grown under UV+photoperiod. These findings open new dimensions for feasible production of biologically active lignans and neolignans by Flax cell cultures. Copyright © 2017 Elsevier B.V. All rights reserved.

UV inactivation of pathogenic and indicator microorganisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, J.C.; Ossoff, S.F.; Lobe, D.C.

1985-06-01

Survival was measured as a function of the dose of germicidal UV light for the bacteria Escherichia coli, Salmonella typhi, Shigella sonnei, Streptococcus faecalis, Staphylococcus aureus, and Bacillus subtilis spores, the enteric viruses poliovirus type 1 and simian rotavirus SA11, the cysts of the protozoan Acanthamoeba castellanii, as well as for total coliforms and standard plate count microorganisms from secondary effluent. The doses of UV light necessary for a 99.9% inactivation of the cultured vegetative bacteria, total coliforms, and standard plate count microorganisms were comparable. However, the viruses, the bacterial spores, and the amoebic cysts required about 3 to 4more » times, 9 times, and 15 times, respectively, the dose required for E. coli. These ratios covered a narrower relative dose range than that previously reported for chlorine disinfection of E. coli, viruses, spores, and cysts.« less

Reproductive, morphological, and phytochemical responses of Arabidopsis thaliana ecotypes to enhanced UV-B radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trumbull, V.L.; McCloud, E.S.; Paige, K.N.

1994-06-01

Two ecotypes of Arabidopsis thaliana, collected from Libya and Norway, were grown in the greenhouse under. UV-B doses of 0 and 10.5 kJ m[sup [minus]2] UV-B[sub BE]. The high UV-B dose simulated midsummer ambient conditions over Libya and a 40% reduction in stratospheric ozone over Norway. The Libyan ectotype, which originated from latitudes where solar UV-B is high, showed no UV-B induced damage to plant growth. However the Norwegian ecotype, which originated from latitudes where solar UV-B is low, showed a significant reduction in plant height, inflorescence weight, and rosette weight in response to enhanced UV-B. Although fruit and seedmore » number for both ecotypes were unaffected by enhanced UV-B radiation the germination success of the seeds harvested from the irradiated Norwegian plants were significantly reduced. The two ecotypes also differed with respect to their accumulation of kaempferol, a putative UV-B protective filter. The Libyan ecotype increased kaempferol concentration by 38% over the 0 kJ treatment whereas the Norwegian ecotype increased by only 15%. These data suggest that, for these ecotypes, variation in UV-B sensitivity may be explained by the differential induction of UV-absorbing leaf pigments.« less

Solar UV radiation exposure of seamen - Measurements, calibration and model calculations of erythemal irradiance along ship routes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feister, Uwe; Meyer, Gabriele; Kirst, Ulrich

2013-05-10

Seamen working on vessels that go along tropical and subtropical routes are at risk to receive high doses of solar erythemal radiation. Due to small solar zenith angles and low ozone values, UV index and erythemal dose are much higher than at mid-and high latitudes. UV index values at tropical and subtropical Oceans can exceed UVI = 20, which is more than double of typical mid-latitude UV index values. Daily erythemal dose can exceed the 30-fold of typical midlatitude winter values. Measurements of erythemal exposure of different body parts on seamen have been performed along 4 routes of merchant vessels.more » The data base has been extended by two years of continuous solar irradiance measurements taken on the mast top of RV METEOR. Radiative transfer model calculations for clear sky along the ship routes have been performed that use satellite-based input for ozone and aerosols to provide maximum erythemal irradiance and dose. The whole data base is intended to be used to derive individual erythemal exposure of seamen during work-time.« less

UV irradiation-induced Raman spectra changes in lead silicate glasses

NASA Astrophysics Data System (ADS)

Jia, Hongzhi; Chen, Guanghui; Wang, Wencheng

2006-12-01

The Raman spectra for a series of lead silicate glasses with different PbO content before and after irradiation with different energy density by the frequency-quadrupled output of a Q-switched YAG laser (266 nm, 10 Hz repetition rate) were measured. The intensity of Pb-O band near 140 cm -1 in the Raman spectra decreases after UV irradiation and no new band appears in the Raman spectra. Exposed to the UV beam with high energy density (150 mJ/cm 2), although the total dose is smaller than the dose with low energy density (50 mJ/cm 2), the intensity of the 140 cm -1 band drops heavilier than exposed to the UV beam with low energy density. This shows that the UV irradiation can cause the broken of Pb-O bond in lead silicate glasses and the broken of Pb-O bond is related to the energy density of UV beam.

Effects of urban agglomeration on surface-UV doses: a comparison of Brewer measurements in Warsaw and Belsk, Poland, for the period 2013-2015

NASA Astrophysics Data System (ADS)

Czerwińska, Agnieszka E.; Krzyścin, Janusz W.; Jarosławski, Janusz; Posyniak, Michał

2016-11-01

Specific aerosols and cloud properties over large urban regions seem to generate an island, similar to the well-known urban heat island, leading to lower ultraviolet (UV) radiation intensity compared to the surrounding less polluted areas, thus creating a shield against excessive human exposure to UV radiation. The present study focuses on differences between erythemal and UVA (324 nm) doses measured by the Brewer spectrophotometers in Warsaw (52.3° N, 21.0° E) and Belsk (51.8° N, 20.8° E). The latter is a rural region located about 60 km south-west of the city. Ratios between erythemal and UVA partly daily doses, obtained during all-sky and cloudless-sky conditions for the period May 2013-December 2015, were analysed to infer a specific cloud and aerosol forcing on the surface UV doses over Warsaw. Radiative model simulations were carried out to find sources of the observed differences between the sites. It was found that Warsaw urban agglomeration induced 8 and 6 % attenuation of the erythemal and UVA doses respectively. This is mostly due to the lower sun elevation in Warsaw during the near-noon measurements and the larger optical depth of the city aerosols and increased cloudiness. It could be hypothesised that the expected stronger absorption of the solar UV radiation by urban aerosols is compensated for here by a higher surface reflectivity over the city.

Tomato plants use non-enzymatic antioxidant pathways to cope with moderate UV-A/B irradiation: A contribution to the use of UV-A/B in horticulture.

PubMed

Mariz-Ponte, N; Mendes, R J; Sario, S; Ferreira de Oliveira, J M P; Melo, P; Santos, C

2018-02-01

Plants developed receptors for solar UV-A/B radiation, which regulate a complex network of functions through the plant's life cycle. However, greenhouse grown crops, like tomato, are exposed to strongly reduced UV radiation, contrarily to their open-field counterparts. A new paradigm of modern horticulture is to supplement adequate levels of UV to greenhouse cultures, inducing a positive mild stress necessary to stimulate oxidative stress pathways and antioxidant mechanisms. Protected cultures of Solanum (cv MicroTom) were supplemented with moderate UV-A (1h and 4h) and UV-B (1min and 5min) doses during the flowering/fruiting period. After 30days, flowering/fruit ripening synchronization were enhanced, paralleled by the upregulation of blue/UV-A and UV-B receptors' genes cry1a and uvr8. UV-B caused moreover an increase in the expression of hy5, of HY5 repressor cop1 and of a repressor of COP1, uvr8. While all UV-A/B conditions increased SOD activity, increases of the generated H 2 O 2 , as well as lipid peroxidation and cell mebrane disruption, were minimal. However, the activity of antioxidant enzymes downstream from SOD (CAT, APX, GPX) was not significant. These results suggest that the major antioxidant pathways involve phenylpropanoid compounds, which also have an important role in UV screening. This hypothesis was confirmed by the increase of phenolic compounds and by the upregulation of chs and fls, coding for CHS and FLS enzymes involved in the phenylpropanoid synthesis. Overall, all doses of UV-A or UV-B were beneficial to flowering/fruiting but lower UV-A/B doses induced lower redox disorders and were more effective in the fruiting process/synchronization. Considering the benefits observed on flowering/fruiting, with minimal impacts in the vegetative part, we demonstrate that both UV-A/B could be used in protected tomato horticulture systems. Copyright © 2017 Elsevier GmbH. All rights reserved.

[Inactivation and reactivation of antibiotic-resistant bacteria during and after UV disinfection in reclaimed water].

PubMed

Huang, Jing-Jing; Tang, Fang; Xi, Jin-Ying; Pang, Yu-Chen; Hu, Hong-Ying

2014-04-01

Prevalence of antibiotic-resistant bacteria in wastewater effluents is concerned as an emerging contaminant. To estimate inactivation and reactivation potentials of antibiotic-resistant bacteria by UV disinfection, inactivation and reactivation of penicillin-, ampicillin-, cephalexin-, chloramphenicol-and rifampicin-resistant bacteria in the secondary effluent were studied under different UV doses. The results showed that the inactivation ratios of penicillin-, ampicillin-, cephalexin-and chloramphenicol-resistant bacteria were higher than 4-log, which was closed to that of total heterotrophic bacteria; however, the inactivation ratio of rifampicin-resistant bacteria was lower (3.7-log) under 20 mJ x cm(-2) UV exposure. After 22 h standing incubation, antibiotic-resistant bacteria widely reactivated. The colony forming ability of antibiotic-resistant bacteria was as high as 3-log when exposed to 20 mJ x cm(-2) UV light. Hence, conventional UV dose can not effectively control reactivation of antibiotic-resistant bacteria in reclaimed water by UV disinfection.

Theoretical study on the spectroscopic properties of CO3(*-).nH2O clusters: extrapolation to bulk.

PubMed

Pathak, Arup K; Mukherjee, Tulsi; Maity, Dilip K

2008-10-24

Vertical detachment energies (VDE) and UV/Vis absorption spectra of hydrated carbonate radical anion clusters, CO(3)(*-).nH(2)O (n=1-8), are determined by means of ab initio electronic structure theory. The VDE values of the hydrated clusters are calculated with second-order Moller-Plesset perturbation (MP2) and coupled cluster theory using the 6-311++G(d,p) set of basis functions. The bulk VDE value of an aqueous carbonate radical anion solution is predicted to be 10.6 eV from the calculated weighted average VDE values of the CO(3)(*-).nH(2)O clusters. UV/Vis absorption spectra of the hydrated clusters are calculated by means of time-dependent density functional theory using the Becke three-parameter nonlocal exchange and the Lee-Yang-Parr nonlocal correlation functional (B3LYP). The simulated UV/Vis spectrum of the CO(3)(*-).8H(2)O cluster is in excellent agreement with the reported experimental spectrum for CO(3)(*-) (aq), obtained based on pulse radiolysis experiments.

Disinfection of Mycobacterium avium subspecies hominissuis in drinking tap water using ultraviolet germicidal irradiation.

PubMed

Schiavano, Giuditta Fiorella; De Santi, Mauro; Sisti, Maurizio; Amagliani, Giulia; Brandi, Giorgio

2017-09-13

Nontuberculous mycobacteria are resistant to conventional water treatments, and are opportunistic human pathogen, particularly in hospitalized patients. The aim of this investigation was to assess the effectiveness of an ultraviolet UV-C lamp treatment against Mycobacterium avium subspecies hominissuis in drinking tap water. Ultraviolet treatments (0-192 mJ/cm 2 ) were performed using UV lamp immerged onto cylindrical glass tubes containing artificially contaminated water. The results showed that susceptibility to UV varied considerably according to the strains and the diameter of the tube. With a dose of 32 mJ/cm 2 , a significant inactivation (p < .05) of 3 log (99.9%) or more was obtained in only 5 of the 14 strains. To obtain a complete inactivation of all strains an irradiation of 192 mJ/cm 2 was needed, a dose that is much higher than the limits recommended by the international standards for UV disinfection of drinking water. In conclusion, it may be difficult to standardize a UV dose for the elimination of waterborne mycobacteria.

Thiopurine Drugs Azathioprine and 6-Mercaptopurine Inhibit Mycobacterium paratuberculosis Growth In Vitro▿

PubMed Central

Shin, Sung Jae; Collins, Michael T.

2008-01-01

The in vitro susceptibility of human- and bovine-origin Mycobacterium paratuberculosis to the thioupurine drugs 6-mercaptopurine (6-MP) and azathioprine (AZA) was established using conventional plate counting methods and the MGIT 960 ParaTB culture system. Both 6-MP and AZA had antibacterial activity against M. paratuberculosis; isolates from Crohn's disease patients tended to be more susceptible than were bovine-origin isolates. Isolates of Mycobacterium avium, used as controls, were generally resistant to both AZA and 6-MP, even at high concentrations (≥64.0 μg/ml). Among rapidly growing mycobacteria, Mycobacterium phlei was susceptible to 6-MP and AZA whereas Mycobacterium smegmatis strains were not. AZA and 6-MP limited the growth of, but did not kill, M. paratuberculosis in a dose-dependent manner. Anti-inflammatory drugs in the sulfonamide family (sulfapyridine, sulfasalazine, and 5-aminosalycilic acid [mesalamine]) had little or no antibacterial activity against M. paratuberculosis. The conventional antibiotics azithromycin and ciprofloxacin, used as control drugs, were bactericidal for M. paratuberculosis, exerting their killing effects on the organism relatively quickly. Simultaneous exposure of M. paratuberculosis to 6-MP and ciprofloxacin resulted in significantly higher CFU than use of ciprofloxacin alone. These data may partially explain the paradoxical response of Crohn's disease patients infected with M. paratuberculosis to treatment with immunosuppressive thiopurine drugs, i.e., they do not worsen with anti-inflammatory treatment as would be expected with a microbiological etiologic pathogen. These findings also should influence the design of therapeutic trials to evaluate antibiotic treatments of Crohn's disease: AZA drugs may confound interpretation of data on therapeutic responses for both antibiotic-treated and control groups. PMID:18070971

Alterations in pain response are partially reversed by methylphenidate (Ritalin) in adults with attention deficit hyperactivity disorder (ADHD).

PubMed

Treister, Roi; Eisenberg, Elon; Demeter, Naor; Pud, Dorit

2015-01-01

Attention deficit hyperactivity disorder (ADHD) is characterized by dysregulation of sensory processing and neurobiology of dopamine. Although cumulative evidence suggests that dopamine is involved in pain processing, pain perception in ADHD subjects and the effect of dopamine agonists such as methylphenidate (MP, Ritalin) on it have rarely been studied. The aims of this study were to (1) psychophysically assess sensitivity to pain in ADHD subjects as compared to controls and (2) examine the effects of MP on pain response in ADHD subjects. Thirty subjects with ADHD and 30 age- and gender-matched controls participated in a preliminary trial. Pain threshold, intensity, and tolerance in response to cold pain stimulation were measured for both groups (ADHD with no treatment). In addition, the ADHD group was reassessed following a single dose of MP treatment. The ADHD subjects "without MP" in comparison with controls displayed significantly shorter cold pain threshold (2.8 ± 2.1 vs. 5.8 ± 2.5 seconds, respectively, P < 0.001) and cold tolerance (21.8 ± 22.3 vs. 62.8 ± 59.8 seconds, respectively P < 0.001). No differences in pain intensities between the groups were found. Following MP treatment, both cold threshold and tolerance in the ADHD subjects increased significantly compared to those with no treatment (3.6 ± 2.5 seconds, P = 0.011, and 46.4 ± 53.3 seconds, P < 0.001, respectively). These results suggest that adults with ADHD are more sensitive to pain compared with controls and that MP may exert antinociceptive properties in these subjects. Randomized, controlled trials are warranted to verify these findings. © 2013 World Institute of Pain.

A phase II randomized placebo-controlled trial of oral N-acetylcysteine for protection of melanocytic nevi against UV-induced oxidative stress in vivo

PubMed Central

Cassidy, Pamela B.; Liu, Tong; Florell, Scott R.; Honeggar, Matthew; Leachman, Sancy A.; Boucher, Kenneth M.; Grossman, Douglas

2016-01-01

Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1–2 MED) using a solar simulator. One day later, the MED was re-determined and the irradiated nevus and a control un-irradiated nevus were removed for histologic analysis and examination of biomarkers of NAC metabolism and UV-induced oxidative stress. Increased expression of 8-oxoguanine, thioredoxin reductase-1, and γ-glutamylcysteine synthase modifier subunit were consistently seen in UV-treated compared to unirradiated nevi. However, no significant differences were observed in these UV-induced changes or in the pre- and post-intervention MED between those patients receiving NAC vs. placebo. Similarly, no significant differences were observed in UV-induced changes between subjects with germline wild-type vs. loss of function mutations in the melanocortin-1 receptor. Nevi showed similar changes of UV-induced oxidative stress in an open-label post-trial study in 10 patients who received NAC 3 h before nevus irradiation. Thus a single oral dose of NAC did not effectively protect nevi from UV-induced oxidative stress under the conditions examined. PMID:27920018

Preliminary results on the photo-transferred thermoluminescence from Ge-doped SiO2 optical fiber

NASA Astrophysics Data System (ADS)

Zulkepely, Nurul Najua; Amin, Yusoff Mohd; Md Nor, Roslan; Bradley, D. A.; Maah, Mohd Jamil; Mat Nawi, Siti Nurasiah; Wahib, Nur Fadira

2015-12-01

A study is made of photo-transferred thermoluminescence (PTTL), the TL being induced by transferring charge carriers from deeper to more superficial traps through energetic light exposure. Potential applications include dose reassessment in radiation dosimetry and also as a useful tool for dating. With incomplete emptying of deep traps following first readout, subsequent UV exposure is shown to lead to charge transfer to more shallow traps. Using Ge-doped SiO2 optical fibers exposed to 60Co gamma rays, the PTTL from the medium has been characterized in terms of the stimulation provided by exposure to a UV lamp and duration of exposure, maximum read-out temperature and pre-gamma irradiation dose. Ge-doped SiO2 optical fibers of flat cross-sectional shape have been used in this study. The efficiency of dose reassessment was compared to that of the highly popular phosphor-based TL detector TLD-100. Results show the maximum temperature of readout to have no measurable effect on the PTTL signal. For doses from 20 to 500 cGy, the method is shown to be effective using a UV lamp of wavelength 254 nm, also being indicative of potential application for doses on either side of the range currently investigated. A study was also made of the effect of UV exposure time on PTTL, seeking to determine the greatest accessible sensitivity and lowest measurable dose.

Manipulating Sensory and Phytochemical Profiles of Greenhouse Tomatoes Using Environmentally Relevant Doses of Ultraviolet Radiation.

PubMed

Dzakovich, Michael P; Ferruzzi, Mario G; Mitchell, Cary A

2016-09-14

Fruits harvested from off-season, greenhouse-grown tomato plants have a poor reputation compared to their in-season, garden-grown counterparts. Presently, there is a gap in knowledge with regard to the role of UV-B radiation (280-315 nm) in determining greenhouse tomato quality. Knowing that UV-B is a powerful elicitor of secondary metabolism and not transmitted through greenhouse glass and some greenhouse plastics, we tested the hypothesis that supplemental UV-B radiation in the greenhouse will impart quality attributes typically associated with garden-grown tomatoes. Environmentally relevant doses of supplemental UV-B radiation did not strongly affect antioxidant compounds of fruits, although the flavonol quercetin-3-O-rutinoside (rutin) significantly increased in response to UV-B. Physicochemical metrics of fruit quality attributes and consumer sensory panels were used to determine if any such differences altered consumer perception of tomato quality. Supplemental UV-A radiation (315-400 nm) pre-harvest treatments enhanced sensory perception of aroma, acidity, and overall approval, suggesting a compelling opportunity to environmentally enhance the flavor of greenhouse-grown tomatoes. The expression of the genes COP1 and HY5 were indicative of adaptation to UV radiation, which explains the lack of marked effects reported in these studies. To our knowledge, these studies represent the first reported use of environmentally relevant doses of UV radiation throughout the reproductive portion of the tomato plant life cycle to positively enhance the sensory and chemical properties of fruits.

Impact on Vitamin D2, Vitamin D4 and Agaritine in Agaricus bisporus Mushrooms after Artificial and Natural Solar UV Light Exposure.

PubMed

Urbain, Paul; Valverde, Juan; Jakobsen, Jette

2016-09-01

Commercial mushroom production can expose mushrooms post-harvest to UV light for purposes of vitamin D2 enrichment by converting the naturally occurring provitamin D2 (ergosterol). The objectives of the present study were to artificially simulate solar UV-B doses occurring naturally in Central Europe and to investigate vitamin D2 and vitamin D4 production in sliced Agaricus bisporus (button mushrooms) and to analyse and compare the agaritine content of naturally and artificially UV-irradiated mushrooms. Agaritine was measured for safety aspects even though there is no rationale for a link between UV light exposure and agaritine content. The artificial UV-B dose of 0.53 J/cm(2) raised the vitamin D2 content to significantly (P < 0.001) higher levels of 67.1 ± 9.9 μg/g dry weight (DW) than sun exposure (3.9 ± 0.8 μg/g dry DW). We observed a positive correlation between vitamin D4 and vitamin D2 production (r(2) = 0.96, P < 0.001) after artificial UV irradiation, with vitamin D4 levels ranging from 0 to 20.9 μg/g DW. The agaritine content varied widely but remained within normal ranges in all samples. Irrespective of the irradiation source, agaritine dropped dramatically in conjunction with all UV-B doses both artificial and natural solar, probably due to its known instability. The biological action of vitamin D from UV-exposed mushrooms reflects the activity of these two major vitamin D analogues (D2, D4). Vitamin D4 should be analysed and agaritine disregarded in future studies of UV-exposed mushrooms.

Ultraviolet B radiation induces impaired lifecycle traits and modulates expression of cytochrome P450 (CYP) genes in the copepod Tigriopus japonicus.

PubMed

Puthumana, Jayesh; Lee, Min-Chul; Park, Jun Chul; Kim, Hui-Su; Hwang, Dae-Sik; Han, Jeonghoon; Lee, Jae-Seong

2017-03-01

To evaluate the effects of ultraviolet B (UV-B) radiation at the developmental, reproductive, and molecular levels in aquatic invertebrates, we measured UV-B-induced acute toxicity, impairments in developmental and reproductive traits, and UV-B interaction with the entire family of cytochrome P450 (CYP) genes in the intertidal benthic copepod Tigriopus japonicus. We found a significant, dose-dependent reduction (P<0.05) in the survival of T. japonicus that began as a developmental delay and decreased fecundity. The 48h LD10 and LD50 were 1.35 and 1.84kJ/m 2 , and the CYP inhibitor (PBO) elevated mortality, confirming the involvement of CYP genes in UV-B induced toxicity. Low-dose UV-B (1.5kJ/m 2 ) induced developmental delays, and higher doses (6-18kJ/m 2 ) caused reproductive impairments in ovigerous females. The significant up-regulation of CYP genes belonging to clans 2/3/MT/4/20 in T. japonicus exposed to UV-B (12kJ/m 2 ) confirmed molecular interaction between UV-B and CYP genes. Moreover, orphan CYPs, such as CYP20A1, provide good insight on the deorphanization of invertebrate CYPs. Overall, these results demonstrate the involvement of UV-B radiation in the expression of all the CYP genes in T. japonicus and their susceptibility to UV-B radiation. This will provide a better understanding of the mechanistic effects of UV-B in copepods through the predicted AhR-mediated up-regulation of CYP genes. Copyright © 2017 Elsevier B.V. All rights reserved.

Serious complications in experiments in which UV doses are effected by using different lamp heights.

PubMed

Flint, Stephan D; Ryel, Ronald J; Hudelson, Timothy J; Caldwell, Martyn M

2009-10-06

Many experiments examining plant responses to enhanced ultraviolet-B radiation (280-315nm) simply compare an enhanced UV-B treatment with ambient UV-B (or no UV-B radiation in most greenhouse and controlled-environment studies). Some more detailed experiments utilize multiple levels of UV-B radiation. A number of different techniques have been used to adjust the UV dose. One common technique is to place racks of fluorescent UV-emitting lamps at different heights above the plant canopy. However, the lamps and associated support structure cast shadows on the plant bed below. We calculated one example of the sequence of shade intervals for two common heights of lamp racks and show the patterns and duration of shade which the plants receive is distributed differently over the course of the day for different heights of the lamp racks. We also conducted a greenhouse experiment with plants (canola, sunflower and maize) grown under unenergized lamp racks suspended at the same two heights above the canopy. Growth characteristics differed in unpredictable ways between plants grown under the two heights of lamp racks. These differences could enhance or obscure potential UV-B effects. Also, differences in leaf mass per unit foliage area, which were observed in this experiment, could contribute to differences in plant UV-B sensitivity. We recommend the use of other techniques for achieving multiple doses of UV-B radiation. These range from simple and inexpensive approaches (e.g., wrapping individual fluorescent tubes in layers of a neutral-density filter such as cheese cloth) to more technical and expensive alternatives (e.g., electronically modulated lamp control systems). These choices should be determined according to the goals of the particular experiment.

Radiomics based targeted radiotherapy planning (Rad-TRaP): a computational framework for prostate cancer treatment planning with MRI.

PubMed

Shiradkar, Rakesh; Podder, Tarun K; Algohary, Ahmad; Viswanath, Satish; Ellis, Rodney J; Madabhushi, Anant

2016-11-10

Radiomics or computer - extracted texture features have been shown to achieve superior performance than multiparametric MRI (mpMRI) signal intensities alone in targeting prostate cancer (PCa) lesions. Radiomics along with deformable co-registration tools can be used to develop a framework to generate targeted focal radiotherapy treatment plans. The Rad-TRaP framework comprises three distinct modules. Firstly, a module for radiomics based detection of PCa lesions on mpMRI via a feature enabled machine learning classifier. The second module comprises a multi-modal deformable co-registration scheme to map tissue, organ, and delineated target volumes from MRI onto CT. Finally, the third module involves generation of a radiomics based dose plan on MRI for brachytherapy and on CT for EBRT using the target delineations transferred from the MRI to the CT. Rad-TRaP framework was evaluated using a retrospective cohort of 23 patient studies from two different institutions. 11 patients from the first institution were used to train a radiomics classifier, which was used to detect tumor regions in 12 patients from the second institution. The ground truth cancer delineations for training the machine learning classifier were made by an experienced radiation oncologist using mpMRI, knowledge of biopsy location and radiology reports. The detected tumor regions were used to generate treatment plans for brachytherapy using mpMRI, and tumor regions mapped from MRI to CT to generate corresponding treatment plans for EBRT. For each of EBRT and brachytherapy, 3 dose plans were generated - whole gland homogeneous ([Formula: see text]) which is the current clinical standard, radiomics based focal ([Formula: see text]), and whole gland with a radiomics based focal boost ([Formula: see text]). Comparison of [Formula: see text] against conventional [Formula: see text] revealed that targeted focal brachytherapy would result in a marked reduction in dosage to the OARs while ensuring that the prescribed dose is delivered to the lesions. [Formula: see text] resulted in only a marginal increase in dosage to the OARs compared to [Formula: see text]. A similar trend was observed in case of EBRT with [Formula: see text] and [Formula: see text] compared to [Formula: see text]. A radiotherapy planning framework to generate targeted focal treatment plans has been presented. The focal treatment plans generated using the framework showed reduction in dosage to the organs at risk and a boosted dose delivered to the cancerous lesions.

The role of early detection and treatment in malaria elimination.

PubMed

Landier, Jordi; Parker, Daniel M; Thu, Aung Myint; Carrara, Verena I; Lwin, Khin Maung; Bonnington, Craig A; Pukrittayakamee, Sasithon; Delmas, Gilles; Nosten, François H

2016-07-15

Falciparum malaria persists in hard-to-reach areas or demographic groups that are missed by conventional healthcare systems but could be reached by trained community members in a malaria post (MP). The main focus of a MP is to provide uninterrupted and rapid access to rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT) too all inhabitants of a village. RDTs allow trained community members to perform malaria diagnosis accurately and prescribe appropriate treatment, reducing as much as possible any delay between the onset of fever and treatment. Early treatment with ACT and with a low-dose of primaquine prevents further transmission from human to mosquito. A functioning MP represents an essential component of any malaria elimination strategy. Implementing large-scale, high-coverage, community-based early diagnosis and treatment through MPs requires few technological innovations but relies on a very well structured organization able to train, supervise and supply MPs, to monitor activity and to perform strict malaria surveillance.

Aggregation of 2-aminobenzimidazole--a combined experimental and theoretical investigation.

PubMed

Angelova, Silvia E; Spassova, Milena I; Deneva, Vera V; Rogojerov, Marin I; Antonov, Liudmil M

2011-06-20

An investigation of 2-aminobenzimidazole was carried out by calculations at HF, MP2, and DFT levels of theory and also by UV and IR spectroscopy. The quantum chemical calculations predict a full shift of the equilibrium towards the amino form, but the absorption spectra in different solvents distinctly show a two-component equilibrium system. Examination of possible equilibria in solution shows that an equilibrium between two dimeric forms of the amino tautomer of 2-aminobenzimidazole explains the spectral observations. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50 strain.

PubMed

Ly, Hoai J; Nishiyama, Shoko; Lokugamage, Nandadeva; Smith, Jennifer K; Zhang, Lihong; Perez, David; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

2017-12-04

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic in ruminants, whereas residual virulence might be a concern for vulnerable populations. It is also important for live-attenuated strains to encode unique genetic markers for the differentiation from wild-type RVFV strains. In this study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain via the introduction of 584 silent mutations. To minimize the impact on protective efficacy, codon usage and codon pair bias were not de-optimized. The resulting rMP12-GM50 strain showed 100% protective efficacy with a single intramuscular dose, raising a 1:853 mean titer of plaque reduction neutralization test. Moreover, outbred mice infected with one of three pathogenic reassortant ZH501 strains, which encoded rMP12-GM50 L-, M-, or S-segments, showed 90%, 50%, or 30% survival, respectively. These results indicate that attenuation of the rMP12-GM50 strain is significantly attenuated via the L-, M-, and S-segments. Recombinant RVFV vaccine strains encoding similar silent mutations will be also useful for the surveillance of reassortant strains derived from vaccine strains in endemic countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Two years comparative studies on biological effects of environmental UV radiation

NASA Astrophysics Data System (ADS)

Grof, P.; Ronto, Gyorgyi; Gaspar, S.; Berces, A.; Szabo, Laszlo D.

1994-07-01

A method has been developed for determination of the biologically effective UV dose based on T7 phage as biosensor. In field experiments clockwork driven telescope has been used for determining doses from direct and global (direct plus diffuse) solar radiation. On fine summer days at mid-latitude this arrangement allowed the following comparisons: measured doses from direct and global radiation obtained at the same time and measuring site reflecting the biological importance of diffuse radiation; direct and global radiation obtained at the same time and measuring site reflecting the biological importance of diffuse radiation; direct and global doses obtained at the same time on different measuring sites (downtown, suburb, outside the town) reflecting the differences caused by air quality; direct and global doses obtained on the same measuring place, in summertime of two different years reflecting the importance of the long-term measurements for estimating the biological risk caused by increased UV-B radiation; measured data and model calculations.

Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia.

PubMed

Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob; Frandsen, Thomas Leth; Hjalgrim, Lisa Lyngsie; Schmiegelow, Kjeld

2016-11-01

Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10 9 /L. Consequently, the absolute degree of myelosuppression is unknown for the individual child and we wanted to evaluate this. A median of 22 (range 8-27) 6MP/MTX metabolite samples and 100 (range 25-130) blood counts during therapy and 10 (range 2-15) off therapy were collected in 50 children with ALL. Differences between off-therapy and on-therapy WBCs [including absolute neutrophil (ANC) and lymphocyte counts (ALC)] were used to retrospectively approximate the absolute myelosuppression (="delta-") and association with age, sex and 6MP/MTX doses explored. We applied linear mixed models to estimate on-therapy counts by 6MP/MTX metabolites: DNA-incorporated thioguanine nucleotides (DNA-TGN), erythrocyte thioguanine nucleotides (ery-TGN), erythrocyte-methylated 6MP metabolites (ery-MeMP) and erythrocyte MTX polyglutamates with 2-6 glutamate residues (ery-MTXpg 2-6 ). On-therapy WBC was correlated with ANC and ALC (r s  = 0.84 and r s  = 0.33, p values <0.001), whereas ANC was weakly correlated with ALC (r s  = -0.11, p < 0.001), and neither significantly correlated with age. Off-therapy ALC, but not ANC, was strongly correlated with age (r s  = -0.68 and -0.18, p < 0.001 and p = 0.22). Delta-ALC decreased with increasing age (r s  = -0.69, p < 0.001). Incorporation of DNA-TGN was positively associated with ery-TGN (p < 0.001), ery-MeMP (p < 0.001) and ery-MTXpg 2-6 (p = 0.047). On-therapy ALC decreased with increasing DNA-TGN level (p < 0.001, model adjusted for off-therapy ALC), whereas on-therapy ANC could not be modeled reliably. Measurements of 6MP/MTX metabolites could supplement blood counts in assessing therapy intensity, but require prospective validation.

Magnetic vs. non-magnetic colloids - A comparative adsorption study to quantify the effect of dye-induced aggregation on the binding affinity of an organic dye.

PubMed

Williams, Tyler A; Lee, Jenny; Diemler, Cory A; Subir, Mahamud

2016-11-01

Due to attractive magnetic forces, magnetic particles (MPs) can exhibit colloidal instability upon molecular adsorption. Thus, by comparing the dye adsorption isotherms of MPs and non-magnetic particles of the same size, shape and functional group it should be possible to characterize the influence of magnetic attraction on MP aggregation. For a range of particle densities, a comparative adsorption study of malachite green (MG(+)) onto magnetic and non-magnetic colloids was carried out using a combination of a separation technique coupled with UV-vis spectroscopy, optical microscopy, and polarization dependent second harmonic generation (SHG) spectroscopy. Significant MP aggregation occurs in aqueous solution due to MG(+) adsorption. This alters the adsorption isotherm and challenges the determination of the adsorption equilibrium constant, Kads. The dye-induced aggregation is directly related to the MG(+) concentration, [MG(+)]. A modified Langmuir equation, which incorporates loss of surface sites due to this aggregation, accurately describes the resulting adsorption isotherms. The Kads of 1.1 (±0.3)×10(7) and a loss of maximum MP surface capacity of 2.8 (±0.7)×10(3)M(-1) per [MG(+)] has been obtained. Additionally, SHG has been established as an effective tool to detect aggregation in nanoparticles. Copyright © 2016 Elsevier Inc. All rights reserved.

The repair of low dose UV light-induced damage to human skin DNA in condition of trace amount Mg 2+

NASA Astrophysics Data System (ADS)

Gao, Fang; Guo, Zhouyi; Zheng, Changchun; Wang, Rui; Liu, Zhiming; Meng, Pei; Zhai, Juan

2008-12-01

Ultraviolet light-induced damage to human skin DNA was widely investigated. The primary mechanism of this damage contributed to form cyclobutane pyrimidine dimmers (CPDs). Although the distribution of UV light-induced CPDs within a defined sequence is similar, the damage in cellular environment which shields the nuclear DNA was higher than that in organism in apparent dose. So we use low UVB light as main study agent. Low dose UV-irradiated HDF-a cells (Human Dermal Fibroblasts-adult cells) which is weaker than epidermic cells were cultured with DMEM at different trace amount of Mg2+ (0mmol/L , 0.1mmol/L , 0.2mmol/L, 0.4mmol/L, 0.8mmol/L, 1.2mmol/L) free-serum DMEM and the repair of DNA strands injured were observed. Treat these cells with DNA strand breaks detection, photoproducts detection and the repair of photoproducts detection. Then quantitate the role of trace amount Mg2+ in repair of UV light-induced damage to human skin. The experiment results indicated that epidermic cells have capability of resistance to UV-radiation at a certain extent. And Mg2+ can regulate the UV-induced damage repair and relative vitality. It can offer a rationale and experiment data to relieve UV light-induced skin disease.

Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors

PubMed Central

Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

2015-01-01

For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection. PMID:26413188

Formation of iodo-trihalomethanes (I-THMs) during disinfection with chlorine or chloramine: Impact of UV/H2O2 pre-oxidation.

PubMed

Zhang, Jie; Liu, Jing; He, Chuan-Shu; Qian, Chen; Mu, Yang

2018-06-04

Ultraviolet/hydrogen peroxide (UV/H 2 O 2 ) pre-oxidation has the potential to induce reactions with dissolved organic matter (DOM) and alter the generation of disinfection byproducts (DBPs). This study evaluated the influence of UV/H 2 O 2 pretreatment on the formation of iodo-trihalomethanes (I-THMs) during disinfection with chlorine or chloramine. The changes of precursors, I - and Br - , after UV/H 2 O 2 pretreatment were investigated, and then, the formation and speciation of I-THMs during chlorination or chloramination after pre-oxidation were explored. Additionally, the effects of UV doses and H 2 O 2 concentrations on the formation and speciation of I-THMs were studied. It was found that UV/H 2 O 2 pretreatment could change larger molecular weight (MW) DOM to smaller MW species, which had less aromatic organic compounds and fluorescence substances. Additionally, insignificant transformations of I - and Br - were observed after UV/H 2 O 2 treatment. Compared to direct disinfection, UV/H 2 O 2 pretreatment resulted in 23.0 ± 3.5% reduction in I-THMs formation during post-chlorination while an enhancement was observed during post-chloramination at a UV dose of 460 mJ/cm 2 and 20 mg/L H 2 O 2 . Moreover, total I-THM concentration increased from 43.7 ± 2.4 to 97.6 ± 14.9 nM with the increase of UV doses from 0 to 1400 mJ/cm 2 during the post-chlorination process, while reduced when the UV fluence was >460 mJ/cm 2 during the post-chloramination. Additionally, the generation of I-THMs during both post-chlorination and post-chloramination was positively related to the H 2 O 2 levels from 0 to 20 mg/L in the UV/H 2 O 2 pretreatment. Copyright © 2018 Elsevier B.V. All rights reserved.

A new tridentate Schiff base Cu(II) complex: synthesis, experimental and theoretical studies on its crystal structure, FT-IR and UV-Visible spectra.

PubMed

Saheb, Vahid; Sheikhshoaie, Iran; Setoodeh, Nasim; Rudbari, Hadi Amiri; Bruno, Giuseppe

2013-06-01

A new Cu(II) complex [Cu(L)(NCS)] has been synthesized, using 1-(N-salicylideneimino)-2-(N,N-methyl)-aminoethane as tridentate ONN donor Schiff base ligand (HL). The dark green crystals of the compound are used for single-crystal X-ray analysis and measuring Fourier Transform Infrared (FT-IR) and UV-Visible spectra. Electronic structure calculations at the B3LYP and MP2 levels of theory are performed to optimize the molecular geometry and to calculate the UV-Visible and FT-IR spectra of the compound. Vibrational assignments and analysis of the fundamental modes of the compound are performed. Time-dependent density functional theory (TD-DFT) method is used to calculate the electronic transitions of the complex. A scaling factor of 1.015 is obtained for vibrational frequencies computed at the B3LYP level using basis sets 6-311G(d,p). It is found that solvent has a profound effect on the electronic absorption spectrum. The UV-Visible spectrum of the complex recorded in DMSO and DMF solution can be correctly predicted by a model in which DMSO and DMF molecules are coordinated to the central Cu atom via their oxygen atoms. Copyright © 2013 Elsevier B.V. All rights reserved.

Efficiency of ocular UV protection by clear lenses

PubMed Central

Rifai, Katharina; Hornauer, Matthias; Buechinger, Ramona; Schoen, Roland; Barraza-Bernal, Maria; Habtegiorgis, Selam; Glasenapp, Carsten; Wahl, Siegfried; Mappes, Timo

2018-01-01

Ocular UV doses accumulate all-day, not only during periods of direct sun exposure. The UV protection efficiency of three clear lenses was evaluated experimentally, validated by simulation, and compared to non-UV protection: a first spectacle lens with a tailored UV absorber, a second spectacle lens, minimizing UV back reflections, as well as a third spectacle lens, combining both. A tailored UV-absorber efficiently reduced overall UV irradiance to 7 %, whereas reduction of back-reflections still left UV irradiance at 42 %. Thus, clear lenses with a tailored UV absorber efficiently protect the eye from UV, supplementing sun glasses wear to an all-day protection scenario. PMID:29675331

Efficiency of ocular UV protection by clear lenses.

PubMed

Rifai, Katharina; Hornauer, Matthias; Buechinger, Ramona; Schoen, Roland; Barraza-Bernal, Maria; Habtegiorgis, Selam; Glasenapp, Carsten; Wahl, Siegfried; Mappes, Timo

2018-04-01

Ocular UV doses accumulate all-day, not only during periods of direct sun exposure. The UV protection efficiency of three clear lenses was evaluated experimentally, validated by simulation, and compared to non-UV protection: a first spectacle lens with a tailored UV absorber, a second spectacle lens, minimizing UV back reflections, as well as a third spectacle lens, combining both. A tailored UV-absorber efficiently reduced overall UV irradiance to 7 %, whereas reduction of back-reflections still left UV irradiance at 42 %. Thus, clear lenses with a tailored UV absorber efficiently protect the eye from UV, supplementing sun glasses wear to an all-day protection scenario.

Efficacy of oral moxidectin against susceptible and resistant isolates of Dirofilaria immitis in dogs.

PubMed

McTier, Tom L; Six, Robert H; Pullins, Aleah; Chapin, Sara; McCall, John W; Rugg, Douglas; Maeder, Steven J; Woods, Debra J

2017-11-09

Monthly topical and sustained-release injectable formulations of moxidectin are currently marketed; however, an oral formulation, while approved at a dose of 3 μg/kg, is not currently marketed in the United States. Although resistance of heartworms to all macrocyclic lactone (ML) heartworm preventives (ivermectin, milbemycin, selamectin and moxidectin) has been demonstrated, to date no data have been reported on the effectiveness of oral moxidectin against recent isolates of Dirofilaria immitis. A total of nine studies were conducted to determine the efficacy of moxidectin against a range of older and recently sourced heartworm isolates. Dogs (groups of three to eight) were inoculated with 50 D. immitis infective larvae (L3) from nine different isolates (MP3, Michigan, JYD-34, ZoeMO-2012, ZoeKy-2013, ZoeLA-2013, GCFL-2014, AMAL-2014 and ZoeAL-2015) and treated 28-30 days later with single oral doses of 3 μg/kg of moxidectin. Additionally, one group of dogs that was inoculated with JYD-34 was treated monthly for 3 consecutive months beginning 30 days post inoculation. Dogs were held for approximately 4 months after the initial (or only) treatment and then necropsied for recovery of adult heartworms. A single dose of 3 μg/kg of moxidectin was 100% effective in preventing the development of five of nine heartworm isolates (MP3, Michigan, ZoeKy, GCFL and ZoeAL isolates), confirming their susceptibility to oral moxidectin at this dose. MP3 and Michigan are isolates sourced from the field more than 9 years ago, while ZoeKy, ZoeAL and GCFL were isolated from the field within the past 2 to 3 years. Against JYD-34, ZoeMO, ZoeLA and AMAL isolates, a single dose of 3 μg/kg of moxidectin was not completely effective, with efficacies of 19%, 82%, 54% and 62%, respectively, demonstrating resistance of these heartworm isolates to oral moxidectin at this dosage. Three consecutive monthly doses of 3 μg/kg of moxidectin were also incompletely effective against the JYD-34 isolate, with an efficacy of 44%. JYD-34 was originally isolated in 2010, while ZoeMO, ZoeLA and AMAL were isolated within the past 2 to 3 years. A single oral dose (3 μg/mg) of moxidectin was 100% effective in preventing the development of ML-susceptible heartworm isolates while being incompletely effective against ML-resistant isolates.

Distinct physiological and metabolic reprogramming by highbush blueberry (Vaccinium corymbosum) cultivars revealed during long-term UV-B radiation.

PubMed

Luengo Escobar, Ana; Alberdi, Miren; Acevedo, Patricio; Machado, Mariana; Nunes-Nesi, Adriano; Inostroza-Blancheteau, Claudio; Reyes-Díaz, Marjorie

2017-05-01

Despite the Montreal protocol and the eventual recovery of the ozone layer over Antarctica, there are still concerns about increased levels of ultraviolet-B (UV-B) radiation in the Southern Hemisphere. UV-B induces physiological, biochemical and morphological stress responses in plants, which are species-specific and different even for closely related cultivars. In woody plant species, understanding of long-term mechanisms to cope with UV-B-induced stress is limited. Therefore, a greenhouse UV-B daily course simulation was performed for 21 days with two blueberry cultivars (Legacy and Bluegold) under UV-B BE irradiance doses of 0, 0.07 and 0.19 W m -2 . Morphological changes, photosynthetic performance, antioxidants, lipid peroxidation and metabolic features were evaluated. We found that both cultivars behaved differently under UV-B exposure, with Legacy being a UV-B-resistant cultivar. Interestingly, Legacy used a combined strategy: initially, in the first week of exposure its photoprotective compounds increased, coping with the intake of UV-B radiation (avoidance strategy), and then, increasing its antioxidant capacity. These strategies proved to be UV-B radiation dose dependent. The avoidance strategy is triggered early under high UV-B radiation in Legacy. Moreover, the rapid metabolic reprogramming capacity of this cultivar, in contrast to Bluegold, seems to be the most relevant contribution to its UV-B stress-coping strategy. © 2016 Scandinavian Plant Physiology Society.

ENVIRONMENTAL TECHNOLOGY VERIFICATION: JOINT (NSF-EPA) VERIFICATION STATEMENT AND REPORT; UV DISINFECTION FOR REUSE APPLICATION, AQUIONICS, INC. BERSONINLINE 4250 UV SYSTEM

EPA Science Inventory

Verification testing of the Aquionics, Inc. bersonInLine® 4250 UV System to develop the UV delivered dose flow relationship was conducted at the Parsippany-Troy Hills Wastewater Treatment Plant test site in Parsippany, New Jersey. Two full-scale reactors were mounted in series. T...

The Impact of UV-dose, Body Surface Area Exposed and Other Factors on Cutaneous Vitamin D Synthesis Measured as Serum 25(OH)D Concentration: Systematic Review and Meta-analysis.

PubMed

Jager, Nadine; Schöpe, Jakob; Wagenpfeil, Stefan; Bocionek, Peter; Saternus, Roman; Vogt, Thomas; Reichrath, Jörg

2018-02-01

To optimize public health campaigns concerning UV exposure, it is important to characterize factors that influence UV-induced cutaneous vitamin D production. This systematic review and meta-analysis investigated the impact of different individual and environmental factors including exposed body surface area (BSA), UVB dose and vitamin D status, on serum 25(OH)D concentration. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses, and Meta-analysis of Observational studies in Epidemiology guidelines, a systematic literature search was conducted (MEDLINE; 01/1960-07/2016) investigating the impact of these factors on vitamin D status after artificial UV exposure as main outcome measure. Summary mean differences [and 95% confidence interval (CI)] were derived from random-effects meta-analysis to account for possible heterogeneity across studies. Meta-regression was conducted to account for impact of UVB dose, baseline 25(OH)D level and BSA. We identified 15 studies, with an estimated mean 25(OH)D rise per standard erythema dose (SED) of 0.19 nmol/l (95% CI 0.11-0.26 nmol/l). Results from meta-regression suggest a significant impact of UV dose and baseline 25(OH)D concentration on serum 25(OH)D level (p<0.01). Single UVB doses between 0.75 and 3 SED resulted in the highest rise of serum 25(OH)D per dose unit. BSA exposed had a smaller, non-proportional, not significant impact. Partial BSA exposure resulted in relatively higher rise compared to whole-body exposure (e.g. exposure of face and hands caused an 8-fold higher rise of serum 25(OH)D concentration/SED/1% BSA compared to whole-body exposure). Our findings support previous reports, estimating that the half-life of serum 25(OH)D varies depending on different factors. Our results indicate that partial BSA exposure (e.g. 10%) with moderate UV doses (e.g. 1 SED) is effective in generating or maintaining a healthy vitamin D status. However, due to limitations that include possible confounding factors such as skin type, which could not be considered, these findings should be interpreted with caution. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry.

PubMed

Moriyama, Takaya; Yang, Yung-Li; Nishii, Rina; Ariffin, Hany; Liu, Chengcheng; Lin, Ting-Nien; Yang, Wenjian; Lin, Dong-Tsamn; Yu, Chih-Hsiang; Kham, Shirley; Pui, Ching-Hon; Evans, William E; Jeha, Sima; Relling, Mary V; Yeoh, Allen Eng-Juh; Yang, Jun J

2017-09-07

Prolonged exposure to thiopurines (eg, mercaptopurine [MP]) is essential for curative therapy in acute lymphoblastic leukemia (ALL), but is also associated with frequent dose-limiting hematopoietic toxicities, which is partly explained by inherited genetic polymorphisms in drug metabolizing enzymes (eg, TPMT ). Recently, our group and others identified germ line genetic variants in NUDT15 as another major cause of thiopurine-related myelosuppression, particularly in Asian and Hispanic people. In this article, we describe 3 novel NUDT15 coding variants (p.R34T, p.K35E, and p.G17_V18del) in 5 children with ALL enrolled in frontline protocols in Singapore, Taiwan, and at St. Jude Children's Research Hospital. Patients carrying these variants experienced significant toxicity and reduced tolerance to MP across treatment protocols. Functionally, all 3 variants led to partial to complete loss of NUDT15 nucleotide diphosphatase activity and negatively influenced protein stability. In particular, the p.G17_V18del variant protein showed extremely low thermostability and was completely void of catalytic activity, thus likely to confer a high risk of thiopurine intolerance. This in-frame deletion was only seen in African and European patients, and is the first NUDT15 risk variant identified in non-Asian, non-Hispanic populations. In conclusion, we discovered 3 novel loss-of-function variants in NUDT15 associated with MP toxicity, enabling more comprehensive pharmacogenetics-based thiopurine dose adjustments across diverse populations. © 2017 by The American Society of Hematology.

Simulation study of natural UV-B radiation on Catla catla and its impact on physiology, oxidative stress, Hsp 70 and DNA fragmentation.

PubMed

Singh, Moirangthem Kameshwor; Sharma, Jai Gopal; Chakrabarti, Rina

2015-08-01

UV-B radiation is a potential stressor to the aquacultural species. Catla catla, catla larvae (1.08±0.065g) were exposed to different doses of UV-B radiation, 0 (control), 504, 1008, 1512 and 2016mJ/cm(2) at a mean radiant energy of 80μW/cm(2) for 21days. The dose of UV-B radiation was selected on the basis of the field study conducted in Lake Naini, Delhi, India (Latitude: 28°41'26″N and Longitude: 77°12″37″E). Significantly (P<0.05) lower survival, average weight and specific growth rate were found in UV-B irradiated larvae compared to the control one. Food conversion ratio was 1.5-4-fold higher in UV-B treated larvae compared to the control one. The carbonyl protein (CP), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) levels were significantly (P <0.05) higher in UV-B irradiated larvae compared to the control group. Among the treated larvae, CP and SOD were significantly (P <0.05) higher in larvae exposed at 1512mJ/cm(2) UV-B. A correlation was found between the CP and SOD (R(2)=0.834). Highest TBARS level was found in 2016mJ/cm(2) UV-B exposed catla. Nitric oxide synthase level was significantly (P <0.05) lower in UV-B exposed larvae compared to the control one. A 3-fold increased Hsp 70 level was recorded in UV-B irradiated catla compared to the control larvae. Comet assay analysis indicated that UV-B irradiation enhanced DNA fragmentation. Tail extent moment and the olive tail moment were significantly (P <0.05) higher in 2016mJ/cm(2) UV-B exposed catla compared to others. The tail length was significantly (P <0.05) higher in 1512 and 2016mJ/cm(2) UV-B exposed larvae compared to the other doses. The present study suggests that the catla is a useful species for the biomonitoring of stress in the aquatic environment. Copyright © 2015 Elsevier B.V. All rights reserved.

Mechanisms of ultraviolet disinfection and chlorination of Escherichia coli: Culturability, membrane permeability, metabolism, and genetic damage.

PubMed

Xu, Limei; Zhang, Chongmiao; Xu, Pengcheng; Wang, Xiaochang C

2018-03-01

Traditional culture methods may underestimate the tolerance of microorganisms to disinfectants because of the existence of viable but nonculturable or sublethally injured cells after disinfection. The selection of a strict method is crucial for the evaluation of disinfection performance. The actions of 2 typical disinfectants - ultraviolet (UV) and chlorine - on the fecal indicator Escherichia coli were investigated by the detection of culturability, membrane permeability, metabolic activity, deoxyribonucleic acid (DNA), and messenger ribonucleic acid (mRNA). During UV disinfection, the irreversible damages in the cell membrane and cellular adenosine triphosphate (ATP) were negligible at low UV doses (<80mJ/cm 2 ). However, membrane permeability was damaged at low doses of chlorine (<5mg/L), leading to leakage of cellular ATP. Our study showed that a slight lesion in DNA was detected even at high doses of UV (400mJ/cm 2 ) and chlorine (>5mg/L) treatments. The decay of mRNA was more rapid than that of DNA. The degradation level of mRNA depended on the choice of target genes. After exposure to 50mJ/cm 2 UV dose or 5mg/L chlorine for 30min, the DNA damage repair function (RecA mRNA) was inhibited. The mRNA involved in the DNA damage repair function can be a potential indicator of bacterial viability. Copyright © 2017. Published by Elsevier B.V.

Comparative studies on the lethal, mutagenic, and recombinogenic effects of ultraviolet -A, -B, -C, and visible light with and without 8-methoxypsoralen in Saccharomyces cerevisiae.

PubMed

Mondon, P; Shahin, M M

1992-05-01

Genetic effects of UV-A, UV-B, UV-C, and the combination of 8-methoxypsoralen (8-MOP) with UV-A or visible light were studied in the haploid strain XV185-14C and diploid strain D5 of Saccharomyces cerevisiae. The induction of his+, lys+, and hom+ reverse mutations was measured in strain XV185-14C. In strain D5 we measured the induction of genetically altered colonies, particularly twin spot colonies arising from a mitotic crossing-over. UV-C and UV-B induced point mutations at the three loci in the haploid strain and mitotic crossing-over and other genetic alterations in the diploid strain. UV-C was more mutagenic and recombinogenic than UV-B. UV-A or visible light alone did not induce genotoxic effects at the doses tested. However, UV-A plus 8-MOP produced lethal and mutagenic effects in the haploid strain XV185-14C, although mutagenic activity was less than that of UV-B. Visible light plus 8-MOP also induced genotoxic effects in strain XV185-14C. In the diploid strain D5, UV-A plus 8-MOP induced a higher frequency of genetic alterations than UV-B at comparative doses. Visible light plus 8-MOP was also genetically active in strain D5. The haploid strain was more sensitive to the lethal effects of UV-C, UV-B, UV-A, and impure visible light plus 8-MOP than the diploid strain.

Effect of UV irradiation on organic matter extracted from treated Ohio River water studied through the use of electrospray mass spectrometry.

PubMed

Magnuson, Matthew L; Kelty, Catherine A; Sharpless, Charles M; Linden, Karl G; Fromme, William; Metz, Deborah H; Kashinkunti, Ramesh

2002-12-01

Ohio River water was treated by settling, sand filtration, and granular activated carbon filtration. It was then irradiated by low-pressure (monochromatic) and medium-pressure (polychromatic) UV lamps to investigate the effects of UV irradiation on the extracted organic matter (EOM). When the EOM, collected by solid phase extraction cartridges, was analyzed by conventional UV spectroscopy and size exclusion chromatography (SEC), no significant changes in the EOM were revealed for various UV doses. Positive and negative electrospray ionization mass spectrometry (ESI-MS) of the EOM produced mass spectra that vary significantly with UV dose. The UV dosage conditions also appear to affect the reactivity of the EOM to subsequent chlorination. The magnitude of the spectral changes is generally greater for medium-pressure lamps than for low pressure and increases with UV exposure. Based on the observed MS peaks, the changes may be due to the presence of lignin, resulting perhaps from photooxidation and/or photo rearrangement of macromolecules in the sample. When chlorination is used for secondary disinfection, these results suggest that it may be important to consider the effects of UV irradiation on the organic matter in the water before applying UV disinfection technology to a particular source water.

A Phase II Randomized Placebo-Controlled Trial of Oral N-acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress In Vivo.

PubMed

Cassidy, Pamela B; Liu, Tong; Florell, Scott R; Honeggar, Matthew; Leachman, Sancy A; Boucher, Kenneth M; Grossman, Douglas

2017-01-01

Oxidative stress plays a role in UV-induced melanoma, which may arise from melanocytic nevi. We investigated whether oral administration of the antioxidant N-acetylcysteine (NAC) could protect nevi from oxidative stress in vivo in the setting of acute UV exposure. The minimal erythemal dose (MED) was determined for 100 patients at increased risk for melanoma. Patients were randomized to receive a single dose (1,200 mg) of NAC or placebo, in double-blind fashion, and then one nevus was irradiated (1-2 MED) using a solar simulator. One day later, the MED was redetermined and the irradiated nevus and a control unirradiated nevus were removed for histologic analysis and examination of biomarkers of NAC metabolism and UV-induced oxidative stress. Increased expression of 8-oxoguanine, thioredoxin reductase-1, and γ-glutamylcysteine synthase modifier subunit were consistently seen in UV-treated compared with unirradiated nevi. However, no significant differences were observed in these UV-induced changes or in the pre- and postintervention MED between those patients receiving NAC versus placebo. Similarly, no significant differences were observed in UV-induced changes between subjects with germline wild-type versus loss-of-function mutations in the melanocortin-1 receptor. Nevi showed similar changes of UV-induced oxidative stress in an open-label post-trial study in 10 patients who received NAC 3 hours before nevus irradiation. Thus, a single oral dose of NAC did not effectively protect nevi from UV-induced oxidative stress under the conditions examined. Cancer Prev Res; 10(1); 36-44. ©2016 AACR. ©2016 American Association for Cancer Research.

Seasonal and diurnal variations in Martian surface ultraviolet irradiation: biological and chemical implications for the Martian regolith

NASA Astrophysics Data System (ADS)

Patel, M. R.; Bérces, A.; Kolb, C.; Lammer, H.; Rettberg, P.; Zarnecki, J. C.; Selsis, F.

2003-01-01

The issue of the variation of the surface ultraviolet (UV) environment on Mars was investigated with particular emphasis being placed on the interpretation of data in a biological context. A UV model has been developed to yield the surface UV irradiance at any time and place over the Martian year. Seasonal and diurnal variations were calculated and dose rates evaluated. Biological interpretation of UV doses is performed through the calculation of DNA damage effects upon phage T7 and Uracil, used as examples for biological dosimeters. A solar UV "hotspot" was revealed towards perihelion in the southern hemisphere, with a significant damaging effect upon these species. Diurnal profiles of UV irradiance are also seen to vary markedly between aphelion and perihelion. The effect of UV dose is also discussed in terms of the chemical environment of the Martian regolith, since UV irradiance can reach high enough levels so as to have a significant effect upon the soil chemistry. We show, by assuming that H2O is the main source of hydrogen in the Martian atmosphere, that the stoichiometrically desirable ratio of 2:1 for atmospheric H and O loss rates to space are not maintained and at present the ratio is about 20:1. A large planetary oxygen surface sink is therefore necessary, in contrast with escape to space. This surface oxygen sink has important implications for the oxidation potential and the toxicology of the Martian soil. UV-induced adsorption of O_{2}^{-} super-radicals plays an important role in the oxidative environment of the Martian surface, and the biologically damaging areas found in this study are also shown to be regions of high subsurface oxidation. Furthermore, we briefly cover the astrobiological implications for landing sites that are planned for future Mars missions

Integrated oxide graphene based device for laser inactivation of pathogenic microorganisms

NASA Astrophysics Data System (ADS)

Grishkanich, Alexsandr; Ruzankina, Julia; Afanasyev, Mikhail; Paklinov, Nikita; Hafizov, Nail

2018-02-01

We develop device for virus disinfection of pathogenic microorganisms. Viral decontamination can be carried out due to hard ultraviolet irradiation and singlet oxygen destroying the genetic material of a virus capsid. UV rays can destroy DNA, leading to the formation of dimers of nucleic acids. This practically does not occur in tissues, tk. UV rays penetrate badly through them, however, the viral particles are small and UV can destroy their genetic material, RNA / DNA and the virus can not replicate. It is with the construction of the ultraviolet laser water disinfection system (UFLOV) based on the continuous and periodic pulsed ultraviolet laser sources (pump) binds to solve sterility and depyrogenation of water. It has been established that small doses of UV irradiation stimulate reproduction, and large doses cause the death of pathogenic microorganisms. The effect of a dose of ultraviolet is the result of photochemical action on the substance of a living bacterial cell or virion. Also complex photodynamic laser inactivation on graphene oxide is realized.

Effects of Increasing Doses of UV-B on Main Phenolic Acids Content, Antioxidant Activity and Estimated Biomass in Lavandin (Lavandula x intermedia).

PubMed

Usano-Alemany, Jaime; Panjai, Lachinee

2015-07-01

Lavandin is a well-known aromatic plant cultivated mainly for its valuable essential oil. Nonetheless, little attention has been paid so far to the quantification of other natural products such as polyphenols. Accordingly, we examined the effect of increasing doses of UV-B radiation on the main phenolic content, antioxidant activity and estimated biomass of one year old lavandin pots compared with pots grown outdoors. Significantly higher total phenolic content and concentration of main polyphenols have been found in outdoor plants. Rosmarinic acid has been described as the major phenolic compound in methanolic extracts (max. 25.9 ± 9.7 mg/g(-1) DW). Furthermore, we found that increasing doses of UV-B promote the plant growth of this species as well as the accumulation of phenolic compounds although with less antioxidant capacity in scavenging DPPH radicals. On the other hand, our results showed a remarkable variability among individual plants regarding the content of major phenolic acids. The application of UV-B doses during plant growth could be a method to promote biomass in this species along with the promotion of higher content of valuable secondary metabolites.

A proposal for in vitro/GFR molecular erythema action spectrum

NASA Astrophysics Data System (ADS)

de Souza, João A. V.; Lorenzini, Fabiane; Rizzatti, Mara R.

2008-08-01

We propose an erythema action spectrum based on experimental molecular measurements named molecular erythema action spectrum or in vitro/GFR, where the acronym GFR represents our research group name, Grupo de Física das Radiaçöes. The in vitro methodology was developed by using a derma tissue simulator (TSD), as a radiation protection shield, and monochromatic ultraviolet (UV) sources of 254, 310, 365, 380, and 400 nm. The irradiance from each source was monitored through spectroradiometry in order to obtain the exposure dose over a period of time. Changes in the chemical structure were monitored by Fourier transform infrared spectroscopy (FTIR) and UV and visible spectroscopy (UV-vis). The samples were analyzed by UV-vis at each 200 up to 1000 J/m2 and at each 400 up to 2000 J/m2. FTIR was performed only for samples exposed to a maximum dose of 2000 J/m2. The in vitro action parameters were obtained by considering the redshift revealed through UV-vis analysis, as being the molecular quantification of minimal erythema, and the chemical bond rupture of TSD molecules associated with erythema, revealed through FTIR. The in vitro/GFR action spectrum shows that UV-A and UV-B radiation are equally responsible for the damage observed in TSD. When this proposal was compared to the CIE erythema action spectrum from ISO [ISO17166 CIE S 007/E, Erythema Reference Action Spectrum and Standard Erythema Dose (CIE Central Bureau, Austria, 1998)], similarities could be observed in wavelengths less than 280 nm in UV-B region. However, for wavelengths higher than 300 nm, the efficiency of this radiation to induce damage, mainly in the UV-A part, was much higher than predicted in CIE model. The increasing concern on UV-A radiation, assumed to be as responsible as UV-B for inducing most of the already observed skin injuries, may be better understood when observing the experimental model presented in in vitro/GFR action spectrum.

Vibrational spectroscopic studies of Isoleucine by quantum chemical calculations.

PubMed

Moorthi, P P; Gunasekaran, S; Ramkumaar, G R

2014-04-24

In this work, we reported a combined experimental and theoretical study on molecular structure, vibrational spectra and NBO analysis of Isoleucine (2-Amino-3-methylpentanoic acid). The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments, thermodynamics properties, NBO analyses, NMR chemical shifts and ultraviolet-visible spectral interpretation of Isoleucine have been studied by performing MP2 and DFT/cc-pVDZ level of theory. The FTIR, FT-Raman spectra were recorded in the region 4000-400 cm(-1) and 3500-50 cm(-1) respectively. The UV-visible absorption spectra of the compound were recorded in the range of 200-800 nm. Computational calculations at MP2 and B3LYP level with basis set of cc-pVDZ is employed in complete assignments of Isoleucine molecule on the basis of the potential energy distribution (PED) of the vibrational modes, calculated using VEDA-4 program. The calculated wavenumbers are compared with the experimental values. The difference between the observed and calculated wavenumber values of most of the fundamentals is very small. (13)C and (1)H nuclear magnetic resonance chemical shifts of the molecule were calculated using the gauge independent atomic orbital (GIAO) method and compared with experimental results. The formation of hydrogen bond was investigated in terms of the charge density by the NBO calculations. Based on the UV spectra and TD-DFT calculations, the electronic structure and the assignments of the absorption bands were carried out. Besides, molecular electrostatic potential (MEP) were investigated using theoretical calculations. Copyright © 2014 Elsevier B.V. All rights reserved.

Improved survival in severe paraquat poisoning with repeated pulse therapy of cyclophosphamide and steroids.

PubMed

Lin, Ja-Liang; Lin-Tan, Dan-Tzu; Chen, Kuan-Hsing; Huang, Wen-Hung; Hsu, Ching-Wei; Hsu, Hsiang-Hao; Yen, Tzung-Hai

2011-06-01

To clarify the efficacy of repeated methylprednisolone (MP) and cyclophosphamide (CP) pulse therapy and daily dexamethasone (DEX) therapy in patients with severe paraquat (PQ) poisoning. A total of 111 patients with severe PQ poisoning and dark-blue color in urine tests within 24 h of intoxication were included prospectively. The control group consisted of 52 patients who were admitted between 1998 and 2001 and who received high doses of CP (2 mg/kg per day) and DEX (5 mg every 6 h) for 14 days. The study group consisted of 59 patients who were admitted from 2002 to 2007 and who received initial MP (1 g) for 3 days and CP (15 mg/kg per day) for 2 days, followed by DEX (5 mg every 6 h) until a PaO(2) of >80 mmHg had been achieved, or treated with repeated 1 g MP for 3 days and 1 g CP for 1 day if the PaO(2) was <60 mmHg. There were no differences between the two groups with regard to baseline data and plasma PQ levels. The study group patients had a lower mortality rate (39/59, 66%) than the control group patients (48/52, 92%; P=0.003, log-rank test). Multivariate Cox regression analysis revealed that the repeated pulse therapy was correlated with decreased hazard ratios (HR) for all-cause mortality (HR=0.50, 95% CI 0.31-0.80; P=0.004) and death from lung fibrosis-related hypoxemia (HR=0.10, 95% CI 0.04-0.25; P<0.001) in severely PQ-intoxicated patients. Repeated pulses of CP and MP, rather than high doses of CP and DEX, may result in a lower mortality rate in patients with severe PQ poisoning. © Copyright jointly held by Springer and ESICM 2011

Synthesis of Deoxyribonucleic Acid After Ultraviolet Irradiation of Sensitive and Resistant Haemophilus influenzae

PubMed Central

Modak, Sohan P.; Setlow, Jane K.

1969-01-01

Synthesis of deoxyribonucleic acid (DNA) has been measured as a function of ultraviolet (UV) radiation dose in wild-type and seven UV-sensitive strains of Haemophilus influenzae. At the UV doses used, all strains were able to resume DNA synthesis, even those which are unable to excise pyrimidine dimers from their DNA. These excisionless strains showed longer UV-induced delays in DNA synthesis than all but one of the other strains. The longest delay was shown by DB117, a strain which can excise dimers but which is recombination deficient and unable to rejoin X ray-induced single-strand breaks. All strains showed a progressive decrease in sensitivity as they approached the stationary phase. PMID:5305934

Conjugation of (E)-5-[2-(Methoxycarbonyl)ethenyl]cytidine to hydrophilic microspheres: development of a mobile microscale UV light actinometer.

PubMed

Fang, Shiyue; Guan, Yousheng; Blatchley, Ernest R; Shen, Chengyue; Bergstrom, Donald E

2008-03-01

( E)-5-[2-(Methoxycarbonyl)ethenyl]cytidine was biotinylated through a diisopropylsilylacetal linkage and attached to the surface of hydrophilic streptavidin-coated microspheres through the high-affinity noncovalent interaction between biotin and streptavidin. The functionalized microspheres form a stable suspension in water. Upon UV irradiation, the nonfluorescent ( E)-5-[2-(methoxycarbonyl)ethenyl]cytidine on the microspheres undergoes photocyclization to produce highly fluorescent 3-beta-D-ribofuranosyl-2,7-dioxopyrido[2,3-d]pyrimidine. The fluorescence intensity of the microspheres can be correlated to the particle-specific UV doses applied at different suspension concentrations. The microspheres allow one to measure the UV dose (fluence) distribution in high-throughput water disinfection systems.

SU-C-201-05: Silicon Array Dosimeter in Situ with Electronic Portal Image Device for Simultaneous Transit Dose and Image Verification in Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deshpande, S; Alhujaili, S; Vial, P

Purpose: To investigate an Electronic Portal Imaging Device (EPID) coupled to a 2D array dosimeter to provide simultaneous imaging and dose verification. Methods: The novel dual detector configuration comprised of a 2D diode array dosimeter, referred to as a Magic Plate (MP) placed directly on a standard EPID. Dose response of the MP was evaluated by measuring the detector’s response with respect to off-axis position and field size with 30 cm of solid water (SW) acting as a transit object in the beam. Measurements were performed with 3, 5, 10 and 15 mm SW build-up and compared to 2D ionisationmore » chamber array (ICA) measurements and the PinnacleTM treatment planning system (TPS) at a source to detector distance of 150 cm with a 6 MV beam. Clinical dosimetric performance was evaluated by measuring a number of intensity-modulated radiation therapy (IMRT) beams in transit geometry. Imaging performance of the EPID was quantified by measuring the contrast-to-noise ratio (CNR) and spatial resolution. Images of a Rando phantom were used for qualitative assessment. Results: Measured MP off-axis and field size response agreed within 2% of TPS and ICA responses when measured using 15 mm SW build-up. Clinical IMRT beams had gamma pass rates of ≥95% at 3%/3mm criteria. Measured CNR and spatial resolution (f50) were 264.96, 210.6, and 0.41, 0.40 with build-up of 5 and 15 mm respectively for the dual detector configuration. CNR and spatial resolution of 643.9 and 0.41 were measured for standard EPID. CNR was quantitatively worse in the dual detector configuration. Differences in imaging performance were not visible in a qualitative assessment using a Rando phantom. Conclusion: Combining a prototype MP 2D dosimeter with a conventional EPID did not significantly detract from the performance of either device and has the potential for simultaneous on-line patient transit dosimetry and image assessment in radiation therapy. Cancer Institute NSW Australia(Research Equipment Grant 10/REG/1-20) and Cancer Council NSW (Grant ID RG 1-06)« less

Comparison of ultraviolet light-emitting diodes and low-pressure mercury-arc lamps for disinfection of water.

PubMed

Sholtes, Kari A; Lowe, Kincaid; Walters, Glenn W; Sobsey, Mark D; Linden, Karl G; Casanova, Lisa M

2016-09-01

Ultraviolet (UV) light-emitting diodes (LEDs) emitting at 260 nm were evaluated to determine the inactivation kinetics of bacteria, viruses, and spores compared to low-pressure (LP) UV irradiation. Test microbes were Escherichia coli B, a non-enveloped virus (MS-2), and a bacterial spore (Bacillus atrophaeus). For LP UV, 4-log10 reduction doses were: E. coli B, 6.5 mJ/cm(2); MS-2, 59.3 mJ/cm(2); and B. atrophaeus, 30.0 mJ/cm(2). For UV LEDs, the 4-log10 reduction doses were E. coli B, 6.2 mJ/cm(2); MS-2, 58 mJ/cm(2); and B. atrophaeus, 18.7 mJ/cm(2). Microbial inactivation kinetics of the two UV technologies were not significantly different for E. coli B and MS-2, but were different for B. atrophaeus spores. UV LEDs at 260 nm are at least as effective for inactivating microbes in water as conventional LP UV sources and should undergo further development in treatment systems to disinfect drinking water.

Influence of dimethyl dicarbonate on the resistance of Escherichia coli to a combined UV-Heat treatment in apple juice

PubMed Central

Gouma, Maria; Gayán, Elisa; Raso, Javier; Condón, Santiago; Álvarez, Ignacio

2015-01-01

Commercial apple juice inoculated with Escherichia coli was treated with UV-C, heat (55°C) and dimethyl dicarbonate – DMDC (25, 50, and 75 mg/L)-, applied separately and in combination, in order to investigate the possibility of synergistic lethal effects. The inactivation levels resulting from each treatment applied individually for a maximum treatment time of 3.58 min were limited, reaching 1.2, 2.9, and 0.06 log10 reductions for UV, heat, and DMDC (75 mg/L), respectively. However, all the investigated combinations resulted in a synergistic lethal effect, reducing the total treatment time and UV dose, with the synergistic lethal effect being higher when larger concentrations of DMDC were added to the apple juice. The addition of 75 mg/L of DMDC prior to the combined UV-C light treatment at 55°C resulted in 5 log10 reductions after only 1.8 min, reducing the treatment time and UV dose of the combined UV-Heat treatment by 44%. PMID:26042117

Removal of Emerging Contaminants and Estrogenic Activity from Wastewater Treatment Plant Effluent with UV/Chlorine and UV/H2O2 Advanced Oxidation Treatment at Pilot Scale

PubMed Central

Kuch, Bertram; Lange, Claudia; Richter, Philipp; Kugele, Amélie; Minke, Ralf

2018-01-01

Effluent of a municipal wastewater treatment plant (WWTP) was treated on-site with the UV/chlorine (UV/HOCl) advanced oxidation process (AOP) using a pilot plant equipped with a medium pressure UV lamp with an adjustable performance of up to 1 kW. Results obtained from parallel experiments with the same pilot plant, where the state of the art UV/H2O2 AOP was applied, were compared regarding the removal of emerging contaminants (EC) and the formation of adsorbable organohalogens (AOX). Furthermore, the total estrogenic activity was measured in samples treated with the UV/chlorine AOP. At an energy consumption of 0.4 kWh/m3 (0.4 kW, 1 m3/h) and in a range of oxidant concentrations from 1 to 6 mg/L, the UV/chlorine AOP had a significantly higher EC removal yield than the UV/H2O2 AOP. With free available chlorine concentrations (FAC) in the UV chamber influent of at least 5 mg/L (11 mg/L of dosed Cl2), the total estrogenic activity could be reduced by at least 97%. To achieve a certain concentration of FAC in the UV chamber influent, double to triple the amount of dosed Cl2 was needed, resulting in AOX concentrations of up to 520 µg/L. PMID:29735959

Removal of Emerging Contaminants and Estrogenic Activity from Wastewater Treatment Plant Effluent with UV/Chlorine and UV/H₂O₂ Advanced Oxidation Treatment at Pilot Scale.

PubMed

Rott, Eduard; Kuch, Bertram; Lange, Claudia; Richter, Philipp; Kugele, Amélie; Minke, Ralf

2018-05-07

Effluent of a municipal wastewater treatment plant (WWTP) was treated on-site with the UV/chlorine (UV/HOCl) advanced oxidation process (AOP) using a pilot plant equipped with a medium pressure UV lamp with an adjustable performance of up to 1 kW. Results obtained from parallel experiments with the same pilot plant, where the state of the art UV/H₂O₂ AOP was applied, were compared regarding the removal of emerging contaminants (EC) and the formation of adsorbable organohalogens (AOX). Furthermore, the total estrogenic activity was measured in samples treated with the UV/chlorine AOP. At an energy consumption of 0.4 kWh/m³ (0.4 kW, 1 m³/h) and in a range of oxidant concentrations from 1 to 6 mg/L, the UV/chlorine AOP had a significantly higher EC removal yield than the UV/H₂O₂ AOP. With free available chlorine concentrations (FAC) in the UV chamber influent of at least 5 mg/L (11 mg/L of dosed Cl₂), the total estrogenic activity could be reduced by at least 97%. To achieve a certain concentration of FAC in the UV chamber influent, double to triple the amount of dosed Cl₂ was needed, resulting in AOX concentrations of up to 520 µg/L.

The effects of different UV-B radiation intensities on morphological and biochemical characteristics in Ocimum basilicum L.

PubMed

Sakalauskaitė, Jurga; Viskelis, Pranas; Dambrauskienė, Edita; Sakalauskienė, Sandra; Samuolienė, Giedrė; Brazaitytė, Aušra; Duchovskis, Pavelas; Urbonavičienė, Dalia

2013-04-01

The effects of short-term ultraviolet B (UV-B) irradiation on sweet basil (Ocimum basilicum L. cv. Cinnamon) plants at the 3-4 leaf pair and flowering stages were examined in controlled environment growth chambers. Plants were exposed to 0 (reference), 2 and 4 kJ UV-B m(-2) day(-1) over 7 days. Exposure of basil plants to supplementary UV-B light resulted in increased assimilating leaf area, fresh biomass and dry biomass. Stimulation of physiological functions in young basil plants under either applied UV-B dose resulted in increased total chlorophyll content but no marked variation in carotenoid content. At the flowering stage the chlorophyll and carotenoid contents of basil were affected by supplementary UV-B radiation, decreasing with enhanced UV-B exposure. Both total antioxidant activity (2,2-diphenyl-1-picrylhydrazyl free radical assay) and total phenolic compound content were increased by UV-B light supplementation. Young and mature basil plants differed in their ascorbic acid content, which was dependent on UV-B dose and plant age. UV-B radiation resulted in decreased nitrate content in young basil plants (3-4 leaf pair stage). These results indicate that the application of short-exposure UV-B radiation beneficially influenced both growth parameters and biochemical constituents in young and mature basil plants. © 2012 Society of Chemical Industry.

Inactivation kinetics of foodborne pathogens by UV-C radiation and its subsequent growth in fresh-cut kailan-hybrid broccoli.

PubMed

Martínez-Hernández, Ginés Benito; Huertas, Juan-Pablo; Navarro-Rico, Javier; Gómez, Perla A; Artés, Francisco; Palop, Alfredo; Artés-Hernández, Francisco

2015-04-01

The inactivation of Escherichia coli, S. Enteritidis and Listeria monocytogenes after UV-C radiation with 0, 2.5, 5, 7.5, 10 and 15 kJ UV-C m(-2) on fresh-cut kailan-hybrid broccoli was explored. Inactivation did not follow linear kinetics. Hence, it was modelled by using the Weibull distribution function, obtaining adjusted R(2) values higher than 94%, indicative of the accuracy of the model to the experimental data. The UV-C doses needed to reduce 1 log cycle the E. coli, S. Enteritidis and L. monocytogenes counts were 1.07, 0.02 and 9.26 kJ m(-2), respectively, being S. Enteritidis the most sensitive microorganism to UV-C radiation while L. monocytogenes was the most resistant. According to experimental data, UV-C doses higher than 2.5 kJ m(-2) did not achieve great microbial reductions. No differences in the growth behaviour of these microorganisms was observed in the treated samples stored under air conditions at 5, 10 and 15 °C, compared to the control. Conclusively, low UV-C doses are effective to reduce E. coli, S. Enteritidis and L. monocytogenes populations in fresh-cut kailan-hybrid broccoli keeping such counts stable during shelf life at 5-10 °C. The current study provides inactivation models for these foodborne pathogens that can be used in microbial risk assessment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of UV/Ag-TiO2/O3 advanced oxidation on unicellular green alga Dunaliella salina: implications for removal of invasive species from ballast water.

PubMed

Wu, Donghai; You, Hong; Du, Jiaxuan; Chen, Chuan; Jin, Darui

2011-01-01

The UV/Ag-TiO2/O3 process was investigated for ballast water treatment using Dunaliella salina as an indicator. Inactivation curves were obtained, and the toxicity of effluent was determined. Compared with individual unit processes using ozone or UV/Ag-TiO2, the inactivation efficiency of D. salina by the combined UV/Ag-TiO2/O3 process was enhanced. The presence of ozone caused an immediate decrease in chlorophyll a (chl-a) concentration. Inactivation efficiency and ch1-a removal efficiency were positively correlated with ozone dose and ultraviolet intensity. The initial total residual oxidant (TRO) concentration of effluent increased with increasing ozone dose, and persistence of TRO resulted in an extended period of toxicity. The results suggest that UV/Ag-TiO2/O3 has potential for ballast water treatment.

Pilot-scale UV/H2O2 study for emerging organic contaminants decomposition.

PubMed

Chu, Xiaona; Xiao, Yan; Hu, Jiangyong; Quek, Elaine; Xie, Rongjin; Pang, Thomas; Xing, Yongjie

2016-03-01

Human behaviors including consumption of drugs and use of personal care products, climate change, increased international travel, and the advent of water reclamation for direct potable use have led to the introduction of significant amounts of emerging organic contaminants into the aqueous environment. In addition, the lower detection limits associated with improved scientific methods of chemical analysis have resulted in a recent increase in documented incidences of these contaminants which previously were not routinely monitored in water. Such contaminants may cause known or suspected adverse ecological and/or human health effects at very low concentrations. Conventional drinking water treatment processes may not effectively remove these organic contaminants. Advanced oxidation process (AOP) is a promising treatment process for the removal of most of these emerging organic contaminants, and has been accepted worldwide as a suitable treatment process. In this study, different groups of emerging contaminants were studied for decomposition efficiency using pilot-scale UV/H2O2 oxidation setup, including EDCs, PPCPs, taste and odor (T&O), and perfluorinated compounds. Results found that MP UV/H2O2 AOP was efficient in removing all the selected contaminants except perfluorinated compounds. Study of the kinetics of the process showed that both light absorption and quantum yield of each compound affected the decomposition performance. Analysis of water quality parameters of the treated water indicated that the outcome of both UV photolysis and UV/H2O2 processes can be affected by changes in the feed water quality.

The feasibility study and characterization of a two-dimensional diode array in "magic phantom" for high dose rate brachytherapy quality assurance.

PubMed

Espinoza, A; Beeksma, B; Petasecca, M; Fuduli, I; Porumb, C; Cutajar, D; Corde, S; Jackson, M; Lerch, M L F; Rosenfeld, A B

2013-11-01

High dose rate (HDR) brachytherapy is a radiation treatment technique capable of delivering large dose rates to the tumor. Radiation is delivered using remote afterloaders to drive highly active sources (commonly (192)Ir with an air KERMA strength range between 20,000 and 40,000 U, where 1 U = 1 μGy m(2)/h in air) through applicators directly into the patient's prescribed region of treatment. Due to the obvious ramifications of incorrect treatment while using such an active source, it is essential that there are methods for quality assurance (QA) that can directly and accurately verify the treatment plan and the functionality of the remote afterloader. This paper describes the feasibility study of a QA system for HDR brachytherapy using a phantom based two-dimensional 11 × 11 epitaxial diode array, named "magic phantom." The HDR brachytherapy treatment plan is translated to the phantom with two rows of 10 (20 in total) HDR source flexible catheters, arranged above and below the diode array "magic plate" (MP). Four-dimensional source tracking in each catheter is based upon a developed fast iterative algorithm, utilizing the response of the diodes in close proximity to the (192)Ir source, sampled at 100 ms intervals by a fast data acquisition (DAQ) system. Using a (192)Ir source in a solid water phantom, the angular response of the developed epitaxial diodes utilized in the MP and also the variation of the MP response as a function of the source-to-detector distance (SDD) were investigated. These response data are then used by an iterative algorithm for source dwelling position determination. A measurement of the average transit speed between dwell positions was performed using the diodes and a fast DAQ. The angular response of the epitaxial diode showed a variation of 15% within 360°, with two flat regions above and below the detector face with less than 5% variation. For SDD distances of between 5 and 30 mm the relative response of the epitaxial diodes used in the MP is in good agreement (within 8%) with radial dose function measurements found within the TG-43 protocol, with SDD of up to 70 mm showing a 40% over response. A method for four-dimensional localization of the HDR source was developed, allowing the source dwell position to be derived within 0.50 mm of the expected position. An estimation of the average transit speed for varying step sizes was determined and was found to increase from (12.8 ± 0.3) up to (38.6 ± 0.4) cm/s for a step size of 2.5 and 50 mm, respectively. Our characterization of the designed QA "magic phantom" with MP in realistic HDR photon fields demonstrates the promising performance for real-time source position tracking in four dimensions and measurements of transit times. Further development of this system will allow a full suite for QA in HDR brachytherapy and analysis, and for future in vivo tracking.

Steroids alter ion transport and absorptive capacity in proximal and distal colon.

PubMed

Sellin, J H; DeSoignie, R C

1985-07-01

Steroids are potent absorbagogues, increasing Na and fluid absorption in a variety of epithelia. This study characterizes the in vitro effects of pharmacological doses of gluco- and mineralocorticoids on transport parameters of rabbit proximal and distal colon. Treatment with methylprednisolone (MP, 40 mg im for 2 days) and desoxycortone acetate (DOCA, 12.5 mg im for 3 days) resulted in a significant increase in short-circuit current (Isc) in distal colon, suggesting an increase in basal Na absorption. Amiloride (10(-4) M) caused a significantly negative Isc in MP-treated tissue, demonstrating a steroid-induced, amiloride-insensitive electrogenic ion transport in distal colon. The effect of two absorbagogues, impermeant anions (SO4-Ringer) and amphotericin, were compared in control and steroid-treated distal colon. In controls, both absorbagogues increased Isc. Impermeant anions caused a rise in Isc in both MP and DOCA tissues, suggesting that the high rate of basal Na absorption had not caused a saturation of the Na pump. The steroid-treated colons, however, did not consistently respond to amphotericin. Amiloride inhibited the entire Isc in MP-treated distal colon that had been exposed to amphotericin; this suggested that amphotericin had not exerted its characteristic effect on the apical membrane of steroid-treated colon. In proximal colon, steroids did not alter basal rates of transport; however, epinephrine-induced Na-Cl absorption was significantly greater in MP-treated vs control (P less than 0.005). Steroids increase the absorptive capacity of both proximal and distal colon for Na, while increasing basal Na absorption only in the distal colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrieving atmospheric transmissivity for biologically active daily dose, in various european sites

NASA Astrophysics Data System (ADS)

de La Casinière, A.; Touré, M. L.; Lenoble, J.; Cabot, T.

2003-04-01

In the frame of the European Project EDUCE, global UV irradiance spectra recorded all along the year in several European sites are stored in a common database located in Finland. From the spectra set of some of these stations, are calculated atmospheric transmissivities for daily doses of four biologically active UV radiation, namely: UV-B, erythema, DNA damage, and plant damage. A transmissivity is defined as the ratio of the ground level value of the daily dose of interest to its corresponding extra-atmospheric value. Multiple linear correlation of the various transmissivities with three predictors (daily sunshine fraction, cosine of the daily minimum SZA, and daily total ozone column) assumed to be independent variables, are done for year 2000. The coefficients obtained from year 2000 correlation in a given site are expected to retrieve, from the local predictors, the daily dose for year 2001 in the same site, the average error being lesser than 10% for monthly mean values, and lesser than 5% for three-monthly mean values, depending on the daily dose type. Comparison of yearly mean daily doses retrieved in a given site from coefficients obtained in other sites is also presented.

Effect of androgen deprivation therapy on intraprostatic tumour volume identified on 18F choline PET/CT for prostate dose painting radiotherapy.

PubMed

Chan, Joachim; Carver, Antony; Brunt, John N H; Vinjamuri, Sobhan; Syndikus, Isabel

2017-03-01

Prostate dose painting radiotherapy requires the accurate identification of dominant intraprostatic lesions (DILs) to be used as boost volumes; these can be identified on multiparametric MRI (mpMRI) or choline positron emission tomography (PET)/CT. Planning scans are usually performed after 2-3 months of androgen deprivation therapy (ADT). We examine the effect of ADT on choline tracer uptake and boost volumes identified on choline PET/CT. Fluoroethylcholine ( 18 F choline) PET/CT was performed for dose painting radiotherapy planning in patients with intermediate- to high-risk prostate cancer. Initially, they were performed at planning. Owing to low visual tracer uptake, PET/CT for subsequent patients was performed at staging. We compared these two approaches on intraprostatic lesions obtained on PET using both visual and automatic threshold methods [prostate maximum standardized uptake value (SUV max ) 60%] when compared with mpMRI. PET/CT was performed during ADT in 11 patients (median duration of 85 days) and before ADT in 29 patients. ADT significantly reduced overall prostate volume by 17%. During ADT, prostate SUV max was lower although it did not reach statistical significance (4.2 vs 6.6, p = 0.06); three patients had no visually identifiable PET DIL; and visually defined PET DILs were significantly smaller than corresponding mpMRI DILs (p = 0.03). However, all patients scanned before ADT had at least one visually identifiable PET DIL, with no significant size difference between MRI and visually defined PET DILs. In both groups, threshold PET produced larger DILs than visual PET. Both PET methods have moderate sensitivity (0.50-0.68) and high specificity (0.85-0.98) for identifying MRI-defined disease. For visual contouring of boost volumes in prostate dose painting radiotherapy, 18 F choline PET/CT should be performed before ADT. For threshold contouring of boost volumes using our PET/CT scanning protocol, threshold levels of above 60% prostate SUV max may be more suitable. Additional use of PET with MRI for radiotherapy planning can significantly change the overall boost volumes compared with using MRI alone. Advances in knowledge: For prostate dose painting radiotherapy, the additional use of 18 F choline PET with MRI can significantly change the overall boost volumes, and PET should be performed before hormone therapy, especially if boost volumes are visually identified.

Median prior constrained TV algorithm for sparse view low-dose CT reconstruction.

PubMed

Liu, Yi; Shangguan, Hong; Zhang, Quan; Zhu, Hongqing; Shu, Huazhong; Gui, Zhiguo

2015-05-01

It is known that lowering the X-ray tube current (mAs) or tube voltage (kVp) and simultaneously reducing the total number of X-ray views (sparse view) is an effective means to achieve low-dose in computed tomography (CT) scan. However, the associated image quality by the conventional filtered back-projection (FBP) usually degrades due to the excessive quantum noise. Although sparse-view CT reconstruction algorithm via total variation (TV), in the scanning protocol of reducing X-ray tube current, has been demonstrated to be able to result in significant radiation dose reduction while maintain image quality, noticeable patchy artifacts still exist in reconstructed images. In this study, to address the problem of patchy artifacts, we proposed a median prior constrained TV regularization to retain the image quality by introducing an auxiliary vector m in register with the object. Specifically, the approximate action of m is to draw, in each iteration, an object voxel toward its own local median, aiming to improve low-dose image quality with sparse-view projection measurements. Subsequently, an alternating optimization algorithm is adopted to optimize the associative objective function. We refer to the median prior constrained TV regularization as "TV_MP" for simplicity. Experimental results on digital phantoms and clinical phantom demonstrated that the proposed TV_MP with appropriate control parameters can not only ensure a higher signal to noise ratio (SNR) of the reconstructed image, but also its resolution compared with the original TV method. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization and optical studies of 90/10 (wt/wt%) PVA/β-chitin blend irradiated with γ-rays.

PubMed

Abd El-Kader, F H; Gaafer, S A; Abd El-Kader, M F H

2014-10-15

X-ray diffraction, IR spectroscopy and UV/visible spectra were studied as a function of gamma irradiation doses (5-100kGy) for 90/10 (wt/wt%) PVA/β-chitin. A new intense reflection peak at 2θ=21.5° appeared in the X-ray spectrum of the sample irradiated at 50kGy γ-dose. Besides, the band centered at 2931cm(-1) in IR spectrum splits into two clearly separated bands around 2919 and 2941cm(-1) for the sample irradiated at 10kGy γ-dose. The disappearance of the absorption band at 280nm of PVA in the blend sample indicates that the ligand PVA becomes opaque in the UV region and provides evidence for the miscibility between homopolymers. The value of absorbance, in UV/visible range, at 10kGy γ-dose was the highest one compared to the other γ-doses. The location of the γ-doses on the chromaticity diagram was different, indicating the change in the spectral colors of the investigated blend. In addition, the absorption edge, band tail and color parameters values were determined as a function of γ-doses. Copyright © 2014 Elsevier B.V. All rights reserved.

Ultraviolet spectral distribution and erythema-weighted irradiance from indoor tanning devices compared with solar radiation exposures.

PubMed

Sola, Yolanda; Baeza, David; Gómez, Miguel; Lorente, Jerónimo

2016-08-01

Concern regarding the impact of indoor tanning devices on human health has led to different regulations and recommendations, which set limits on erythema-weighted irradiance. Here, we analyze spectral emissions from 52 tanning devices in Spanish facilities and compare them with surface solar irradiance for different solar zenith angles. Whereas most of the devices emitted less UV-B radiation than the midday summer sun, the unweighted UV-A irradiance was 2-6 times higher than solar radiation. Moreover, the spectral distributions of indoor devices were completely different from that of solar radiation, differing in one order of magnitude at some UV-A wavelengths, depending on the lamp characteristics. In 21% of the devices tested, the erythema-weighted irradiance exceeded 0.3Wm(-2): the limit fixed by the European standard and the Spanish regulation. Moreover, 29% of the devices fall within the UV type 4 classification, for which medical advice is required. The high variability in erythema-weighted irradiance results in a wide range of exposure times to reach 1 standard erythemal dose (SED: 100Jm(-2)), with 62% of devices requiring exposures of <10min to reach 1 SED. Nevertheless, the unweighted UV-A dose during this time period would be from 1.4 to 10.3 times more than the solar UV-A dose. Copyright © 2016 Elsevier B.V. All rights reserved.

[Oligonucleotide derivatives in the nucleic acid hybridization analysis. I. Covalent immobilization of oligonucleotide probes onto the nylon].

PubMed

Dmitrienko, E V; Pyshnaia, I A; Pyshnyĭ, D V

2010-01-01

The features of UV-induced immobilization of oligonucleotides on a nylon membranes and the effectiveness of enzymatic labeling of immobilized probes at heterophase detection of nucleic acids are studied. Short terminal oligothymidilate (up to 10 nt) sequences are suggested to attach to the probe via a flexible ethylene glycol based linker. The presence of such fragment enhances the intensity of immobilization and reduces UV-dependent degradation of the targeted (sequence-specific) part of the probe by reducing the dose needed for the immobilization of DNA. The optimum dose of UV-irradiation is determined to be ~0.4 J/cm(2) at the wavelength 254 nm. This dose provides high level of hybridization signal for immobilized probes with various nucleotide composition of the sequence specific moiety. The amide groups of the polyamide are shown to play the key role in the photoinduced immobilization of nucleic acids, whereas the primary amino groups in the structure of PA is not the center responsible for the covalent binding of DNA by UV-irradiation, as previously believed. Various additives in the soaking solution during the membrane of UV-dependent immobilization of probes are shown to influence its effectiveness. The use of alternative to UV-irradiation system of radical generation are shown to provide the immobilization of oligonucleotides onto the nylon membrane.

The effects of UV radiation during the vegetative period on antioxidant compounds and postharvest quality of broccoli (Brassica oleracea L.).

PubMed

Topcu, Yasin; Dogan, Adem; Kasimoglu, Zehra; Sahin-Nadeem, Hilal; Polat, Ersin; Erkan, Mustafa

2015-08-01

In this study, the effects of supplementary UV radiation during the vegetative period on antioxidant compounds, antioxidant activity and postharvest quality of broccoli heads during long term storage was studied. The broccolis were grown under three different doses of supplementary UV radiation (2.2, 8.8 and 16.4 kJ/m(2)/day) in a soilless system in a glasshouse. Harvested broccoli heads were stored at 0 °C in modified atmosphere packaging for 60 days. The supplementary UV radiation (280-315 nm) during the vegetative period significantly decreased total carotenoid, the chlorophyll a and chlorophyll b content but increased the ascorbic acid, total phenolic and flavonoid contents of broccolis. All supplementary UV treatments slightly reduced the antioxidant activity of the broccolis, however, no remarkable change was observed between 2.2 and 8.8 kJ/m(2) radiation levels. The sinigrin and glucotropaeolin contents of the broccolis were substantially increased by UV treatments. The prolonged storage period resulted in decreased ascorbic acid, total phenolic and flavonoid contents, as well as antioxidant activity. Discoloration of the heads, due to decreased chlorophyll and carotenoid contents, was also observed with prolonged storage duration. Glucosinolates levels showed an increasing tendency till the 45th day of storage, and then their levels started to decline. The weight loss of broccoli heads during storage progressively increased with storage time in all treatments. Total soluble solids, solids content and titratable acidity decreased continuously during storage. Titratable acidity was not affected by UV radiation doses during the storage time whereas soluble solids and solids content (dry matter) were significantly affected by UV doses. Supplementary UV radiation increased the lightness (L*) and chroma (C*) values of the broccoli heads. Pre-harvest UV radiation during vegetative period seems to be a promising tool for increasing the beneficial health components of broccolis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Ship-borne measurements of erythemal UV irradiance and ozone content in various climate zones.

PubMed

Wuttke, Sigrid; El Naggar, Saad; Bluszcz, Thaddäus; Schrems, Otto

2007-10-01

Ship-borne measurements of spectral as well as biologically effective UV irradiance have been performed on the German research vessel Polarstern during the Atlantic transect from Bremerhaven, Germany (53.5 degrees N, 8.5 degrees E), to Cape Town, South Africa (33.6 degrees S, 18.3 degrees E), from 13 October to 17 November 2005. Such measurements are required to study UV effects on marine organisms. They are also necessary to validate satellite-derived surface UV irradiance. Cloud free radiative transfer calculations support the investigation of this latitudinal dependence. Input parameters, such as total ozone column and aerosol optical depth have been measured on board as well. Using these measured parameters, the modelled cloudless noontime UVA irradiance (320-400 nm) shows the expected dependence on varying minimum solar zenith angles (SZA) at different latitudes. The modelled cloudless noontime UVB irradiance (290-320 nm) does not show this clear dependence on SZA due to the strong influence of ozone absorption in this spectral range. The maximum daily dose of erythemal irradiance of 5420 J m(-1) was observed on 14 November 2005, when the ship was in the tropical Atlantic south of the equator. The expected UV maximum should have been observed with the sun in the zenith during local noon (11 November). Stratiform clouds reduced the dose to 3835 J m(-1). In comparison, the daily erythemal doses in the mid-latitudinal Bay of Biscay only reached values between 410 and 980 J m(-1) depending on cloud conditions. The deviation in daily erythemal dose derived from different instruments is around 5%. The feasibility to perform ship-borne measurements of spectral UV irradiance is demonstrated.

Photoinduced Intramolecular Bifurcate Hydrogen Bond: Unusual Mutual Influence of the Components.

PubMed

Sigalov, Mark V; Shainyan, Bagrat A; Sterkhova, Irina V

2017-09-01

A series of 7-hydroxy-2-methylidene-2,3-dihydro-1H-inden-1-ones with 2-pyrrolyl (3), 4-dimethylaminophenyl (4), 4-nitrophenyl (5), and carboxyl group (6) as substituents at the exocyclic double bond was synthesized in the form of the E-isomers (4-6) or predominantly as the Z-isomer (3) which in solution is converted to the E-isomer. The synthesized compounds and their model analogues were studied by NMR spectroscopy, X-ray analysis, and MP2 theoretical calculations. The E-isomers having intramolecular O-H···O═C hydrogen bond are converted by UV irradiation to the Z-isomers having bifurcated O-H···O···H-X hydrogen bond. Unexpected shortening (and, thus, strengthening) of the O-H···O═C component of the bifurcated hydrogen bond upon the formation of the C═O···H-X hydrogen bond was found experimentally, proved theoretically (MP2), and explained by a roundabout interaction of the H-donor (HX) and H-acceptor (C═O) via the system of conjugated bonds.

Moisture migration, microstructure damage and protein structure changes in porcine longissimus muscle as influenced by multiple freeze-thaw cycles.

PubMed

Zhang, Mingcheng; Li, Fangfei; Diao, Xinping; Kong, Baohua; Xia, Xiufang

2017-11-01

This study investigated the effects of multiple freeze-thaw (F-T) cycles on water mobility, microstructure damage and protein structure changes in porcine longissimus muscle. The transverse relaxation time T 2 increased significantly when muscles were subjected to multiple F-T cycles (P<0.05), which means that immobile water shifted to free water and the free water mobility increased. Multiple F-T cycles caused sarcomere shortening, Z line fractures, and I band weakening and also led to microstructural destruction of muscle tissue. The decreased free amino group content and increased dityrosine in myofibrillar protein (MP) revealed that multiple F-T cycles caused protein cross-linking and oxidation. In addition, the results of size exclusion chromatography, circular dichroism spectra, UV absorption spectra, and intrinsic fluorescence spectroscopy indirectly proved that multiple F-T cycles could cause protein aggregation and degradation, α-helix structure disruption, hydrophobic domain exposure, and conformational changes of MP. Overall, repeated F-T cycles changed the protein structure and water distribution within meat. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biologically effective surface UV climatology at Rome and Aosta, Italy

NASA Astrophysics Data System (ADS)

Siani, Anna Maria; Modesti, Sarah; Casale, Giuseppe Rocco; Diemoz, Henri; Colosimo, Alfredo

2013-05-01

Given the beneficial and harmful effects of UV radiation on human health, our study aims to provide a characterization of erythemal and vitamin D dose rates at two Italian sites, Rome and Aosta, subject to quite different environmental conditions. Based on the respective UV climatologies, exposure times needed to induce erythema or vitamin D photoproduction are provided as a function of the UV index.

Magnetic Resonance Studies of Photosensitizers and Their Effect in Tumors

DTIC Science & Technology

2003-08-01

Peng, Q. J. Nal. Cancer Inst., 1998, 90, 889. ( c ) Bonnett, R . J. Heterocycl.Chem. 2002, 39, 455. 2. Sherman, W. M.; Allen, C . M.; and van Lier, J. E ...was reached around 2 hrs. The absorption, distribution and elimination were obtained using equation C = Ae" + De"ft + E e " t 5 Where a ,13 and y are the...phenyl]-2,8-diethyl-7,8-dihydroxy-3,7,12,18- tetramethyl-13,17-bis(2-methoxycarbonylethyl)porphyrin (30). Mp 172-174 ’ C ; UV-vis [CH 2C12, nm ( e , f’cm

An action spectrum for UV-B radiation and the rat lens.

PubMed

Merriam, J C; Löfgren, S; Michael, R; Söderberg, P; Dillon, J; Zheng, L; Ayala, M

2000-08-01

To determine an action spectrum for UV-B radiation and the rat lens and to show the effect of the atmosphere and the cornea on the action spectrum. One eye of young female rats was exposed to 5-nm bandwidths of UV-B radiation (290, 295, 300, 305, 310, and 315 nm). Light scattering of exposed and nonexposed lenses was measured 1 week after irradiation. A quadratic polynomial was fit to the dose-response curve for each wave band. The dose at each wave band that produced a level of light scattering greater than 95% of the nonexposed lenses was defined as the maximum acceptable dose (MAD). Transmittance of the rat cornea was measured with a fiberoptic spectrophotometer. The times to be exposed to the MAD in Stockholm (59.3 degrees N) and La Palma (28 degrees N) were compared. Significant light scattering was detected after UV-B at 295, 300, 305, 310, and 315 nm. The lens was most sensitive to UV-B at 300 nm. Correcting for corneal transmittance showed that the rat lens is at least as sensitive to UV radiation at 295 nm as at 300 nm. The times to be exposed to the MAD at each wave band were greater in Stockholm than in La Palma, and in both locations the theoretical time to be exposed to the MAD was least at 305 nm. After correcting for corneal transmittance, the biological sensitivity of the rat lens to UV-B is at least as great at 295 nm as at 300 nm. After correcting for transmittance by the atmosphere, UV-B at 305 nm is the most likely wave band to injure the rat lens in both Stockholm and La Palma.

Phencyclidine Disrupts the Auditory Steady State Response in Rats

PubMed Central

Leishman, Emma; O’Donnell, Brian F.; Millward, James B.; Vohs, Jenifer L.; Rass, Olga; Krishnan, Giri P.; Bolbecker, Amanda R.; Morzorati, Sandra L.

2015-01-01

The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule. PMID:26258486

Latitudinal variation in ambient UV-B radiation is an important determinant of Lolium perenne forage production, quality, and digestibility

PubMed Central

Comont, David; Winters, Ana; Gomez, Leonardo D; McQueen-Mason, Simon J; Gwynn-Jones, Dylan

2013-01-01

Few studies to date have considered the responses of agriculturally important forage grasses to UV-B radiation. Yet grasses such as Lolium perenne have a wide current distribution, representing exposure to a significant variation in ambient UV-B. The current study investigated the responses of L. perenne (cv. AberDart) to a simulated latitudinal gradient of UV-B exposure, representing biologically effective UV-B doses at simulated 70, 60, 50, 40, and 30° N latitudes. Aspects of growth, soluble compounds, and digestibility were assessed, and results are discussed in relation to UV-B effects on forage properties and the implications for livestock and bio-ethanol production. Aboveground biomass production was reduced by approximately 12.67% with every 1 kJ m–2 day–1 increase in biologically weighted UV-B. As a result, plants grown in the highest UV-B treatment had a total biomass of just 13.7% of controls. Total flavonoids were increased by approximately 76% by all UV-B treatments, while hydroxycinnamic acids increased in proportion to the UV-B dose. Conversely, the digestibility of the aboveground biomass and concentrations of soluble fructans were reduced by UV-B exposure, although soluble sucrose, glucose, and fructose concentrations were unaffected. These results highlight the capacity for UV-B to directly affect forage productivity and chemistry, with negative consequences for digestibility and bioethanol production. Results emphasize the need for future development and distribution of L. perenne varieties to take UV-B irradiance into consideration. PMID:23580749

Radiation damage of all-silica fibers in the UV region

NASA Astrophysics Data System (ADS)

Gombert, Joerg; Ziegler, M.; Assmus, J.; Klein, Karl-Friedrich; Nelson, Gary W.; Clarkin, James P.; Pross, H.; Kiefer, J.

1999-04-01

Since several years, UVI-fibers having higher solarization- resistance are well known stimulating new fiber-optic applications in the UV-region below 250 nm. Besides the description of the improved transmission properties of UV- light from different UV-sources, the mechanisms of improvement have been discussed in detail. The UV-defects, mainly the E'- center with the UV-absorption band around 215 nm, were passivated by using hydrogen-doping. Besides DUV-light, ionizing radiation like Gamma-radiation or X-rays can create similar defects in the UV-region. In the past, the radiation- damage in the UV-region was studied on silica bulk samples: again, E'-centers were generated. Up to now, no UV- transmission through a 1 m long fiber during or after Gamma- radiation had been observed. However, the hydrogen in the UVI- fibers behaves the same for Gamma-irradiation, leading to a passivation of the radiation-induced defects and an improved transmission in the UV-C region below 250 nm. On this report, the influence of total dose and fiber diameter on the UV- damage after irradiation will be described and discussed. In addition, we will include annealing studies, with and without UV-light. Based on our results, the standard process of Gamma- sterilization with a total dose of approx. 2 Mrad can be used for UVI-fibers resulting in a good UV-transmission below 320 nm. Excimer-laser light at 308 nm (XeCl) and 248 nm (KrF) and deuterium-lamp light with the full spectrum starting at 200 nm can also be transmitted.

Antioxidant responses of damiana (Turnera diffusa Willd) to exposure to artificial ultraviolet (UV) radiation in an in vitro model; part I; UV-C radiation.

PubMed

Soriano-Melgar, Lluvia de Abril Alexandra; Alcaraz-Meléndez, Lilia; Méndez-Rodríguez, Lía C; Puente, María Esther; Rivera-Cabrera, Fernando; Zenteno-Savín, Tania

2014-05-01

Ultraviolet type C (UV-C) radiation has higher energy than the UV-B radiation and has been less studied because it is completely absorbed by the ozone layer. However, artificial UV-C radiation can generate diverse modifications in the plants. Given that exposure to UV-C for short periods of time increases the antioxidant content, improving the appearance and shelf-life of products, its potential application in postharvest treatments to modify the antioxidant content of medicinal plants, such as damiana (Turnera diffusa), is novel and relevant. To determine the effects of UV-C radiation on enzymatic and non-enzymatic antioxidant defenses, as well as oxidative damage levels, in damiana (Turnera diffusa) plants in vitro. UV-C radiation decreased superoxide dismutase (SOD, EC 1.15.1.1) and total peroxidases (POX, EC 1.11.1) activities, the concentration of chlorophylls (a and b), carotenes, vitamin C, and total antioxidant capacity. UV-C radiation increased the phenolic compound levels in damiana. Loss of antioxidant defenses was higher in damiana plants exposed to higher UV-C doses and/or for longer periods. This study suggests that UV-C radiation induces oxidative stress, evidenced as increased protein carbonyls and phenolic compound content, in damiana (T. diffusa). Low dose, short exposure to UV-C stimulates phenolic compound content in damiana. Thus, controlled UV-C treatments could be used as postharvest treatment to increase phenolic compound content in damiana plants. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

OVATION Prime -2013: Solar Wind Driven Precipitation Model Extended to Higher Geomagnetic Activity Levels (Invited)

NASA Astrophysics Data System (ADS)

Newell, P. T.; Liou, K.; Zhang, Y.; Paxton, L.; Sotirelis, T.; Mitchell, E. J.

2013-12-01

OVATION Prime is an auroral precipitation model parameterized by solar wind driving. Distinguishing features of the model include an optimized solar wind-magnetosphere coupling function (dΦMP/dt) which predicts auroral power far better than Kp or other traditional parameters, the separation of aurora into categories (diffuse aurora, monoenergetic, broadband, and ion), the inclusion of seasonal variations, and separate parameter fits for each MLATxMLT bin, thus permitting each type of aurora and each location to have differing responses to season and solar wind input (as indeed they do). We here introduce OVATION Prime-2013, an upgrade to the 2008 version currently widely available. The most notable advantage of OP-2013 is that it uses UV images from the GUVI instrument on the satellite TIMED for high disturbance levels (dΦMP/dt > 12,000 (nT2/3 (km/s)4/3 which roughly corresponds to Kp = 5+ or 6-). The range of validity is thought to be about 0 < dΦMP/dt = 30000 (say Kp = 8 or 8+). Other upgrades include a reduced susceptibility to salt and pepper noise, and smoother interpolation across the postmidnight data gap. We will also provide a comparison of the advantages and disadvantages of other current precipitation models, especially OVATION-SuperMAG, which produces particularly good estimates for total auroral power, at the expense of working best on an historical basis. OVATION Prime-2013, for high solar wind driving, as TIMED GUVI data takes over from DMSP

Resistance of a lizard (the green anole, Anolis carolinensis; Polychridae) to ultraviolet radiation-induced immunosuppression

USGS Publications Warehouse

Cope, R.B.; Fabacher, D.L.; Lieske, C.; Miller, C.A.

2001-01-01

The green anole (Anolis carolinensis) is the most northerly distributed of its Neotropical genus. This lizard avoids a winter hibernation phase by the use of sun basking behaviors. Inevitably, this species is exposed to high doses of ambient solar ultraviolet radiation (UVR). Increases in terrestrial ultraviolet-B (UV-B) radiation secondary to stratospheric ozone depletion and habitat perturbation potentially place this species at risk of UVR-induced immunosuppression. Daily exposure to subinflammatory UVR (8 kJ/m2/day UV-B, 85 kJ/m2/day ultraviolet A [UV-A]), 6 days per week for 4 weeks (total cumulative doses of 192 kJ/m2 UV-B, 2.04 × 103 kJ/m2 UV-A) did not suppress the anole's acute or delayed type hypersensitivity (DTH) response to horseshoe crab hemocyanin. In comparison with the available literature UV-B doses as low as 0.1 and 15.9 kJ/m2 induced suppression of DTH responses in mice and humans, respectively. Exposure of anoles to UVR did not result in the inhibition of ex vivo splenocyte phagocytosis of fluorescein labeled Escherichia coli or ex vivo splenocyte nitric oxide production. Doses of UV-B ranging from 0.35 to 45 kJ/m2 have been reported to suppress murine splenic/peritoneal macrophage phagocytosis and nitric oxide production. These preliminary studies demonstrate the resistance of green anoles to UVR-induced immunosuppression. Methanol extracts of anole skin contained two peaks in the ultraviolet wavelength range that could be indicative of photoprotective substances. However, the resistance of green anoles to UVR is probably not completely attributable to absorption by UVR photoprotective substances in the skin but more likely results from a combination of other factors including absorption by the cutis and absorption and reflectance by various components of the dermis.

The effects of two different doses of ultraviolet-A light exposure on nitric oxide metabolites and cardiorespiratory outcomes.

PubMed

Monaghan, Chris; McIlvenna, Luke C; Liddle, Luke; Burleigh, Mia; Weller, Richard B; Fernandez, Bernadette O; Feelisch, Martin; Muggeridge, David J; Easton, Chris

2018-05-01

The present study investigated different doses of ultraviolet-A (UV-A) light on plasma nitric oxide metabolites and cardiorespiratory variables. Ten healthy male participants completed three experimental conditions, 7 days apart. Participants were exposed to no light (CON); 10 J cm 2 (15 min) of UV-A light (UVA10) and 20 J cm 2 (30 min) of UV-A light (UVA20) in a randomized order. Plasma nitrite [NO 2 - ] and nitrate [NO 3 - ] concentrations, blood pressure (BP), and heart rate (HR) were recorded before, immediately after exposure and 30 min post-exposure. Whole body oxygen utilization ([Formula: see text]), resting metabolic rate (RMR) and skin temperature were recorded continuously. None of the measured parameters changed significantly during CON (all P > 0.05). [Formula: see text] and RMR were significantly reduced immediately after UVA10 (P < 0.05) despite no change in plasma [NO 2 - ] (P > 0.05). Immediately after exposure to UVA20, plasma [NO 2 - ] was higher (P = 0.014) and [Formula: see text] and RMR tended to be lower compared to baseline (P = 0.06). There were no differences in [NO 2 - ] or [Formula: see text] at the 30 min time point in any condition. UV-A exposure did not alter systolic BP, diastolic BP or MAP (all P > 0.05). UV-A light did not alter plasma [NO 3 - ] at any time point (all P > 0.05). This study demonstrates that a UV-A dose of 20 J cm 2 is necessary to increase plasma [NO 2 - ] although a smaller dose is capable of reducing [Formula: see text] and RMR at rest. Exposure to UV-A did not significantly reduce BP in this cohort of healthy adults. These data suggest that exposure to sunlight has a meaningful acute impact on metabolic function.

Organic micropollutants (OMPs) in natural waters: Oxidation by UV/H2O2 treatment and toxicity assessment.

PubMed

Rozas, Oscar; Vidal, Cristiane; Baeza, Carolina; Jardim, Wilson F; Rossner, Alfred; Mansilla, Héctor D

2016-07-01

Organic micropollutants (OMPs) are ubiquitous in natural waters even in places where the human activity is limited. The presence of OMPs in natural water sources for human consumption encourages the evaluation of different water purification technologies to ensure water quality. In this study, the Biobío river (Chile) was selected since the watershed includes urban settlements and economic activities (i.e. agriculture, forestry) that incorporate a variety of OMPs into the aquatic environment, such as pesticides, pharmaceuticals and personal care products. Atrazine (herbicide), caffeine (psychotropic), diclofenac (anti-inflammatory) and triclosan (antimicrobial) in Biobío river water and in different stages of a drinking and two wastewater treatment plants downstream Biobío river were determined using solid phase extraction (SPE) and liquid chromatography/tandem mass spectrometry (LC-MS/MS) and electrospray ionization (ESI). Quantification of these four compounds showed concentrations in the range of 8 ± 2 to 55 ± 10 ng L(-1) in Biobío river water, 11 ± 2 to 74 ± 21 ng L(-1) in the drinking water treatment plant, and 60 ± 10 to 15,000 ± 1300 ng L(-1) in the wastewater treatment plants. Caffeine was used as an indicator of wastewater discharges. Because conventional water treatment technologies are not designed to eliminate some emerging organic pollutants, alternative treatment processes, UV and UV/H2O2, were employed. The transformation of atrazine, carbamazepine (antiepileptic), diclofenac and triclosan was investigated at laboratory scale. Both processes were tested at different UV doses and the Biobío river water matrix effects were evaluated. Initial H2O2 concentration used was 10 mg L(-1). Results showed that, the transformation profile obtained using UV/H2O2 at UV doses up to 900 mJ cm(-2), followed the trend of diclofenac > triclosan > atrazine > carbamazepine. Furthermore acute toxicity tests with Daphnia magna were carried out after UV/H2O2 treatments of the OMPs mixture studied. At the lower UV doses tested (300 mJ cm(-2)) a higher toxicity was observed, suggesting the formation of toxic intermediates in the course of the reaction. As expected, at higher UV doses the toxicity declined. Considering the treatment of the mixture of ATZ, CBZ, DCL and TCS with a UV dose of 1200 mJ cm(-2) and 10 mg L(-1) of H2O2 the acute toxicity results exhibits values for Daphnia magna immobilization equal to 20 and 42% evaluated after 24 and 48 h, respectively. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis, characterization, quantum chemical calculations and evaluation of antioxidant properties of 1,3,4-thiadiazole derivatives including 2- and 3-methoxy cinnamic acids

NASA Astrophysics Data System (ADS)

Gür, Mahmut; Muğlu, Halit; Çavuş, M. Serdar; Güder, Aytaç; Sayıner, Hakan S.; Kandemirli, Fatma

2017-04-01

A series of 1,3,4-thiadiazole derivatives including 2- and 3-methoxy cinnamic acids were synthesized, and their structures were elucidated by the UV, IR, 1H NMR, 13C NMR spectroscopies and elemental analysis. The UV and IR calculations of the molecules were performed by using B3LYP, HF and MP2 methods with selected 6-311++G(2d,2p), 6-311++G(3df,3pd) and cc-pvtz basis sets. Dipole moment, polarizability, chemical hardness/softness and electronegativity were also calculated and analyzed. Experimental FT-IR spectra and UV-Vis spectrum of the compounds were compared with theoretical data. Furthermore, antioxidant activities of the compounds were practised via different test methods such as 2,2-diphenyl-1-picryl-hydrazyl (DPPHrad), N,N-dimethyl-p-phenylenediamine (DMPDrad +), and 2,2‧-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTSrad +) scavenging activity assays. When compared with standards (BHA-Butylated hydroxyanisole, RUT-Rutin, and TRO-Trolox), it was observed that especially XIII and XIV which include methoxy groups at the o- and m-positions, respectively, had effective activities.

Wastewater disinfection alternatives: chlorine, ozone, peracetic acid, and UV light.

PubMed

Mezzanotte, V; Antonelli, M; Citterio, S; Nurizzo, C

2007-11-01

Disinfection tests were carried out at pilot scale to compare the disinfection efficiency of ozone, sodium hypochlorite (NaOCl), peracetic acid (PAA), and UV irradiation. Total coliforms, fecal coliforms, and Escherichia coli were monitored as reference microorganisms. Total heterotrophic bacteria (THB) were also enumerated by cytometry. At similar doses, NaOCl was more effective than PAA, and its action was less affected by contact time. The results obtained by ozonation were comparable for total coliforms, fecal coliforms, and E. coli. On the contrary, some differences among the three indicators were observed for NaOCl, PAA, and UV. Differences increased with increasing values of the disinfectant concentration times contact time (C x t) and were probably the result of different initial counts, as total coliforms include fecal coliforms, which include E. coli. The UV irradiation lead to complete E. coli removals, even at low doses (10 to 20 mJ/cm2). Total heterotrophic bacteria appeared to be too wide a group to be a good disinfection indicator; no correlation was found among THB inactivation, dose, and contact time.

Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

PubMed

Urbain, Paul; Jakobsen, Jette

2015-09-23

The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon.

Evaluation of a commercial automatic treatment planning system for liver stereotactic body radiation therapy treatments.

PubMed

Gallio, Elena; Giglioli, Francesca Romana; Girardi, Andrea; Guarneri, Alessia; Ricardi, Umberto; Ropolo, Roberto; Ragona, Riccardo; Fiandra, Christian

2018-02-01

Automated treatment planning is a new frontier in radiotherapy. The Auto-Planning module of the Pinnacle 3 treatment planning system (TPS) was evaluated for liver stereotactic body radiation therapy treatments. Ten cases were included in the study. Six plans were generated for each case by four medical physics experts. The first two planned with Pinnacle TPS, both with manual module (MP) and Auto-Planning one (AP). The other two physicists generated two plans with Monaco TPS (VM). Treatment plan comparisons were then carried on the various dosimetric parameters of target and organs at risk, monitor units, number of segments, plan complexity metrics and human resource planning time. The user dependency of Auto-Planning was also tested and the plans were evaluated by a trained physician. Statistically significant differences (Anova test) were observed for spinal cord doses, plan average beam irregularity, number of segments, monitor units and human planning time. The Fisher-Hayter test applied to these parameters showed significant statistical differences between AP e MP for spinal cord doses and human planning time; between MP and VM for monitor units, number of segments and plan irregularity; for all those between AP and VM. The two plans created by different planners with AP were similar to each other. The plans created with Auto-Planning were comparable to the manually generated plans. The time saved in planning enables the planner to commit more resources to more complex cases. The independence of the planner enables to standardize plan quality. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Effectiveness of Saccharomyces boulardii in a rat model of colitis.

PubMed

Soyturk, Mujde; Saygili, Saba Mukaddes; Baskin, Huseyin; Sagol, Ozgul; Yilmaz, Osman; Saygili, Fatih; Akpinar, Hale

2012-11-28

To investigate the effects of Saccharomyces boulardii (S. boulardii) in an experimental rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thirty-two Wistar albino female rats were categorized into five groups. On the first day of the study, 50 mg TNBS was administered via a rectal catheter in order to induce colitis in all rats, except those in the control group. For 14 d, the rats were fed a standard diet, without the administration of any additional supplements to either the control or TNBS groups, in addition to 1 mg/kg per day S. boulardii to the S. boulardii group, 1 mg/kg per day methyl prednisolone (MP) to the MP group. The animals in the S. boulardii + MP group were coadministered these doses of S. boulardii and MP. During the study, weight loss, stool consistency, and the presence of obvious blood in the stool were evaluated, and the disease activity index (DAI) for colitis was recorded. The intestines were examined and colitis was macro- and microscopically scored. The serum and tissue levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were determined, and fungemia was evaluated in the blood samples. The mean DAI scores for the MP and S. boulardii + MP groups was significantly lower than the TNBS group (3.69 ± 0.61 vs 4.46 ± 0.34, P = 0.018 and 3.77 ± 0.73 vs 4.46 ± 0.34, P = 0.025, respectively). While no significant differences between the TNBS and the S. boulardii or MP groups could be determined in terms of serum NO levels, the level of serum NO in the S. boulardii + MP group was significantly higher than in the TNBS and S. boulardii groups (8.12 ± 4.25 μmol/L vs 3.18 ± 1.19 μmol/L, P = 0.013; 8.12 ± 4.25 μmol/L vs 3.47 ± 1.66 μmol/L, P = 0.012, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were significantly lower than the TNBS group (16.62 ± 2.27 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002; 14.66 ± 5.18 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.003; 11.95 ± 2.34 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were similar. The mean serum and tissue TNF-α levels were determined to be 12.97 ± 18.90 pg/mL and 21.75 ± 15.04 pg/mL in the control group, 18.25 ± 15.44 pg/mL and 25.27 ± 11.95 pg/mL in the TNBS group, 20.59 ± 16.15 pg/mL and 24.39 ± 13.06 pg/mL in the S. boulardii group, 9.05 ± 5.13 pg/mL and 24.46 ± 10.85 pg/mL in the MP group, and 13.95 ± 10.17 pg/mL and 24.26 ± 10.37 pg/mL in the S. boulardii + MP group. Significant differences in terms of the levels of serum and tissue TNF-α and the macroscopic and microscopic scores were not found between the groups. S. boulardii fungemia was not observed in any of the rats. However, Candida fungemia was detected in one rat (14%) in the TNBS group, two rats (28%) in the S. boulardii group, three rats (50%) in the MP group, and three rats (42%) in S. boulardii + MP group. S. boulardii does not demonstrate considerable effects on the DAI, pathological scores, or cytokine levels but does decrease the tissue NO levels.

Effectiveness of Saccharomyces boulardii in a rat model of colitis

PubMed Central

Soyturk, Mujde; Saygili, Saba Mukaddes; Baskin, Huseyin; Sagol, Ozgul; Yilmaz, Osman; Saygili, Fatih; Akpinar, Hale

2012-01-01

AIM: To investigate the effects of Saccharomyces boulardii (S. boulardii) in an experimental rat model of trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: Thirty-two Wistar albino female rats were categorized into five groups. On the first day of the study, 50 mg TNBS was administered via a rectal catheter in order to induce colitis in all rats, except those in the control group. For 14 d, the rats were fed a standard diet, without the administration of any additional supplements to either the control or TNBS groups, in addition to 1 mg/kg per day S. boulardii to the S. boulardii group, 1 mg/kg per day methyl prednisolone (MP) to the MP group. The animals in the S. boulardii + MP group were coadministered these doses of S. boulardii and MP. During the study, weight loss, stool consistency, and the presence of obvious blood in the stool were evaluated, and the disease activity index (DAI) for colitis was recorded. The intestines were examined and colitis was macro- and microscopically scored. The serum and tissue levels of tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were determined, and fungemia was evaluated in the blood samples. RESULTS: The mean DAI scores for the MP and S. boulardii + MP groups was significantly lower than the TNBS group (3.69 ± 0.61 vs 4.46 ± 0.34, P = 0.018 and 3.77 ± 0.73 vs 4.46 ± 0.34, P = 0.025, respectively). While no significant differences between the TNBS and the S. boulardii or MP groups could be determined in terms of serum NO levels, the level of serum NO in the S. boulardii + MP group was significantly higher than in the TNBS and S. boulardii groups (8.12 ± 4.25 μmol/L vs 3.18 ± 1.19 μmol/L, P = 0.013; 8.12 ± 4.25 μmol/L vs 3.47 ± 1.66 μmol/L, P = 0.012, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were significantly lower than the TNBS group (16.62 ± 2.27 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002; 14.66 ± 5.18 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.003; 11.95 ± 2.34 μmol/L vs 29.72 ± 6.10 μmol/L, P = 0.002, respectively). The tissue NO levels in the S. boulardii, MP and S. boulardii + MP groups were similar. The mean serum and tissue TNF-α levels were determined to be 12.97 ± 18.90 pg/mL and 21.75 ± 15.04 pg/mL in the control group, 18.25 ± 15.44 pg/mL and 25.27 ± 11.95 pg/mL in the TNBS group, 20.59 ± 16.15 pg/mL and 24.39 ± 13.06 pg/mL in the S. boulardii group, 9.05 ± 5.13 pg/mL and 24.46 ± 10.85 pg/mL in the MP group, and 13.95 ± 10.17 pg/mL and 24.26 ± 10.37 pg/mL in the S. boulardii + MP group. Significant differences in terms of the levels of serum and tissue TNF-α and the macroscopic and microscopic scores were not found between the groups. S. boulardii fungemia was not observed in any of the rats. However, Candida fungemia was detected in one rat (14%) in the TNBS group, two rats (28%) in the S. boulardii group, three rats (50%) in the MP group, and three rats (42%) in S. boulardii + MP group. CONCLUSION: S. boulardii does not demonstrate considerable effects on the DAI, pathological scores, or cytokine levels but does decrease the tissue NO levels. PMID:23197891

Alternative strawberry disease management strategy: combing low UV-C irradiation in dark, disabling pathogen’s UV-C repair mechanism, and preventing pathogen establishment with biocontrol agents

USDA-ARS?s Scientific Manuscript database

The limitations of current fungicides necessitate a search for new approaches. Low-dose or sub-lethal UV-C irradiation (12.36 J/m2) alone is not effective in controlling fungal diseases, especially when the plants are exposed to UV-C irradiation during the day. We found, however, that application ...

Detection of ultraviolet radiation using tissue equivalent radiochromic gel materials

NASA Astrophysics Data System (ADS)

Bero, M. A.; Abukassem, I.

2009-05-01

Ferrous Xylenol-orange Gelatin gel (FXG) is known to be sensitive to ionising radiation such as γ and X-rays. The effect of ionising radiation is to produce an increase in the absorption over a wide region of the visible spectrum, which is proportional to the absorbed dose. This study demonstrates that FXG gel is sensitive to ultraviolet radiation and therefore it could functions as UV detector. Short exposure to UV radiation produces linear increase in absorption measured at 550nm, however high doses of UV cause the ion indicator colour to fad away in a manner proportional to the incident UV energy. Light absorbance increase at the rate of 1.1% per minute of irradiation was monitored. The exposure level at which the detector has linear response is comparable to the natural summer UV radiation. Evaluating the UV ability to pass through tissue equivalent gel materials shows that most of the UV gets absorbed in the first 5mm of the gel materials, which demonstrate the damaging effects of this radiation type on human skin and eyes. It was concluded that FXG gel dosimeter has the potential to offer a simple, passive ultraviolet radiation detector with sensitivity suitable to measure and visualises the natural sunlight UV exposure directly by watching the materials colour changes.

Distribution of Boreal Toad Populations in Relation to Estimated UV-B Dose in Glacier National Park, Montana, USA

EPA Science Inventory

This work provides information on amphibian distributions as well as the range of UV-B exposure in mountain habitats, and will be of use to scientists interested in tracking changes in amphibian distributions and abundance, and spatial and temporal patterns of UV-B exposure

UV/TiO2 photocatalytic disinfection of carbon-bacteria complexes in activated carbon-filtered water: Laboratory and pilot-scale investigation.

PubMed

Zhao, Jin Hui; Chen, Wei; Zhao, Yaqian; Liu, Cuiyun; Liu, Ranbin

2015-01-01

The occurrence of carbon-bacteria complexes in activated carbon filtered water has posed a public health problem regarding the biological safety of drinking water. The application of combined process of ultraviolet radiation and nanostructure titanium dioxide (UV/TiO2) photocatalysis for the disinfection of carbon-bacteria complexes were assessed in this study. Results showed that a 1.07 Lg disinfection rate can be achieved using a UV dose of 20 mJ cm(-2), while the optimal UV intensity was 0.01 mW cm(-2). Particle sizes ≥8 μm decreased the disinfection efficiency, whereas variation in particle number in activated carbon-filtered water did not significantly affect the disinfection efficiency. Photoreactivation ratio was reduced from 12.07% to 1.69% when the UV dose was increased from 5 mJ cm(-2) to 20 mJ cm(-2). Laboratory and on-site pilot-scale experiments have demonstrated that UV/TiO2 photocatalytic disinfection technology is capable of controlling the risk posed by carbon-bacteria complexes and securing drinking water safety.

Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies.

PubMed

Xu, Chun; Goß, Annika Verena; Dorneburg, Carmen; Debatin, Klaus-Michael; Wei, Jiwu; Beltinger, Christian

2018-01-01

Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase clinical trials. However, pre-existing immunity against measles might be a hurdle for OMV therapy. OMV was inactivated with short-wavelength ultraviolet light (UV-C). Loss of replication and oncolytic activity of UV-inactivated OMV were confirmed by tissue culture infective dose 50 (TCID 50 ) assay using Vero cells and by flow cytometry using Jurkat cells. An enzyme-linked immunosorbent assay was performed to verify that UV-inactivated OMV remained antigenic. Different doses of UV-inactivated OMV were pre-cultured in media supplemented with measles immune serum. The mixture was transferred to Jurkat cells and active OMV was added. Active OMV-induced death of Jurkat cells was monitored by flow cytometry. UV-inactivation abrogates OMV replication while maintaining its antigenicity. UV-inactivated OMV sequesters pre-existing anti-MV antibodies in Jurkat cell culture, thereby protecting active OMV from neutralization and preserving oncolytic activity. We prove the principle that a non-replicating OMV can serve as a "decoy" for neutralizing anti-MV antibodies, thereby allowing antitumor activity of OMV.

UV exposure in cars.

PubMed

Moehrle, Matthias; Soballa, Martin; Korn, Manfred

2003-08-01

There is increasing knowledge about the hazards of solar and ultraviolet (UV) radiation to humans. Although people spend a significant time in cars, data on UV exposure during traveling are lacking. The aim of this study was to obtain basic information on personal UV exposure in cars. UV transmission of car glass samples, windscreen, side and back windows and sunroof, was determined. UV exposure of passengers was evaluated in seven German middle-class cars, fitted with three different types of car windows. UV doses were measured with open or closed windows/sunroof of Mercedes-Benz E 220 T, E 320, and S 500, and in an open convertible car (Mercedes-Benz CLK). Bacillus subtilis spore film dosimeters (Viospor) were attached to the front, vertex, cheeks, upper arms, forearms and thighs of 'adult' and 'child' dummies. UV wavelengths longer than >335 nm were transmitted through car windows, and UV irradiation >380 nm was transmitted through compound glass windscreens. There was some variation in the spectral transmission of side windows according to the type of glass. On the arms, UV exposure was 3-4% of ambient radiation when the car windows were shut, and 25-31% of ambient radiation when the windows were open. In the open convertible car, the relative personal doses reached 62% of ambient radiation. The car glass types examined offer substantial protection against short-wave UV radiation. Professional drivers should keep car windows closed on sunny days to reduce occupational UV exposure. In individuals with polymorphic light eruption, produced by long-wave UVA, additional protection by plastic films, clothes or sunscreens appears necessary.

The effect of ultraviolet radiation on choroidal melanocytes and melanoma cell lines: cell survival and matrix metalloproteinase production.

PubMed

Lai, Kenneth; Di Girolamo, Nick; Conway, Robert M; Jager, Martine J; Madigan, Michele C

2007-05-01

Ultraviolet radiation (UVR) can induce DNA damage and regulate the expression of factors important for tumour growth and metastasis, including matrix metalloproteinases (MMPs). Epidemiological studies suggest that chronic UVR exposure, especially during early adulthood, may be a risk factor in patients with choroidal melanoma. However, the effects of UV(R)-B on human choroidal melanocyte survival and growth are unknown. In this study, we investigated if UV(R)-B affected the in vitro survival, growth and MMP production of choroidal melanocytes and melanoma cells. Cultures of primary choroidal melanocytes and melanoma cell lines (OCM-1 and OCM-8) were exposed to UV(R)-B (0-30 mJ/cm(2)). The cell morphology and growth were examined, and cell viability was assessed using an MTT assay. Gelatin zymography was used to assess the enzymatic activity for MMP-2 and -9 in conditioned media following UV(R)-B treatment. UV(R)-B > or =20 mJ/cm(2) was cytotoxic for choroidal melanocytes. Cytotoxic doses of 5 to 10 mJ/cm(2) were found for OCM-8 and OCM-1 melanoma cell lines. Low levels of UV(R)-B (2.5 and 3.5 mJ/cm(2)) significantly reduced melanoma cell viability after 48 h, although melanocyte viability was not affected by doses of UV(R)-B <10 mJ/cm(2). Conditioned media from melanoma cells and melanocytes displayed pro-MMP-2 activity independent of UV(R)-B. Control and UV(R)-B-treated OCM-1 cells secreted active MMP-2 up to 72 h. Pro-MMP-9 activity was seen from 36 h for control and UV(R)-B-treated OCM-1 and OCM-8 cells. Melanocytes appeared more resistant to physiological doses of UV(R)-B than melanoma cells; the potential of melanocytes to initially survive DNA damage following UV(R)-B exposure may be relevant to the subsequent transformation of melanocytes to melanomas. Although UV(R)-B did not induce the production and/or activation of MMP-2 and -9 in melanocytes or melanoma cells, we are currently investigating whether DNA damage-response genes such as p53 and p21 can be regulated following UVR exposure, and whether they are important for choroidal melanoma development.

In-line UV spectroscopy for the quantification of low-dose active ingredients during the manufacturing of pharmaceutical semi-solid and liquid formulations.

PubMed

Bostijn, N; Hellings, M; Van Der Veen, M; Vervaet, C; De Beer, T

2018-07-12

UltraViolet (UV) spectroscopy was evaluated as an innovative Process Analytical Technology (PAT) - tool for the in-line and real-time quantitative determination of low-dosed active pharmaceutical ingredients (APIs) in a semi-solid (gel) and a liquid (suspension) pharmaceutical formulation during their batch production process. The performance of this new PAT-tool (i.e., UV spectroscopy) was compared with an already more established PAT-method based on Raman spectroscopy. In-line UV measurements were carried out with an immersion probe while for the Raman measurements a non-contact PhAT probe was used. For both studied formulations, an in-line API quantification model was developed and validated per spectroscopic technique. The known API concentrations (Y) were correlated with the corresponding in-line collected preprocessed spectra (X) through a Partial Least Squares (PLS) regression. Each developed quantification method was validated by calculating the accuracy profile on the basis of the validation experiments. Furthermore, the measurement uncertainty was determined based on the data generated for the determination of the accuracy profiles. From the accuracy profile of the UV- and Raman-based quantification method for the gel, it was concluded that at the target API concentration of 2% (w/w), 95 out of 100 future routine measurements given by the Raman method will not deviate more than 10% (relative error) from the true API concentration, whereas for the UV method the acceptance limits of 10% were exceeded. For the liquid formulation, the Raman method was not able to quantify the API in the low-dosed suspension (0.09% (w/w) API). In contrast, the in-line UV method was able to adequately quantify the API in the suspension. This study demonstrated that UV spectroscopy can be adopted as a novel in-line PAT-technique for low-dose quantification purposes in pharmaceutical processes. Important is that none of the two spectroscopic techniques was superior to the other for both formulations: the Raman method was more accurate in quantifying the API in the gel (2% (w/w) API), while the UV method performed better for API quantification in the suspension (0.09% (w/w) API). Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of UV-C on the physiology and biochemical profile of fresh Piper nigrum berries.

PubMed

Collings, Emma R; Alamar Gavidia, M Carmen; Cools, Katherine; Redfern, Sally; Terry, Leon A

2018-02-01

Application of UV-C has been shown to enhance the biochemical profile of various plant materials. This could be used to increase biochemical load, reducing the amount of material required but still impart equivalent flavour. As spices, such as black pepper ( Piper nigrum L.), are typically dried to low moisture content to create a stable product for transportation and storage, little work has explored the use of modern postharvest treatments to enhance flavour. In this work, fresh P. nigrum berries were exposed to four UV-C doses (0, 1, 5 and 15 kJ m -2 ) and subsequently stored at 5 °C for ca . 4 weeks. Two separate experiments (early and late season) were conducted across one season. Replicate P. nigrum berry clusters were stored separately within continuously ventilated 13 L boxes. Real-time respiration rate ( ex situ ), ethylene production, fruit colour and water potential were measured at regular intervals during storage. In addition, piperine and essential oils were assessed using a simple newly developed method which enabled both compound groups to be simultaneously extracted and subsequently quantified. UV-C was found to cause significant changes in colour (from green to brown) whilst also altering the biochemical composition (piperine and essential oils), which was influenced by UV-C dose and berry maturity. Low to medium UV-C doses could potentially enhance flavour compounds in black pepper enabling processors to create products with higher biochemical load.

Ecologically relevant UV-B dose combined with high PAR intensity distinctly affect plant growth and accumulation of secondary metabolites in leaves of Centella asiatica L. Urban.

PubMed

Müller, Viola; Albert, Andreas; Barbro Winkler, J; Lankes, Christa; Noga, Georg; Hunsche, Mauricio

2013-10-05

We investigated the effects of environmentally relevant dose of ultraviolet (UV)-B and photosynthetic active radiation (PAR) on saponin accumulation in leaves on the example of Centella asiatica L. Urban. For this purpose, plants were exposed to one of four light regimes i.e., two PAR intensities with or without UV-B radiation. The experiment was conducted in technically complex sun simulators under almost natural irradiance and climatic conditions. As observed, UV-B radiation increased herb and leaf production as well as the content of epidermal flavonols, which was monitored by non-destructive fluorescence measurements. Specific fluorescence indices also indicate an increase in the content of anthocyanins under high PAR; this increase was likewise observed for the saponin concentrations. In contrast, UV-B radiation had no distinct effects on saponin and sapogenin concentrations. Our findings suggest that besides flavonoids, also saponins were accumulated under high PAR protecting the plant from oxidative damage. Furthermore, glycosylation of sapogenins seems to be important either for the protective function and/or for compartmentalization of the compounds. Moreover, our study revealed that younger leaves contain higher amounts of saponins, while in older leaves the sapogenins were the most abundant constituents. Concluding, our results proof that ambient dose of UV-B and high PAR intensity distinctly affect the accumulation of flavonoids and saponins, enabling the plant tissue to adapt to the light conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Methylparaben-induced decrease in collagen production and viability of cultured human dermal fibroblasts.

PubMed

Majewska, Natalia; Zaręba, Ilona; Surażyński, Arkadiusz; Galicka, Anna

2017-09-01

Parabens owing to their many advantageous properties are widely applied in cosmetics, food products and pharmaceuticals. However, recent research results have shown that they possess the ability to accumulate in the human body and exert many adverse effects. In this study, the impact of methylparaben (MP) as the most frequently used preservative in cosmetics, on human dermal fibroblasts and collagen production was evaluated. In cells treated with 0.01, 0.03 and 0.05% MP a dose-dependent decrease in collagen biosynthesis was revealed, which was positively correlated with the activity of prolidase responsible for the recovery of proline. Consequently, the concentration of total collagen secreted into the medium was markedly diminished. A similar reduction in expression of the major skin collagen type I at both the protein and mRNA level as well as collagen type III and VI at the mRNA level was also detected. The decrease in the collagen level may result not only from the reduced synthesis but also increased degradation owing to MP-induced activation of pro-MMP-2 (72 kDa). The increase in activity of MMP-2 (66 kDa) was accompanied by a reduction in the inhibitory activity of TIMP-2. In addition, an inhibitory effect of MP on cell survival and proliferation was revealed in this study. The increased expression and nuclear translocation of caspase-3 as well as increased Bax and decreased Bcl-2 expression may suggest MP-induced cell apoptosis. In summary, we have provided new data on the adverse effects of methylparaben on human dermal fibroblasts and the main structural protein of the skin. Further studies on the mechanisms responsible for its action are in progress. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

[Relationship between single nucleotide polymorphisms in thiopurine methyltransferase gene and tolerance to thiopurines in acute leukemia].

PubMed

Ma, Xiao-li; Zhu, Ping; Wu, Min-yuan; Li, Zhi-gang; Hu, Ya-mei

2003-12-01

For the purpose of clarifying the influence of thiopurine methyltransferase (TPMT) gene single nucleotide polymorphisms (SNPs) on the efficacy of thiopurines and risk for its toxicity and therefore improving the safety and efficacy of thiopurines, the authors investigated TPMT genotype in acute leukemia in children who were intolerant to the treatment with 6-mercap topurine (6-MP). TPMT genotype was determined in an unrelated population of 250 Chinese healthy blood donors and 280 children with acute leukemia. TPMT genotyping assay was based on polymerase chain reaction (PCR), restriction digestion of PCR products, denaturing high-performance liquid chromatography (DHPLC) and direct DNA sequencing in the TPMT * 2 (G238C), TPMT * 3A (G460A, A719G) and TPMT * 3C (A719G). There were 10 TPMT * 1/TPMT * 3C heterozygotes in 280 children. The frequency of the polymorphism was 3.6%. All the involved alleles were TPMT * 3C. Of the 160 children acute leukemia evaluated, 45 (26%) were intolerant to 6-MP. Presentations included hepatotoxicity and hematological toxicity. Six out of 45 children were heterozygous, while the other 39 were wild type homozygous. Before dosage adjustments for thiopurine, the hematologic toxicity and hepatotoxicity in TPMT heterozygous individuals occurred more frequently than in homozygous. Therefore, cases of TPMT heterozygotes experienced more missed doses of 6-MP. TPMT genotype is associated with tolerance in acute leukemia in children. The heterozygote individuals have low TPMT activity. Therefore the frequencies of hemtopoietic toxicity and hepatoxicity are high after using 6-MP. Detection of SNPs in the TPMT genes is useful in identifying children before administration of 6-MP.

[UV-induced DNA damage and protective effects of antioxidants on DNA damage in human lens epithelial cells studied with comet assay].

PubMed

Wu, Zhi-hong; Wang, Mian-rong; Yan, Qi-chang; Pu, Wei; Zhang, Jin-song

2006-11-01

To investigate the mechanism of UV-induced DNA damage and repair and the protective effects of antioxidants on DNA damage in human lens epithelial cells. Human lens epithelial cells were irradiated at UV-doses 0.0 (control group), 2.5, 5.0, 7.5, 10.0 mJ/cm(2) (treated group 1 - 4). The amounts of DNA single strand breaks (SSB) were measured with the alkaline comet assay (CA). The spontaneous repair of DNA SSB after exposure to UV at 10.0 mJ/cm(2) was also determined in human lens epithelial cells. Human lens epithelial cells were treated with different concentration of VitaminC (VitC), taurine, superoxide dismutase (SOD) and epigallocatechin gallate (EGCG) before and after ultraviolet radiation, the effects of antioxidants on DNA damage was examined with alkaline comet assay. The amount of DNA SSB in control group and treated groups 1 - 4 showed increased tendency, was dose-dependent to the dose of UV irradiation, the differences of DNA SSB in 5 group were significantly (P < 0.01). UV-induced DNA SSB at 10.0 mJ/cm(2) in human lens epithelial cells, the half repair time was 60 minutes. Human lens epithelial cells were treated with different concentrations of taurine, SOD and EGCG before ultraviolet radiation. The differences of DNA damage in control and various antioxidant treated groups was statistically significant (F = 6.591, 13.542, 4.626 in cells treated with taurine, SOD and EGCG, respectively, P < 0.01), the difference of VitC effect on DNA in control and treated group were not significantly (F = 1.451, P > 0.05). Human lens epithelial cells were treated with different concentration of VitC, taurine, SOD and EGCG after ultraviolet radiation. The differences of DNA damage between the control and treated group were statistically significant (F = 6.571, 4.810, 6.824, 9.182 in cells treated with VitC, taurine, SOD and EGCG, respectively, P < 0.01). The differences of protective effects on DNA damage in these four different kinds of antioxidants added before UV irradiation were statistically significant (P < 0.01). The differences of protective effects on DNA damage in these four different kinds of antioxidant added after UV irradiation were not significantly (P > 0.05). UV irradiation has a dose-dependent effect on the DNA SSB of lens epithelial cells. Exogenesis VitC, taurine, SOD, EGCG possess protective effective to UV-induced DNA damage. SOD is one of the most powerful antioxidants if added before the UV irradiation and followed by EGCG, taurine and VitC orderly. Four kinds of antioxidants show no apparently differences added after UV-irradiation. SOD and EGCG both are powerful antioxidants.

Inactivation of Microbiological Contaminants in Drinking Water by Ultraviolet Light Technology: NeoTech Aqua Solutions, Inc.; Ultraviolet Water Treatment System, NeoTech D438™ (Report and VS)

EPA Science Inventory

The NeoTech Aqua Solutions, Inc. D438™ UV Water Treatment System was tested to validate the UV dose delivered by the system using biodosimetry and a set line approach. The set line for 40 mJ/cm2 measured Reduction Equivalent Dose (RED) was based on validation testing at three (3)...

Exposure to 4,4'-methylenediphenyl diisocyanate (MDI) during moulding of rigid polyurethane foam: determination of airborne MDI and urinary 4,4'-methylenedianiline (MDA).

PubMed

Kääriä, K; Hirvonen, A; Norppa, H; Piirilä, P; Vainio, H; Rosenberg, C

2001-04-01

Occupational exposure to 4,4'-methylenediphenyl diisocyanate (MDI) was measured during moulding of rigid polyurethane foam. The aim of the study was to find out whether an MDI-derived urinary amine metabolite could be detected in the urine of workers exposed to apparently low levels of MDI. Airborne MDI was sampled on 1-(2-methoxyphenyl)-piperazine (2MP)-impregnated glass fibre filters and determined by high-performance liquid chromatography (HPLC) using ultraviolet (UV) and electrochemical (EC) detection. The limit of detection of MDI was 3 ng ml-1 for a 20 microliters injection. The precision of sample preparation, expressed as relative standard deviation (RSD), was 1.3% with UV detection and 2.1% with EC detection at a concentration of 70 ng MDI ml-1 (n = 6). The 2MP-MDI derivative was stable at +4 degrees C up to eight weeks. The accuracy of the method was validated in an international quality control programme. Workers (n = 57) from three different factories participated in the study. Urinary 4,4'-methylenedianiline (MDA) metabolite was determined after acid hydrolysis as heptafluorobutyric anhydride derivatives by gas chromatography-mass spectrometry using chemical ionisation and monitoring negative ions. The limit of detection in urine was 0.2 nmol l-1. The precision of six analyses for a urine sample spiked to a concentration of 1 nmol l-1 was 29% (RSD). The MDI concentrations were below the limit of detection in most (64%) of the air samples collected in the worker's breathing zone. Still, detectable amounts of MDA were found in 97% of the urine samples. Monitoring of urinary MDA appears to be an appropriate method of assessing MDI exposure in work environments with low or undetectable MDI concentrations in the workplace air.

Visualizing and quantifying dose distribution in a UV reactor using three-dimensional laser-induced fluorescence.

PubMed

Gandhi, Varun N; Roberts, Philip J W; Kim, Jae-Hong

2012-12-18

Evaluating the performance of typical water treatment UV reactors is challenging due to the complexity in assessing spatial and temporal variation of UV fluence, resulting from highly unsteady, turbulent nature of flow and variation in UV intensity. In this study, three-dimensional laser-induced fluorescence (3DLIF) was applied to visualize and quantitatively analyze a lab-scale UV reactor consisting of one lamp sleeve placed perpendicular to flow. Mapping the spatial and temporal fluence delivery and MS2 inactivation revealed the highest local fluence in the wake zone due to longer residence time and higher UV exposure, while the lowest local fluence occurred in a region near the walls due to short-circuiting flow and lower UV fluence rate. Comparing the tracer based decomposition between hydrodynamics and IT revealed similar coherent structures showing the dependency of fluence delivery on the reactor flow. The location of tracer injection, varying the height and upstream distance from the lamp center, was found to significantly affect the UV fluence received by the tracer. A Lagrangian-based analysis was also employed to predict the fluence along specific paths of travel, which agreed with the experiments. The 3DLIF technique developed in this study provides new insight on dose delivery that fluctuates both spatially and temporally and is expected to aid design and optimization of UV reactors as well as validate computational fluid dynamics models that are widely used to simulate UV reactor performances.

Chemical UV Filters Mimic the Effect of Progesterone on Ca2+ Signaling in Human Sperm Cells.

PubMed

Rehfeld, A; Dissing, S; Skakkebæk, N E

2016-11-01

Progesterone released by cumulus cells surrounding the egg induces a Ca 2+ influx into human sperm cells via the cationic channel of sperm (CatSper) Ca 2+ channel and controls multiple Ca 2+ -dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic the physiological action of progesterone on CatSper, thus affecting Ca 2+ signaling in human sperm cells. We examined 29 UV filters allowed in sunscreens in the United States and/or the European Union for their ability to induce Ca 2+ signals in human sperm by applying measurements of the intracellular free Ca 2+ concentration. We found that 13 UV filters induced a significant Ca 2+ signal at 10 μM. Nine UV filters induced Ca 2+ signals primarily by activating the CatSper channel. The UV filters 3-benzylidene camphor (3-BC) and benzylidene camphor sulfonic acid competitively inhibited progesterone-induced Ca 2+ signals. Dose-response relations for the UV filters showed that the Ca 2+ signal-inducing effects began in the nanomolar-micromolar range. Single-cell Ca 2+ measurements showed a Ca 2+ signal-inducing effect of the most potent UV filter, 3-BC, at 10 nM. Finally, we demonstrated that the 13 UV filters acted additively in low-dose mixtures to induce Ca 2+ signals. In conclusion, 13 of 29 examined UV filters (44%) induced Ca 2+ signals in human sperm. Nine UV filters primarily activated CatSper and thereby mimicked the effect of progesterone. The UV filters 3-BC and benzylidene camphor sulfonic acid competitively inhibited progesterone-induced Ca 2+ signals. In vivo exposure studies are needed to investigate whether UV filter exposure affects human fertility.

Distribution patterns of lentic-breeding amphibians in relation to ultraviolet radiation exposure in western North America

USGS Publications Warehouse

Adams, Michael J.; Hossack, B.R.; Knapp, R.A.; Corn, P.S.; Diamond, S.A.; Trenham, P.C.; Fagre, D.B.

2005-01-01

An increase in ultraviolet-B (UV-B) radiation has been posited to be a potential factor in the decline of some amphibian population. This hypothesis has received support from laboratory and field experiments showing that current levels of UV-B can cause embryo mortality in some species, but little research has addressed whether UV-B is influencing the distribution of amphibian populations. We compared patterns of amphibian presence to site-specific estimates of UV-B dose at 683 ponds and lakes in Glacier, Olympic, and Sequoia–Kings Canyon National Parks. All three parks are located in western North America, a region with a concentration of documented amphibian declines. Site-specific daily UV-B dose was estimated using modeled and field-collected data to incorporate the effects of elevation, landscape, and water-column dissolved organic carbon. Of the eight species we examined (Ambystoma gracile, Ambystoma macrodactylum, Bufo boreas, Pseudacris regilla, Rana cascadae, Rana leuteiventris, Rana muscosa, Taricha granulosa), two species (T. granulosa and A. macrodactylum) had quadratic relationships with UV-B that could have resulted from negative UV-B effects. Both species were most likely to occur at moderate UV-B levels. Ambystoma macrodactylum showed this pattern only in Glacier National Park. Occurrence of A. macrodactylum increased as UV-B increased in Olympic National Park despite UV-B levels similar to those recorded in Glacier. We also found marginal support for a negative association with UV-B for P. regilla in one of the two parks where it occurred. We did not find evidence of a negative UV-B effect for any other species. Much more work is still needed to determine whether UV-B, either alone or in concert with other factors, is causing widespread population losses in amphibians.

Space-based estimation of the solar UV-B doses for psoriasis heliotherapy in Poland using OMI data for the period 2005-2011.

PubMed

Krzyścin, J W; Jarosławski, J; Rajewska-Więch, B; Sobolewski, P S; Narbutt, J; Lesiak, A; Pawlaczyk, M; Janouch, M

2012-12-05

A UV model is proposed to reconstruct the biologically weighted doses at the ground-level, erythemal, vitamin D(3), and antipsoriatic effective doses, based on the space data from the Ozone Monitoring Instrument on board of NASA EOS Aura spacecraft for the period 2005-2011. The model is training using the results of spectral UV measurements carried out at Belsk, Poland. The model outcome is verified using the UV spectra measured at Hradec Kralove, Czech Republic. The model uncertainty is almost the same for all examined action spectra and comparable to that found in earlier studies on differences between the satellite overpasses and ground-based erythemal data. Antipsoriatic doses, taken during 2h exposure periods near local noon, are reconstructed for selected sites in Poland to find if heliotherapy would be an alternative to standard treatment of psoriasis by tube irradiation in medical cabinets. Mountain-resort in the southern Poland, Zakopane, and rural-site in Central Poland, Belsk, are among the best location of potential heliotherapy centers in Poland for late spring/summer season. Łeba, resort on the Baltic Sea coast, is a potential heliotherapy center in June and July. The methodology to disclose possible heliotherapy periods over the territory of Poland could be extended to any region. It would help to prepare an optimal schedule of antipsoriatic heliotherapy that accounts for local weather conditions and medical standards of using UV cabinets. Copyright © 2012 Elsevier B.V. All rights reserved.

The activity of the inosine triphosphate pyrophosphatase affects toxicity of 6-mercaptopurine during maintenance therapy for acute lymphoblastic leukemia in Japanese children.

PubMed

Tanaka, Yoichi; Manabe, Atsushi; Nakadate, Hisaya; Kondoh, Kensuke; Nakamura, Kozue; Koh, Katsuyoshi; Utano, Tomoyuki; Kikuchi, Akira; Komiyama, Takako

2012-05-01

The association between inosine triphosphate pyrophosphatase (ITPA) activity and toxicity of 6-mercaptopurine (6-MP) was retrospectively evaluated in 65 Japanese children with acute lymphoblastic leukemia (ALL). Patients with an ITPA activity of less than 126 μmol/h/gHb presented with hepatotoxicity more frequently than those with higher ITPA activity (p<0.01). The average 6-MP dose during maintenance therapy administered to two patients with the ITPA deficiency was lower than that given to the other patients. Measuring ITPA activity is important for ensuring the safety of maintenance therapy for Asians with ALL because thiopurine S-methyl transferase mutations are rare in the Asian population. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effectiveness of UV-C radiation for facility-wide environmental disinfection to reduce health care-acquired infections.

PubMed

Napolitano, Nathanael A; Mahapatra, Tanmay; Tang, Weiming

2015-12-01

Health care-acquired infections (HAIs) constitute an increasing threat for patients worldwide. Potential contributors of HAIs include environmental surfaces in health care settings, where ultraviolet-C radiation (UV-C) is commonly used for disinfection. This UV-C intervention-based pilot study was conducted in a hospital setting to identify any change in the incidence of HAIs before and after UV-C intervention, and to determine the effectiveness of UV-C in reducing pathogens. In a hospital in Culver City, CA, during 2012-2013, bactericidal doses of UV-C radiation (254 nm) were delivered through a UV-C-based mobile environmental decontamination unit. The UV-C dosing technology and expertise of the specifically trained personnel were provided together as a dedicated service model by a contracted company. The incidence of HAIs before and after the intervention period were determined and compared. The dedicated service model dramatically reduced HAIs (incidence difference, 1.3/1000 patient-days, a 34.2% reduction). Reductions in the total number and incidence proportions (28.8%) of HAIs were observed after increasing and maintaining the coverage of UV-C treatments. The dedicated service model was found to be effective in decreasing the incidence of HAIs, which could reduce disease morbidity and mortality in hospitalized patients. This model provides a continuously monitored and frequently UV-C-treated patient environment. This approach to UV-C disinfection was associated with a decreased incidence of HAIs. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Short- and long-term physiological responses of grapevine leaves to UV-B radiation.

PubMed

Martínez-Lüscher, J; Morales, F; Delrot, S; Sánchez-Díaz, M; Gomés, E; Aguirreolea, J; Pascual, I

2013-12-01

The present study aimed at evaluating the short- and long-term effects of UV-B radiation on leaves of grapevine Vitis vinifera (cv. Tempranillo). Grapevine fruit-bearing cuttings were exposed to two doses of supplemental biologically effective UV-B radiation (UV-BBE) under glasshouse-controlled conditions: 5.98 and 9.66kJm(-2)d(-1). The treatments were applied either for 20d (from mid-veraison to ripeness) or 75d (from fruit set to ripeness). A 0kJm(-2)d(-1) UV-B treatment was included as control. The main effects of UV-B were observed after the short-term exposure (20d) to 9.66kJm(-2)d(-1). Significant decreases in net photosynthesis, stomatal conductance, sub-stomatal CO2 concentration, the actual photosystem II (PSII) efficiency, total soluble proteins and de-epoxidation state of the VAZ cycle were observed, whereas the activities of several antioxidant enzymes increased significantly. UV-B did not markedly affect dark respiration, photorespiration, the maximum potential PSII efficiency (Fv/Fm), non-photochemical quenching (NPQ), as well as the intrinsic PSII efficiency. However, after 75d of exposure to 5.98and 9.66kJm(-2)d(-1) UV-B most photosynthetic and biochemical variables were unaffected and there were no sign of oxidative damage in leaves. The results suggest a high long-term acclimation capacity of grapevine to high UV-B levels, associated with a high accumulation of UV-B absorbing compounds in leaves, whereas plants seemed to be tolerant to moderate doses of UV-B. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Inactivation of antibiotic resistance genes in municipal wastewater by chlorination, ultraviolet, and ozonation disinfection.

PubMed

Zhuang, Yao; Ren, Hongqiang; Geng, Jinju; Zhang, Yingying; Zhang, Yan; Ding, Lili; Xu, Ke

2015-05-01

This study investigated the inactivation of two antibiotic resistance genes (ARGs)-sul1 and tetG, and the integrase gene of class 1 integrons-intI1 by chlorination, ultraviolet (UV), and ozonation disinfection. Inactivation of sul1, tetG, and intI1 underwent increased doses of three disinfectors, and chlorine disinfection achieved more inactivation of ARGs and intI1 genes (chlorine dose of 160 mg/L with contact time of 120 min for 2.98-3.24 log reductions of ARGs) than UV irradiation (UV dose of 12,477 mJ/cm(2) for 2.48-2.74 log reductions of ARGs) and ozonation disinfection (ozonation dose of 177.6 mg/L for 1.68-2.55 log reductions of ARGs). The 16S rDNA was more efficiently removed than ARGs by ozone disinfection. The relative abundance of selected genes (normalized to 16S rDNA) increased during ozonation and with low doses of UV and chlorine disinfection. Inactivation of sul1 and tetG showed strong positive correlations with the inactivation of intI1 genes (for sul1, R (2)  = 0.929 with p < 0.01; for tetG, R (2)  = 0.885 with p < 0.01). Compared to other technologies (ultraviolet disinfection, ozonation disinfection, Fenton oxidation, and coagulation), chlorination is an alternative method to remove ARGs from wastewater effluents. At a chlorine dose of 40 mg/L with 60 min contact time, the selected genes inactivation efficiency could reach 1.65-2.28 log, and the cost was estimated at 0.041 yuan/m(3).

Pulsed UV laser light on Escherichia coli and Saccharomyces cerevisiae suspended in non-alcoholic beer

PubMed Central

Hosseini, SM; Azar-Daryany, MK; Massudi, R; Elikaei, A

2011-01-01

Background The aim of this study was to investigate the effect of pulsed ultra-violet (UV) irradiation on inactivation of beer spoilage microorganisms. UV irradiation is nowadays cost effective enough to compete with traditional biological, physical, and chemical treatment technologies and has become an alternative to such methods. Material and Methods Photoinactivation effects of pulsed UV laser with the wavelengths of 355 and 266 nm, which inactivate typical prokaryotic (Escherichia coli) and eukaryotic (Saccharomyces cerevisiae) microorganisms, were examined with different doses and exposure times. Results A dose of 100 J/cm2 of the 355 nm pulsed UV laser was able to reduce about 1 to 2 log (88.75%) of E.coli with the population of 1.6×108 colony-forming units (CFU/ml), and 97% of 3.2×107, 3×106, 5.5×105, and 9×104 CFU/ml. In the case of 266 nm, more than 99% reduction in E. coli serial dilutions was inactivated, using 10 J/cm2 with exception of 7×104 CFU/ml which was not detected any bacterial growth using 5 J/cm2. In addition, 50, 40, and 20 J/cm2 energy were used successfully to inactivate S. cerevisiae at the populations of 5.4×106, 7×105, 5×104 and 4×103 CFU/ml, respectively. As a result, pulsed UV Laser with 266 nm was strong enough to inactivate a high titer of bacterial and yeast indicator standards suspended in non-alcoholic beer in comparison with 355nm doses. Conclusion Results indicate that pulsed UV technology, in principle, is an attractive alternative to conventional methods for the inactivation of indicator microorganisms and has potential in irradiation of unpasteurized beer. PMID:22347580

Characteristics and fate of natural organic matter during UV oxidation processes.

PubMed

Ahn, Yongtae; Lee, Doorae; Kwon, Minhwan; Choi, Il-Hwan; Nam, Seong-Nam; Kang, Joon-Wun

2017-10-01

Advanced oxidation processes (AOPs) are widely used in water treatments. During oxidation processes, natural organic matter (NOM) is modified and broken down into smaller compounds that affect the characteristics of the oxidized NOM by AOPs. In this study, NOM was characterized and monitored in the UV/hydrogen peroxide (H 2 O 2 ) and UV/persulfate (PS) processes using a liquid chromatography-organic carbon detector (LC-OCD) technique, and a combination of excitation-emission matrices (EEM) and parallel factor analysis (PARAFAC). The percentages of mineralization of NOM in the UV/H 2 O 2 and UV/PS processes were 20.5 and 83.3%, respectively, with a 10 mM oxidant dose and a contact time of 174 s (UV dose: approximately 30,000 mJ). Low-pressure, Hg UV lamp (254 nm) was applied in this experiment. The steady-state concentration of SO 4 - was 38-fold higher than that of OH at an oxidant dose of 10 mM. With para-chlorobenzoic acid (pCBA) as a radical probe compound, we experimentally determined the rate constants of Suwannee River NOM (SRNOM) with OH (k OH/NOM  = 3.3 × 10 8  M -1 s -1 ) and SO 4 - (k SO4-/NOM  = 4.55 × 10 6  M -1 s -1 ). The hydroxyl radical and sulfate radical showed different mineralization pathways of NOM, which have been verified by the use of LC-OCD and EEM/PARAFAC. Consequently, higher steady-state concentrations of SO 4 - , and different reaction preferences of OH and SO 4 - with the NOM constituent had an effect on the mineralization efficiency. Copyright © 2017 Elsevier Ltd. All rights reserved.

UV Tolerance of Spoilage Microorganisms and Acid-Shocked and Acid-Adapted Escherichia coli in Apple Juice Treated with a Commercial UV Juice-Processing Unit.

PubMed

Usaga, Jessie; Padilla-Zakour, Olga I; Worobo, Randy W

2016-02-01

The enhanced thermal tolerance and survival responses of Escherichia coli O157:H7 in acid and acidified foods is a major safety concern for the production of low-pH products, including beverages. Little is known about this phenomenon when using UV light treatments. This study was conducted to evaluate the effects of strain (E. coli O157:H7 strains C7927, ATCC 35150, ATCC 43895, and ATCC 43889 and E. coli ATCC 25922) and physiological state (control-unadapted, acid adapted, and acid shocked) on the UV tolerance of E. coli in apple juice treated under conditions stipulated in current U.S. Food and Drug Administration regulations. A greater than 5-log reduction of E. coli was obtained under all tested conditions. A significant effect of strain (P < 0.05) was observed, but the physiological state did not influence pathogen inactivation (P ≥ 0.05). The UV sensitivity of three spoilage microorganisms (Aspergillus niger, Penicillium commune, and Alicyclobacillus acidoterrestris) was also determined at UV doses of 0 to 98 mJ/cm(2). Alicyclobacillus was the most UV sensitive, followed by Penicillium and Aspergillus. Because of the nonsignificant differences in UV sensitivity of E. coli in different physiological states, the use of an unadapted inoculum would be adequate to conduct challenge studies with the commercial UV unit used in this study at a UV dose of 14 mJ/cm(2). The high UV tolerance of spoilage microorganisms supports the need to use a hurdle approach (e.g., coupling of refrigeration, preservatives, and/or other technologies) to extend the shelf life of UV-treated beverages.

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181.

PubMed

Schmitt, J; Haufe, E; Trautmann, F; Schulze, H-J; Elsner, P; Drexler, H; Bauer, A; Letzel, S; John, S M; Fartasch, M; Brüning, T; Seidler, A; Dugas-Breit, S; Gina, M; Weistenhöfer, W; Bachmann, K; Bruhn, I; Lang, B M; Bonness, S; Allam, J P; Grobe, W; Stange, T; Westerhausen, S; Knuschke, P; Wittlich, M; Diepgen, T L

2018-02-01

Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting. © 2017 British Association of Dermatologists.

Rapid transcriptome responses of maize (Zea mays) to UV-B in irradiated and shielded tissues

PubMed Central

Casati, Paula; Walbot, Virginia

2004-01-01

Background Depletion of stratospheric ozone has raised terrestrial levels of ultraviolet-B radiation (UV-B), an environmental change linked to an increased risk of skin cancer and with potentially deleterious consequences for plants. To better understand the processes of UV-B acclimation that result in altered plant morphology and physiology, we investigated gene expression in different organs of maize at several UV-B fluence rates and exposure times. Results Microarray hybridization was used to assess UV-B responses in directly exposed maize organs and organs shielded by a plastic that absorbs UV-B. After 8 hours of high UV-B, the abundance of 347 transcripts was altered: 285 were increased significantly in at least one organ and 80 were downregulated. More transcript changes occurred in directly exposed than in shielded organs, and the levels of more transcripts were changed in adult compared to seedling tissues. The time course of transcript abundance changes indicated that the response kinetics to UV-B is very rapid, as some transcript levels were altered within 1 hour of exposure. Conclusions Most of the UV-B regulated genes are organ-specific. Because shielded tissues, including roots, immature ears, and leaves, displayed altered transcriptome profiles after exposure of the plant to UV-B, some signal(s) must be transmitted from irradiated to shielded tissues. These results indicate that there are integrated responses to UV-B radiation above normal levels. As the same total UV-B irradiation dose applied at three intensities elicited different transcript profiles, the transcriptome changes exhibit threshold effects rather than a reciprocal dose-effect response. Transcriptome profiling highlights possible signaling pathways and molecules for future research. PMID:15003119

Solar UV dose patterns in Italy.

PubMed

Meloni, D; Casale, G R; Siani, A M; Palmieri, S; Cappellani, F

2000-06-01

Since 1992 solar ultraviolet (UV) spectral irradiance (290-325 nm) has been measured at two Italian stations of Rome (urban site) and Ispra (semirural site) using Brewer spectrophotometry. The data collected under all sky conditions, are compared with the output of a sophisticated radiative transfer model (System for Transfer of Atmospheric Radiation--STAR model). The STAR multiple scattering scheme is able to cope with all physical processes relevant to the UV transfer through the atmosphere. The experience so far acquired indicates that, in spite of the unavoidable uncertainties in the input parameters (ozone, aerosol, surface albedo, pressure, temperature, relative humidity, cloud cover), measured and computed clear sky iradiances are in reasonable agreement. The STAR model is applied to build up the solar UV geographic patterns in Italy: the daily dose in the range 290-325 nm is computed at about 70 sites where a thorough and homogeneous climatology is available. For each month the concept of an idealized "standard day" is introduced and the surface distribution of solar UV field determined. The map of solar UV patterns for Italy, available for the first time, meets the study requirements in the field of skin and eye epidemiology, as well as in other investigations dealing with the impact of UV on the biosphere. The results are interpreted in terms of atmospheric and meteorological parameters modulating UV radiation reaching the ground.

Low pressure ultraviolet studies for inactivation of Giardia muris cysts.

PubMed

Hayes, S L; Rice, E W; Ware, M W; Schaefer, F W

2003-01-01

The research was initiated to confirm earlier ultraviolet (u.v.) light inactivation studies performed on Giardia cysts using excystation as the viability indicator. Following this, a comparison of in vitro excystation and animal infectivity was performed for assessing cyst viability after exposure to low-pressure u.v. irradiation. Cysts of Giardia muris were inactivated using a low-pressure u.v. light source. Giardia muris was employed as a surrogate for the human pathogen Giardia lamblia. Cyst viability was determined by both in vitro excystation and animal infectivity. Cyst doses were counted using a flow cytometer for the animal infectivity experiments. Using in vitro excystation as the viability indicator, fluences as high as approximately 200 mJ cm(-2) did not prevent some cysts from excysting, thus verifying earlier work. Using animal infectivity, u.v. fluences of 1.4, 1.9 and 2.3 mJ cm(-2) yielded log10 reductions ranging from 0.3 to >or= 4.4. Results indicate that in vitro excystation is not a reliable indicator of G. muris cyst viability after u.v. disinfection. Very low doses of u.v. light rendered G. muris cysts non-infective in the mouse model employed. Data presented represent the only complete u.v. inactivation curve for G. muris. This research provides evidence that u.v. can be an effective barrier against Giardia spp. in the treatment of drinking water supplies.

Calibration of optimal use parameters for an ultraviolet light-emitting diode in eliminating bacterial contamination on needleless connectors.

PubMed

Hutchens, M P; Drennan, S L; Cambronne, E D

2015-06-01

Needleless connectors may develop bacterial contamination and cause central-line-associated bloodstream infections (CLABSI) despite rigorous application of best-practice. Ultraviolet (UV) light-emitting diodes (LED) are an emerging, increasingly affordable disinfection technology. We tested the hypothesis that a low-power UV LED could reliably eliminate bacteria on needleless central-line ports in a laboratory model of central-line contamination. Needleless central-line connectors were inoculated with Staphylococcus aureus. A 285 nm UV LED was used in calibrated fashion to expose contaminated connectors. Ports were directly applied to agar plates and flushed with sterile saline, allowing assessment of bacterial survival on the port surface and in simulated usage flow-through fluid. UV applied to needleless central-line connectors was highly lethal at 0·5 cm distance at all tested exposure times. At distances >1·5 cm both simulated flow-through and port surface cultures demonstrated significant bacterial growth following UV exposure. Logarithmic-phase S. aureus subcultures were highly susceptible to UV induction/maintenance dosing. Low-power UV LED doses at fixed time and distance from needleless central-line connector ports reduced cultivable S. aureus from >10(6) CFU to below detectable levels in this laboratory simulation of central-line port contamination. Low-power UV LEDs may represent a feasible alternative to current best-practice in connector decontamination. © 2015 The Society for Applied Microbiology.

The impact of background organic matter and alkalinity on the degradation of the pesticide metaldehyde by two advanced oxidation processes: UV/H₂O₂ and UV/TiO₂.

PubMed

Autin, Olivier; Hart, Julie; Jarvis, Peter; MacAdam, Jitka; Parsons, Simon A; Jefferson, Bruce

2013-04-15

The impact of background constituents on the degradation of trace levels of micropollutants by two advanced oxidation processes: UV/H₂O₂ and UV/TiO₂ was studied. Experimental results demonstrated that the background scavenging rate rather than the concentration of micropollutant controls the required UV irradiation dose. The character of the natural organic matter had a limited impact on scavenging when the water source remains unchanged, however, a periodic bleed of hydrophobic material may substantially increase the minimum UV dose required to reach the desired micropollutant concentration. Moreover, in the case of UV/TiO₂, high concentrations of background organic matter do not only act as scavengers but also saturate the TiO₂ surface. Alkalinity inhibits the efficacy of UV/TiO₂ photocatalysis due to the formation of large TiO₂ aggregates. The study also demonstrated that the use of synthetic waters for treatability test purposes was an acceptable approach as long as both the background organic matter and the alkalinity were matched to that of the projected application. Finally spiking micropollutants at higher concentrations does not alter the significance of the findings as long as the background constituents represent more than 85% of the total scavenging rate. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effect of UV-C exposure on larval survival of the dreissenid quagga mussel

USGS Publications Warehouse

Stewart-Malone, Alecia; Misamore, Michael; Wilmoth, Siri K.; Reyes, Alejandro; Wong, Wai Hing; Gross, Jackson

2015-01-01

The rapid spread of quagga mussels (Dreissena rostriformis bugensis) has lead to their invasion of Lake Mead, Nevada, the largest reservoir in North America and partially responsible for providing water to millions of people in the southwest. Current strategies for mitigating the growth and spread of quagga mussels primarily include physical and chemical means of removing adults within water treatment, delivery, and hydropower facilities. In the present study, germicidal ultraviolet light (UV-C) was used to target the larval stage of wild-caught quagga mussel. The lethal effect of UV-C was evaluated at four different doses, 0.0, 13.1, 26.2, and 79.6 mJ/cm2. Tested doses were determined based on results from preliminary trials. The results demonstrate that germicidal UV-C is effective in controlling the free-swimming life history stages of larval quagga mussels.

The Effect of UV-C Exposure on Larval Survival of the Dreissenid Quagga Mussel

PubMed Central

Stewart-Malone, Alecia; Misamore, Michael; Wilmoth, Siri; Reyes, Alejandro; Wong, Wai Hing; Gross, Jackson

2015-01-01

The rapid spread of quagga mussels (Dreissena rostriformis bugensis) has lead to their invasion of Lake Mead, Nevada, the largest reservoir in North America and partially responsible for providing water to millions of people in the southwest. Current strategies for mitigating the growth and spread of quagga mussels primarily include physical and chemical means of removing adults within water treatment, delivery, and hydropower facilities. In the present study, germicidal ultraviolet light (UV-C) was used to target the larval stage of wild-caught quagga mussel. The lethal effect of UV-C was evaluated at four different doses, 0.0, 13.1, 26.2, and 79.6 mJ/cm2. Tested doses were determined based on results from preliminary trials. The results demonstrate that germicidal UV-C is effective in controlling the free-swimming life history stages of larval quagga mussels. PMID:26186734

Interactive lethal and mutagenic effects of ultraviolet light and bleomycin in yeast: synergism or antagonism?

PubMed

Lillo, O L; Severgnini, A A; Nunes, E M

1997-11-01

The mutagenic interactions of ultraviolet light and bleomycin in haploid populations of Saccharomyces cerevisiae were analyzed. Survival and mutation frequency as a function of different bleomycin concentrations after one conditioning dose of UV radiation were determined. Furthermore, corresponding interaction functions and sensitization factors were calculated. A synergistic interaction between UV light and bleomycin was shown for both lethal and mutagenic events when the cells were in nutrient broth during the treatments. Conversely, the interaction between UV light and bleomycin was antagonistic when the cells were in deionized water during the treatment. The magnitude of lethal and mutagenic interactions depends on dose, and thus presumably on the number of lesions. The observed interactions between UV light and bleomycin suggest that the mechanism that is most likely involved is the induction of repair systems with different error probabilities during the delay of cell division.

Variations in the S and P regions of the hepatitis B virus genome under immunosuppression in vitro and in vivo.

PubMed

Shen, Zhong-Yang; Zheng, Wei-Ping; Deng, Yong-Lin; Song, Hong-Li

2012-10-01

To provide a basis for improved prevention and treatment of hepatitis B virus (HBV) re-infection after liver transplantation, variations in the S and P genes of HBV under immunosuppression in vitro and their association with patient prognosis were investigated. For the in vitro study, HepG2.2.15 hepatocellular carcinoma cells stably producing HBV particles were treated with the immunosuppressants methylprednisolone (MP) and tacrolimus (FK506) at doses found to be non-toxic by the methylthiazolyl tetrazolium (MTT) cell viability assay. MP dose-dependently inhibited HBV DNA expression in HepG2.2.15 cells, while FK506 did not, as determined by quantitative real-time PCR (qRT-PCR). By gene sequencing, both MP and FK506 were found to cause variations in HBV S, P, and S/P overlapping regions. MP- but not FK506-induced mutations were common in the glucocorticoid response element of the P region, while both immunosuppressants caused mutations outside the nucleoside analogue resistance sites. For the in vivo study, 14 patients with HBV-related end-stage liver disease re-infected after liver transplantation, and 20 cases without HBV re-infection as controls, were studied. Seventy-five percent of re-infected recipients showed multi-loci amino acid mutations at different sites besides lamivudine (LAM)-resistant loci in the P region, including in the glucocorticoid response element. Fifty percent of re-infected recipients had mutations in the "a" determinant region and flanking sequences. Re-infection was associated with negative serum hepatitis B immunoglobulin (HBIG), as measured by a microparticle capture enzyme immunoassay. Nucleotide mutations in the S region caused missense or synonymous mutations, which caused synonymous mutations in the overlapping P region. These results showed that effects of immunosuppressants on HBV genes in vitro were different from those in clinical recipients. Positive HBV DNA and gene mutations pre-transplantation were factors affecting re-infection post-transplantation. Multiple mutations found in the P and S genes suggest that the formation of quasispecies contributes to HBV re-infection after liver transplantation.

Complete data preparation flow for Massively Parallel E-Beam lithography on 28nm node full-field design

NASA Astrophysics Data System (ADS)

Fay, Aurélien; Browning, Clyde; Brandt, Pieter; Chartoire, Jacky; Bérard-Bergery, Sébastien; Hazart, Jérôme; Chagoya, Alexandre; Postnikov, Sergei; Saib, Mohamed; Lattard, Ludovic; Schavione, Patrick

2016-03-01

Massively parallel mask-less electron beam lithography (MP-EBL) offers a large intrinsic flexibility at a low cost of ownership in comparison to conventional optical lithography tools. This attractive direct-write technique needs a dedicated data preparation flow to correct both electronic and resist processes. Moreover, Data Prep has to be completed in a short enough time to preserve the flexibility advantage of MP-EBL. While the MP-EBL tools have currently entered an advanced stage of development, this paper will focus on the data preparation side of the work for specifically the MAPPER Lithography FLX-1200 tool [1]-[4], using the ASELTA Nanographics Inscale software. The complete flow as well as the methodology used to achieve a full-field layout data preparation, within an acceptable cycle time, will be presented. Layout used for Data Prep evaluation was one of a 28 nm technology node Metal1 chip with a field size of 26x33mm2, compatible with typical stepper/scanner field sizes and wafer stepping plans. Proximity Effect Correction (PEC) was applied to the entire field, which was then exported as a single file to MAPPER Lithography's machine format, containing fractured shapes and dose assignments. The Soft Edge beam to beam stitching method was employed in the specific overlap regions defined by the machine format as well. In addition to PEC, verification of the correction was included as part of the overall data preparation cycle time. This verification step was executed on the machine file format to ensure pattern fidelity and accuracy as late in the flow as possible. Verification over the full chip, involving billions of evaluation points, is performed both at nominal conditions and at Process Window corners in order to ensure proper exposure and process latitude. The complete MP-EBL data preparation flow was demonstrated for a 28 nm node Metal1 layout in 37 hours. The final verification step shows that the Edge Placement Error (EPE) is kept below 2.25 nm over an exposure dose variation of 8%.

The effect of ultraviolet radiation on the cornea - experimental study.

PubMed

Golu, Andreea; Gheorghişor, Irina; Bălăşoiu, A T; Baltă, Fl; Osiac, E; Mogoantă, L; Bold, Adriana

2013-01-01

Ultraviolet (UV) radiation in high doses may have harmful effects on the eye. The sources of UV radiation are the sun, as well as some artificial sources such as UV lamps or voltaic arcs. Chronic exposure to UV can cause damage to the anterior pole of the eye, ranging from minor (pterygium) to serious photokeratitis. In our study, we applied a UV dose of 6.5 J/cm(2) in the wavelength range of 290-400 nm, for five consecutive days per rat anterior pole of the eye. Seven days after the last dose of radiation, the animals were sacrificed, harvesting both the irradiated and the non-irradiated eye. Histological and immunohistochemical examination of the lesions revealed that the greatest damage to the epithelium was recorded prior to and 2/3 of the remaining corneal stroma. The epithelial lesions we found varied from pseudokeratosis and detachment of the Bowman epithelium membrane to deep epithelial necrosis. Within the corneal stroma, we observed the formation of interstitial edema with disruption of the collagen structure. We also noticed the presence of an inflammatory infiltrate composed mainly of lymphocytes and CD68+ and CD163+ macrophages, as well as the occurrence of vascular devices. These consisted of angiogenesis capillaries with structured wall composed mainly of endothelial CD34+ precursor cells and a basal membrane rich in collagen IV fibers.

UV-induced lethal sectoring and pure mutant clones in yeast.

PubMed

Hannan, M A; Duck, P; Nasim, A

1976-08-01

The induction of lethal sectoring and pure mutant clones by ultraviolet light has been studied in a homogeneous G1 population of Saccharomyces cerevisiae grown in a normal growth medium. At the lowest UV dose of 250 ergs, which corresponds to a shoulder in the survival curve, all mutants appeared as pure clones. At higher doses the frequency of mosaic mutants progressively increased. These results indicate a relationship between the highest frequency of complete mutants and the maximum repair activity. In addition, the frequency of lethal sectoring at all doses tested was too low to account for the origin of pure mutant clones.

Daily, seasonal, and latitudinal variations in solar ultraviolet A and B radiation in relation to vitamin D production and risk for skin cancer.

PubMed

Grigalavicius, Mantas; Moan, Johan; Dahlback, Arne; Juzeniene, Asta

2016-01-01

Solar ultraviolet (UV) radiation varies with latitude, time of day, and season. Both spectral UV composition and ambient UV dose lead to different health outcomes at different latitudes. Finding the optimal time for sun exposure, whereby the positive effects of UV exposure (vitamin D) are facilitated and the negative effects (skin cancer, photoimmunosuppression) avoided are the most important consideration in modern skin cancer prevention programs. This paper focuses on the latitude dependency of UVB, UVA, vitamin D production, and skin cancer risk in Caucasians. Biologically effective UVB (280-315 nm) and UVA (315-400 nm) doses were calculated using radiative transfer models with appropriate climatologic data for selected locations. Incidences of squamous cell carcinoma (SCC) and cutaneous melanoma (CM) were retrieved from cancer registries and published articles. Annual doses of UVA radiation decrease much less with increasing latitude than annual doses of UVB. Incidences of CM also decrease less steeply with increasing latitude than incidences of SCC. As SCC is caused mainly by UVB, these observations support the assumption that UVA plays an important role in the development of CM. The variations in UVA (relevant to CM) and UVB (relevant to vitamin D production) over 1 day differ: the UVB : UVA ratio is maximal at noon. The best way to obtain a given dose of vitamin D with minimal carcinogenic risk is through a non-burning exposure in the middle of the day, rather than in the afternoon or morning. © 2015 The International Society of Dermatology.

The Effect of p53 Status of Tumor Cells on Radiosensitivity of Irradiated Tumors With Carbon-Ion Beams Compared With γ-Rays or Reactor Neutron Beams.

PubMed

Masunaga, Shin-Ichiro; Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Sakurai, Yoshinori; Tanaka, Hiroki; Tano, Keizo; Sanada, Yu; Suzuki, Minoru; Maruhashi, Akira; Ono, Koji

2015-08-01

The aim of the study was to clarify the effect of p53 status of tumor cells on radiosensitivity of solid tumors following accelerated carbon-ion beam irradiation compared with γ-rays or reactor neutron beams, referring to the response of intratumor quiescent (Q) cells. Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into hind legs of nude mice. Tumor-bearing mice received 5-bromo-2'-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays or accelerated carbon-ion beams at a high or reduced dose-rate. Other tumor-bearing mice received reactor thermal or epithermal neutrons at a reduced dose-rate. Immediately or 9 hours after the high dose-rate irradiation (HDRI), or immediately after the reduced dose-rate irradiation (RDRI), the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The difference in radiosensitivity between the total (P + Q) and Q cells after γ-ray irradiation was markedly reduced with reactor neutron beams or carbon-ion beams, especially with a higher linear energy transfer (LET) value. Following γ-ray irradiation, SAS/neo tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/mp53 tumors that showed little repair capacity. In both total and Q cells within both SAS/neo and SAS/mp53 tumors, carbon-ion beam irradiation, especially with a higher LET, showed little recovery capacity through leaving an interval between HDRI and the assay or decreasing the dose-rate. The recovery from radiation-induced damage after γ-ray irradiation was a p53-dependent event, but little recovery was found after carbon-ion beam irradiation. With RDRI, the radiosensitivity to reactor thermal and epithermal neutron beams was slightly higher than that to carbon-ion beams. For tumor control, including intratumor Q-cell control, accelerated carbon-ion beams, especially with a higher LET, and reactor thermal and epithermal neutron beams were very useful for suppressing the recovery from radiation-induced damage irrespective of p53 status of tumor cells.

The Effect of p53 Status of Tumor Cells on Radiosensitivity of Irradiated Tumors With Carbon-Ion Beams Compared With γ-Rays or Reactor Neutron Beams

PubMed Central

Masunaga, Shin-ichiro; Uzawa, Akiko; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Sakurai, Yoshinori; Tanaka, Hiroki; Tano, Keizo; Sanada, Yu; Suzuki, Minoru; Maruhashi, Akira; Ono, Koji

2015-01-01

Background The aim of the study was to clarify the effect of p53 status of tumor cells on radiosensitivity of solid tumors following accelerated carbon-ion beam irradiation compared with γ-rays or reactor neutron beams, referring to the response of intratumor quiescent (Q) cells. Methods Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into hind legs of nude mice. Tumor-bearing mice received 5-bromo-2’-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays or accelerated carbon-ion beams at a high or reduced dose-rate. Other tumor-bearing mice received reactor thermal or epithermal neutrons at a reduced dose-rate. Immediately or 9 hours after the high dose-rate irradiation (HDRI), or immediately after the reduced dose-rate irradiation (RDRI), the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. Results The difference in radiosensitivity between the total (P + Q) and Q cells after γ-ray irradiation was markedly reduced with reactor neutron beams or carbon-ion beams, especially with a higher linear energy transfer (LET) value. Following γ-ray irradiation, SAS/neo tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/mp53 tumors that showed little repair capacity. In both total and Q cells within both SAS/neo and SAS/mp53 tumors, carbon-ion beam irradiation, especially with a higher LET, showed little recovery capacity through leaving an interval between HDRI and the assay or decreasing the dose-rate. The recovery from radiation-induced damage after γ-ray irradiation was a p53-dependent event, but little recovery was found after carbon-ion beam irradiation. With RDRI, the radiosensitivity to reactor thermal and epithermal neutron beams was slightly higher than that to carbon-ion beams. Conclusion For tumor control, including intratumor Q-cell control, accelerated carbon-ion beams, especially with a higher LET, and reactor thermal and epithermal neutron beams were very useful for suppressing the recovery from radiation-induced damage irrespective of p53 status of tumor cells. PMID:28983338

Solar UV-A and UV-B radiation fluxes at two Alpine stations at different altitudes

NASA Astrophysics Data System (ADS)

Blumthaler, M.; Ambach, W.; Rehwald, W.

1992-03-01

Daily totals of UV-A and UV-B radiation fluxes and global radiation were measured since 1981 at Jungfraujoch (3576 m) a.s.l.) and in Innsbruck (577 m a.s.l.) in their seasonal course. The altitude effect of annual totals yields 19%/1000 m (UV-B), 11%/1000 m (UV-A) and 9%/1000 m (global radiation) with reference to Innsbruck station. The ratio of the daily totals of UV-B/global radiation shows a significant seasonal course with the maximum in summer, whereas the ratio of the daily totals of UV-A/global radiation shows no significant seasonal variation. The biological effective doses of erythema reaction, delayed tanning and immediate tanning by UV-A and UV-B radiant exposure are reported in the seasonal course at Jungfraujoch and in Innsbruck.

The total ozone and UV solar radiation over Stara Zagora, Bulgaria

NASA Astrophysics Data System (ADS)

Mendeva, B.; Gogosheva, Ts.; Petkov, B.; Krastev, D.

Direct ground-based UV measurements and the total ozone content (TOC) over Stara Zagora, Bulgaria are presented. The observations are conducted by a scanning spectrophotometer, which measures the direct solar radiation in the range 290 - 360 nm with 1 nm resolution. For the time period 1998 -- 2003 the TOC data show seasonal variations, typical for the middle latitudes -- maximum in the spring and minimum in the autumn. The comparison of these TOC ground-based data to TOC satellite-borne data from the Global Ozone Monitoring Experiment (GOME) shows a seasonal dependence of the differences between the ground-based and satellite data. The relation between the UV radiation and TOC is investigated. Clear negative relationship is recognized between the total ozone and the irradiance of the wavelength 305 nm. The opposition of the two variables is significant ( r = - 0,62 ± 0,18) at 98 % confidence level. Yet, for 325 nm it is almost independent with the total ozone. The dependence of the UV-B radiation on the solar zenith angle at given TOC is also analyzed. A decrease of all wavelengths intensities with increase of the solar zenith angle is obtained but with different rate for each of them. The direct sun UV doses for some specific biological effects (erythema and eyes) are obtained as the integral in the wavelength interval 290-330 nm of the measured UV solar spectrum, weighted with an action spectrum, typical for each effect. The estimation of the radiation amplification factor RAF shows that the ozone reduction by 1% increases the erythemal dose by 2,3 %.The eye-damaging doses are more influenced by the TOC changes and in this case RAF=-2,7%. The amount of these biological doses is in a direct ratio with the solar altitude over the horizon. This dependence is more markedly expressed at lower total ozone content in the atmosphere.

Real-Time Monitoring of Vaccination Campaign Performance Using Mobile Phones - Nepal, 2016.

PubMed

Oh, David H; Dabbagh, Alya; Goodson, James L; Strebel, Peter M; Thapa, Sanjita; Giri, Jagat Narain; Shakya, Sagar Ratna; Khanal, Sudhir

2016-10-07

In 2012, the Global Vaccine Action Plan* established a goal to achieve measles and rubella elimination in five of the six World Health Organization (WHO) regions (194 countries) by 2020 (1). Measles elimination strategies aim to achieve ≥95% coverage with 2 routine doses of measles-containing vaccine (2), and implement supplementary immunization activities (SIAs) † in settings where routine coverage is low or where there are subpopulations at high risk. To ensure SIA quality and to achieve ≥95% SIA coverage nationally, rapid convenience monitoring (RCM) is used during or immediately after SIAs (3,4). The objective of RCM is to find unvaccinated children and to identify reasons for nonvaccination in areas with persons at high risk, to enable immediate implementation of corrective actions (e.g., reassigning teams to poorly vaccinated areas, modifying the timing of vaccination, or conducting mop-up vaccination activities). This report describes pilot testing of RCM using mobile phones (RCM-MP) during the second phase of an SIA in Nepal in 2016. Use of RCM-MP resulted in 87% timeliness and 94% completeness of data reporting and found that, although 95% of children were vaccinated, 42% of areas required corrective vaccination activities. RCM-MP challenges included connecting to mobile networks, small phone screen size, and capturing Global Positioning System (GPS) coordinates. Nonetheless, use of RCM-MP led to faster data transmission, analysis, and decision-making and to increased accountability among levels of the health system.

Proof-of-principle that a decoy virus protects oncolytic measles virus against neutralizing antibodies

PubMed Central

Dorneburg, Carmen; Debatin, Klaus-Michael; Wei, Jiwu; Beltinger, Christian

2018-01-01

Background Attenuated oncolytic measles virus (OMV) is a promising antitumor agent in early-phase clinical trials. However, pre-existing immunity against measles might be a hurdle for OMV therapy. Methods OMV was inactivated with short-wavelength ultraviolet light (UV-C). Loss of replication and oncolytic activity of UV-inactivated OMV were confirmed by tissue culture infective dose 50 (TCID50) assay using Vero cells and by flow cytometry using Jurkat cells. An enzyme-linked immunosorbent assay was performed to verify that UV-inactivated OMV remained antigenic. Different doses of UV-inactivated OMV were pre-cultured in media supplemented with measles immune serum. The mixture was transferred to Jurkat cells and active OMV was added. Active OMV-induced death of Jurkat cells was monitored by flow cytometry. Results UV-inactivation abrogates OMV replication while maintaining its antigenicity. UV-inactivated OMV sequesters pre-existing anti-MV antibodies in Jurkat cell culture, thereby protecting active OMV from neutralization and preserving oncolytic activity. Conclusion We prove the principle that a non-replicating OMV can serve as a “decoy” for neutralizing anti-MV antibodies, thereby allowing antitumor activity of OMV. PMID:29750140

Effect of UV irradiation on aflatoxin reduction: a cytotoxicity evaluation study using human hepatoma cell line.

PubMed

Patras, Ankit; Julakanti, Sharath; Yannam, Sudheer; Bansode, Rishipal R; Burns, Mallory; Vergne, Matthew J

2017-11-01

In this proof-of-concept study, the efficacy of a medium-pressure UV (MPUV) lamp source to reduce the concentrations of aflatoxin B 1 , aflatoxin B 2 , and aflatoxin G 1 (AFB 1, AFB 2 , and AFG 1 ) in pure water is investigated. Irradiation experiments were conducted using a collimated beam system operating between 200 to 360 nm. The optical absorbance of the solution and the irradiance of the lamp are considered in calculating the average fluence rate. Based on these factors, the UV dose was quantified as a product of average fluence rate and treatment time. Known concentrations of aflatoxins were spiked in water and irradiated at UV doses ranging from 0, 1.22, 2.44, 3.66, and 4.88 J cm -2 . The concentration of aflatoxins was determined by HPLC with fluorescence detection. LC-MS/MS product ion scans were used to identify and semi-quantify degraded products of AFB 1 , AFB 2 , and AFG 1 . It was observed that UV irradiation significantly reduced aflatoxins in pure water (p < 0.05). Irradiation doses of 4.88 J cm -2 reduced concentrations 67.22% for AFG 1 , 29.77% for AFB 2 , and 98.25% for AFB 1 (p < 0.05). Using this technique, an overall reduction of total aflatoxin content of ≈95% (p < 0.05) was achieved. We hypothesize that the formation of ˙OH radicals initiated by UV light may have caused photolysis of AFB 1 , AFB 2 , and AFG 1 molecules. In cell culture studies, our results demonstrated that the increase of UV dosage decreased the aflatoxin-induced cytotoxicity in HepG 2 cells. Therefore, our research finding suggests that UV irradiation can be used as an effective technique for the reduction of aflatoxins.

A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues.

PubMed

Hibbert, Sarah A; Watson, Rachel E B; Gibbs, Neil K; Costello, Patrick; Baldock, Clair; Weiss, Anthony S; Griffiths, Christopher E M; Sherratt, Michael J

2015-08-01

Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm(2)) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure as a consequence of an evolutionary pressure to express sacrificial protein sunscreens which reduce UVR penetration and hence mitigate tissue damage. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues

PubMed Central

Hibbert, Sarah A.; Watson, Rachel E.B.; Gibbs, Neil K.; Costello, Patrick; Baldock, Clair; Weiss, Anthony S.; Griffiths, Christopher E.M.; Sherratt, Michael J.

2015-01-01

Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm2) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure as a consequence of an evolutionary pressure to express sacrificial protein sunscreens which reduce UVR penetration and hence mitigate tissue damage. PMID:25911998

Ultraviolet-B radiation modifies the quantitative and qualitative profile of flavonoids and amino acids in grape berries.

PubMed

Martínez-Lüscher, J; Torres, N; Hilbert, G; Richard, T; Sánchez-Díaz, M; Delrot, S; Aguirreolea, J; Pascual, I; Gomès, E

2014-06-01

Grapevine cv. Tempranillo fruit-bearing cuttings were exposed to supplemental ultraviolet-B (UV-B) radiation under controlled conditions, in order to study its effect on grape traits, ripening, amino acids and flavonoid profile. The plants were exposed to two doses of UV-B biologically effective (5.98 and 9.66kJm(-2)d(-1)), applied either from fruit set to ripeness or from the onset of veraison to ripeness. A 0kJm(-2)d(-1) treatment was included as a control. UV-B did not significantly modify grape berry size, but increased the relative mass of berry skin. Time to reach ripeness was not affected by UV-B, which may explain the lack of changes in technological maturity. The concentration of must extractable anthocyanins, colour density and skin flavonols were enhanced by UV-B, especially in plants exposed from fruit set. The quantitative and qualitative profile of grape skin flavonols were modified by UV-B radiation. Monosubstituted flavonols relative abundance increased proportionally to the accumulated UV-B doses. Furthermore, trisubstituted forms, which where predominant in non-exposed berries, were less abundant as UV-B exposure increased. Although total free amino acid content remained unaffected by the treatments, the increased levels of gamma-aminobutyric acid (GABA), as well as the decrease in threonine, isoleucine, methionine, serine and glycine, revealed a potential influence of UV-B on the GABA-mediated signalling and amino acid metabolism. UV-B had an overall positive impact on grape berry composition. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of the efficacy of gamma and UV irradiation in sanitization of fresh carrot juice

NASA Astrophysics Data System (ADS)

Jo, Cheorun; Lee, Kyung Haeng

2012-08-01

As there is no pasteurization procedure for the manufacture of fresh vegetable juice, both industry and consumers have sought a method for improving the storage stability and shelf-life of this category of products. In this study, the effects of commercially available, non-thermal pasteurization processes, such as gamma and UV irradiation, were compared for their efficacy in sanitizing fresh carrot juice (FCJ). FCJ was manufactured, packaged, and gamma irradiated with doses of 0, 1, 3, and 5 kGy. The manufactured FCJ was also passed through 4 UV light lamps at doses of 3.67, 4.69, and 6.50 kGy. The total aerobic bacterial count of the FCJ approached the legal limit (105 CFU/mL) after manufacturing. Both treatments were effective in reducing the number of total aerobic bacteria, and the reduced number was maintained during storage for 7 days. Gamma irradiation was more effective in suppressing microbial growth during storage. When the doses for UV treatment and gamma irradiation were higher, the inactivation effects were higher. The reduction of ascorbic acid content was greater upon gamma irradiation than UV treatment. No difference was found in the contents of flavonoids and polyphenols in FCJ after either treatment. After 3 days of refrigerated storage, the sensory scores of gamma- or UV-irradiated FCJ were superior to those of the control. The results indicate that both non-thermal treatments were effective in improving storage stability and extending shelf-life, but gamma irradiation was slightly better in suppressing microbial growth after treatment.

Interactive effects of supplemental ultraviolet-B radiation and indole-3-acetic acid on Coleus forskohlii Briq.: Alterations in morphological-, physiological-, and biochemical characteristics and essential oil content.

PubMed

Takshak, Swabha; Bhushan Agrawal, Shashi

2018-01-01

Ultraviolet (UV)-B radiation and the growth hormone indole-3-acetic acid (IAA) have been known to cause various changes in plants at morphological and physiological levels as individual entities, but their interactive effects on the overall plant performance remain practically unknown. The present study was conducted under near-natural field conditions to evaluate the effects of supplemental (s)-UV-B (ambient+3.6kJm -2 day -1 ) treatment alone, and in combination with two doses of IAA (200ppm and 400ppm) exogenously applied as foliar spray on various growth-, morphological-, physiological-, and biochemical parameters of an indigenous medicinal plant, Coleus forskohlii. Under s-UV-B, the plant growth and morphology were adversely affected (along with reductions in protein- and chlorophyll contents) with concomitant increase in secondary metabolites (as substantiated by an increase in the activities of various enzymes of the phenylpropanoid pathway) and cumulative antioxidative potential (CAP), suggesting the plant's capability of adaptive resilience against UV-B. The essential oil content of the plant was, however, compromised reducing its pharmaceutical value. IAA application at both doses led to a reversal in the effects caused by s-UV-B radiation alone; both the plant growth as well as the essential oil content improved, especially at the higher IAA dose, suggesting its ameliorative role against UV-B induced oxidative stress, and also in improving the plant's medicinal value. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo immunomodulatory, cumulative skin irritation, sensitization and effect of d-limonene on permeation of 6-mercaptopurine through transdermal drug delivery.

PubMed

Chandrashekar, N S; Hiremath, Shobha Rani Rajeev

2008-04-01

Using skin as a port for systemic drug administration, transdermal drug delivery has expanded greatly over the last two decades. Our aim was to formulate the single layer drug-in-adhesive transdermal patch for 6-mercaptopurine (6-MP). In vitro permeation study was carried out using modified Franz diffusion cell with and without of different concentration of d-limonene in human cadaver skin. In vivo immunomodulatory was carried out in mice, cumulative skin irritation, sensitization and patch adherence study was done in both mice and human subjects. 6-MP flux increased from 43+/-12.2 microg/cm2h (control) to 162.8+/-32.2 microg/cm2h (6% w/v d-limonene) data was significant (p<0.05), with decrease in the lag time to 35+/-9.3 min compared to control of 90 +/-15.3 min. In vivo immunomodulatory effect was shown in the Balb/c mice with 100 mumol/kg/body wt of animal for 5d (one dose/d) of d-limonene. WBC count of 13469 cells/mm peak was observed on 12th day, bone marrow cells of 26.3 x 10(6) cells/femur and alpha-esterase positive cells of 1259+/-328.4 cells/4000 bone marrow cells. Cumulative skin irritation, sensitisation and patch adherence in animals and human subjects showed no skin irritation and sensitization. Patch adhesion was greater than 90.0% respectively in both human subjects and mice. The percentage of human subjects with adhesive residue was significantly less with scores of zero. d-Limonene proved as good chemical enhancer by increasing in the skin permeability with shortened the lag time. It proved that therapeutic amount of 6-MP can be delivered through transdermal drug delivery.

A Double-Blind, Active-Controlled Clinical Trial of Sodium Bicarbonate and Calcium Gluconate in the Treatment of Bilateral Osteoarthritis of the Knee.

PubMed

Caamaño, María Del Carmen; García-Padilla, Sandra; Duarte-Vázquez, Miguel Ángel; González-Romero, Karla Elena; Rosado, Jorge L

2017-01-01

To evaluate the effect of intra-articular injections of sodium bicarbonate with a single (SBCG1) or double dose (SBCG2) of calcium gluconate administered monthly compared with methylprednisolone (MP) for treatment of knee osteoarthritis. A 3-month, randomized, double-blind clinical trial with patients diagnosed with knee osteoarthritis (OA). The outcome variables were the Western Ontario-McMaster University Osteoarthritis Index (WOMAC) and the Lequesne functional index. After 3 months, all treatments significantly improved in overall WOMAC and Lequesne scores. Mean changes (95% confidence interval) in WOMAC total score and the Lequesne index, respectively, for SBCG1 (-12.5 [-14.3, -10.7]; -9.0 [-11.4, -6.7]) and SBCG2 (-12.3 [-14.3, -10.4]; -8.9 [-10.4, -7.4]) were significantly greater than for MP (-5.0 [-7.2, -2.8]; -3.2 [-4.9, -1.5]) ( P < .001). Intra-articular injections of sodium bicarbonate and calcium gluconate are useful for short-term relief of OA symptoms in patients with bilateral knee osteoarthritis. Both treatments are more effective than MP injections in the reduction of knee OA symptoms. Clinicaltrials.gov NCT00977444.

Amelioration of ultraviolet-induced photokeratitis in mice treated with astaxanthin eye drops.

PubMed

Lennikov, Anton; Kitaichi, Nobuyoshi; Fukase, Risa; Murata, Miyuki; Noda, Kousuke; Ando, Ryo; Ohguchi, Takeshi; Kawakita, Tetsuya; Ohno, Shigeaki; Ishida, Susumu

2012-01-01

Ultraviolet (UV) acts as low-dose ionizing radiation. Acute UVB exposure causes photokeratitis and induces apoptosis in corneal cells. Astaxanthin (AST) is a carotenoid, present in seafood, that has potential clinical applications due to its high antioxidant activity. In the present study, we examined whether topical administration of AST has preventive and therapeutic effects on UV-photokeratitis in mice. C57BL/6 mice were administered with AST diluted in polyethylene glycol (PEG) in instillation form (15 μl) to the right eye. Left eyes were given vehicle alone as controls. Immediately after the instillation, the mice, under anesthesia, were irradiated with UVB at a dose of 400 mJ/cm². Eyeballs were collected 24 h after irradiation and stained with H&E and TUNEL. In an in vitro study, mouse corneal epithelial (TKE2) cells were cultured with AST before UV exposure to quantify the UV-derived cytotoxicity. UVB exposure induced cell death and thinning of the corneal epithelium. However, the epithelium was morphologically well preserved after irradiation in AST-treated corneas. Irradiated corneal epithelium was significantly thicker in eyes treated with AST eye drops, compared to those treated with vehicles (p<0.01), in a doses dependent manner. Significantly fewer apoptotic cells were observed in AST-treated eyes than controls after irradiation (p<0.01). AST also reduced oxidative stress in irradiated corneas. The in vitro study showed less cytotoxicity of TKE2 cells in AST-treated cultures after UVB-irradiation (p<0.01). The cytoprotective effect increased with the dose of AST. Topical AST administration may be a candidate treatment to limit the damages by UV irradiation with wide clinical applications.

Combination treatment with 6-mercaptopurine and allopurinol in HepG2 and HEK293 cells - Effects on gene expression levels and thiopurine metabolism.

PubMed

Haglund, Sofie; Vikingsson, Svante; Almer, Sven; Söderman, Jan

2017-01-01

Combination treatment with low-dose thiopurine and allopurinol (AP) has successfully been used in patients with inflammatory bowel disease with a so called skewed thiopurine metabolite profile. In red blood cells in vivo, it reduces the concentration of methylated metabolites and increases the concentration of the phosphorylated ones, which is associated with improved therapeutic efficacy. This study aimed to investigate the largely unknown mechanism of AP on thiopurine metabolism in cells with an active thiopurine metabolic pathway using HepG2 and HEK293 cells. Cells were treated with 6-mercaptopurine (6MP) and AP or its metabolite oxypurinol. The expression of genes known to be associated with thiopurine metabolism, and the concentration of thiopurine metabolites were analyzed. Gene expression levels were only affected by AP in the presence of 6MP. The addition of AP to 6MP affected the expression of in total 19 genes in the two cell lines. In both cell lines the expression of the transporter SLC29A2 was reduced by the combined treatment. Six regulated genes in HepG2 cells and 8 regulated genes in HEK293 cells were connected to networks with 18 and 35 genes, respectively, present at known susceptibility loci for inflammatory bowel disease, when analyzed using a protein-protein interaction database. The genes identified as regulated as well as the disease associated interacting genes represent new candidates for further investigation in the context of combination therapy with thiopurines and AP. However, no differences in absolute metabolite concentrations were observed between 6MP+AP or 6MP+oxypurinol vs. 6MP alone in either of the two cell lines. In conclusion; the effect of AP on gene expression levels requires the presence of 6MP, at least in vitro. Previously described AP-effects on metabolite concentrations observed in red blood cells in vivo could not be reproduced in our cell lines in vitro. AP's effects in relation to thiopurine metabolism are complex. The network-identified susceptibility genes represented biological processes mainly associated with purine nucleotide biosynthetic processes, lymphocyte proliferation, NF-KB activation, JAK-STAT signaling, and apoptotic signaling at oxidative stress.

Combination treatment with 6-mercaptopurine and allopurinol in HepG2 and HEK293 cells – Effects on gene expression levels and thiopurine metabolism

PubMed Central

Haglund, Sofie; Vikingsson, Svante; Almer, Sven; Söderman, Jan

2017-01-01

Combination treatment with low-dose thiopurine and allopurinol (AP) has successfully been used in patients with inflammatory bowel disease with a so called skewed thiopurine metabolite profile. In red blood cells in vivo, it reduces the concentration of methylated metabolites and increases the concentration of the phosphorylated ones, which is associated with improved therapeutic efficacy. This study aimed to investigate the largely unknown mechanism of AP on thiopurine metabolism in cells with an active thiopurine metabolic pathway using HepG2 and HEK293 cells. Cells were treated with 6-mercaptopurine (6MP) and AP or its metabolite oxypurinol. The expression of genes known to be associated with thiopurine metabolism, and the concentration of thiopurine metabolites were analyzed. Gene expression levels were only affected by AP in the presence of 6MP. The addition of AP to 6MP affected the expression of in total 19 genes in the two cell lines. In both cell lines the expression of the transporter SLC29A2 was reduced by the combined treatment. Six regulated genes in HepG2 cells and 8 regulated genes in HEK293 cells were connected to networks with 18 and 35 genes, respectively, present at known susceptibility loci for inflammatory bowel disease, when analyzed using a protein-protein interaction database. The genes identified as regulated as well as the disease associated interacting genes represent new candidates for further investigation in the context of combination therapy with thiopurines and AP. However, no differences in absolute metabolite concentrations were observed between 6MP+AP or 6MP+oxypurinol vs. 6MP alone in either of the two cell lines. In conclusion; the effect of AP on gene expression levels requires the presence of 6MP, at least in vitro. Previously described AP-effects on metabolite concentrations observed in red blood cells in vivo could not be reproduced in our cell lines in vitro. AP’s effects in relation to thiopurine metabolism are complex. The network-identified susceptibility genes represented biological processes mainly associated with purine nucleotide biosynthetic processes, lymphocyte proliferation, NF-KB activation, JAK-STAT signaling, and apoptotic signaling at oxidative stress. PMID:28278299

Heavy-ion-induced sucrose radicals investigated using EPR and UV spectroscopy

PubMed Central

Nakagawa, Kouichi; Karakirova, Yordanka; Yordanov, Nicola D.

2015-01-01

The potential use of a sucrose dosimeter for estimating both linear energy transfer (LET) and the absorbed dose of heavy ion and X-ray radiation was investigated. The stable free radicals were produced when sucrose was irradiated with heavy ions, such as helium, carbon, silicon and neon ions, and when the X-ray radiation was similar to the obtained electron paramagnetic resonance (EPR) spectra, which were ∼7 mT wide and composed of several hyperfine structures. In addition, the total spin concentration resulting from heavy-ion irradiation increased linearly as the absorbed dose increased, and decreased logarithmically as the LET increased. These empirical relations imply that the LET at a certain dose can be determined from the spin concentration. For sucrose and alanine, both cross-sections following C-ion irradiation with a 50 Gy dose were ∼1.3 × 10−12 [μm2], taking into account the molecular size of the samples. The values of these cross-sections imply that multiple ionizing particles were involved in the production of stable radicals. Furthermore, UV absorbance at 267 nm of an aqueous solution of irradiated sucrose was found to linearly increase with increasing absorbed dose. Therefore, the EPR and UV results suggest that sucrose can be a useful dosimeter for heavy-ion irradiation. PMID:25480828

Determination of curcumin in biologically active supplements and food spices using a mesofluidic platform with fluorescence detection.

PubMed

Petrova, Anastasiia; Dar'in, Dmitriy; Ivanov, Aleхander; Moskvin, Leonid; Ishimatsu, Ryoichi; Nakano, Koji; Imato, Toshihiko; Bulatov, Andrey

2016-10-01

A mesofluidic platform (MP) with fluorescence detection based on a stepwise injection analysis (SWIA) was used for the determination of curcumin in biologically active supplements and food spices. The main units of the MP are a mixing chamber (MC) and an optical channel with a quartz capillary inside. The MC provides rapid and complete mixing solutions by gas bubbling. The proposed method is based on the new rapid and sensitive reaction of curcumin with a fluorescence reagent - 4-(2,3,3-trimethyl-3H-indolium-1-yl)butane-1-sulfonate (TIBS). The fluorescence intensity of TIBS is greatly quenched in the presence of curcumin in an alkaline medium. The linear range was from 1 to 10µM of curcumin, and the limit of detection, calculated as 3σ of a blank test (n=5), was found to be 0.3µM. The sample throughput was 24h(-1). The proposed method was successfully applied for the determination of curcumin in biologically active supplements and samples of food spices. The obtained data were in good agreement with those measured by a HPLC-UV method. Copyright © 2016 Elsevier B.V. All rights reserved.

Space Environmental Effects on Materials and Processes

NASA Technical Reports Server (NTRS)

Sabbann, Leslie M.

2009-01-01

The Materials and Processes (M&P) Branch of the Structural Engineering Division at Johnson Space Center (JSC) seeks to uphold the production of dependable space hardware through materials research, which fits into NASA's purpose of advancing human exploration, use, and development of space. The Space Environmental Effects projects fully support these Agency goals. Two tasks were assigned to support M&P. Both assignments were to further the research of material behavior outside of Earth's atmosphere in order to determine which materials are most durable and safe to use in space for mitigating risks. One project, the Materials on International Space Station Experiments (MISSE) task, was to compile data from International Space Station (ISS) experiments to pinpoint beneficial space hardware. The other project was researching the effects on composite materials of exposure to high doses of radiation for a Lunar habitat project.

UV-laser photochemistry of isoxazole isolated in a low-temperature matrix.

PubMed

Nunes, Cláudio M; Reva, Igor; Pinho e Melo, Teresa M V D; Fausto, Rui

2012-10-05

The photochemistry of matrix-isolated isoxazole, induced by narrowband tunable UV-light, was investigated by infrared spectroscopy, with the aid of MP2/6-311++G(d,p) calculations. The isoxazole photoreaction starts to occur upon irradiation at λ = 240 nm, with the dominant pathway involving decomposition to ketene and hydrogen cyanide. However, upon irradiation at λ = 221 nm, in addition to this decomposition, isoxazole was also found to isomerize into several products: 2-formyl-2H-azirine, 3-formylketenimine, 3-hydroxypropenenitrile, imidoylketene, and 3-oxopropanenitrile. The structural and spectroscopic assignment of the different photoisomerization products was achieved by additional irradiation of the λ = 221 nm photolyzed matrix, using UV-light with λ ≥ 240 nm: (i) irradiation in the 330 ≤ λ ≤ 340 nm range induced direct transformation of 2-formyl-2H-azirine into 3-formylketenimine; (ii) irradiation with 310 ≤ λ ≤ 318 nm light induced the hitherto unobserved transformation of 3-formylketenimine into 3-hydroxypropenenitrile and imidoylketene; (iii) irradiation with λ = 280 nm light permits direct identification of 3-oxopropanenitrile; (iv) under λ = 240 nm irradiation, tautomerization of 3-hydroxypropenenitrile to 3-oxopropanenitrile is observed. On the basis of these findings, a detailed mechanistic proposal for isoxazole photochemistry is presented.

Inactivation of indigenous coliform bacteria in unfiltered surface water by ultraviolet light.

PubMed

Cantwell, Raymond E; Hofmann, Ron

2008-05-01

This study examined the potential for naturally occurring particles to protect indigenous coliform from ultraviolet (UV) disinfection in four surface waters. Tailing in the UV dose-response curve of the bacteria was observed in 3 of the 4 water samples after 1.3-2.6-log of log-linear inactivation, implying particle-related protection. The impact of particles was confirmed by comparing coliform UV inactivation data for parallel filtered (11 microm pore-size nylon filters) and unfiltered surface water. In samples from the Grand River (UVT: 65%/cm; 5.4 nephelometric turbidity units (NTU)) and the Rideau Canal (UVT: 60%/cm; 0.84 NTU), a limit of approximately 2.5 log inactivation was achieved in the unfiltered samples for a UV dose of 20 mJ/cm2 while both the filtered samples exhibited >3.4-log inactivation of indigenous coliform bacteria. The results suggest that particles as small as 11 microm, naturally found in surface water with low turbidity (<3NTU), are able to harbor indigenous coliform bacteria and offer protection from low-pressure UV light.

UV-biosensor for visual indication of vitamin D synthesis

NASA Astrophysics Data System (ADS)

Orlova, T. N.; Terenetskaya, I. P.

2008-04-01

Excessive UV doses have adverse effects on human health, but proper amount of UV is beneficial for people and is essential in the natural production of vitamin D# in skin. Most of broadband UV-radiometers that have an output in sunburn units are incapable to record correctly the vitamin D synthetic capacity of sunlight because of the difference between the CIE erythema and 'Vitamin D synthesis' action spectra. The liquid-crystalline UV sensor based on provitamin D photoconversions has been developed for direct observation of vitamin D synthesis under UV irradiation. UV-induced transformation of provitamin D in cholesteric liquid-crystalline matrix is accompanied by the change of cholesteric pitch value in the LC cell. The developed UV biosensor makes possible both instrumental and visual monitoring of the vitamin D synthetic capacity of sunlight and/or artificial UV source.

ENVIRONMENTAL TECHNOLOGY VERIFICATION: JOINT (NSF-EPA) VERIFICATION STATEMENT AND REPORT FOR THE UV DISINFECTION OF SECONDARY EFFLUENTS, SUNTEC, INC. MODEL LPX200 DISINFECTION SYSTEM - 03/09/WQPC-SWP

EPA Science Inventory

Verification testing of the SUNTEC LPX200 UV Disinfection System to develop the UV delivered dose flow relationship was conducted at the Parsippany-Troy Hills wastewater treatment plant test site in Parsippany, New Jersey. Two lamp modules were mounted parallel in a 6.5-meter lon...

Reduction of Microbial Contaminants in Drinking Water by Ultraviolet Light Technology: ETS UV MODEL UVL-200-4 (Report and Statement)

EPA Science Inventory

Final technical report provides test methods used and verification results to be published on ETV web sites. The ETS UV System Model UVL-200-4 was tested to validate the UV dose delivered by the system using biodosimetry and a set line approach. The set line for 40 mJ/cm2 Red...

Assessment of the breakdown products of solar/UV induced photolytic degradation of food dye tartrazine.

PubMed

dos Santos, Tuane Cristina; Zocolo, Guilherme Julião; Morales, Daniel Alexandre; Umbuzeiro, Gisela de Aragão; Zanoni, Maria Valnice Boldrin

2014-06-01

The food dye tartrazine (CI 19140) was exposed to UV irradiation from an artificial source, a mercury vapor lamp, and a natural one, sunlight. It was observed that conditions such as energy dose, irradiation time, pH and initial dye concentration affected its discoloration. There was 100% of color removal, after 30min of irradiation, when a dye solution 1×10(-5)molL(-1) was submitted to an energy dose of 37.8Jcm(-2). Liquid Chromatography coupled to Diode Array Detection and Mass Spectrometry confirmed the cleavage of the chromophore group and the formation of five by-products at low concentration. Although by-products were formed, the Salmonella/microsome mutagenicity assay performed for both, the dye solution at a dose of 5.34mg/plate and the solutions obtained after exposure to UV irradiation, did not present mutagenic activity for TA98 and TA100 with and without S9. Copyright © 2014 Elsevier Ltd. All rights reserved.

Wavelength dependent recovery of UV-mediated damage: Tying up the loose ends of optical based powdery mildew management.

PubMed

Suthaparan, Aruppillai; Pathak, Ranjana; Solhaug, Knut Asbjørn; Gislerød, Hans Ragnar

2018-01-01

Controlled environment chamber experiments at Petri dish level were conducted to examine the wavelength and dose dependent efficacy of ultraviolet (UV) radiation, the recovery action potential of optical radiation applied concomitantly/subsequently to effective UV treatment, and the lapse time between UV treatment and subsequent exposure to recovery wavelength on germination efficiency of Oidium neolycopersici conidia. Conidia of eight- to nine-day-old colonies were dusted on water agar surface in Petri dishes and exposed to UV treatments (without lid). Immediately after UV treatments, Petri dishes were sealed and incubated in darkness or differing optical environments generated using seven different radiation sources (range 290nm to 780nm). Twenty-four hours after UV treatment, fifty conidia from each sample were assessed for germination. Compared to non-UV controls, <10% of the conidia germinated after 30s of exposure to 254nm or 283nm UV and subsequent dark incubation. Conidia germination was almost negligible if the exposure duration increased to 4min. Germination was about 60% with broad spectrum UV after 1min of exposure, and about 35% after 2 to 4min of exposure. There was no reduction of conidia germination with the exposure of ≤4min with 310nm. With the tested wavelength and dose ranges, germination recovery was effective in the 350nm to 500nm range. Germination efficiency of conidia treated with effective UV was significantly higher (>73%) if incubated subsequently in the 350nm to 500nm range (germination recovery). Furthermore, germination recovery depends on the characteristics of UV treatment (wavelength, and duration of exposure) and the lapse time between UV treatment and subsequent exposure to optical radiation in the recovery range. The findings of this study provide key criteria for wavelength selection, combination and application time in the optical radiation range, enabling improved design of optical based management strategies against powdery mildews. Copyright © 2017 Elsevier B.V. All rights reserved.

Intensification of UV-C tertiary treatment: Disinfection and removal of micropollutants by sulfate radical based Advanced Oxidation Processes.

PubMed

Rodríguez-Chueca, J; García-Cañibano, C; Lepistö, R-J; Encinas, Á; Pellinen, J; Marugán, J

2018-04-21

This study explores the enhancement of UV-C tertiary treatment by sulfate radical based Advanced Oxidation Processes (SR-AOPs), including photolytic activation of peroxymonosulfate (PMS) and persulfate (PS) and their photocatalytic activation using Fe(II). Their efficiency was assessed both for the inactivation of microorganisms and the removal or micropollutants (MPs) in real wastewater treatment plant effluents. Under the studied experimental range (UV-C dose 5.7-57 J/L; UV-C contact time 3 to 28 s), the photolysis of PMS and PS (0.01 mM) increased up to 25% the bacterial removal regarding to UV-C system. The photolytic activation of PMS led to the total inactivation of bacteria (≈ 5.70 log) with the highest UV-C dose (57 J/L). However, these conditions were insufficient to remove the MPs, being required oxidant's dosages of 5 mM to remove above 90% of carbamazepine, diclofenac, atenolol and triclosan. The best efficiencies were achieved by the combination of PMS or PS with Fe(II), leading to the total removal of the MPs using a low UV-C dosage (19 J/L), UV-C contact time (9 s) and reagent's dosages (0.5 mM). Finally, high mineralization was reached (>50%) with photocatalytic activation of PMS and PS even with low reagent's dosages. Copyright © 2018 Elsevier B.V. All rights reserved.

Controlling sunbathing safety during the summer holidays - The solar UV campaign at Baltic Sea coast in 2015.

PubMed

Guzikowski, Jakub; Czerwińska, Agnieszka E; Krzyścin, Janusz W; Czerwiński, Michał A

2017-08-01

Information regarding the intensity of surface UV radiation, provided for the public, is frequently given in terms of a daily maximum UV Index (UVI), based on a prognostic model. The quality of the UV forecast depends on the accuracy of column amount of ozone and cloudiness prediction. Daily variability of UVI is needed to determine the risk of the UV overexposure during outdoor activities. Various methods of estimating the temporary UVI and the maximum duration of UV exposures (received a dose equal to minimal erythemal dose - MED), at the site of sunbathing, were compared. The UV indices were obtained during a field experiment at the Baltic Sea coast in the period from 13th to 24th July 2015. The following UVI calculation models were considered: UVI measurements by simple hand-held biometers (Silver Crest, Oregon Scientific, or more advanced Solarmeter 6.5), our smartphone models based on cloud cover observations at the site and the cloudless-sky UVI forecast (available for any site for all smartphone users) or measured UVI, and the 24h weather predictions by the ensemble set of 10 models (with various cloud parameterizations). The direct UV measurements, even by a simple biometer, provided useful UVI estimates. The smartphone applications yielded a good agreement with the UV measurements. The weather prediction models for cloudless-sky conditions could provide valuable information if almost cloudless-sky conditions (cloudless-sky or slightly scattered clouds) were observed at the sunbathing site. Copyright © 2017 Elsevier B.V. All rights reserved.

UV-B Irradiation Changes Specifically the Secondary Metabolite Profile in Broccoli Sprouts: Induced Signaling Overlaps with Defense Response to Biotic Stressors

PubMed Central

Mewis, Inga; Schreiner, Monika; Nguyen, Chau Nhi; Krumbein, Angelika; Ulrichs, Christian; Lohse, Marc; Zrenner, Rita

2012-01-01

Only a few environmental factors have such a pronounced effect on plant growth and development as ultraviolet light (UV). Concerns have arisen due to increased UV-B radiation reaching the Earth’s surface as a result of stratospheric ozone depletion. Ecologically relevant low to moderate UV-B doses (0.3–1 kJ m–2 d–1) were applied to sprouts of the important vegetable crop Brassica oleracea var. italica (broccoli), and eco-physiological responses such as accumulation of non-volatile secondary metabolites were related to transcriptional responses with Agilent One-Color Gene Expression Microarray analysis using the 2×204 k format Brassica microarray. UV-B radiation effects have usually been linked to increases in phenolic compounds. As expected, the flavonoids kaempferol and quercetin accumulated in broccoli sprouts (the aerial part of the seedlings) 24 h after UV-B treatment. A new finding is the specific UV-B-mediated induction of glucosinolates (GS), especially of 4-methylsulfinylbutyl GS and 4-methoxy-indol-3-ylmethyl GS, while carotenoids and Chl levels remained unaffected. Accumulation of defensive GS metabolites was accompanied by increased expression of genes associated with salicylate and jasmonic acid signaling defense pathways and up-regulation of genes responsive to fungal and bacterial pathogens. Concomitantly, plant pre-exposure to moderate UV-B doses had negative effects on the performance of the caterpillar Pieris brassicae (L.) and on the population growth of the aphid Myzus persicae (Sulzer). Moreover, insect-specific induction of GS in broccoli sprouts was affected by UV-B pre-treatment. PMID:22773681

The total ozone and UV solar radiation over Stara Zagora, Bulgaria

NASA Astrophysics Data System (ADS)

Mendeva, B. D.; Gogosheva, Ts. N.; Petkov, B. H.; Krastev, D. G.

The results from direct ground-based solar UV irradiance measurements and the total ozone content (TOC) over Stara Zagora (42° 25'N, 25° 37'E), Bulgaria are presented. During the period 1999-2003 the TOC data show seasonal variations, typical for the middle latitudes - maximum in the spring and minimum in the autumn. The comparison between TOC ground-based data and Global Ozone Monitoring Experiment (GOME) satellite-borne ones shows a seasonal dependence of the differences between them. A strong negative relationship between the total ozone and the 305 nm wavelength irradiance was found. The dependence between the two variables is significant ( r = -0.62 ± 0.18) at 98% confidence level. The direct sun UV doses for some specific biological effects (erythema and eyes) are obtained. The estimation of the radiation amplification factor RAF shows that the ozone reduction by 1% increases the erythemal dose by 2.3%. The eye-damaging doses are more influenced by the TOC changes and in this case RAF = -2.7%. The amount of these biological doses depended on the solar altitude over the horizon. This dependence was not so strong when the total ozone content in the atmosphere was lower.

Reduction of Zika virus infectivity in platelet concentrates after treatment with ultraviolet C light and in plasma after treatment with methylene blue and visible light.

PubMed

Fryk, Jesse J; Marks, Denese C; Hobson-Peters, Jody; Watterson, Daniel; Hall, Roy A; Young, Paul R; Reichenberg, Stefan; Tolksdorf, Frank; Sumian, Chryslain; Gravemann, Ute; Seltsam, Axel; Faddy, Helen M

2017-11-01

Zika virus (ZIKV) has emerged as a potential threat to transfusion safety worldwide. Pathogen inactivation is one approach to manage this risk. In this study, the efficacy of the THERAFLEX UV-Platelets system and THERAFLEX MB-Plasma system to inactivate ZIKV in platelet concentrates (PCs) and plasma was investigated. PCs spiked with ZIKV were treated with the THERAFLEX UV-Platelets system at 0.05, 0.10, 0.15, and 0.20 J/cm 2 UVC. Plasma spiked with ZIKV was treated with the THERAFLEX MB-Plasma system at 20, 40, 60, and 120 J/cm 2 light at 630 nm with at least 0.8 µmol/L methylene blue (MB). Samples were taken before the first and after each illumination dose and tested for residual virus. For each system the level of viral reduction was determined. Treatment of PCs with THERAFLEX UV-Platelets system resulted in a mean of 5 log reduction in ZIKV infectivity at the standard UVC dose (0.20 J/cm 2 ), with dose dependency observed with increasing UVC dose. For plasma treated with MB and visible light, ZIKV infectivity was reduced by a mean of at least 5.68 log, with residual viral infectivity reaching the detection limit of the assay at 40 J/cm 2 (one-third the standard dose). Our study demonstrates that the THERAFLEX UV-Platelets system and THERAFLEX MB-Plasma system can reduce ZIKV infectivity in PCs and pooled plasma to the detection limit of the assays used. These findings suggest both systems have the capacity to be an effective option to manage potential ZIKV transfusion transmission risk. © 2017 AABB.

Optimal Chemotherapy for Leukemia: A Model-Based Strategy for Individualized Treatment

PubMed Central

Jayachandran, Devaraj; Rundell, Ann E.; Hannemann, Robert E.; Vik, Terry A.; Ramkrishna, Doraiswami

2014-01-01

Acute Lymphoblastic Leukemia, commonly known as ALL, is a predominant form of cancer during childhood. With the advent of modern healthcare support, the 5-year survival rate has been impressive in the recent past. However, long-term ALL survivors embattle several treatment-related medical and socio-economic complications due to excessive and inordinate chemotherapy doses received during treatment. In this work, we present a model-based approach to personalize 6-Mercaptopurine (6-MP) treatment for childhood ALL with a provision for incorporating the pharmacogenomic variations among patients. Semi-mechanistic mathematical models were developed and validated for i) 6-MP metabolism, ii) red blood cell mean corpuscular volume (MCV) dynamics, a surrogate marker for treatment efficacy, and iii) leukopenia, a major side-effect. With the constraint of getting limited data from clinics, a global sensitivity analysis based model reduction technique was employed to reduce the parameter space arising from semi-mechanistic models. The reduced, sensitive parameters were used to individualize the average patient model to a specific patient so as to minimize the model uncertainty. Models fit the data well and mimic diverse behavior observed among patients with minimum parameters. The model was validated with real patient data obtained from literature and Riley Hospital for Children in Indianapolis. Patient models were used to optimize the dose for an individual patient through nonlinear model predictive control. The implementation of our approach in clinical practice is realizable with routinely measured complete blood counts (CBC) and a few additional metabolite measurements. The proposed approach promises to achieve model-based individualized treatment to a specific patient, as opposed to a standard-dose-for-all, and to prescribe an optimal dose for a desired outcome with minimum side-effects. PMID:25310465

Tolerance of entomopathogenic fungi to ultraviolet radiation: a review on screening of strains and their formulation.

PubMed

Fernandes, Éverton K K; Rangel, Drauzio E N; Braga, Gilberto U L; Roberts, Donald W

2015-08-01

Ultraviolet radiation from sunlight is probably the most detrimental environmental factor affecting the viability of entomopathogenic fungi applied to solar-exposed sites (e.g., leaves) for pest control. Most entomopathogenic fungi are sensitive to UV radiation, but there is great inter- and intraspecies variability in susceptibility to UV. This variability may reflect natural adaptations of isolates to their different environmental conditions. Selecting strains with outstanding natural tolerance to UV is considered as an important step to identify promising biological control agents. However, reports on tolerance among the isolates used to date must be analyzed carefully due to considerable variations in the methods used to garner the data. The current review presents tables listing many studies in which different methods were applied to check natural and enhanced tolerance to UV stress of numerous entomopathogenic fungi, including several well-known isolates of these fungi. The assessment of UV tolerance is usually conducted with conidia using dose-response methods, wherein the UV dose is calculated simply by multiplying the total irradiance by the period (time) of exposure. Although irradiation from lamps seldom presents an environmentally realistic spectral distribution, laboratory tests circumvent the uncontrollable circumstances associated with field assays. Most attempts to increase field persistence of microbial agents have included formulating conidia with UV protectants; however, in many cases, field efficacy of formulated fungi is still not fully adequate for dependable pest control.

UV TREATMENT FOR CONTROL OF AEROMONAS (RM.C.M.6)

EPA Science Inventory

The data and related interpretations that will be developed in this research will form the scientific basis for analysis, design, and regulation of polychromatic UV disinfection systems. At present, only minimal data regarding the wavelength-specific nature of microbial dose-resp...

A Fe(II)/citrate/UV/PMS process for carbamazepine degradation at a very low Fe(II)/PMS ratio and neutral pH: The mechanisms.

PubMed

Ling, Li; Zhang, Dapeng; Fan, Chihhao; Shang, Chii

2017-11-01

A novel Fe(II)/citrate/UV/PMS process for degrading a model micropollutant, carbamazepine (CBZ), at a low Fe(II)/PMS ratio and neutral pH has been proposed in this study, and the mechanisms of radical generation in the system was explored. With a UV dose of 302.4 mJ/cm 2 , an initial pH of 7, and CBZ, PMS, Fe(II) and citrate at initial concentrations of 10, 100, 12 and 26 μM, respectively, the CBZ degradation efficiency reached 71% in 20 min in the Fe(II)/citrate/UV/PMS process, which was 4.7 times higher than that in either the citrate/UV/PMS or Fe(II)/citrate/PMS process. The enhanced CBZ degradation in the Fe(II)/citrate/UV/PMS process was mainly attributed to the continuous activation of PMS by the UV-catalyzed regenerated Fe(II) from a Fe(III)-citrate complex, [Fe 3 O(cit) 3 H 3 ] 2- , which not only maintained Fe(III) soluble at neutral pH, but also increased 6.6 and 2.6 times of its molar absorbance and quantum yield as compared to those of ionic Fe(III), respectively. In the Fe(II)/citrate/UV/PMS process, the SO 4 •- produced from the fast reaction between PMS and the initially-added Fe(II) contributed 11% of CBZ degradation. The PMS activation by the UV radiation and regenerated Fe(II) contributed additional 14% and 46% of CBZ removal, respectively. The low iron and citrate doses and the fast radical generation at neutral pH make the Fe(II)/citrate/UV/PMS process suitable for degrading recalcitrant organic compounds in potable water. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of Radon and UV Exposure on Skin Cancer Mortality in Switzerland.

PubMed

Vienneau, Danielle; de Hoogh, Kees; Hauri, Dimitri; Vicedo-Cabrera, Ana M; Schindler, Christian; Huss, Anke; Röösli, Martin

2017-06-16

Skin cancer incidence in Switzerland is among the highest in the world. In addition to exposure to ultraviolet (UV) radiation, radon alpha particles attached to aerosols can adhere to the skin and potentially cause carcinogenic effects. We investigated the effects of radon and UV exposure on skin cancer mortality. Cox proportional hazard regression was used to study the association between exposures and skin cancer mortality in adults from the Swiss National Cohort. Modeled radon exposure and erythemal-weighted UV dose were assigned to addresses at baseline. Effect estimates were adjusted for sex, civil status, mother tongue, education, job position, neighborhood socioeconomic position, and UV exposure from outdoor occupation. The study included 5.2 million adults (mean age 48 y) and 2,989 skin cancer deaths, with 1,900 indicating malignant melanoma (MM) as the primary cause of death. Adjusted hazard ratios (HR) for MM at age 60 were 1.16 (95% CI: 1.04, 1.29) per 100 Bq/m 3 radon and 1.11 (1.01, 1.23) per W/m 2 in UV dose. Radon effects decreased with age. Risk of MM death associated with residential UV exposure was higher for individuals engaged in outdoor work with UV exposure (HR 1.94 [1.17, 3.23]), though not statistically significantly different compared to not working outdoors (HR 1.09 [0.99, 1.21], p =0.09). There is considerable variation in radon and UV exposure across Switzerland. Our study suggests both are relevant risk factors for skin cancer mortality. A better understanding of the role of the UV radiation and radon exposure is of high public health relevance. https://doi.org/10.1289/EHP825.

Effects of Radon and UV Exposure on Skin Cancer Mortality in Switzerland

PubMed Central

de Hoogh, Kees; Hauri, Dimitri; Vicedo-Cabrera, Ana M.; Schindler, Christian; Huss, Anke; Röösli, Martin

2017-01-01

Background: Skin cancer incidence in Switzerland is among the highest in the world. In addition to exposure to ultraviolet (UV) radiation, radon alpha particles attached to aerosols can adhere to the skin and potentially cause carcinogenic effects. Objectives: We investigated the effects of radon and UV exposure on skin cancer mortality. Methods: Cox proportional hazard regression was used to study the association between exposures and skin cancer mortality in adults from the Swiss National Cohort. Modeled radon exposure and erythemal-weighted UV dose were assigned to addresses at baseline. Effect estimates were adjusted for sex, civil status, mother tongue, education, job position, neighborhood socioeconomic position, and UV exposure from outdoor occupation. Results: The study included 5.2 million adults (mean age 48 y) and 2,989 skin cancer deaths, with 1,900 indicating malignant melanoma (MM) as the primary cause of death. Adjusted hazard ratios (HR) for MM at age 60 were 1.16 (95% CI: 1.04, 1.29) per 100Bq/m3 radon and 1.11 (1.01, 1.23) per W/m2 in UV dose. Radon effects decreased with age. Risk of MM death associated with residential UV exposure was higher for individuals engaged in outdoor work with UV exposure (HR 1.94 [1.17, 3.23]), though not statistically significantly different compared to not working outdoors (HR 1.09 [0.99, 1.21], p=0.09). Conclusions: There is considerable variation in radon and UV exposure across Switzerland. Our study suggests both are relevant risk factors for skin cancer mortality. A better understanding of the role of the UV radiation and radon exposure is of high public health relevance. https://doi.org/10.1289/EHP825 PMID:28686556

Can UV radiation-blocking soft contact lenses attenuate UV radiation to safe levels during summer months in the southern United States?

PubMed

Walsh, James E; Bergmanson, Jan P G; Saldana, Gerardo; Gaume, Amber

2003-01-01

Peak solar UV radiation (UVR) intensities are typically experienced in summer months. People living in the southern states of the United States, where the UVR frequently exceeds the recommended minimum erythema dose (MED), are at particular risk, especially outdoor workers. The present study analyzed summertime MED readings in Houston, TX, to assess the frequency of intensities regarded as unhealthy. The study also sought to assess whether UV-blocking hydrogel contact lenses provide ocular protection from these high doses. Readings, taken at midday using a UVR biometer, were analyzed to assess the potential UVR risk. The spectral response of the meter, modified by the spectral transmission curves of the contact lenses, allowed us to mathematically assess the ocular protection provided. In addition, ambient UVR measurements were taken at midday, using a portable UVR radiometer. The detector was adapted so that a standard diameter hydrogel contact lens could be placed over it to quantify the UV-blocking capabilities of the lens. The MED readings showed that the recommended safety standards were exceeded approximately at local midday 90% of the time. Model calculations and empirical data demonstrated that contact lenses attenuated the MED readings by up to 90%, bringing them well within the recommended Environmental Protection Agency safety standards. The efficacy of the model used in this study was verified through direct comparison of the modeled and measured data. UV-blocking hydrogel soft contact lenses reduce the MED to the human eye and therefore limit the lifetime ocular dose. These lenses are highly recommended to prevent the development of UVR-related ocular pathologic conditions.

A method to generate surface UV radiation maps over Europe using GOME, Meteosat, and ancillary geophysical data

NASA Astrophysics Data System (ADS)

Verdebout, Jean

2000-02-01

This paper presents a method for generating surface ultraviolet (UV) radiation maps over Europe, with a spatial resolution of 0.05°, and potentially on a half-hour basis. The UV irradiance is obtained by interpolation in a look-up table (LUT), the entries of which are solar zenith angle, total column ozone amount, cloud liquid water thickness, near-surface horizontal visibility, surface elevation, and UV albedo. Both satellite (Meteosat, GOME) and nonsatellite (synoptic observations, meteorological model results, digital elevation model) data are exploited to assign values to the influencing factors. With the help of another LUT simulating the visible signal, Meteosat data are processed to retrieve the cloud liquid water thickness. The radiative transfer calculations are performed with the UVspec code. A preliminary step consists in generating an effective surface Meteosat albedo map from a series of 10 consecutive days. In this process the well-known difficulty of distinguishing clouds from snow-covered surfaces is encountered. An attempt is made to partially resolve the ambiguity by using the Meteosat infrared channel and modeled snow cover data. After additional empirical cloud filtering, the effective albedo map is used as a baseline to estimate the cloud liquid water thickness. The UV surface albedo is assigned uniform values for land and sea/ocean, except in the presence of snow. In this case it is given a value proportional to the Meteosat effective albedo. The total column ozone is extracted from the level 3 GOME products. The aerosol optical thickness is mapped by gridding the daily measurements performed by ˜1000 ground stations. The digital elevation model is the GTOPO30 data set from the U.S. Geological Survey. European wide UV dose rate maps are presented for one day in April 1997, and the influence of the various factors is illustrated. A daily integrated dose map was also generated using 27 Meteosat acquisitions at half-hour intervals on the same day. The dose map produced in this way takes into account the evolution of the cloud field and is thought to be more accurate than if it were estimated from one data take, in particular at the relatively high spatial resolution of the product. Finally, a preliminary comparison of modeled dose rate and daily dose with measurements performed with a ground instrument is discussed.

Imprint Characteristics by Photo-Induced Solidification of Liquid Polymer

NASA Astrophysics Data System (ADS)

Komuro, Masanori; Taniguchi, Jun; Inoue, Seiji; Kimura, Naoya; Tokano, Yuji; Hiroshima, Hiroshi; Matsui, Shinji

2000-12-01

Nanoimprint lithography is an attractive technology for LSIs era below 40-nm critical dimension from the viewpoints of high-throughput and low-cost equipment. In order to avoid a pattern placement error due to thermal expansion in the conventional thermal imprint process, we attempted to replicate the mold pattern onto a liquid polymer, which was solidified using ultra-violet (UV) light irradiation at room temperature. The liquid polymer used here was supplied by TEIJIN SEIKI Co., and termed TSR-820. It was spin coated on slide glass to produce approximately 1.5-μm-thick polymer film. The thickness remained after UV exposure and rinsing in acetone was observed at the dose of 10 J/cm2 and it saturated about a UV exposure dose of 100 J/cm2 with an increase in the exposure dose. The mold fabricated of quartz plate was first pressed onto the polymer film at about 100 kg/cm2 and then the UV light was irradiated using an imprint apparatus developed for this work. After releasing the mold from the film, the substrate was rinsed in acetone to remove the residual liquid polymer. Eventually the minimum feature size of 100-nm line and 300-nm space pattern was successfully replicated in the polymer with good fidelity.

Solar UV exposure of primary schoolchildren in Valencia, Spain.

PubMed

Serrano, María-Antonia; Cañada, Javier; Moreno, Juan Carlos

2011-04-01

To quantify schoolchildren's exposure to ultraviolet erythemal radiation (UVER), personal dosimeters (VioSpor) were used to measure biologically effective ultraviolet (UV) radiation received in the course of their daily school activities. The study took place in two primary schools in Valencia (39°28'N), Spain, for several weeks from March 2008 until May 2009, with two age groups (6-8 years and 10-11 years) and involved about 47 schoolchildren. The median daily UV exposure values for all age groups and solar height intervals considered in the study ranged from 1.31 to 2.11 standard erythemal doses (SEDs). Individual UV exposure was analyzed as a function of age, gender and dosimeter position. Significant statistical differences were found between different age groups, with the younger age group receiving higher statistically significant UVER exposure. It was also found that boys received significantly higher UVER exposure than girls. It was also noted that shoulder dosimeters registered higher readings than wrist dosimeters. Exposure ratio (ER) is defined as the ratio between the personal dose on a selected anatomical site and the corresponding ambient dose on a horizontal plane. The median ER for all age groups and solar height intervals in the study range from 4.5% to 10.7%, with higher values at lower solar heights.

Integrated chemical and toxicological investigation of UV-chlorine/chloramine drinking water treatment.

PubMed

Lyon, Bonnie A; Milsk, Rebecca Y; DeAngelo, Anthony B; Simmons, Jane Ellen; Moyer, Mary P; Weinberg, Howard S

2014-06-17

As the use of alternative drinking water treatment increases, it is important to understand potential public health implications associated with these processes. The objective of this study was to evaluate the formation of disinfection byproducts (DBPs) and cytotoxicity of natural organic matter (NOM) concentrates treated with chlorine, chloramine, and medium pressure ultraviolet (UV) irradiation followed by chlorine or chloramine, with and without nitrate or iodide spiking. The use of concentrated NOM conserved volatile DBPs and allowed for direct analysis of the treated water. Treatment with UV prior to chlorine in ambient (unspiked) samples did not affect cytotoxicity as measured using an in vitro normal human colon cell (NCM460) assay, compared to chlorination alone when toxicity is expressed on the basis of dissolved organic carbon (DOC). Nitrate-spiked UV+chlorine treatment produced greater cytotoxicity than nitrate-spiked chlorine alone or ambient UV+chlorine samples, on both a DOC and total organic halogen basis. Samples treated with UV+chloramine were more cytotoxic than those treated with only chloramine using either dose metric. This study demonstrated the combination of cytotoxicity and DBP measurements for process evaluation in drinking water treatment. The results highlight the importance of dose metric when considering the relative toxicity of complex DBP mixtures formed under different disinfection scenarios.

Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in Hairless Mice after UV-B Irradiation.

PubMed

Oba, Chisato; Morifuji, Masashi; Ichikawa, Satomi; Ito, Kyoko; Kawahata, Keiko; Yamaji, Taketo; Asami, Yukio; Itou, Hiroyuki; Sugawara, Tatsuya

2015-01-01

Exposure to ultraviolet-B (UV-B) irradiation causes skin barrier defects. Based on earlier findings that milk phospholipids containing high amounts of sphingomyelin (SM) improved the water content of the stratum corneum (SC) in normal mice, here we investigated the effects of dietary milk SM on skin barrier defects induced by a single dose of UV-B irradiation in hairless mice. Nine week old hairless mice were orally administrated SM (146 mg/kg BW/day) for a total of ten days. After seven days of SM administration, the dorsal skin was exposed to a single dose of UV-B (20 mJ/cm2). Administration of SM significantly suppressed an increase in transepidermal water loss and a decrease in SC water content induced by UV-B irradiation. SM supplementation significantly maintained covalently-bound ω-hydroxy ceramide levels and down-regulated mRNA levels of acute inflammation-associated genes, including thymic stromal lymphopoietin, interleukin-1 beta, and interleukin-6. Furthermore, significantly higher levels of loricrin and transglutaminase-3 mRNA were observed in the SM group. Our study shows for the first time that dietary SM modulates epidermal structures, and can help prevent disruption of skin barrier function after UV-B irradiation.

The PUR Experiment on the EXPOSE-R facility: biological dosimetry of solar extraterrestrial UV radiation

NASA Astrophysics Data System (ADS)

Bérces, A.; Egyeki, M.; Fekete, A.; Horneck, G.; Kovács, G.; Panitz, C.

2015-01-01

The aim of our experiment Phage and Uracil Response was to extend the use of bacteriophage T7 and uracil biological dosimeters for measuring the biologically effective ultraviolet (UV) dose in the harsh extraterrestrial radiation conditions. The biological detectors were exposed in vacuum-tightly cases in the European Space Agency (ESA) astrobiological exposure facility attached to the external platform of Zvezda (EXPOSE-R). EXPOSE-R took off to the International Space Station (ISS) in November 2008 and was installed on the External platform of the Russian module Zvezda of the ISS in March 2009. Our goal was to determine the dose-effect relation for the formation of photoproducts (i.e. damage to phage DNA and uracil, respectively). The extraterrestrial solar UV radiation ranges over the whole spectrum from vacuum-UV (λ<200 nm) to UVA (315 nm<λ<400 nm), which causes photolesions (photoproducts) in the nucleic acids/their components either by photoionization or excitation. However, these wavelengths cause not only photolesions but in a wavelength-dependent efficiency the reversion of some photolesions, too. Our biological detectors measured in situ conditions the resultant of both reactions induced by the extraterrestrial UV radiation. From this aspect the role of the photoreversion in the extension of the biological UV dosimetry are discussed.

Comparison of skin responses from macroscopic and microscopic UV challenges

NASA Astrophysics Data System (ADS)

Seo, InSeok; Bargo, Paulo R.; Chu, Melissa; Ruvolo, Eduardo; Kollias, Nikiforos

2011-03-01

The minimal erythema dose induced by solar-simulated radiation is a useful measure of UV sensitivity of skin. Most skin phototests have been conducted by projecting a flat field of UV radiation onto the skin in an area greater than 15 cm × 15 cm with an increment of radiation doses. In this study, we investigated the responses of human skin to solar-simulated radiation of different field sizes. Twelve human subjects of skin phototype I-IV were exposed to solar-simulated radiation (SSR) on their upper inner arm or on their lower back with a series of doses in increments of 20% in order to determine the threshold dose to induce a minimal perceptible erythema response (MED). Each dose was delivered with a liquid light guide (8 mm diameter on the back or 6 mm on the upper inner arm) and with quartz optical fibers of 200 μm diameter. The resulting skin responses were evaluated visually and investigated with a reflectance confocal microscope and imaging. The erythema response to the microscopic challenge was always diffuse with no clear boundaries extending to several times the exposed site diameter at doses greater than 2 MED. The skin returned to normal appearance from the microscopic challenge after two weeks of exposure while change in appearance for the larger areas persisted for several weeks to months. This new modality of testing provides the possibility to study skin at the microscopic level with a rapid recovery following challenge.

ESTIMATION OF UV RADIATION DOSE IN NORTHERN MINNESOTA WETLANDS

EPA Science Inventory

The ultraviolet (UV) B wavelength range (280 nm to 320 nm) of solar radiation can be a significant biological stressor, and has been hypothesized to be partially responsible for amphibian declines and malformation. This hypothesis has been difficult to evaluate, in part, because ...

Development of a molecular method for testing the effectiveness of UV systems on-site.

PubMed

Nizri, Limor; Vaizel-Ohayon, Dalit; Ben-Amram, Hila; Sharaby, Yehonatan; Halpern, Malka; Mamane, Hadas

2017-12-15

We established a molecular method for quantifying ultraviolet (UV) disinfection efficacy using total bacterial DNA in a water sample. To evaluate UV damage to the DNA, we developed the "DNA damage" factor, which is a novel cultivation-independent approach that reveals UV-exposure efficiency by applying a simple PCR amplification method. The study's goal was to prove the feasibility of this method for demonstrating the efficiency of UV systems in the field using flow-through UV reactors. In laboratory-based experiments using seeded bacteria, the DNA damage tests demonstrated a good correlation between PCR products and UV dose. In the field, natural groundwater sampled before and after being subjected to the full-scale UV reactors was filtered, and the DNA extracted from the filtrate was subjected to PCR amplification for a 900-bp fragment of the 16S rRNA gene with initial DNA concentrations of 0.1 and 1 ng/μL. In both cases, the UV dose predicted and explained a significant proportion of the variance in the log inactivation ratio and DNA damage factor. Log inactivation ratio was very low, as expected in groundwater due to low initial bacterial counts, whereas the DNA damage factor was within the range of values obtained in the laboratory-based experiments. Consequently, the DNA damage factor reflected the true performance of the full-scale UV system during operational water flow by using the indigenous bacterial array present in a water sample. By applying this method, we were able to predict with high confidence, the UV reactor inactivation potential. For method validation, laboratory and field iterations are required to create a practical field calibration curve that can be used to determine the expected efficiency of the full-scale UV system in the field under actual operation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of gamma radiation on commercial food packaging films—study of changes in UV/VIS spectra

NASA Astrophysics Data System (ADS)

Moura, E. A. B.; Ortiz, A. V.; Wiebeck, H.; Paula, A. B. A.; Silva, A. L. A.; Silva, L. G. A.

2004-09-01

The effects of gamma irradiation doses up to 100 kGy on the optical properties of different commercial packaging films were studied in this paper. The packaging films analyzed were: polyethylene "LDPE", amide 6-amide 6.6 copolymer "PA6-PA6.6" and poly(ethylene terephthalate) "PET". An investigation on film samples before and after irradiation was performed by UV/VIS spectroscopy. The results showed that, in the absorption spectra of irradiated LDPE and PA6-PA6.6 films, a red-shift in the wavelength of the UV cutoff and a marked reduction in % transmittance (at low wavelengths) occur with increasing radiation dose. With respect to PET samples, no significant changes were observed in either light absorption or transmittance.

UV doses and skin effects during psoriasis climate therapy

NASA Astrophysics Data System (ADS)

Randeberg, Lise L.; Hernandez-Palacios, Julio; Lilleeng, Mila; Nilsen, Lill Tove; Krogstad, Anne-Lene

2011-03-01

Psoriasis is a common autoimmune disease with inflammatory symptoms affecting skin and joints. One way of dealing with psoriasis is by controlled solar UV exposure treatment. However, this treatment should be optimized to get the best possible treatment effect and to limit negative side effects such as erythema and an increased risk of skin cancer. In this study 24 patients at Valle Marina Treatment Center in Gran Canaria were monitored throughout a treatment period of three weeks starting at the beginning of November. The total UV dose to the location was monitored by UV-meters placed on the roof of the treatment centere, and the patients wore individual film dosimeters throughout the treatment period. Skin parameters were accessed by reflection spectroscopy (400-850nm). This paper presents preliminary findings from the skin measurements in the visible part of the spectrum, such as blood oxygenation, erythema and melanin indexes. Reflection spectroscopy was found to be a good tool for such treatment monitoring.

Transformation of Saccharomyces cerevisiae with UV-irradiated single-stranded plasmid.

PubMed

Zgaga, Z

1991-08-01

UV-irradiated single-stranded replicative plasmids were used to transform different yeast strains. The low doses of UV used in this study (10-75 J/m2) caused a significant decrease in the transforming efficiency of plasmid DNA in the Rad+ strain, while they had no effect on transformation with double-stranded plasmids of comparable size. Neither the rev3 mutation, nor the rad18 or rad52 mutations influenced the efficiency of transformation with irradiated single-stranded plasmid. However, it was found to be decreased in the double rev3 rad52 mutant. Extracellular irradiation of plasmid that contains both URA3 and LEU2 genes (psLU) gave rise to up to 5% Leu- transformants among selected Ura+ ones in the repair-proficient strain. Induction of Leu- transformants was dose-dependent and only partially depressed in the rev3 mutant. These results suggest that both mutagenic and recombinational repair processes operate on UV-damaged single-stranded DNA in yeast.

Effects of Aloe Vera on Spinal Cord Ischemia-Reperfusion Injury of Rats.

PubMed

Yuksel, Yasemin; Guven, Mustafa; Kaymaz, Burak; Sehitoglu, Muserref Hilal; Aras, Adem Bozkurt; Akman, Tarik; Tosun, Murat; Cosar, Murat

2016-12-01

The purpose of this study was to evaluate the possible protective/therapeutic effects of aloe vera (AV) on ischemia-reperfusion injury (I/R) of spinal cord in rats. A total of 28 Wistar Albino rats were divided into four random groups of equal number (n = 7). Group I (control) had no medication or surgery; Group II underwent spinal cord ischemia and was given no medication; Group III was administered AV by gastric gavage for 30 days as pre-treatment; Group IV was administered single dose intraperitoneal methylprednisolone (MP) after the ischemia. Nuclear respiratory factor-1 (NRF1), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were evaluated. Tissue samples were examined histopathologically and neuronal nitric oxide synthase (nNOS) and nuclear factor-kappa B (NF-κB) protein expressions were assessed by immunohistochemical staining. NRF1 and SOD levels of ischemia group were found to be lower compared to the other groups. MDA levels significantly increased after I/R. Treatment with AV and MP resulted in reduced MDA levels and also alleviated hemorrhage, edema, inflammatory cell migration and neurons were partially protected from ischemic injury. When AV treatment was compared with MP, there was no statistical difference between them in terms of reduction of neuronal damage. I/R injury increased NF-κB and nNOS expressions. AV and MP treatments decreased NF-κB and nNOS expressions. It was observed that aloe vera attenuated neuronal damage histopathologically and biochemically as pretreatment. Further studies may provide more evidence to determine the additional role of aloe vera in spinal cord ischemia reperfusion injury.

Antiretroviral pharmacokinetics in mothers and breastfeeding infants from 6 to 24 weeks post partum: results of the BAN Study

PubMed Central

Corbett, Amanda H; Kayira, Dumbani; White, Nicole R; Davis, Nicole L; Kourtis, Athena P; Chasela, Charles; Martinson, Francis; Phiri, Grace; Musisi, Bonaface; Kamwendo, Deborah; Hudgens, Michael G; Hosseinipour, Mina C; Nelson, Julie AE; Ellington, Sascha R; Jamieson, Denise J; van der Horst, Charles; Kashuba, Angela

2014-01-01

Background An intensive, prospective, open-label pharmacokinetic (PK) study in a subset of HIV-infected mothers and their uninfected infants enrolled in the Breastfeeding, Antiretroviral, and Nutrition study was performed to describe drug exposure and antiviral response. Methods Women using Combivir®[zidovudine (ZDV)+ lamivudine (3TC)]+Aluvia®[lopinavir/ritonavir(LPV/RTV)] were enrolled. Breast milk (BM) and mother and infant plasma (MP, IP) samples were obtained over 6hrs after observed dosing at 6, 12, or 24wks post-partum for drug concentrations and HIV RNA. Results 30 mother/infant pairs (10 each at 6, 12,and 24wks post-partum) were enrolled. Relative to MP, BM concentrations of ZDV and 3TC were 35% and 21% higher, while LPV and RTV were 80% lower. Only 3TC was detected in IP with concentrations 96% and 98% lower than MP and BM, respectively. Concentrations in all matrices were similar at 6-24wks. The majority (98.3%) of BM concentrations were >HIVwt IC50, with one having detectable virus. There was no association between PK parameters and MP or BM HIV RNA. Conclusions ZDV and 3TC concentrated in BM while LPV and RTV did not, possibly due to protein binding and drug transporter affinity. Undetectable to low ARV concentrations in IP suggests prevention of transmission while breast feeding may be due to ARV effects on systemic or BM HIV RNA in the mother. Low IP 3TC exposure may predispose an infected infant to HIV resistance, necessitating testing and treating infants early. PMID:24464632

Mom Power: Preliminary Outcomes of a Group Intervention to Improve Mental Health and Parenting Among High-Risk Mothers

PubMed Central

Muzik, Maria; Rosenblum, Katherine L.; Alfafara, Emily A.; Schuster, Melisa M.; Miller, Nicole M.; Waddell, Rachel M.; Kohler, Emily Stanton

2015-01-01

Purpose Maternal psychopathology and traumatic life experiences may adversely impact family functioning, the quality of the parent-child relationship and the attachment bond, placing the child’s early social-emotional development at risk. Attachment-based parenting interventions may be particularly useful in decreasing negative outcomes for children exposed to risk contexts, yet high risk families frequently do not engage in programs to address mental health and/or parenting needs. This study evaluated the effects of Mom Power (MP), a 13-session parenting and self-care skills group program for high-risk mothers and their young children (age <6 years old), focused on enhancing mothers’ mental health, parenting competence and engagement in treatment. Methods Mothers were referred from community health providers for a Phase 1 trial to assess feasibility, acceptability and pilot outcomes. At baseline, many reported several identified risk factors, including trauma exposure, psychopathology, poverty and single parenthood. 99 mother-child pairs were initially recruited into the MP program with 68 women completing and providing pre- and post- self-report measures assessing demographics and trauma history (pre-assessment only), maternal mental health (depression and PTSD), parenting and intervention satisfaction. Results Results indicate that MP participation was associated with reduction in depression, PTSD and caregiving helplessness. A dose response relationship was evident in that, despite baseline equivalence, women who attended ≥70% of the 10 groups (completers; N=68) improved on parenting and mental health outcomes, in contrast to non-completers (N=12). Effects were most pronounced for women with a mental health diagnosis at baseline. The intervention was perceived as helpful and user-friendly. Conclusions Results indicate that MP is feasible, acceptable and holds promise for improving maternal mental health and parenting competence among high-risk dyads. Further research is warranted to evaluate the efficacy of MP using randomized controlled designs. PMID:25577336

Effects of near-ultraviolet light on mutations, intragenic and intergenic recombinations in Saccharomyces cerevisiae.

PubMed

Machida, I; Saeki, T; Nakai, S

1986-03-01

The effects of far (254 nm) and near (290-350 nm) ultraviolet (UV) light on mutations, intragenic and intergenic recombinations were compared in diploid strains of Saccharomyces cerevisiae. At equivalent survival levels there was not much difference in the induction of nonsense and missense mutations between far- and near-UV radiations. However, frameshift mutations were induced more frequently by near-UV than by far-UV radiation. Near-UV radiation induced intragenic recombination (gene conversion) as efficiently as far-UV radiation and the induced levels were similar in both radiations at equitoxic doses. A strikingly higher frequency was observed for the intergenic recombination induced by near-UV radiation than by far-UV radiation when compared at equivalent survival levels. Photoreactivation reduced the frequency only slightly in far-UV induced intergenic recombination and not at all in near-UV induction. These results indicate that near-UV damage involves strand breakage in addition to pyrimidine dimers and other lesions induced, whereas far-UV damage consists largely of photoreactivable lesions, pyrimidine dimers, and near-UV induced damage is more efficient for the induction of crossing-over.

Invasion and initial replication of ultraviolet irradiated waterborne infective stages of Myxobolus cerebralis results in immunity to whirling disease in rainbow trout.

PubMed

Hedrick, Ronald P; McDowell, Terry S; Adkison, Mark A; Myklebust, Karin A; Mardones, Fernando O; Petri, Brian

2012-06-01

Myxobolus cerebralis is a microscopic metazoan parasite (Phylum Myxozoa: Myxosporea) associated with salmonid whirling disease. There are currently no vaccines to minimise the serious negative economical and ecological impacts of whirling disease among populations of salmonid fish worldwide. UV irradiation has been shown to effectively inactivate the waterborne infective stages or triactinomyxons of M. cerbralis in experimental and hatchery settings but the mechanisms by which the parasite is compromised are unknown. Treatments of triactinomyxons with UV irradiation at doses from 10 to 80 mJ/cm(2) either prevented (20-80 mJ/cm(2)) or significantly inhibited (10 mJ/cm(2)) completion of the parasite life cycle in experimentally exposed juvenile rainbow trout (Oncorhynchus mykiss). However, even the highest doses of UV irradiation examined (80 mJ/cm(2)) did not prevent key steps in the initiation of parasite infection, including attachment and penetration of the epidermis of juvenile rainbow trout as demonstrated by scanning electron and light microscopy. Furthermore, replication of UV-treated parasites within the first 24h following invasion of the caudal fin was suggested by the detection of concentrations of parasite DNA by quantitative PCR comparable to that among fish exposed to an equal concentration of untreated triactinomyxons. Subsequent development of parasites treated with an 80 mJ/cm(2) dose of UV irradiation however, was impaired as demonstrated by the decline and then lack of detection of parasite DNA; a trend beginning at 10 days and continuing thereafter until the end of the study at 46 days post parasite exposure. Treatments of triactinomyxons with a lower dose of UV irradiation (20 mJ/cm(2)) resulted in a more prolonged survival with parasite DNA detected, although at very low concentrations, in fish up to 49 days post parasite exposure. The successful invasion but only short-term survival of parasites treated with UV in rainbow trout resulted in a protective response to challenges with fully infective triactinomyxons. Prior treatments of juvenile rainbow trout with UV-treated triactinomyxons (10 and 20 mJ/cm(2)) resulted in a reduced prevalence of infection and significantly lower concentrations of cranial myxospores (two direct measures of the severity of whirling disease) compared with trout receiving no prior treatments when assessed 5 months post parasite exposure to fully infective triactinomyxons. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

UV-C tolerance of symbiotic Trebouxia sp. in the space-tested lichen species Rhizocarpon geographicum and Circinaria gyrosa: role of the hydration state and cortex/screening substances

NASA Astrophysics Data System (ADS)

Sánchez, Francisco Javier; Meeßen, Joachim; del Carmen Ruiz, M.; Sancho, Leopoldo G.; Ott, Sieglinde; Vílchez, Carlos; Horneck, Gerda; Sadowsky, Andres; de la Torre, Rosa

2014-01-01

Many experiments were carried out in order to evaluate the survival capacity of extremotolerant lichens when facing harsh conditions, including those of outer space or of simulated Martian environment. For further progress, a deeper study on the physiological mechanisms is needed that confer the unexpected levels of resistance detected on these symbiotic organisms. In this work, the response of the lichenized green algae Trebouxia sp. (a predominant lichen photobiont) to increasing doses of UV-C radiation is studied. UV-C (one of the most lethal factors to be found in space together with vacuum and cosmic-ionizing radiation with high atomic number and energy (HZE) particles) has been applied in the present experiments up to a maximum dose analogue to 67 days in Low Earth Orbit (LEO). For that purpose we selected two extremotolerant and space-tested lichen species in which Trebouxia sp. is the photosynthetic partner: the crustose lichen Rhizocarpon geographicum and the fruticose lichen Circinaria gyrosa. In order to evaluate the effect of the physiological state of the lichen thallus (active when wet and dormant when dry) and of protective structures (cortex and photoprotective pigments) on the resistance of the photobiont to UV-C, four different experimental conditions were tested: (1) dry intact samples, (2) wet intact samples, (3) dry samples without cortex/acetone-rinsed and (4) wet samples without cortex/acetone-rinsed. After irradiation and a 72 hours period of recovery, the influence of UV-C on the two lichen's photobiont under each experimental approach was assessed by two complimentary methods: (1) By determining the photosystem II (PSII) activity in three successive 24 hours intervals (Mini-PAM fluorometer) to investigate the overall state of the photosynthetic process and the resilience of Trebouxia sp. (2) By performing high performance liquid chromatography (HPLC)-quantification of four essential photosynthetic pigments (chlorophyll a, chlorophyll b, β-carotene and lutein) of one sample of each species and dose. Results indicate that the physiological state of the thallus is the most important factor impairing the tolerance of Trebouxia sp. to UV-C radiation in both lichen species. Desiccated thalli were demonstrated to be more resistant to UV-C. No clear influence of UV-C radiation on the carotenoid content was detected. Comparing the respective doses applied, the individuals of R. geographicum are more sensitive than C. gyrosa.

Three operation modes of the vitamin-D-biodosimeter

NASA Astrophysics Data System (ADS)

Terenetskaya, Irina P.

2016-04-01

The original UV biodosimeter for an in situ monitoring of the vitamin-D-synthetic capacity of sunlight and/or artificial UV sources is based on the same photoreaction in vitro by which vitamin D is synthesized in human skin from initial provitamin D via photo- and thermo-induced monomolecular isomerizations. Therefore, targets for UV photons in the biodosimeter are the provitamin D molecules embedded in specially designed UV transparent and stable matrix. The dosimeter response to UV radiation is photoinduced conversion of provitamin D into previtamin D which is immediate precursor of vitamin D. Thus, biological `antirachitic' UV dose is determined by the amount of accumulated previtamin D. To follow the photoreaction course in real time three operation modes of varying complexity have been developed.

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprine or 6-mercaptopurine intolerant IBD patients

PubMed Central

de Boer, Nanne KH; Derijks, Luc JJ; Gilissen, Lennard PL; Hommes, Daniel W; Engels, Leopold GJB; de Boer, Sybrand Y; den Hartog, Gijsbertus; Hooymans, Piet M; Mäkelburg, Anja BU; Westerveld, Barend D; Naber, Anton HJ; Mulder, Chris JJ; de Jong, Dirk J

2005-01-01

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 year. METHODS: Database analysis. RESULTS: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%) and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had splenomegaly. CONCLUSION: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials. PMID:16222751

From ultraviolet to Prussian blue: a spectral response for the cyanotype process and a safe educational activity to explain UV exposure for all ages.

PubMed

Turner, J; Parisi, A V; Downs, N; Lynch, M

2014-12-01

Engaging students and the public in understanding UV radiation and its effects is achievable using the real time experiment that incorporates blueprint paper, an "educational toy" that is a safe and easy demonstration of the cyanotype chemical process. The cyanotype process works through the presence of UV radiation. The blueprint paper was investigated to be used as not only engagement in discussion for public outreach about UV radiation, but also as a practical way to introduce the exploration of measurement of UV radiation exposure and as a consequence, digital image analysis. Tests of print methods and experiments, dose response, spectral response and dark response were investigated. Two methods of image analysis for dose response calculation are provided using easy to access software and two methods of pixel count analysis were used to determine spectral response characteristics. Variation in manufacture of the blueprint paper product indicates some variance between measurements. Most importantly, as a result of this investigation, a preliminary spectral response range for the radiation required to produce the cyanotype reaction is presented here, which has until now been unknown.

Inactivation of carotenoid-producing and albino strains of Neurospora crassa by visible light, blacklight, and ultraviolet radiation.

PubMed Central

Blanc, P L; Tuveson, R W; Sargent, M L

1976-01-01

Suspensions of Neurospora crassa conidia were inactivated by blacklight (BL) radiation (300 to 425 nm) in the absence of exogenous photosensitizing compounds. Carotenoid-containing wild-type conidia were less sensitive to BL radiation than albino conidia, showing a dose enhancement factor (DEF) of 1.2 for dose levels resulting in less than 10% survival. The same strains were about equally sensitive to shortwave ultraviolet (UV) inactivation. The kinetics of BL inactivation are similar to those of photodynamic inactivation by visible light in the presence of a photosensitizing dye (methylene blue). Only limited inactivation by visible light in the absence of exogenous photosensitizers was observed. BL and UV inactivations are probably caused by different mechanisms since wild-type conidia are only slightly more resistant to BL radiation (DEF = 1.2 at 1.0% survival) than are conidia from a UV-sensitive strain (upr-1, uvs-3). The BL-induced lethal lesions are probably no cyclobutyl pyrimidine dimers since BL-inactivated Haemophilus influenzae transforming deoxyribonucleic acid is not photoreactivated by N. crassa wild-type enzyme extracts, whereas UV-inactivated transforming deoxyribonucleic acid is photoreactivable with this treatment. PMID:128556

Technical Note: Evaluation of a 160-mm/256-row CT scanner for whole-heart quantitative myocardial perfusion imaging.

PubMed

So, Aaron; Imai, Yasuhiro; Nett, Brian; Jackson, John; Nett, Liz; Hsieh, Jiang; Wisenberg, Gerald; Teefy, Patrick; Yadegari, Andrew; Islam, Ali; Lee, Ting-Yim

2016-08-01

The authors investigated the performance of a recently introduced 160-mm/256-row CT system for low dose quantitative myocardial perfusion (MP) imaging of the whole heart. This platform is equipped with a gantry capable of rotating at 280 ms per full cycle, a second generation of adaptive statistical iterative reconstruction (ASiR-V) to correct for image noise arising from low tube voltage potential/tube current dynamic scanning, and image reconstruction algorithms to tackle beam-hardening, cone-beam, and partial-scan effects. Phantom studies were performed to investigate the effectiveness of image noise and artifact reduction with a GE Healthcare Revolution CT system for three acquisition protocols used in quantitative CT MP imaging: 100, 120, and 140 kVp/25 mAs. The heart chambers of an anthropomorphic chest phantom were filled with iodinated contrast solution at different concentrations (contrast levels) to simulate the circulation of contrast through the heart in quantitative CT MP imaging. To evaluate beam-hardening correction, the phantom was scanned at each contrast level to measure the changes in CT number (in Hounsfield unit or HU) in the water-filled region surrounding the heart chambers with respect to baseline. To evaluate cone-beam artifact correction, differences in mean water HU between the central and peripheral slices were compared. Partial-scan artifact correction was evaluated from the fluctuation of mean water HU in successive partial scans. To evaluate image noise reduction, a small hollow region adjacent to the heart chambers was filled with diluted contrast, and contrast-to-noise ratio in the region before and after noise correction with ASiR-V was compared. The quality of MP maps acquired with the CT system was also evaluated in porcine CT MP studies. Myocardial infarct was induced in a farm pig from a transient occlusion of the distal left anterior descending (LAD) artery with a catheter-based interventional procedure. MP maps were generated from the dynamic contrast-enhanced (DCE) heart images taken at baseline and three weeks after the ischemic insult. Their results showed that the phantom and animal images acquired with the CT platform were minimally affected by image noise and artifacts. For the beam-hardening phantom study, changes in water HU in the wall surrounding the heart chambers greatly reduced from >±30 to ≤ ± 5 HU at all kVp settings except one region at 100 kVp (7 HU). For the cone-beam phantom study, differences in mean water HU from the central slice were less than 5 HU at two peripheral slices with each 4 cm away from the central slice. These findings were reproducible in the pig DCE images at two peripheral slices that were 6 cm away from the central slice. For the partial-scan phantom study, standard deviations of the mean water HU in 10 successive partial scans were less than 5 HU at the central slice. Similar observations were made in the pig DCE images at two peripheral slices with each 6 cm away from the central slice. For the image noise phantom study, CNRs in the ASiR-V images were statistically higher (p < 0.05) than the non-ASiR-V images at all kVp settings. MP maps generated from the porcine DCE images were in excellent quality, with the ischemia in the LAD territory clearly seen in the three orthogonal views. The study demonstrates that this CT system can provide accurate and reproducible CT numbers during cardiac gated acquisitions across a wide axial field of view. This CT number fidelity will enable this imaging tool to assess contrast enhancement, potentially providing valuable added information beyond anatomic evaluation of coronary stenoses. Furthermore, their results collectively suggested that the 100 kVp/25 mAs protocol run on this CT system provides sufficient image accuracy at a low radiation dose (<3 mSv) for whole-heart quantitative CT MP imaging.

Simultaneous atrazine degradation and E. coli inactivation by simulated solar photo-Fenton-like process using persulfate.

PubMed

Garkusheva, Natalya; Matafonova, Galina; Tsenter, Irina; Beck, Sara; Batoev, Valeriy; Linden, Karl

2017-07-29

This work evaluated the feasibility of a photo-Fenton-like process using persulfate (PS) and ferrous iron (Fe 2+ ) under simulated solar radiation for degrading the herbicide atrazine (ATZ, 6-Chloro-N-ethyl-N'-isopropyl-1,3,5-triazine-2,4-diamine) and inactivating E. coli. Milli Q water, lake water, and diluted wastewater effluents were spiked both simultaneously and separately with ATZ (4 mg/L) and E. coli (10 5 CFU/mL), and exposed to treatment. A method for determining the average irradiance throughout the water media in the UV(A+B) range of the Xe lamp emission was developed for bench-scale experiments. These values were used to calculate the UV(A+B) fluences and the solar UV(A+B) energy doses per unit of volume (Q UV(A+B) , kJ/L). The obtained kinetic data were presented versus energy dose. Treatment of lake water at near-neutral pH was ineffective via the photo-Fenton-like process, attaining only 20% ATZ removal and 1-log reduction of E. coli. In Milli Q water and wastewater, the complete degradation of ATZ in the absence of bacteria was observed at an average energy dose of 1.5 kJ/L (60 min), while in the presence of cells the degradation efficiency was ∼60%. When ATZ was present, E. coli inactivation was also affected in Milli Q water, with 1.4-log reduction (93%) at a dose of 1.6 kJ/L (60 min), whereas in wastewater complete inactivation was achieved at a lower dose of 1.3 kJ/L (45 min). The energy requirements on a Q UV(A+B) basis for simultaneous 90% ATZ removal and 99.99% E. coli inactivation in Milli Q water and wastewater were shown to be less than 10 kJ/L. This suggests the solar/PS/Fe 2+ system is promising for simultaneous treatment and disinfection of wastewater effluents.

European light dosimeter network (ELDONET): 1998 data

NASA Astrophysics Data System (ADS)

Häder, D.-P.; Lebert, M.; Colombetti, G.; Figueroa, F.

2001-03-01

The European light dosimeter network of over 40 stations has been established in Europe and other continents equipped with three-channel filter dosimeters to measure solar radiation in three channels, UV-B (280-315 nm), UV-A (315-400 nm) and photosynthetically active radiation (PAR). The recorded data have been evaluated, and the monthly doses in all three channels show a strong latitudinal dependence from northern Sweden to the Canary Islands. There are a few remarkable exceptions such as the data recorded at the high mountain station on the Zugspitze (German Alps) and unequal doses at stations at comparable latitudes which indicate the impact of local weather conditions and mean sunshine hours. While generally peak values are recorded in the months of June and July, the UV-B maxima are shifted later into the year, which is due to the antagonistic functions of decreasing solar angles and increasing transparency of the atmosphere as the total column ozone decreases in the second half of the year for the Northern Hemisphere. This is supported by comparison with modelled total column ozone and satellite-based measurements. Also the ratios of UV-B:UV-A and UV-B:PAR as well as UV-A:PAR peak during the summer months, with the exception of the northernmost station at Abisko (north Sweden) where the UV-A:PAR ratio peaks in the winter months which is due to the specific photoclimatic conditions north of the polar circle. The penetration of solar radiation into the water column was found to strongly depend on the transparency of the water column. In Gran Canaria more than 10% of the surface UV-B penetrated to 4-5 m depth. The path of the solar eclipse on 11 August 1999 could be followed in several stations with different degrees of occlusion of the sun disk.

Antioxidant responses of damiana (Turnera diffusa Willd) to exposure to artificial ultraviolet (UV) radiation in an in vitro model; part ii; UV-B radiation.

PubMed

Soriano-Melgar, Lluvia de Abril Alexandra; Alcaraz-Meléndez, Lilia; Méndez-Rodríguez, Lía C; Puente, María Esther; Rivera-Cabrera, Fernando; Zenteno-Savín, Tania

2014-05-01

Ultraviolet type B (UV-B) radiation effects on medicinal plants have been recently investigated in the context of climate change, but the modifications generated by UV-B radiation might be used to increase the content of antioxidants, including phenolic compounds. To generate information on the effect of exposure to artificial UV-B radiation at different highdoses in the antioxidant content of damiana plants in an in vitro model. Damiana plantlets (tissue cultures in Murashige- Skoog medium) were irradiated with artificial UV-B at 3 different doses (1) 0.5 ± 0.1 mW cm-2 (high) for 2 h daily, (2) 1 ± 0,1 mW cm-2 (severe) for 2 h daily, or (3) 1 ± 0.1 mW cm-2 for 4 h daily during 3 weeks. The concentration of photosynthetic pigments (chlorophylls a and b, carotenoids), vitamins (C and E) and total phenolic compounds, the enzymatic activity of superoxide dismutase (SOD, EC 1.15.1.1) and total peroxidases (POX, EC 1.11.1), as well as total antioxidant capacity and lipid peroxidation levels were quantified to assess the effect of high artificial UV-B radiation in the antioxidant content of in vitro damiana plants. Severe and high doses of artificial UV-B radiation modified the antioxidant content by increasing the content of vitamin C and decreased the phenolic compound content, as well as modified the oxidative damage of damiana plants in an in vitro model. UV-B radiation modified the antioxidant content in damiana plants in an in vitro model, depending on the intensity and duration of the exposure. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

The deceptive nature of UVA tanning versus the modest protective effects of UVB tanning on human skin.

PubMed

Miyamura, Yoshinori; Coelho, Sergio G; Schlenz, Kathrin; Batzer, Jan; Smuda, Christoph; Choi, Wonseon; Brenner, Michaela; Passeron, Thierry; Zhang, Guofeng; Kolbe, Ludger; Wolber, Rainer; Hearing, Vincent J

2011-02-01

The relationship between human skin pigmentation and protection from ultraviolet (UV) radiation is an important element underlying differences in skin carcinogenesis rates. The association between UV damage and the risk of skin cancer is clear, yet a strategic balance in exposure to UV needs to be met. Dark skin is protected from UV-induced DNA damage significantly more than light skin owing to the constitutively higher pigmentation, but an as yet unresolved and important question is what photoprotective benefit, if any, is afforded by facultative pigmentation (i.e. a tan induced by UV exposure). To address that and to compare the effects of various wavelengths of UV, we repetitively exposed human skin to suberythemal doses of UVA and/or UVB over 2 weeks after which a challenge dose of UVA and UVB was given. Although visual skin pigmentation (tanning) elicited by different UV exposure protocols was similar, the melanin content and UV-protective effects against DNA damage in UVB-tanned skin (but not in UVA-tanned skin) were significantly higher. UVA-induced tans seem to result from the photooxidation of existing melanin and its precursors with some redistribution of pigment granules, while UVB stimulates melanocytes to up-regulate melanin synthesis and increases pigmentation coverage, effects that are synergistically stimulated in UVA and UVB-exposed skin. Thus, UVA tanning contributes essentially no photoprotection, although all types of UV-induced tanning result in DNA and cellular damage, which can eventually lead to photocarcinogenesis. 2010 John Wiley & Sons A/S. This article is a US Government work and is in the public domain in the USA.

UV-induced transformation of four halobenzoquinones in drinking water.

PubMed

Qian, Yichao; Wang, Wei; Boyd, Jessica M; Wu, Minghuo; Hrudey, Steve E; Li, Xing-Fang

2013-05-07

Halobenzoquinones (HBQs) are a group of emerging disinfection byproducts (DBPs) found in treated drinking water. Because the use of UV treatment for disinfection is becoming more widespread, it is important to understand how the HBQs may be removed or changed due to UV irradiation. Water samples containing four HBQs, 2,6-dichloro-1,4-benzoquinone (DCBQ), 2,3,6-trichloro-1,4-benzoquinone (TCBQ), 2,6-dichloro-3-methyl-1,4-benzoquinone (DCMBQ), and 2,6-dichloro-1,4-benzoquinone (DBBQ), were treated using a modified bench scale collimated beam device, mimicking UV treatment. Water samples before and after UV irradiation were analyzed for the parent compounds and products using a high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method. As much as 90% of HBQs (0.25 nmol L(-1)) in both pure water and tap water were transformed to other products after UV254 irradiation at 1000 mJ cm(-2). The major products of the four HBQs were identified as 3-hydroxyl-2,6-dichloro-1,4-benzoquinone (OH-DCBQ) from DCBQ, 5-hydroxyl-2,6-dichloro-3-methyl-1,4-benzoquinone (OH-DCMBQ) from DCMBQ, 5-hydroxyl-2,3,6-trichloro-1,4-benzoquinone (OH-TCBQ) from TCBQ, and 3-hydroxyl-2,6-dibromo-1,4-benzoquinone (OH-DBBQ) from DBBQ. These four OH-HBQs were further modified to monohalogenated benzoquinones when the UV dose was higher than 200 mJ cm(-2). These results suggested possible pathways of UV-induced transformation of HBQs to other compounds. Under the UV dose commonly used in water treatment plants, it is likely that HBQs are partially converted to other halo-DBPs. The occurrence and toxicity of these mixed DBPs warrant further investigation to understand whether they pose a health risk.

Application of UV-irradiated Fe(III)-nitrilotriacetic acid (UV-Fe(III)NTA) and UV-NTA-Fenton systems to degrade model and natural occurring naphthenic acids.

PubMed

Zhang, Ying; Chelme-Ayala, Pamela; Klamerth, Nikolaus; Gamal El-Din, Mohamed

2017-07-01

Naphthenic acids (NAs) are a highly complex mixture of organic compounds naturally present in bitumen and identified as the primary toxic constituent of oil sands process-affected water (OSPW). This work investigated the degradation of cyclohexanoic acid (CHA), a model NA compound, and natural occurring NAs during the UV photolysis of Fe(III)-nitrilotriacetic acid (UV-Fe(III)NTA) and UV-NTA-Fenton processes. The results indicated that in the UV-Fe(III)NTA process at pH 8, the CHA removal increased with increasing NTA dose (0.18, 0.36 and 0.72 mM), while it was independent of the Fe(III) dose (0.09, 0.18 and 0.36 mM). Moreover, the three Fe concentrations had no influence on the photolysis of the Fe(III)NTA complex. The main responsible species for the CHA degradation was hydroxyl radical (OH), and the role of dissolved O 2 in the OH generation was found to be negligible. Real OSPW was treated with the UV-Fe(III)NTA and UV-NTA-Fenton advanced oxidation processes (AOPs). The removals of classical NAs (O 2 -NAs), oxidized NAs with one additional oxygen atom (O 3 -NAs) and with two additional oxygen atoms (O 4 -NAs) were 44.5%, 21.3%, and 25.2% in the UV-Fe(III)NTA process, respectively, and 98.4%, 86.0%, and 81.0% in the UV-NTA-Fenton process, respectively. There was no influence of O 2 on the NA removal in these two processes. The results also confirmed the high reactivity of the O 2 -NA species with more carbons and increasing number of rings or double bond equivalents. This work opens a new window for the possible treatment of OSPW at natural pH using these AOPs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Growth, spectral, optical, laser damage threshold and DFT investigations on 2-amino 4-methyl pyridinium 4-methoxy benzoate (2A4MP4MB): A potential organic third order nonlinear optical material for optoelectronic applications

NASA Astrophysics Data System (ADS)

Krishnakumar, M.; Karthick, S.; Thirupugalmani, K.; Babu, B.; Vinitha, G.

2018-05-01

In present investigation, single crystals of organic charge transfer complex, 2-amino-4-methyl pyridinium-4-methoxy benzoate (2A4MP4MB) was grown by controlled slow evaporation solution growth technique using methanol as a solvent at room temperature. Single crystal XRD analysis confirmed the crystal system and lattice parameters of 2A4MP4MB. The crystalline nature, presence of various vibrational modes and other chemical bonds in the compound have been recognized and confirmed by powder X-ray diffraction, FT-IR and FT-Raman spectroscopic techniques respectively. The presence of various proton and carbon positions in title compound was confirmed using 1H NMR and 13C NMR spectral studies. The wide optical operating window and cut-off wavelength were identified and band gap value of the title compound was calculated using UV-vis-NIR study. The specific heat capacity (cp) values of the title compound, 1.712 J g-1·K-1 at 300 K and 13.6 J g-1 K-1 at 433 K (melting point) were measured using Modulated Differential Scanning Calorimetric studies (MDSC). From Z-scan study, nonlinear refractive index (n2), nonlinear absorption (β) and third order nonlinear susceptibility (χ(3)) values were determined. The self-defocusing effect and saturable absorption behavior of the material were utilized to exhibit the optical limiting action at λ = 532 nm by employing the same continuous wave (cw) Nd: YAG laser source. The laser damage threshold (LDT) study of title compound was carried out using Nd: YAG laser of 532 nm wavelength. The Vickers' micro hardness test was carried out at room temperature and obtained results were investigated using classical Meyer's law. In addition, DFT calculations were carried out for the first time for this compound. These characterization studies performed on the title compound planned to probe the valuable and safe region of optical, thermal and mechanical properties to improve efficacy of 2A4MP4MB single crystals in optoelectronic device applications.

Isolation of uv-sensitive variants of human FL cells by a viral suicide method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiomi, T.; Sato, K.

A new method (viral suicide method) for the isolation of uv-sensitive mutants is described. Colonies of mutagenized human FL cells were infected with uv-irradiated Herpes simplex viruses and surviving ones which seemed to be deficient in host cell reactivation (HCR) were examined for their uv sensitivity. Nineteen of 238 clones examined were sensitive to uv irradiation at the time of the isolation. After recloning, four of these clones have been studied and two (UVS-1 and UVS-2) of them are stable in their uv sensitivity for 4 months in culture. uv sensitivity of UVS-1, UVS-2, and the parental FL cells aremore » as follows: the extrapolation numbers (n) are 2.2, 2.1, and 1.8 and mean lethal doses (DO) are 2.9, 3.7, and 7.8 J/m/sup 2/ for UVS-1, UVS-2, and the parental FL cells, respectively. They are no more sensitive than FL cells to x-irradiation. The ability of HCR in UVS-2 cells is apparently lower than that in FL cells, whereas UVS-1 cells are the same as FL cells in the ability.« less

Characterization of ferrous-methylthymol blue-polyvinyl alcohol gel dosimeters using nuclear magnetic resonance and optical techniques

NASA Astrophysics Data System (ADS)

Rabaeh, Khalid A.; Eyadeh, Molham M.; Hailat, Tariq F.; Aldweri, Feras M.; Alheet, Samer M.; Eid, Rania M.

2018-07-01

A new composition of Ferrous sulphate-Metheylthymol blue (MTB)-Polyvinyl alcohol (PVA) dosimeter is introduced in this work and evaluated using nuclear magnetic resonance (NMR) and absorbance spectrophotometry techniques. The Fricke-MTB-PVA dosimeters were irradiated using a medical linear accelerator in a cubic water phantom. The dose response of the dosimeters was investigated using NMR in terms of spin-spin relaxation rate (R2), and ultraviolet and visible regions (UV-Vis) spectrophotometry in terms of absorbance. The dosimeter presents a linear dose response for doses up to 20 Gy with UV-Vis and 40 Gy with NMR method. The sample with 0.1 mM MTB, 5% PVA by weight showed highest dose sensitivity for both techniques. The Fricke-MTB-PVA dosimeter developed in this work has a significant advance over the Fricke-MTB-gelatin system: the NMR sensitivity was remarkably improved; the auto-oxidation rate was seven times lower, and no significant dose rate or photon energy effects were observed.

QUANTIFYING ULTRAVIOLET RADIATION DOSE RELATIVE TO WETLAND HABITAT VARIABLES FOR THE ASSESSMENT OF RISK TO AMPHIBIANS

EPA Science Inventory

Ultraviolet B radiation (UV-B) has increased globally over the last several decades due to reduction of stratospheric ozone. UV-B may also increase when climate change alters cloud cover, rainfall, and distributions of vegetation. In aquatic systems, these factors can also intera...

40 CFR 86.145-82 - Calculations; particulate emissions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... final reported test results for the mass particulate (Mp) in grams/mile shall be computed as follows. Mp = 0.43(Mp1 + Mp2)/(Dct + Ds) + 0.57(Mp3 + Mp2)/(Dht = Ds) where: (1) Mp1 = Mass of particulate...) for determination.) (2) Mp2 = Mass of particulate determined from the “stabilized” phase of the cold...