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Sample records for delta aminolevulinic acid

  1. 21 CFR 862.1060 - Delta-aminolevulinic acid test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Delta-aminolevulinic acid test system. 862.1060 Section 862.1060 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  2. Delta-aminolevulinic acid dehydratase (ALAD) polymorphism in lead exposed Bangladeshi children and its effect on urinary aminolevulinic acid (ALA)

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    Tasmin, Saira, E-mail: rimzim1612@yahoo.com [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Furusawa, Hana [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Ahmad, Sk. Akhtar [Department of Occupational and Environmental Health, Bangladesh Institute of Health Sciences, 125/1, Darus Salam, Mirpur, Dhaka 1216 (Bangladesh); Faruquee, M.H. [Department of Public Health, State University of Bangladesh, 77 Satmasjid Road, Dhanmondi, Dhaka 1205 (Bangladesh); Watanabe, Chiho [Department of Human Ecology, School of International Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2015-01-15

    Background and objective: Lead has long been recognized as a harmful environmental pollutant. People in developing countries like Bangladesh still have a higher risk of lead exposure. Previous research has suggested that the delta-aminolevulinic acid dehydratase (ALAD) genotype can modify lead toxicity and individual susceptibility. As children are more susceptible to lead-induced toxicity, this study investigated whether the ALAD genotype influenced urinary excretion of delta-aminolevulinic acid (U-ALA) among children exposed to environmental lead in Bangladesh. Methods: Subjects were elementary schoolchildren from a semi-urban industrialized area in Bangladesh. A total of 222 children were studied. Blood and urine were collected to determine ALAD genotypes, blood lead levels and urinary aminolevulinic acid (U-ALA). Results: The mean BPb level was 9.7 µg/dl for the study children. BPb was significantly positively correlated with hemoglobin (p<0.01). In total, allele frequency for ALAD 1 and 2 was 0.83 and 0.17 respectively. The mean U-ALA concentration was lower in ALAD1-2/2-2 carriers than ALAD1-1 carriers for boys (p=0.001). But for girls, U-ALA did not differ significantly by genotype (p=0.26). When U-ALA was compared by genotype at the same exposure level in a multiple linear regression analysis, boys who were ALAD1-2/2-2 carriers still had a lower level of U-ALA compared to ALAD1-1carriers. Conclusion: This study provides information about the influence of ALAD polymorphism and its association with U-ALA in Bangladeshi children. Our results indicate that the ALAD1-2/2-2 genotype may have a protective effect in terms of U-ALA for environmentally lead exposed boys. - Highlights: • High blood lead level for the environmentally exposed schoolchildren. • BPb was significantly correlated with U-ALA and Hb. • Effect of ALAD genotype on U-ALA is differed by sex. • Lower U-ALA in ALAD2 than ALAD1 carriers only for boys at same exposure.

  3. [delta-Aminolevulinate dehydratase deficiency].

    Science.gov (United States)

    Fujita, H; Ishida, N; Akagi, R

    1995-06-01

    delta-Aminolevulinate dehydratase (ALAD: E. C. 4.2.1.24), the second enzyme in the heme biosynthetic pathway, condenses two moles of delta-aminolevulinic acid to form porphobilinogen. ALAD deficiency is well known to develop signs and symptoms of typical hepatic porphyria, and classified into three categories as follows: (i) ALAD porphyria, a genetic defect of the enzyme, (ii) tyrosinemia type I, a genetic defect of fumarylacetoacetase in the tyrosine catabolic pathway, producing succinylacetone (a potent inhibitor of ALAD), and (iii) ALAD inhibition by environmental hazards, such as lead, trichloroethylene, and styrene. In the present article, we will describe molecular and biochemical mechanisms to cause the enzyme defect to discuss the significance of ALAD defect on human health.

  4. Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase in Pregnant Women.

    Science.gov (United States)

    La-Llave-León, Osmel; Méndez-Hernández, Edna M; Castellanos-Juárez, Francisco X; Esquivel-Rodríguez, Eloísa; Vázquez-Alaniz, Fernando; Sandoval-Carrillo, Ada; García-Vargas, Gonzalo; Duarte-Sustaita, Jaime; Candelas-Rangel, Jorge L; Salas-Pacheco, José M

    2017-04-18

    Blood lead levels (BLLs) and delta-aminolevulinic acid dehydratase (ALAD) activity are considered biomarkers of lead exposure and lead toxicity, respectively. The present study was designed to investigate the association between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of 633 pregnant women aged 13-43 years participated in this study. Blood lead was measured by a graphite furnace atomic absorption spectrometer. ALAD activity was measured spectrophotometrically. Mean blood lead was 2.09 ± 2.34 µg/dL; and 26 women (4.1%) crossed the Centers for Disease Control (CDC) recommended level of 5 µg/dL. ALAD activity was significantly lower in women with levels of lead ≥5 µg/dL compared to those with BLLs lead and ALAD activity was observed in the fourth quartile of BLLs (r = -0.113; p lead concentrations ≥2.2 µg/dL ALAD activity was negatively correlated with BLLs (r = -0.413; p lead in blood above 2.2 µg/dL.

  5. Association between Blood Lead Levels and Delta-Aminolevulinic Acid Dehydratase in Pregnant Women

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    Osmel La-Llave-León

    2017-04-01

    Full Text Available Blood lead levels (BLLs and delta-aminolevulinic acid dehydratase (ALAD activity are considered biomarkers of lead exposure and lead toxicity, respectively. The present study was designed to investigate the association between BLLs and ALAD activity in pregnant women from Durango, Mexico. A total of 633 pregnant women aged 13–43 years participated in this study. Blood lead was measured by a graphite furnace atomic absorption spectrometer. ALAD activity was measured spectrophotometrically. Mean blood lead was 2.09 ± 2.34 µg/dL; and 26 women (4.1% crossed the Centers for Disease Control (CDC recommended level of 5 µg/dL. ALAD activity was significantly lower in women with levels of lead ≥5 µg/dL compared to those with BLLs < 5 µg/dL (p = 0.002. To reduce the influence of extreme values on the statistical analysis, BLLs were analyzed by quartiles. A significant negative correlation between blood lead and ALAD activity was observed in the fourth quartile of BLLs (r = −0.113; p < 0.01. Among women with blood lead concentrations ≥2.2 µg/dL ALAD activity was negatively correlated with BLLs (r = −0.413; p < 0.01. Multiple linear regression demonstrated that inhibition of ALAD in pregnant women may occur at levels of lead in blood above 2.2 µg/dL.

  6. Biosynthesis of 1-aminocyclopropane-1-carboxylic acid and ethylene from delta-aminolevulinic acid in ripening tomato fruits

    Energy Technology Data Exchange (ETDEWEB)

    El-Rayes, D.E.D.A.

    1987-01-01

    A new pathway for ethylene (C/sub 2/H/sub 4/) biosynthesis, which utilizes delta-aminolevulinic acid (ALA) as a precursor of 1-aminocyclopropane-1-carboxylic acid (ACC), the immediate precursor of C/sub 2/H/sub 4/, is presented. ALA enhanced ACC accumulation to 410% and C/sub 2/H/sub 4/ production to 232% of the control. The C/sub 2/H/sub 4/ production rate varied with the ALA concentration and the stage of tomato fruit development. As the ALA concentration increased from zero to 40 mM, the C/sub 2/H/sub 4/ production rate increased. Both treated and untreated pericarp discs from fruits at the pink stage of development yielded the largest C/sub 2/H/sub 4/ production rate. Radioactivity from (2,3-/sup 3/H)ALA was detected in both ACC and C/sub 2/H/sub 4/, and radioactivity from (4-/sup 14/C)ALA was detected in ACC and CO/sub 2/ but not in C/sub 2/H/sub 4/. However, radioactivity from (5-/sup 14/C)ALA was detected in CO/sub 2/, and its amount was greater than that obtained from (4-/sup 14/C)ALA. Neither ACC nor C/sub 2/H/sub 4/ showed any radioactivity when (5-/sup 14/C)ALA was supplied to the fruit discs. In addition, when (2,3-/sup 3/H)ALA or (4-/sup 14/C)ALA was supplied to the fruit discs, radioactivity was detected in other metabolites such as fumarate, succinate, malate, glutamate, glutamine, ..cap alpha..-ketoglutarate, and methionine, but the amount of radioactivity was insignificant as compared with the amount of radioactivity found in C/sub 2/H/sub 4/ and ACC.

  7. Dependence between the level of delta-aminolevulinic acid in urine and some parameters with workers of the Zletovo battery factory in Probistip

    OpenAIRE

    Stavreva Veselinovska, Snezana; Zivanovic, Jordan

    1998-01-01

    Lead has the key part in relation to intoxication by heavy metals. The aim of this determination of correlation between the level of delta-aminolevulinic acid in urine and some other parameters with workers professionally expose to the influence of lead in different parts of the factory producing batteries "Zletovo" in Probistip. The material being used for analysis was the urine 256 persons of both sexses, age level 20-50 years.

  8. A gas chromatography-mass spectrometry method for the determination of delta-aminolevulinic acid in plant leaves.

    Science.gov (United States)

    Hijaz, Faraj; Killiny, Nabil

    2016-05-20

    Delta-aminolevulinic (δ-ALA) acid is an important intermediate for tetrapyrroles biosynthesis and it has recently received great attention in plant physiology and human toxicology. However, the colorimetric method which is the most common method for determination of δ-ALA is time consuming and is not specific. In this study, a method for determination of δ-ALA in plant tissues was developed based on the trimethylsilyl (TMS) derivative of the pyrrole formed from the reaction of δ-ALA with ethyl acetoacetate via Knorr condensation. The δ-ALA in the HCl extract was reacted with ethyl acetoacetate to form a pyrrole. Then, the pyrrole compound was extracted using ethyl acetate and the solvent was evaporated to dryness. The dried sample was derivatized to its TMS ester and analyzed using GC-MS. The concentration of δ-ALA in citrus leaves incubated with levulinic acid was also determined by the conventional colorimetric method. The linear range was 10-200ppm in the full scan mode and 0.1-20ppm in the selected ion monitoring (SIM). The limit of detection was 6ppm in the full scan and 0.05ppm in SIM mode, representing a four-fold increase in sensitivity compared to the colorimetric method. The GC-MS method developed in this study is simple, accurate, sensitive, and could also be used to measure δ-ALA in other biological samples.

  9. Effects of Delta-Aminolevulinic Acid Dehydratase Polymorphisms on Susceptibility to Lead in Han Subjects from Southwestern China

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    Pin Sun

    2012-07-01

    Full Text Available This study is to determine the distribution of the delta-aminolevulinic acid dehydratase (ALAD polymorphism among Han subjects of the Chinese population and to study whether the polymorphism in the ALAD gene modifies the toxicity of lead in lead-exposed workers. For this purpose we conducted a cross-sectional study on 156 Chinese workers who were exposed to lead in lead-acid battery and electric-flex manufacturing plants. The authors found that the allele frequencies of ALAD1 and ALAD2 were 0.9679 and 0.0321, respectively. Workers with the ALAD 1-1 genotype were associated with higher blood lead levels than those with the ALAD 1-2 genotype. Blood and urine lead levels were much higher in storage battery workers than in cable workers. The self-conscious symptom survey showed that the incidences of debilitation, amnesia and dreaminess were much higher in those had more than five years of tenure or contact with lead on the job within the ALAD 1-1 genotype subgroup. Laboratory examinations showed that serum iron and zinc levels in workers’ with the ALAD 1-2 genotype were higher than those with the ALAD 1-1 genotype, especially in storage-battery workers. Correlation analysis indicated that the blood lead level negatively correlated with serum calcium, iron and zinc level. The data of this study suggest that the ALAD gene polymorphism and serum ion levels may modify the kinetics of lead in blood. Therefore, the authors recommend that an adequate intake of dietary calcium, iron, and zinc or the calcium, iron, and zinc supplementation should be prescribed to Chinese lead exposed workers.

  10. Separation and partial characterization of enzymes catalyzing delta-aminolevulinic acid formation in Synechocystis sp. PCC 6803.

    Science.gov (United States)

    Rieble, S; Beale, S I

    1991-09-01

    Formation of the universal tetrapyrrole precursor, delta-aminolevulinic acid (ALA), from glutamate via the five-carbon pathway requires three enzymes: glutamyl-tRNA synthetase, glutamyl-tRNA reductase, and glutamate-1-semialdehyde (GSA) aminotransferase. All three enzymes were separated from extracts of the unicellular cyanobacterium Synechocystis sp. PCC 6803, and two of them, glutamyl-tRNA synthetase and GSA aminotransferase, were partially characterized. After an initial high speed centrifugation and differentiatial ammonium sulfate fractionation of cell extract, the enzymes were separated by successive affinity chromatography on Reactive Blue 2-Sepharose and 2',5'-ADP-agarose. All three enzyme fractions were required to reconstitute ALA formation from glutamate. The apparent native molecular masses of glutamyl-tRNA synthetase and GSA aminotransferase were determined by gel filtration chromatography to be 63 and 98 kDa, respectively. Neither glutamyl-tRNA synthetase nor GSA aminotransferase activity was affected by hemin concentrations up to 10 and 30 microM, respectively, and neither activity was affected by protochlorophyllide concentrations up to 2 microM. GSA aminotransferase was inhibited 50% by 0.5 microM gabaculine. The gabaculine inhibition was reversible for up to 1 h after its addition, if the gabaculine was removed by gel filtration before the enzyme was incubated with substrate. However, irreversible inactivation was obtained by preincubating the enzyme at 30 degrees C either for several hours with gabaculine alone or for a few minutes with both gabaculine and GSA. Neither pyridoxal phosphate nor pyridoxamine phosphate significantly affected the activity of GSA aminotransferase at physiologically relevant concentrations, and neither of these compounds reactivated the gabaculine-inactivated enzyme. It was noted that the presence of pyridoxamine phosphate in the ALA assay mixture produced a false positive color reaction even in the absence of enzyme.

  11. Lead in Missouri Streams: Monitoring Pollution from Mining with an Assay for Erythrocyte [delta]-Aminolevulinic Acid Dehydratase (ALA-D) in Fish Blood

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The activity of the erythrocyte enzyme d-aminolevulinic acid dehydratase (ALA-D) has long been used as a biomarker of lead exposure in humans and waterfowl and, more...

  12. Aminolevulinic Acid Topical

    Science.gov (United States)

    ... on or under the skin that result from exposure to sunlight and can develop into skin cancer) of the ... acid will make your skin very sensitive to sunlight (likely to get sunburn). Avoid exposure of treated skin to direct sunlight or bright ...

  13. Comparison of colorimetric and HPLC methods for determination of delta-aminolevulinic acid in urine with reference to dose-response relationship in occupational exposure to lead.

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    Fukui, Yoshinari; Miki, Mieko; Ukai, Hirohiko; Okamoto, Satoru; Takada, Shiro; Ikeda, Masayuki

    2005-10-01

    Both traditional colorimetry and recently developed HPLC-fluorometry have been in use for determination of delta-aminolevulinic acid in urine (ALA-U), an effect marker of occupational exposure to lead (Pb). The present study was initiated to compare the values by the two methods on an epidemiology basis among workers occupationally exposed to lead (Pb), to estimate quantitatively the colorimetry-associated increment over the values by the HPLC method, to evaluate ALA-U determination in occupational health service for Pb-exposed workers, and to identify a critical Pb-B to induce an elevation in ALA-U. For this purpose, blood and urine samples were collected from three groups of Pb-exposed workers (both men and women in combination, including smokers) and analyzed for Pb in blood (Pb-B; measured in all subjects) and ALA-U (by colorimetry or HPLC), i.e., Group 1 (164 subjects with urinalysis by the two methods), Group 2 (2,923 subjects by colorimetry), and Group 3 (2,540 subjects by HPLC). ALA-U when measured by colorimetry was higher than the values by HPLC, and that the mean difference on a group basis was 1.4 mg/l (in a range of 1.1 to 1.8 mg/l), irrespective of Pb-B levels. It was also found that the increase in ALA-U was small when Pb-B was relatively low (e.g., < or = 40 microg/100 ml), and that the increase on a group basis in response to an increase in Pb-B from 5 to 40 microg/100 ml was as small as < or = 0.6 mg/l. Thus, ALA-U appeared to be not a sensitive marker of Pb effects at low Pb-B levels. ALA-U however increased substantially with a point of inflection at the Pb-B level of about 17-34 microg/100 ml. Thus it was concluded that ALA-U as measured by colorimetry is greater than ALA-U by HPLC by 1.4 mg/l on average irrespective of intensity of Pb-exposure, which may induce bias in evaluation of health effect, and that ALA-U levels will increase when Pb-B is in excess of 17-34 microg/100 ml.

  14. Source and impact of lead contamination on {delta}-aminolevulinic acid dehydratase activity in several marine bivalve species along the Gulf of Cadiz

    Energy Technology Data Exchange (ETDEWEB)

    Company, R.; Serafim, A.; Lopes, B.; Cravo, A. [CIMA, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Kalman, J.; Riba, I.; DelValls, T.A. [Catedra UNESCO/UNITWIN/WiCop, Department of Physical-Chemistry, Faculty Marine and Environmental Sciences, University of Cadiz, 11510 Puerto Real, Cadiz (Spain); Blasco, J. [Instituto Ciencias Marinas Andalucia (CSIC), Campus Rio San Pedro, 11510 Puerto Real, Cadiz (Spain); Delgado, J. [Department of Geology, University of Huelva, Avda Fuerzas Armadas s/n, 21071 Huelva (Spain); Sarmiento, A.M. [Catedra UNESCO/UNITWIN/WiCop, Department of Physical-Chemistry, Faculty Marine and Environmental Sciences, University of Cadiz, 11510 Puerto Real, Cadiz (Spain); Department of Geology, University of Huelva, Avda Fuerzas Armadas s/n, 21071 Huelva (Spain); Nieto, J.M. [Department of Geology, University of Huelva, Avda Fuerzas Armadas s/n, 21071 Huelva (Spain); Shepherd, T.J.; Nowell, G. [Department of Earth Sciences, University of Durham, Science Laboratories, Durham DH1 3LE (United Kingdom); Bebianno, M.J., E-mail: mbebian@ualg.pt [CIMA, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2011-01-17

    Coastal areas and estuaries are particularly sensitive to metal contamination from anthropogenic sources and in the last few decades the study of space-time distribution and variation of metals has been extensively researched. The Gulf of Cadiz is no exception, with several rivers draining one of the largest concentrations of sulphide deposits in the world, the Iberian Pyrite Belt (IPB). Of these rivers, the Guadiana, one of the most important in the Iberian Peninsula, together with smaller rivers like the Tinto and Odiel, delivers a very high metal load to the adjacent coastal areas. The purpose of this work was to study the source and impact of lead (Pb) drained from historical or active mining areas in the IPB on the activity of a Pb inhibited enzyme ({delta}-aminolevulinic acid dehydratase, ALAD) in several bivalve species along the Gulf of Cadiz. Seven marine species (Chamelea gallina, Mactra corallina, Donax trunculus, Cerastoderma edule, Mytilus galloprovincialis, Scrobicularia plana and Crassostrea angulata) were collected at 12 sites from Mazagon, near the mouth of the rivers Tinto and Odiel (Spain), to Cacela Velha (Ria Formosa lagoon system, Portugal). Lead concentrations, ALAD activity and lead isotope ratios ({sup 206}Pb/{sup 204}Pb, {sup 207}Pb/{sup 204}Pb and {sup 208}Pb/{sup 204}Pb) were determined in the whole soft tissues. The highest Pb concentrations were determined in S. plana (3.50 {+-} 1.09 {mu}g g{sup -1} Pb d.w.) and D. trunculus (1.95 {+-} 0.10 {mu}g g{sup -1} Pb d.w.), while M. galloprovincialis and C. angulata showed the lowest Pb levels (<0.38 {mu}g g{sup -1} Pb d.w.). In general, ALAD activity is negatively correlated with total Pb concentration. However this relationship is species dependent (e.g. linear for C. gallina ALAD = -0.36[Pb] + 0.79; r = 0.837; or exponential for M. galloprovincialis ALAD = 2.48e{sup -8.3[Pb]}; r = 0.911). This indicates that ALAD activity has considerable potential as a biomarker of Pb and moreover, in

  15. Terapêutica fotodinâmica com ácido delta-aminolevulínico em neoplasias queratinocíticas superficiais Photodynamic therapy with delta-aminolevulinic acid for superficial keratinocytic neoplasms

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    Renato Marchiori Bakos

    2003-04-01

    %, dor em cinco (6,7% e prurido em um caso (1,3%. A maioria dos casos (60% apresentou boa tolerância ao tratamento, não havendo efeitos paralelos dignos de nota. CONCLUSÕES: Os resultados obtidos no trabalho assemelham-se, em parte, aos relatados na literatura com aplicação única da terapêutica fotodinâmica com ácido delta-aminolevulínico em neoplasias queratinocíticas superficiais, principalmente nas ceratoses actínicas e na doença de Bowen.BACKGROUND: Photodynamic therapy (PDT is a treatment technique in which photosensitizing substances are applied in tissues and excited with specific wavelengths of light energy to obtain cell destruction through photoactive cytotoxic substances. This method has been used in several skin neoplasms, with quite successful results. OBJECTIVES: To study the effects of one single session of topical delta-aminolevulinic acid (ALA irradiated with incoherent light, in actinic keratosis (AK, superficial basal cell carcinoma (BCC and Bowen's disease (BD. PATIENT AND METHODS: Eighty skin lesions, in 52 patients, were treated with an incoherent light source prototype built by the Service of Biomedical Engineering of Hospital de Clínicas de Porto Alegre (HCPA, after the application of 20% ALA under occlusion. Thirty two (40% were superficial BCC, 37 (46.3% AK, and 11 (13.7% BD. Diagnosis was confirmed by biopsy and histology in 23 cases (28.7%. RESULTS: Follow up was not available in five lesions. From the remaining 75, 41 (54.6% were completely resolved, 22 (29.4% showed partial remission, and 12 (16.0% were considered as treatment failures. Considering the 35 treated AK, 23 (65.7% presented complete response, 7 (20% improved, and 5 (14.3% showed no benefit after treatment. Thirty BCC were treated, 10 (33.3% completely resolved, 13 (43.4% improved, and 7 (23.3% remained unaffected. From 10 treated BD, 8 (80% resolved and 2 (20% improved. Observed side effects were burning sensation in 24 lesions (32%, pain in 5 (6.7%, and itch in

  16. 5-Aminolevulinic acid-mediated photodynamic therapy for bladder cancer.

    Science.gov (United States)

    Inoue, Keiji

    2017-02-01

    Photodynamic therapy using 5-aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in cancer cells is excited by visible red or green light irradiation, and reactive oxygen is produced and injures cancer cells. Photodynamic therapy using 5-aminolevulinic acid less markedly influences the surrounding normal cells and tissue as a result of no accumulation of protoporphyrin IX, being a low-invasive, less harmful treatment localized to cancer. Furthermore, photodynamic therapy using 5-aminolevulinic acid is painless, requiring no anesthesia because localized lesions are treated at a low-energy level, and repeatedly applicable, unlike radiotherapy, and so is expected to be a new low-invasive treatment based on a concept completely different from existing treatments. In fact, photodynamic therapy using 5-aminolevulinic acid for bladder cancer was clinically demonstrated mainly for treatment-resistant bladder carcinoma in situ, and favorable outcomes have been obtained. Photodynamic therapy using 5-aminolevulinic acid are photodynamic technologies based on the common biological characteristic of cancers, and are expected as novel therapeutic strategies for many types of cancer. © 2017 The Japanese Urological Association.

  17. Delta aminolevulinate dehydratase (ALA-D) activity in human and experimental diabetes mellitus.

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    Fernández-Cuartero, B; Rebollar, J L; Batlle, A; Enriquez de Salamanca, R

    1999-01-01

    The haem pathway is impaired in porphyrias and a frequent coexistence of diabetes mellitus and porphyria disease has been reported. We have therefore decided to investigate delta-aminolevulinate dehydratase, one of the more sensitive enzymes in the haem pathway, in both human diabetic patients and diabetic rats. We have studied 131 diabetes mellitus patients, 32 insulin dependent and 99 non-insulin dependent. The latter group was further subdivided according to treatment: diet alone (n = 24), diet plus oral hypoglycemic agents (n = 28) and diet plus insulin (n = 47). We have also performed similar studies in the rat model of diabetes mellitus, induced in 11 Wistar rats by streptozotocin. Control groups of both humans and animals were used. Erythrocytic aminolevulinate dehydratase activity was reduced in both insulin dependent and non-insulin dependent diabetic patients as compared to their controls (p glycosilated hemoglobin concentration (p < 0.05) and in non-insulin dependent diabetes mellitus to the glycemia (p < 0.01). In the diabetic rat, aminolevulinate dehydratase activity was diminished on both erythrocytes (p < 0.01) and hepatic tissue (p < 0.01) when compared to the control group. The decrease in activity of erythrocyte aminolevulinate dehydratase observed in diabetic patients, may represent an additional and useful parameter for the assessment of the severity of carbohydrate metabolism impairment.

  18. Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta-aminolevulinate dehydratase from rat liver and cucumber leaves

    Directory of Open Access Journals (Sweden)

    M. Farina

    2002-06-01

    Full Text Available The interaction of the product of H2O2 and (PhSe2 with delta-aminolevulinate dehydratase (delta-ALA-D from mammals and plants was investigated. (PhSe2 inhibited rat hepatic delta-ALA-D with an IC50 of 10 µM but not the enzyme from cucumber leaves. The reaction of (PhSe2 with H2O2 for 1 h increased the inhibitory potency of the original compound and the IC50 for animal delta-ALA-D inhibition was decreased from 10 to 2 µM. delta-ALA-D from cucumber leaves was also inhibited by the products of reaction of (PhSe2 with H2O2 with an IC50 of 4 µM. The major product of reaction of (PhSe2 with H2O2 was identified as seleninic acid and produced an intermediate with a lambdamax at 265 nm after reaction with t-BuSH. These results suggest that the interaction of (PhSe2 with mammal delta-ALA-D requires the presence of cysteinyl residues in close proximity. Two cysteine residues in spatial proximity have been recently described for the mammalian enzyme. Analysis of the primary structure of plant delta-ALA-D did not reveal an analogous site. In contrast to (PhSe2, seleninic acid, as a result of the higher electrophilic nature of its selenium atom, may react with additional cysteinyl residue(s in mammalian delta-ALA-D and also with cysteinyl residues from cucumber leaves located at a site distinct from that found at the B and A sites in mammals. Although the interaction of organochalcogens with H2O2 may have some antioxidant properties, the formation of seleninic acid as a product of this reaction may increase the toxicity of organic chalcogens such as (PhSe2.

  19. Delta-aminolevulinate dehydratase activity and oxidative stress markers in preeclampsia.

    Science.gov (United States)

    de Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B; Kober, Helena; Neme, Walter S; Gallarreta, Francisco M P; Gonçalves, Thissiane L

    2016-12-01

    Preeclampsia is an important pregnancy-specific multisystem disorder characterized by the onset of hypertension and proteinuria. It is of unknown etiology and involves serious risks for the pregnant women and fetus. One of the main factors involved in the pathophysiology of preeclampsia is oxidative stress, where excess free radicals produce harmful effects, including damage to macromolecules such as lipids, proteins and DNA. In addition, the sulfhydryl delta-aminolevulinate dehydratase enzyme (δ-ALA-D) that is part of the heme biosynthetic pathway in pro-oxidant conditions can be inhibited, which may result in the accumulation of 5-aminolevulinic acid (ALA), associated with the overproduction of free radicals, suggesting it to be an indirect marker of oxidative stress. As hypertensive pregnancy complications are a major cause of morbidity and mortality maternal and fetal where oxidative stress appears to be an important factor involved in preeclampsia, the aim of this study was to evaluate the activity of δ-ALA-D and classic oxidative stress markers in the blood of pregnant women with mild and severe preeclampsia. The analysis and quantification of the following oxidative stress markers were performed: thiobarbituric acid-reactive species (TBARS); presence of protein and non-protein thiol group; quantification of vitamin C; Catalase and δ-ALA--D activities in samples of blood of pregnant women with mild preeclampsia (n=25), with severe preeclampsia (n=30) and in a control group of healthy pregnant women (n=30). TBARS was significantly higher in women with preeclampsia, while the presence of thiol groups, levels of vitamin C, catalase and δ-ALA-D activity were significantly lower in groups of pregnant women with preeclampsia compared with healthy women. In addition, the results showed no significant difference between groups of pregnant women with mild and severe preeclampsia. The data suggest a state of increased oxidative stress in pregnant women with

  20. Efficacy of 5-Aminolevulinic Acid Photodynamic Therapy in treatment of nasal inverted papilloma.

    Science.gov (United States)

    Zhang, Yunjie; Yang, Yuguang; Zou, Xianbiao

    2013-12-01

    Evaluate the efficacy of 5-Aminolevulinic Acid Photodynamic Therapy (PDT) in medical treatment of nasal inverted papilloma (NIP). Three patients with nasal inverted papilloma were treated with 5-Aminolevulinic Acid Photodynamic Therapy at our department from April to September 2012. The efficacy and adverse effects of 5-Aminolevulinic Acid Photodynamic Therapy were evaluated during 6-8 months of follow-up medical examination. After treated with 5-Aminolevulinic Acid Photodynamic Therapy, the nasal inverted papillomas were removed. No recurrence was found during the 6-8 months of follow-up medical examination. The major adverse effects were mild erosion, pain, and exudation. 5-Aminolevulinic Acid Photodynamic Therapy appears to be an effective treatment of nasal inverted papilloma. It can clear the papilloma lesions and is well tolerated by the patients. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Photodynamic diagnosis following intravesical instillation of aminolevulinic acid (ALA): first clinical experiences in urology

    Science.gov (United States)

    Baumgartner, Reinhold; Kriegmair, M.; Stepp, Herbert G.; Lumper, W.; Heil, Peter; Riesenberg, Rainer; Stocker, Susanne; Hofstetter, Alfons G.

    1993-06-01

    Delta Aminolevulinic acid (ALA), a precursor of Protoporphyrin IX (PP IX) in hem biosynthesis has been topically applied in urinary bladders in order to study its potential as fluorescent tumor marker. Preclinical experiments have been performed on chemically induced tumors in rats, revealing a ratio of PP IX-fluorescence intensity up to 20:1 in tumors as compared to healthy urothelium. Synthesis of PP IX has been stimulated in 56 patients by intravesical instillation of a pH-neutral ALA-solution. After an incubation time of two to four hours strong red fluorescence was endoscopically observed even in tiny superficial tumors. Brightness and contrast allows visualization of early stage urothelial diseases with naked eyes and without the necessity suppressing background fluorescence or violet excitation light.

  2. Photodynamic Detection of Peritoneal Metastases Using 5-Aminolevulinic Acid (ALA

    Directory of Open Access Journals (Sweden)

    Yutaka Yonemura

    2017-03-01

    Full Text Available In the past, peritoneal metastasis (PM was considered as a terminal stage of cancer. From the early 1990s, however, a new comprehensive treatment consisting of cytoreductive surgery and perioperative chemotherapy has been established to improve long-term survival for selected patients with PM. Among prognostic indicators after the treatment, completeness of cytoreduction is the most independent predictors of survival. However, peritoneal recurrence is a main cause of recurrence, even after complete cytoreduction. As a cause of peritoneal recurrence, small PM may be overlooked at the time of cytoreductive surgery (CRS, therefore, development of a new method to detect small PM is desired. Recently, photodynamic diagnosis (PDD was developed for detection of PM. The objectives of this review were to evaluate whether PDD using 5-aminolevulinic acid (ALA could improve detection of small PM.

  3. Degradation mechanism and stability of 5-aminolevulinic acid.

    Science.gov (United States)

    Bunke, A; Zerbe, O; Schmid, H; Burmeister, G; Merkle, H P; Gander, B

    2000-10-01

    The physiological substance and precursor of the heme synthesis 5-aminolevulinic acid (ALA) is a promising prodrug for photodiagnosis and photodynamic therapy of epithelial tumors, particularly in urological and gynecological tissues. For the clinical use of this substance, a chemically stable and sterile drug formulation is required. In the present study, degradation mechanism of ALA in aqueous solution and possibilities to improve its stability were examined. A capillary electrophoretic method was developed that was suitable for the quantification of ALA and of two degradation products. The intermediate degradation product was 2, 5-dicarboxyethyl-3,6-dihydropyrazine, which was further oxidized to 2,5-dicarboxyethylpyrazine. The structures of the degradation products were proven by (1)H and (13)C nuclear magnetic resonance spectroscopy. ALA degradation was very efficiently inhibited by adjusting the pH of the aqueous solution to a value market introduction.

  4. Photodynamic therapy with 5-aminolevulinic acid: basic principles and applications

    Science.gov (United States)

    Pottier, Roy H.; Kennedy, James C.

    1996-01-01

    Numerous photosensitizing pigments that absorb visible light and are selectively retained in neoplastic tissue are being investigated as potential photochemotherapeutic agents. While much emphasis is being placed on the synthesis of new, far-red absorbing photosensitizers, an alternative approach has been to stimulate the human body to produce its own natural photosensitizer, namely protoporphyrin IX (PpIX). Exogenous 5-aminolevulinic acid (ALA) is rapidly bioconverted into PP by mitochondria, the process being particularly efficient in tumor cells. Since PpIX has a natural and rapid clearing mechanism (via the capture of iron in the process of being converted into heme), ALA-PDT does not suffer from lingering skin phototoxicity. ALA may be introduced orally, intravenously, or topically, and ALA-PDT has been shown to be effective in the treatment of both malignant and non-malignant lesions.

  5. Effects of aluminum sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice

    Directory of Open Access Journals (Sweden)

    Schetinger M.R.C.

    1999-01-01

    Full Text Available The purpose of the present study was to investigate the in vitro and in vivo effects of aluminum sulfate on delta-aminolevulinic acid dehydratase (ALA-D activity from the brain, liver and kidney of adult mice (Swiss albine. In vitro experiments showed that the aluminum sulfate concentration needed to inhibit the enzyme activity was 1.0-5.0 mM (N = 3 in brain, 4.0-5.0 mM (N = 3 in liver and 0.0-5.0 mM (N = 3 in kidney. The in vivo experiments were performed on three groups for one month: 1 control animals (N = 8; 2 animals treated with 1 g% (34 mM sodium citrate (N = 8 and 3 animals treated with 1 g% (34 mM sodium citrate plus 3.3 g% (49.5 mM aluminum sulfate (N = 8. Exposure to aluminum sulfate in drinking water inhibited ALA-D activity in kidney (23.3 ± 3.7%, mean ± SEM, P<0.05 compared to control, but enhanced it in liver (31.2 ± 15.0%, mean ± SEM, P<0.05. The concentrations of aluminum in the brain, liver and kidney of adult mice were determined by graphite furnace atomic absorption spectrometry. The aluminum concentrations increased significantly in the liver (527 ± 3.9%, mean ± SEM, P<0.05 and kidney (283 ± 1.7%, mean ± SEM, P<0.05 but did not change in the brain of aluminum-exposed mice. One of the most important and striking observations was the increase in hepatic aluminum concentration in the mice treated only with 1 g% sodium citrate (34 mM (217 ± 1.5%, mean ± SEM, P<0.05 compared to control. These results show that aluminum interferes with delta-aminolevulinate dehydratase activity in vitro and in vivo. The accumulation of this element was in the order: liver > kidney > brain. Furthermore, aluminum had only inhibitory properties in vitro, while in vivo it inhibited or stimulated the enzyme depending on the organ studied.

  6. Biological formation of 5-aminolevulinic acid by photosynthetic bacteria

    Institute of Scientific and Technical Information of China (English)

    LIU Xiu-yan; XU Xiang-yang; MA Qing-lan; WU Wei-hong

    2005-01-01

    In this study, 7 stains of Rhodopseudomonas sp. were selected from 36 photosynthetic bacteria stains storied in our laboratory.Rhodopseudomonas sp. strain 99-28 has the highest 5-aminolevulinic acid(ALA) production ability in these 7 strains. Rhodopseudomonas sp. 99-28 strain was mutated using ultraviolet radiation and a mutant strain L-1, which ALA production is higher than wild strain 99-28 about one times, was obtained. The elements affecting ALA formation of strain 99-28 and L-1 were studied. Under the optimal condition(pH 7.5,supplement of ALA dehydratase(ALAD) inhibitor, levulinic acid(LA) and precursors of ALA synthesis, glycine and succinat, 3000 Ix of light density), ALA formation of mutant L-1 was up to 22.15 mg/L. Strain L-1 was used to treat wastewater to remove CODCr and produce ALA. ALA production was 2.819 my/L, 1.531 rog/L, 2.166 mg/L, and 2.424 mg/L in monosodium glutamate wastewater(MGW),succotash wastewater(SW), brewage wastewater(BW), and citric acid wastewater(CAW) respectively. More than 90% of CODCr was removed in four kinds of wastewater. When LA, glycin and succinate were supplied, ALA production was dramatically increased,however, CODCr could hardly be removed.

  7. Comparative Study of Photodynamic Therapy with Topical Methyl Aminolevulinate versus 5-Aminolevulinic Acid for Facial Actinic Keratosis with Long-Term Follow-Up

    OpenAIRE

    Ko, Dong-Yeob; Kim, Ki-Ho; Song, Ki-Hoon

    2014-01-01

    Background Few studies have compared the efficacy, cosmetic outcomes, and adverse events between 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and methyl aminolevulinate-PDT (MAL-PDT) for actinic keratoses (AKs) in Asian ethnic populations with dark-skin. Objective We retrospectively compared the long-term efficacy, recurrence rates, cosmetic outcomes, and safety of ALA-PDT versus MAL-PDT for facial AKs in Koreans. Methods A total of 222 facial AKs in 58 patients were included in this ...

  8. Leishmania spp: Delta-aminolevulinate-inducible neogenesis of porphyria by genetic complementation of incomplete heme biosynthesis pathway

    Science.gov (United States)

    Dutta, Sujoy; Furuyama, Kazumichi; Sassa, Shigeru; Chang, Kwang-Poo Chang

    2008-01-01

    To further develop the Leishmania model for porphyria based on their deficiencies in heme biosynthesis, three Old World species were doubly transfected as before for Leishmania amazonensis with cDNAs, encoding the 2nd and 3rd enzymes in the pathway. Expression of the transgenes was verified immunologically at the protein level and functionally by uroporphyrin neogenesis that occurs only after exposure of the double-transfectants to delta-aminolevulinate. All species examined were equally deficient in heme biosynthesis, as indicated by the accumulation of uroporphyrin as the sole porphyrin and the production of coproporphyrin upon further transfection of one representative species with the downstream gene. The results obtained thus demonstrate that at least the first five enzymes for heme biosynthesis are absent in all species examined, rendering their transfectants inducible with aminolevulinate to accumulate porphyrins and thus useful as cellular models for human porphyrias. PMID:18164705

  9. Pleiotropic effects of 5-aminolevulinic acid in mouse brain.

    Science.gov (United States)

    Lavandera, Jimena; Rodríguez, Jorge; Ruspini, Silvina; Meiss, Roberto; Zuccoli, Johanna Romina; Martínez, María Del Carmen; Gerez, Esther; Batlle, Alcira; Buzaleh, Ana María

    2016-08-01

    5-Aminolevulinic acid (ALA) seems to be responsible for the neuropsychiatric manifestations of acute intermittent porphyria (AIP). Our aim was to study the effect of ALA on the different metabolic pathways in the mouse brain to enhance our knowledge about the action of this heme precursor on the central nervous system. Heme metabolism, the cholinergic system, the defense enzyme system, and nitric oxide metabolism were evaluated in the encephalon of CF-1 mice receiving a single (40 mg/kg body mass) or multiple doses of ALA (40 mg/kg, every 48 h for 14 days). We subsequently found ALA accumulation in the encephalon of the mice. ALA also altered the brain cholinergic system. After one dose of ALA, a decrease in superoxide dismutase activity and a reduction in glutathione levels were detected, whereas malondialdehyde levels and catalase activity were increased. Heme oxygenase was also increased as an antioxidant response to protect the encephalon against injury. All nitric oxide synthase isoforms were induced by ALA, these changes were more significant for the inducible isoform in glial cells. In conclusion, ALA affected several metabolic pathways in mouse encephalon. Data indicate that a rapid response to oxidative stress was developed; however, with long-term intoxication, the redox balance was probably restored, thereby minimizing oxidative damage.

  10. 5-aminolevulinic acid in photodynamic diagnosis and therapy of urological malignancies

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    Nelius, Thomas; de Riese, Werner T. W.

    2003-06-01

    Completeness and certainty of tumor detection are very important issues in clinical oncology. Recent technological developments in ultrasound, radiologic and magnetic resonance imaging diagnostics are very promising, but could not improve the detection rate of early stage malignancies. One of the most promising new approaches is the use of 5-aminolevulinic acid, a potent photosensitizer, in photodynamic diagnosis and therapy. 5-aminolevulinic acid is meanwhile a well-established tool in the photodynamic diagnosis of bladder cancer. It has been shown to improve the sensitivity of detection of superficial tumors and carcinoma in situ, which enables to reduce the risk of tumor recurrence related to undetected lesions or incomplete transurethral resection of the primary lesions. The use of 5-aminolevulinic acid is steadily expanding in diagnostics of urological malignancies. First clinical results are now reported in detection of urethral and ureteral lesions as well as in urine fluorescence cytology. Furthermore, due to the selective accumulation in transitional cell carcinoma of the bladder, 5-aminolevulinic acid may be an ideal candidate for photodynamic therapy in superficial bladder cancer. Summarizing the data of multiple clinical trials, 5-aminolevulinic acid is a promising agent in photodynamic diagnostics and treatment of superficial bladder cancer.

  11. Photodynamic inactivation of Klebsiella pneumoniae biofilms and planktonic cells by 5-aminolevulinic acid and 5-aminolevulinic acid methyl ester.

    Science.gov (United States)

    Liu, Chengcheng; Zhou, Yingli; Wang, Li; Han, Lei; Lei, Jin'e; Ishaq, Hafiz Muhammad; Nair, Sean P; Xu, Jiru

    2016-04-01

    The treatment of Klebsiella pneumoniae, particularly extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae, is currently a great challenge. Photodynamic antimicrobial chemotherapy is a promising approach for killing antibiotic-resistant bacteria. The aim of this study was to evaluate the capacity of 5-aminolevulinic acid (5-ALA) and its derivative 5-ALA methyl ester (MAL) in the presence of white light to cause photodynamic inactivation (PDI) of K. pneumoniae planktonic and biofilm cells. In the presence of white light, 5-ALA and MAL inactivated planktonic cells in a concentration-dependent manner. Biofilms were also sensitive to 5-ALA and MAL-mediated PDI. The mechanisms by which 5-ALA and MAL caused PDI of ESBL-producing K. pneumonia were also investigated. Exposure of K. pneumonia to light in the presence of either 5-ALA or MAL induced cleavage of genomic DNA and the rapid release of intracellular biopolymers. Intensely denatured cytoplasmic contents and aggregated ribosomes were also detected by transmission electron microscopy. Scanning electron microscopy showed that PDI of biofilms caused aggregated bacteria to detach and that the bacterial cell envelope was damaged. This study provides insights into 5-ALA and MAL-mediated PDI of ESBL-producing K. pneumoniae.

  12. RNA is required for enzymatic conversion of glutamate to delta-aminolevulinate by extracts of Chlorella vulgaris.

    Science.gov (United States)

    Weinstein, J D; Beale, S I

    1985-05-15

    Formation of delta-aminolevulinic acid (ALA) from glutamete catalyzed by a soluble extract from the unicellular green alga, Chlorella vulgaris, was abolished after incubation of the cell extract with bovine pancreatic ribonuclease A (RNase). Cell extract was prepared for the ALA formation assay by high-speed centrifugation and gel-filtration through Sephadex G-25 to remove insoluble and endogenous low-molecular-weight components. RNA hydrolysis products did not affect ALA formation, and RNase did not affect the ability of ATP and NADPH to serve as reaction substrates, indicating that the effect of RNase cannot be attributed to degradation of reaction substrates or transformation of a substrate or cofactor into an inhibitor. The effect of RNase was blocked by prior addition of placental RNase inhibitor (RNasin) to the cell extract, but RNasin did not reverse the effect of prior incubation of the cell extract with RNase, indicating that RNase does not act by degrading a component generated during the ALA-forming reaction, but instead degrades an essential component already present in active cell extract at the time the ALA-forming reaction is initiated. After inactivation of the cell extract by incubation with RNase, followed by administration of RNasin to block further RNase action, ALA-forming activity could be restored to a higher level than originally present by addition of a C. vulgaris tRNA-containing fraction isolated from an active ALA-forming preparation by phenol extraction and DEAE-cellulose chromatography. Baker's yeast tRNA, wheat germ tRNA, Escherichia coli tRNA, and E. coli tRNAglu type II were unable to reconstitute ALA-forming activity in RNase-treated cell extract, even though the cell extract was capable of catalyzing the charging of some of these RNAs with glutamate.

  13. 5-Aminolevulinic acid and the hepatic oxidative stress in the early phase of experimental hexachlorobenzene intoxication Ácido delta-aminolevulinico e estresse oxidativo hepático na fase inicial da intoxicação experimental por hexaclorobenzeno

    OpenAIRE

    Tânia Cristina Higashi Sawada; Vanessa Vitoriano da Silva; Sonia Barros; Cristina Dislich Röpke; Silvia Berlanga de Moraes Barros

    2004-01-01

    This work evaluated the levels of 5-aminolevulinic acid (ALA) in the liver of rats exposed to different doses of HCB (25,50, and 100 mg/kg b.w. for 4 weeks) and correlated them with lipid peroxidation parameters. Levels of ALA were determined by high-pressure liquid chromatography after derivatization with acetylacetone and formaldehyde, followed by fluorescence detection. The methodology was carefully validated, nonetheless hepatic levels of ALA in all animals treated or not were below the d...

  14. Photofrin and 5-aminolevulinic acid permeation through oral mucosa in vitro

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    Flock, Stephen T.; Alleman, Anthony; Lehman, Paul; Blevins, Steve; Stone, Angie; Fink, Louis; Dinehart, Scott; Stern, Scott J.

    1994-07-01

    Photofrin and 5-aminolevulinic acid are photosensitizers that show promise in the photodynamic treatment of cancer, port-wine stains, atherosclerosis and viral lesions. Photofrin is a mixture of porphyrins which, upon the absorption of light, become temporarily cytotoxic. One side-effect associated with the use of Photofrin is long-term cutaneous photosensitivity. It is possible that topical application of this photosensitizing dye will ameliorate such a side-effect. Another way to avoid the cutaneous photosensitivity in photodynamic therapy is to use 5- aminolevulinic acid, which is a porphyrin precursor that causes an increase in the synthesis and concentration of the photosensitizer protoporphyrin IX. 5-aminolevulinic acid is usually applied topically, and so minimizes cutaneous photosensitivity while maximizing the local protoporphyrin concentration. There are a host of disorders in oral mucosa that are potentially treatable by photodynamic therapy. However, since stratum corneum presents an impermeable barrier to many pharmaceuticals, it is not clear that topical application of the photosensitizer will result in a clinically relevant tissue concentration. We have therefore studied the permeation behavior of Photofrin and 5-aminolevulinic acid by applying them to the surface of ex vivo oral mucosa tissue positioned by a Franz diffusion cell. In order to increase the permeability of the photosensitizer across the stratum corneum, we studied the effects of four different drug carriers: phosphate buffered saline, dimethylsulfoxide, ethanol and Azone with isopropyl alcohol.

  15. Níveis de chumbo e atividade da desidratase do ácido delta-aminolevulínico (delta-ALAD) no sangue da população da Grande São Paulo, Brasil Levels of lead and delta-aminolevulinic acid dehydratase activity in the blood of Greater S. Paulo (Brazil) population groups

    OpenAIRE

    Nilda A.G.G. de Fernícola; Azevedo,Fausto A. de

    1981-01-01

    Foram feitas determinações de chumbo e atividade da delta-ALAD no sangue de 3 amostras populacionais da Grande São Paulo (Brasil). Um grupo (A) de área de escassa exposição ambiental ao chumbo, um grupo (B) exposto principalmente a fontes móveis de emissão de chumbo e um grupo (C) vizinho a uma indústria de recuperação de chumbo. Cada grupo foi subdividido conforme sexo e hábito de fumar. A plumbemia do grupo C (20,5 µg/100 ml) foi significantemente maior que as dos grupos A (11,2 µg/100 ml) ...

  16. Reactive oxygen species involved cancer cellular specific 5-aminolevulinic acid uptake in gastric epithelial cells.

    Science.gov (United States)

    Ito, Hiromu; Tamura, Masato; Matsui, Hirofumi; Majima, Hideyuki J; Indo, Hiroko P; Hyodo, Ichinosuke

    2014-03-01

    Photodynamic therapy and photodynamic diagnosis using 5-aminolevulinic acid (ALA) are clinically useful for cancer treatments. Cancer cells have been reported that 5-aminolevulinic acid is incorporated via peptide transporter 1, which is one of the membrane transport proteins, and has been reported to be significantly expressed in various gastrointestinal cancer cells such as Caco-2. However, the mechanism of this protein expression has not been elucidated. Concentration of reactive oxygen species (ROS) is higher in cancer cells in comparison with that of normal cells. We have previously reported that ROS derived from mitochondria is likely related to invasions and proliferations of cancer cells. Since 5-aminolevulinic acid is the most important precursor of heme which is necessary protein for cellular proliferations, mitochondrial ROS (mitROS) may be also related to peptide transporter 1 expressions. In this study, we used a rat gastric mucosal cell line RGM1 and its cancer-like mutated cell line RGK1, and we clarified the ALA uptake mechanism and its relations between mitROS and peptide transporter 1 expression in RGK1. We also used our self-established stable clone of cell which over-expresses manganese superoxide dismutase, a mitROS scavenger. We studied differences of the photodynamic therapy effects in these cells after ALA administrations to clear the influence of mitROS.

  17. Comparison of blood lead and blood and plasma δ-aminolevulinic acid concentrations as biomarkers for lead poisoning in cattle.

    Science.gov (United States)

    Kang, Hwan Goo; Bischoff, Karyn; Ebel, Joseph G; Cha, Sang Ho; McCardle, James; Choi, Cheong Up

    2010-11-01

    Lead (Pb) concentrations in whole blood and δ-aminolevulinic acid (ALA) concentrations in plasma and whole blood from 37 cattle with suspected Pb exposure were determined in order to investigate the usefulness of ALA as a biological indicator for Pb poisoning in cattle. Cows were divided into 4 groups based on blood Pb, as follows: ppb (group 1), 30-100 ppb (group 2), 100-300 ppb (group 3), and >300 ppb (group 4). The derivatization reaction for ALA was improved by a greater than 2-fold measure in whole blood and by a 10-fold measure in plasma by adding 75 and 50 µl of 0.1 N HCl, respectively. Blood Pb concentrations ranged from ppb to 1,006 ppb (185.5 ± 254.9 ppb), with 17 samples containing >50 ppb Pb. Delta-aminolevulinic acid concentrations in whole blood and plasma ranged from ppb to 96.9 ppb (77.4 ± 8.4 ppb) and from ppb to 24.0 ppb (4.6 ± 3.8 ppb), respectively. Whole blood ALA did not correlate with blood lead concentrations in any group. Increase in plasma ALA concentration was dependent on blood Pb concentration. There was no correlation between blood Pb concentration and plasma ALA concentration in group 2 (n  =  4), but correlation coefficients were 0.736 in group 3 and 0.807 in group 4, respectively. The correlation coefficient was increased to 0.851 when groups 3 and 4 were combined. Based on these observations, in cattle, plasma ALA is a more reliable biological biomarker for Pb exposure than is blood ALA.

  18. Lack of association of delta-aminolevulinate dehydratase polymorphisms with blood lead levels and hemoglobin in Romanian women from a lead-contaminated region.

    Science.gov (United States)

    Rabstein, Sylvia; Unfried, Klaus; Ranft, Ulrich; Illig, Thomas; Kolz, Melanie; Mambetova, Chinara; Vlad, Mariana; Roman, Cecilia; Weiss, Tobias; Becker, Doreen; Brüning, Thomas; Pesch, Beate

    2008-01-01

    As part of a project on environmental pollution, this study aimed to evaluate associations between blood lead (BPb) levels, hemoglobin (Hb) content, and single-nucleotide polymorphisms (SNPs) of delta-aminolevulinic acid dehydratase (ALAD) gene in 129 unrelated women from Romania. Five SNPs (rs1805313, rs2228083, rs1805312, rs1800435, rs1139488) were analyzed with respect to haplotype structure and impact on BPb levels and Hb content with proportional odds and analysis of covariance models. Combinations of SNPs were rare (16%). Low haplotype diversity was found with seven haplotypes. One rare haplotype implied the C allele of rs1800435, often referred to as the ALAD2 allele (frequency 8.6%). The putative risk genotype (CC) occurred in only one woman with BPb below 0.5 microg/dl. Median BPb was 4.8 microg/dl and differed markedly by community with a level of 12.5 microg/dl near a mining-spill region. Hb was regular (interquartile range 12.3-13.7 g/dl) and not correlated with BPb, although quantitatively lower in women living near the spill region. No significant associations were found for BPb or Hb with SNPs, haplotypes, or diplotypes. BPb levels were higher in this region than in populations from industrialized countries but without hematotoxic effects. An impact of ALAD2 on BPb or Hb was not seen in these women.

  19. Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp.

    Science.gov (United States)

    Di Nuzzo, Sergio; Cortelazzi, Chiara; Boccaletti, Valeria; Zucchi, Alfredo; Conti, Maria Luisa; Montanari, Paola; Feliciani, Claudio; Fabrizi, Giuseppe; Pagliarello, Calogero

    2015-09-01

    Photodynamic therapy with 5-methyl-aminolevulinate and photodynamic therapy with trichloroacetic acid 50% are the two techniques utilized in the management of actinic keratosis. This study was planned to compare the efficacy, adverse effects, recurrence and cosmetic outcome of these option therapies in patients with multiple actinic keratosis of the scalp. Thirteen patients with multiple actinic keratosis were treated with one of the two treatments on half of the scalp at baseline, while the other treatment was performed on the other half 15 days apart, randomly. Efficacy, adverse effects, cosmetic outcome and recurrence were recorded at follow-up visit at 1, 3, 6 and 12 months. Photodynamic therapy with 5 methyl-aminolevulinate was more effective than trichloroacetic acid although less tolerated by patients as it was more painful. Early adverse effects were almost the same even if trichloroacetic acid leads also to crust formation and to a worse cosmetic outcome characterized by hypopigmentation. Recurrence was lower in the area treated with photodynamic therapy. Trichloroacetic acid 50% is less effective than photodynamic therapy with 5 methyl-aminolevulinate in the treatment of multiple actinic keratosis of the scalp although better tolerated by patients. As this technique is less painful and less expensive than photodynamic therapy, we hypothesize and suggest that more sequential treatments could lead to better results. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Homology modeling of human γ-butyric acid transporters and the binding of pro-drugs 5-aminolevulinic acid and methyl aminolevulinic acid used in photodynamic therapy.

    Directory of Open Access Journals (Sweden)

    Yan Baglo

    Full Text Available Photodynamic therapy (PDT is a safe and effective method currently used in the treatment of skin cancer. In ALA-based PDT, 5-aminolevulinic acid (ALA, or ALA esters, are used as pro-drugs to induce the formation of the potent photosensitizer protoporphyrin IX (PpIX. Activation of PpIX by light causes the formation of reactive oxygen species (ROS and toxic responses. Studies have indicated that ALA and its methyl ester (MAL are taken up into the cells via γ-butyric acid (GABA transporters (GATs. Uptake via GATs into peripheral sensory nerve endings may also account for one of the few adverse side effects of ALA-based PDT, namely pain. In the present study, homology models of the four human GAT subtypes were constructed using three x-ray crystal structures of the homologous leucine transporter (LeuT as templates. Binding of the native substrate GABA and the possible substrates ALA and MAL was investigated by molecular docking of the ligands into the central putative substrate binding sites in the outward-occluded GAT models. Electrostatic potentials (ESPs of the putative substrate translocation pathway of each subtype were calculated using the outward-open and inward-open homology models. Our results suggested that ALA is a substrate of all four GATs and that MAL is a substrate of GAT-2, GAT-3 and BGT-1. The ESP calculations indicated that differences likely exist in the entry pathway of the transporters (i.e. in outward-open conformations. Such differences may be exploited for development of inhibitors that selectively target specific GAT subtypes and the homology models may hence provide tools for design of therapeutic inhibitors that can be used to reduce ALA-induced pain.

  1. Evidence that isolated developing chloroplasts are capable of synthesizing chlorophyll b from 5-aminolevulinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Laiqiang; Hoffman, N.E. (Carnegie Institution of Washington, Stanford, CA (USA))

    1990-09-01

    Developing chloroplasts isolated from cucumber (Cucumis sativus L. var Beit Alpha) cotyledons are capable of incorporating ({sup 14}C)5-aminolevulinic acid into chlorophyll (Chl) b and Chl a when incubated under photosynthetic illumination. Thin layer chromatography and high pressure liquid chromatography were employed to analyze the pigments. The specific radioactivity in Chl a was over three times higher than that found in Chl b. Both Chl a and b synthesizing activities in organello decayed rapidly at approximately the same rate. We conclude that concomitant synthesis of Chl a/b-binding apoprotein is not required for Chl b synthesis.

  2. Recent advances in photodynamic diagnosis of gastric cancer using 5-aminolevulinic acid.

    Science.gov (United States)

    Koizumi, Noriaki; Harada, Yoshinori; Minamikawa, Takeo; Tanaka, Hideo; Otsuji, Eigo; Takamatsu, Tetsuro

    2016-01-21

    Photodynamic diagnosis based on 5-aminolevulinic acid-induced protoporphyrin IX has been clinically applied in many fields based upon its evidenced efficacy and adequate safety. In order to establish a personalized medicine approach for treating gastric cancer patients, rapid intraoperative detection of malignant lesions has become important. Feasibility of photodynamic diagnosis using 5-aminolevulinic acid for gastric cancer patients has been investigated, especially for the detection of peritoneal dissemination and lymph node metastasis. This method enables intraoperative real-time fluorescence detection of peritoneal dissemination, exhibiting higher sensitivity than white light observation without histopathological examination. The method also enables detection of metastatic foci within excised lymph nodes, exhibiting a diagnostic accuracy comparable to that of a current molecular diagnostics technique. Although several complicating issues still need to be resolved, such as the effect of tissue autofluorescence and the insufficient depth penetration of excitation light, this simple and rapid method has the potential to become a useful diagnostic tool for gastric cancer, as well as urinary bladder cancer and glioma.

  3. Enhanced 5-aminolevulinic acid-gold nanoparticle conjugate-based photodynamic therapy using pulse laser

    Science.gov (United States)

    Xu, Hao; Yao, Cuiping; Wang, Jing; Chang, Zhennan; Zhang, Zhenxi

    2016-02-01

    The low bioavailability is a crucial limitation for the application of 5-aminolevulinic acid (ALA) in theranostics. In this research, 5-aminolevulinic acid and gold nanoparticle conjugates (ALA-GNPs) were synthesized to improve the bioavailability of ALA and to investigate the impact of ALA photodynamic therapy (ALA-PDT) in Hela cells. A 532 nm pulse laser and light-emitting diode (central wavelengths 502 nm) were jointly used as light sources in PDT research. The results show a 532 nm pulse laser can control ALA release from ALA-GNPs by adjusting the pulse laser dose. This laser control release may be attributed to the heat generation from GNPs under pulse laser irradiation, which indicates accurately adjusting the pulse laser dose to control the drug release in the cell interior can be considered as a new cellular surgery modality. Furthermore, the PDT results in Hela cells indicate the enhancement of ALA release by pulse laser before PDT can promote the efficacy of cell eradication in the light-emitting diode PDT (LED-PDT). This laser mediated drug release system can provide a new online therapy approach in PDT and it can be utilized in the optical monitor technologies based individual theranostics.

  4. The possibility of using 5-aminolevulinic acid in lead phytoextraction process

    Directory of Open Access Journals (Sweden)

    Zbigniew Jarosz

    2013-04-01

    Full Text Available Studies conducted in the greenhouse involving a sunflower (Helianthus annuus L. grown in medium containing 200 mg Pb ∙ dm -3 which were designed to evaluate the impact of foliar nutrition with 5-aminolevulinic acid (5-ALA on the chemical composition of sunflower in reference to possible use of this plant in the process of induced phytoextraction. The study revealed from 4.8% to 34.1% increase in aboveground matter of sunflower which was sprayed by 5-ALA solution at concentrations of 0.01-0.1 ppm in comparison with plants grown in a medium containing 200 mg Pb ∙ dm -3 with no 5-ALA spraying. The sunflower leaves sprayed by 5-ALA solution contained from 3.78% to 27.1% more lead in comparison to plants not sprayed by this agent. As well as remarkable decrease in lead content from 17.4 to 33.4% was recorded in the roots of sunflower sprayed by 5-ALA solution. The lead content in plant shoots was independent from foliar application of 5-aminolevulinic acid

  5. Clinical utility of 5-aminolevulinic acid HCl to better visualize and more completely remove gliomas

    Directory of Open Access Journals (Sweden)

    Halani SH

    2016-09-01

    Full Text Available Sameer H Halani,1 D Cory Adamson1,2 1Department of Neurosurgery, Emory University School of Medicine, Atlanta, GA, USA; 2Neurosurgery Section, Atlanta VA Medical Center, Decatur, GA, USA Abstract: Surgical resection is typically the first line of treatment for gliomas. However, the neurosurgeon faces a major challenge in achieving maximal resection in high-grade gliomas as these infiltrative tumors make it difficult to discern tumor margins from normal brain with conventional white-light microscopy alone. To aid in resection of these infiltrative tumors, fluorescence-guided surgery has gained much popularity in intraoperative visualization of malignant gliomas, with 5-aminolevulinic acid (5-ALA leading the way. First introduced in an article in Neurosurgery, 5-ALA has since become a safe, effective, and inexpensive method to visualize and improve resection of gliomas. This has undoubtedly led to improvements in the clinical course of patients as demonstrated by the increased overall and progression-free survival in patients with such devastating disease. This literature review aims to discuss the major studies and trials demonstrating the clinical utility of 5-ALA and its ability to aid in complete resection of malignant gliomas. Keywords: aminolevulinic acid, 5-ALA, fluorescence, glioblastoma multiforme, high-grade glioma, resection

  6. Terapêutica fotodinâmica com ácido delta-aminolevulínico e luz de diodos em ceratoses actínicas Photodynamic therapy with delta-aminolevulinic acid and light-emitting diodes in actinic keratosis

    OpenAIRE

    Clarice Gabardo Ritter; Isabel Cristina Palma Kuhl; Carolina Lenhardt; Marlene Laks Weissbluth; Renato Marchiori Bakos

    2010-01-01

    FUNDAMENTOS: A terapêutica fotodinâmica é técnica de tratamento em que se aplica uma substância fotossensibilizante nos tecidos ativada por uma fonte de luz de comprimento de onda específico, gerando destruição celular seletiva. Estudam-se novas fontes de luz que possam ser usadas no tratamento de ceratoses actínicas. OBJETIVOS: Avaliar a efetividade da terapêutica fotodinâmica com ácido delta-aminolevulínico utilizando como fonte de luz um aparelho emissor de luz de diodos no tratamento de c...

  7. Limites de aplicabilidade da determinação do ácido delta-aminolevulínico urinário como teste screening na avaliação da intoxicação profissional pelo chumbo Applicability limits of urinary delta-aminolevulinic acid as a screening test to evaluate professional intoxication by lead

    OpenAIRE

    Cristiane Caldeira; Rita de Cassia Oliveira da Costa Mattos; Armando Meyer; Josino Costa Moreira

    2000-01-01

    A aplicabilidade da determinação da concentração do ácido delta-aminolevulínico urinário (ALA-U) no controle da saúde de trabalhadores expostos ocupacionalmente ao chumbo foi realizada em dois grupos de trabalhadores. Os valores médios de Pb-S para os dois grupos foram 17,3 µg/dl (6,2-39,4) e 61,5 µg/dl (41,1-91,0), respectivamente. As concentrações de ALA-U foram determinadas por HPLC e por espectrofotometria. Uma correlação significativa (p

  8. Comparison of aminolevulinic acid and hexylester aminolevulinate induced protoporphyrin IX fluorescence for the detection of ovarian carcinoma metastases: an experimental study

    Science.gov (United States)

    Ascencio, Manuel; Regis, Claudia; Mordon, Serge; Collinet, Pierre

    2009-06-01

    The present study aimed at comparing the photo detection of peritoneal micrometastases in an ovarian cancer model following administration of two precursors of protoporphyrin IX (PpIX): aminolevulinic acid (ALA) and hexylester aminolevulinate (He-ALA). ALA or He-ALA (100mg/kg) was injected in the peritoneum cavity of 16 rats with induced peritoneal metastases of ovarian cancer. Two hours later, the tumours were visualized laparoscopically using both white light for standard exploration and blue light for fluorescence (D-light, Karl Storz, Tuttlingen, Germany). Peritoneal micrometastases were counted. The distribution of PpIX through the peritoneum was studied on frozen biopsies using fluorescence microscopy and correlated with pathological findings. The number of micrometastases detected by the fluorescence blue mode was significantly higher (pcancer cells. Macroscopically fluorescing nodules were histopathology confirmed as malignant. In conclusion, He-ALA is an excellent precursor for PpIX synthesis giving the highest PpIX fluorescence contrast between normal and tumoral peritoneum. Imaging with He-ALA improves the detection of peritoneal metastases comparing to ALA.

  9. Accumulation of porphyrins in Propionibacterium acnes by 5-aminolevulinic acid and its esters.

    Science.gov (United States)

    Ogata, Arisa; Hasunuma, Yuya; Kikuchi, Emii; Ishii, Takuya; Ishizuka, Masahiro; Tokuoka, Yoshikazu

    2017-09-01

    We have investigated the accumulation of porphyrins in Propionibacterium acnes (P.acnes) by 5-aminolevulinic acid hydrochloride (ALA) and its esters, ALA methyl ester hydrochloride (mALA), ALA octyl ester hydrochloride (oALA), and ALA benzyl ester hydrochloride (bALA). From the fluorescence spectra of porphyrins accumulated in P.acnes, the order of porphyrin accumulation is as follows: ALA≫mALA≈bALA>oALA (≈0). Moreover, the PDT efficacy is reduced in the order of ALA>mALA≈bALA>oALA (≈without additives). These results confirm that ALA is superior to ALA esters in accumulating porphyrins in P.acnes. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Optical spectroscopy by 5-aminolevulinic acid hexylester induced photodynamic treatment in rat bladder cancer

    Science.gov (United States)

    Larsen, Eivind L. P.; Randeberg, Lise L.; Gederaas, Odrun A.; Arum, Carl-Jørgen; Krokan, Hans E.; Hjelme, Dag R.; Svaasand, Lars O.

    2006-02-01

    Photodynamic therapy (PDT) is a treatment modality which has been shown to be effective for both malignant and non-malignant diseases. New photosensitizers such as 5-aminolevulinic acid hexylester (hALA) may increase the efficiency of PDT. Monitoring of the tissue response provides important information for optimizing factors such as drug and light dose for this treatment modality. Optical spectroscopy may be suited for this task. To test the efficacy of hALA induced PDT, a study on rats with a superficial bladder cancer model, in which a bladder cancer cell line (AY-27) is instilled, will be performed. Preliminary studies have included a PDT feasibility study on rats, fluorescence spectroscopy on AY-27 cell suspensions, and optical reflection and fluorescence spectroscopy in rat bladders in vivo. The results from the preliminary studies are promising, and the study on hALA induced PDT treatment of bladder cancer will be continued.

  11. Utilization of 5-aminolevulinic acid in the photodynamic therapy of tumors: biochemical and photobiological aspects

    Science.gov (United States)

    Pottier, Roy H.; Kennedy, James C.

    1994-03-01

    Inherent in both plants and animals is the natural porphyrin, Protoporphyrin IX (Pp). Although Pp does not appear to have any intrinsic biological activity, it is a potent natural photosensitizer. When activated with ultraviolet or visible light, this photosensitizer can induce significant photodynamic effects on tissues, cells, subcellular elements, and macromolecules via the production of singlet oxygen. The biosynthesis of endogenous Pp is under strict enzymatic control. It is possible to bypass a rate controlling step and induce large, transient concentrations of Pp by the addition of exogenous 5-aminolevulinic acid (ALA). ALA may be administered systemically or topically. Much larger amounts of Pp are produced in certain types of tumor tissue than in adjacent normal tissue. Topically applied ALA can be used to treat a variety of skin lesions, including actinic keratosis, basal cell carcinomas and psoriasis.

  12. Treatment of actinic cheilitis by photodynamic therapy with 5-aminolevulinic acid and blue light activation.

    Science.gov (United States)

    Zaiac, Martin; Clement, Annabelle

    2011-11-01

    Actinic cheilitis (AC), a common disorder of the lower lip, should be treated early to prevent progression to invasive squamous cell carcinoma. This study evaluated the safety and efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) activated by blue light for the treatment of AC. Fifteen patients with clinically evident or biopsy-proven AC received two treatments with ALA PDT with blue light activation. Treatments were spaced three to five weeks apart. Most patients achieved 65% to 75% clearance three to five weeks after the first treatment and all achieved more than 75% clearance one month after the second treatment. Three patients achieved complete clearance. Pain and burning during irradiation were absent or mild. All patients said they would repeat the procedure. ALA PDT with 417 nm blue light is a promising option for the treatment of AC of the lower lip.

  13. OPTIMIZATIONS FOR 5-AMINOLEVULINIC ACID BASED PHOTODYNAMIC THERAPY IN PURGING LEUKEMIA CELL HL60

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To optimize experimental parameters for the photosensitization of 5-aminolevulinic acid (ALA) in promyelocytic leukemia cell HL60 and compare them with normal human peripheral blood mononuclear cell (PBMC). Methods ALA incubation time, wavelength applied to irradiate, concentration of ALA incubated, irradiation fluence may modulate the effect of 5-aminolevulinic acid based Photodynamic Therapy (ALA-PDT).The high-pressure mercury lamps of 400W served as light source, the interference filter of 410nm, 432nm, 545nm, 577nm were used to select the specific wavelength. Fluorescence microscope was used to detect the fluorescence intensity and location of protoporphyrin IX (PpIX) endogenously produced by ALA. MTT assay was used to measure the survival of cell. Flow cytometry with ANNEXIN V FITC kit (contains annexin V FITC, binding buffer and PI) was used to detect the mode of cell death. Results ① 1mmol/L ALA incubated 1×105/mL HL60 cell line for 4 hours, the maximum fluorescence of ALA induced PpIX was detected in cytomembrane. ② Irradiated with 410nm for 14.4J/cm2 can result in the minimum survivability of HL60 cell. ③ The main mode of HL60 cell death caused by ALA-PDT is necrosis. Conclusion ALA for 1mmol/L, 4 hours for dark incubation time, 410nm for irradiation wavelength, 14.4J/cm2 for irradiation fluence were the optimal parameters to selectively eliminate promyelocytic leukemia cell HL60 by ALA based PDT. The photosensitization of ALA based PDT caused the necrosis of HL60 cell, so it could be used for inactivation of certain leukemia cells.

  14. Limites de aplicabilidade da determinação do ácido delta-aminolevulínico urinário como teste screening na avaliação da intoxicação profissional pelo chumbo Applicability limits of urinary delta-aminolevulinic acid as a screening test to evaluate professional intoxication by lead

    Directory of Open Access Journals (Sweden)

    Cristiane Caldeira

    2000-01-01

    Full Text Available A aplicabilidade da determinação da concentração do ácido delta-aminolevulínico urinário (ALA-U no controle da saúde de trabalhadores expostos ocupacionalmente ao chumbo foi realizada em dois grupos de trabalhadores. Os valores médios de Pb-S para os dois grupos foram 17,3 µg/dl (6,2-39,4 e 61,5 µg/dl (41,1-91,0, respectivamente. As concentrações de ALA-U foram determinadas por HPLC e por espectrofotometria. Uma correlação significativa (pThe relationship between concentrations of ALA-U and Pb-S for two groups of workers is reported. The first group consisted of workers from a telephone company, and the second, of workers from battery factories with average Pb-S equivalent to 17,3 µg/dl (6,2-39,4 and 61,5 µg/dl (41,1-91,0, respectively. The aim of this study was to evaluate the utilization of ALA-U levels as a screening test for different levels of lead in blood by means of High Performance Liquid Chromatography (HPLC and of spectrophotometry. A significant correlation was found between measured ALA and levels of blood lead (R = 0,739 - first group; R = 0,902 - second group; p < 0,001. The validity of ALA-U test to evaluate different levels of lead in blood was also studied. By using ALA levels of 3 mg/g creatinine as a threshold to detect levels of lead in blood equal to or higher than 20 µg/dl, the test results, for the workers in the first group, showed sensitivity of 92% and specificity of 90%. In both groups, the false positives as well as the false negatives were lower than 10%, which was enough to validate the test.

  15. [Production of 5-aminolevulinic acid from organic industrial wastewater by photosynthetic bacteria].

    Science.gov (United States)

    Xiuyan, Liu; Xiangyang, Xu; Min, Ye; Shuo, Xiang

    2008-09-01

    We used Rhodopseudomonas strains with high-yield of 5-aminolevulinic acid (ALA) to produce ALA from wastewater of producing monosodium glutamate, citric acid, beer, and soybean product. Cultivation was carried out under anaerobic light condition (3000 Lux) at 30 degrees C. For comparison, we tested the addition of levulinic acid (LA), glycin and succinate to the substrate to increase the production of ALA, effect of sterilization of the wastewater for both strains. Cell mass concentration (OD660) and the content of ALA were determined with spectrophotometer. Without adding levulinic acid (LA), glycin and succinate, the growth of strain 99-28 reached plateau after 72-96 h. The maxiam ALA production was obtained at 96 h. Both the yield of ALA and the Chemical Oxygen Demand (CODcr) removal rate of monosodium glutamate waster water were the highest in all tested wasterwaters. When LA, glycin and succinate were added, ALA production of strain 99-28 was significantly increased whereas the CODcr removal was adversely affected. Non-sterial wasterwater slightly reduced the growth and CODcr removal rate of strain 99-28, however the ALA production could be strongly reduced with the addition of LA, glycin and succinate. The growth and CODcr removal of mutant strain L-1 was similar with strain 99-28, but its ALA production was much higher than that of strain 99-28. The Rhodopseudomonas strains screened in our laboratory can use organic wasterwater as substrates to produce ALA and remove CODcr.

  16. In vitro evaluation of 5-aminolevulinic acid (ALA loaded PLGA nanoparticles

    Directory of Open Access Journals (Sweden)

    Shi L

    2013-07-01

    Full Text Available Lei Shi,1 Xiuli Wang,1 Feng Zhao,2 Hansen Luan,2 Qingfeng Tu,1 Zheng Huang,3 Hao Wang,2 Hongwei Wang1,41Shanghai Skin Disease Hospital, Shanghai, People's Republic of China; 2National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China; 3Ministry of Education (MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Normal University, Fuzhou, People's Republic of China; 4Huadong Hospital, Fudan University, Shanghai, People's Republic of ChinaBackground: 5-Aminolevulinic acid (ALA is a prodrug for topical photodynamic therapy. The effectiveness of topical ALA can be limited by its bioavailability. The aim of this study was to develop a novel ALA delivery approach using poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs.Methods: A modified double emulsion solvent evaporation method was used to prepare ALA loaded PLGA NPs (ALA PLGA NPs. The characteristics, uptake, protoporphyrin IX fluorescence kinetics, and cytotoxicity of ALA PLGA NPs toward a human skin squamous cell carcinoma cell line were examined.Results: The mean particle size of spherical ALA PLGA NPs was 65.6 nm ± 26 nm with a polydispersity index of 0.62. The encapsulation efficiency was 65.8% ± 7.2% and ALA loading capacity was 0.62% ± 0.27%. When ALA was dispersed in PLGA NPs, it turned into an amorphous phase. ALA PLGA NPs could be taken up by squamous cell carcinoma cells and localized in the cytoplasm. The protoporphyrin IX fluorescence kinetics and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay showed that ALA PLGA NPs were more effective than free ALA of the same concentration.Conclusion: PLGA NPs provide a promising ALA delivery strategy for topical ALA-photodynamic therapy of skin squamous cell carcinoma.Keywords: 5-Aminolevulinic acid (ALA, nanoparticles, poly(lactic-co-glycolic acid (PLGA, skin squamous cell carcinoma, photodynamic therapy (PDT

  17. Herbicide clomazone effects on δ-aminolevulinic acid activity and metabolic parameters in Cyprinus carpio.

    Science.gov (United States)

    Menezes, Charlene; Leitemperger, Jossiele; Murussi, Camila; Toni, Cândida; Araújo, Maria do Carmo Santos; Farias, Iria Luiza; Perazzo, Giselle Xavier; Barbosa, Nilda Vargas; Loro, Vania Lucia

    2014-04-01

    The objective of this study was to investigate δ-aminolevulinic acid (δ-ALA-D) activity and metabolic parameters of Cyprinus carpio exposed to clomazone herbicide. Fish were exposed 2.5, 5, 10 and 20 mg L(-1) of clomazone for 192 h. Results indicated that δ-ALA-D activity was decreased in the gills at concentrations of 5 and 10 mg L(-1). Liver glycogen increased, while muscle and gill glycogen levels decreased at 5, 10 and 20 mg L(-1). Glucose was increased in the gills and plasma. Lactate decreased in the gills and liver and increased in the muscle. Protein and amino acids levels increased in the liver and gills and decreased in the muscle. At a clomazone concentration of 20 mg L(-1), ammonia increased in the gills and muscle and decreased in the liver. The results indicated that the metabolic parameters of glycogen, lactate, protein and amino acids in liver, muscle and gills, blood glucose levels, and the enzyme δ-ALA-D in gills may be useful indicators of clomazone toxicity in carp.

  18. Clinical applications of 5-aminolevulinic acid-mediated fluorescence for gastric cancer.

    Science.gov (United States)

    Namikawa, Tsutomu; Yatabe, Tomoaki; Inoue, Keiji; Shuin, Taro; Hanazaki, Kazuhiro

    2015-08-07

    5-aminolevulinic acid (ALA) is a naturally occurring amino acid that is a protoporphyrin IX (PpIX) precursor and a next-generation photosensitive substance. After exogenous administration of ALA, PpIX specifically accumulates in cancer cells owing to the impaired metabolism of ALA to PpIX in mitochondria, which results in a red fluorescence following irradiation with blue light and the formation of singlet oxygen. Fluorescence navigation by photodynamic diagnosis (PDD) using ALA provides good visualization and detection of gastric cancer lesions and is a potentially valuable diagnostic tool for gastric cancer for evaluating both the surgical resection margins and extension of the lesion. Furthermore, PDD using ALA might be used to detect peritoneal metastases during preoperative staging laparoscopy, where it could provide useful information for the selection of a therapeutic approach. Another promising application for this modality is in the evaluation of lymph node metastases. Photodynamic therapy (PDT) using ALA to cause selective damage based on the accumulation of a photosensitizer in malignant tissue is expected to be a non-invasive endoscopic treatment for superficial early gastric cancer. ALA has the potential to be used not only as a diagnostic agent but also as a therapeutic drug, resulting in a new strategy for cancer diagnosis and therapy. Here, we review the current use of PDD and PDT in gastric cancer and evaluate its future potential beyond conventional modalities combined with a light energy upconverter, a light-emitting diode and near-infrared rays as light sources.

  19. 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice.

    Science.gov (United States)

    Li, Yongning; Zhou, Qi; Hu, Zheng; Yang, Bin; Li, Qingsong; Wang, Jianhua; Zheng, Jinhua; Cao, Wenwu

    2015-01-01

    Sonodynamic therapy (SDT) is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA)-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro. The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM), ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined. Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2) for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (Ptreatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (posteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (posteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.

  20. Regulation of ion homeostasis by aminolevulinic acid in salt-stressed wheat seedlings

    Energy Technology Data Exchange (ETDEWEB)

    Türk, Hülya, E-mail: hulyaa.turk@hotmail.com [Biology Department, Science Faculty, Ataturk University, Erzurum (Turkey); East Anatolian High Technology Research and Application Center, Ataturk University, Erzurum (Turkey); Genişel, Mucip, E-mail: m.genisel@hotmail.com [Department of Crop and Animal Production, Vocational High School, Agri (Turkey); Erdal, Serkan, E-mail: serkanerdal25@hotmail.com [Biology Department, Science Faculty, Ataturk University, Erzurum (Turkey)

    2016-04-18

    Salinity is regarded as a worldwide agricultural threat, as it seriously limits plant development and productivity. Salt stress reduces water uptake in plants by disrupting the osmotic balance of soil solution. In addition, it creates a damaged metabolic process by causing ion imbalance in cells. In this study, we aim to examine the negative effects of 5-aminolevulinic acid (ALA) (20 mg/l) on the ion balance in wheat seedling leaves exposed to salt stress (150 mM). Sodium is known to be highly toxic for plant cells at high concentrations, and is significantly increased by salt stress. However, it can be reduced by combined application of ALA and salt, compared to salt application alone. On the other hand, while the K{sup +}/Na{sup +} ratio was reduced by salt stress, ALA application changed this ratio in favor of K{sup +}. Manganese, iron, and copper were also able to reduce stress. However, ALA pre-treatment resulted in mineral level increments. Conversely, the stress-induced rise in magnesium, potassium, calcium, phosphorus, zinc, and molybdenum were further improved by ALA application. These data clearly show that ALA has an important regulatory effect of ion balance in wheat leaves.

  1. 5-Aminolevulinic Acid Fluorescence in High Grade Glioma Surgery: Surgical Outcome, Intraoperative Findings, and Fluorescence Patterns

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    Alessandro Della Puppa

    2014-01-01

    Full Text Available Background. 5-Aminolevulinic acid (5-ALA fluorescence is a validated technique for resection of high grade gliomas (HGG; the aim of this study was to evaluate the surgical outcome and the intraoperative findings in a consecutive series of patients. Methods. Clinical and surgical data from patients affected by HGG who underwent surgery guided by 5-ALA fluorescence at our Department between June 2011 and February 2014 were retrospectively evaluated. Surgical outcome was evaluated by assessing the resection rate as gross total resection (GTR>98% and GTR>90%. We finally stratified data for recurrent surgery, tumor location, tumor size, and tumor grade (IV versus III grade sec. WHO. Results. 94 patients were finally enrolled. Overall GTR>98% and GTR>90% was achieved in 93% and 100% of patients. Extent of resection (GTR>98% was dependent on tumor location, tumor grade (P<0.05, and tumor size (P<0.05. In 43% of patients the boundaries of fluorescent tissue exceeded those of tumoral tissue detected by neuronavigation, more frequently in larger (57% (P<0.01 and recurrent (60% tumors. Conclusions. 5-ALA fluorescence in HGG surgery enables a GTR in 100% of cases even if selection of patients remains a main bias. Recurrent surgery, and location, size, and tumor grade can predict both the surgical outcome and the intraoperative findings.

  2. The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.

    Directory of Open Access Journals (Sweden)

    Maiko Hayashi

    Full Text Available Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.

  3. The effect of iron ion on the specificity of photodynamic therapy with 5-aminolevulinic acid.

    Science.gov (United States)

    Hayashi, Maiko; Fukuhara, Hideo; Inoue, Keiji; Shuin, Taro; Hagiya, Yuichiro; Nakajima, Motowo; Tanaka, Tohru; Ogura, Shun-ichiro

    2015-01-01

    Recently, photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) has been widely used in cancer therapy. ALA administration results in tumor-selective accumulation of the photosensitizer protoporphyrin IX (PpIX) via the heme biosynthetic pathway. Although ALA-PDT has selectivity for tumor cells, PpIX is accumulated into cultured normal cells to a small extent, causing side effects. The mechanism of tumor-selective PpIX accumulation is not well understood. The purpose of the present study was to identify the mechanism of tumor-selective PpIX accumulation after ALA administration. We focused on mitochondrial labile iron ion, which is the substrate for metabolism of PpIX to heme. We investigated differences in iron metabolism between tumor cells and normal cells and found that the amount of mitochondrial labile iron ion in cancer was lower than that in normal cells. This finding could be because of the lower expression of mitoferrins, which are the mitochondrial iron transporters. Accordingly, we added sodium ferrous citrate (SFC) with ALA as a source of iron. As a result, we observed the accumulation of PpIX only in tumor cells, and only these cells showed sensitivity to ALA-PDT. Taken together, these results suggest that the uptake abilities of iron ion into mitochondria play a key role in tumor-selective PpIX accumulation. Using SFC as a source of iron might thus increase the specificity of ALA-PDT effects.

  4. Light-induced cytotoxicity after aminolevulinic acid treatment is mediated by heme and not by iron.

    Science.gov (United States)

    Breusing, Nicolle; Grimm, Stefanie; Mvondo, Dagmar; Flaccus, Andrea; Biesalski, Hans Konrad; Grune, Tilman

    2010-04-02

    Photodynamic therapy (PDT) is a promising antitumor treatment strategy. However, effectiveness of PDT is limited due to an initiation of rescue responses in tumor cells, including the induction of heme oxygenase-1 (HO-1). Furthermore, the main sources of free radical production in PDT-induced oxidative stress are not clear. Here, human melanoma cells were loaded with the photosensitizer 5-aminolevulinic acid and exposed to non-thermal light of 420-800 nm at different doses. It was shown that inhibition of HO-1 activity by zinc protoporphyrin IX increased PDT-induced cytotoxicity in a dose-dependent manner. Interestingly, the cytotoxic effects were not diminished by the simultaneous application of the iron chelator desferrioxamine. Importantly, PDT together with non-toxic doses of hemin increased the number of dead cells. From these results can be concluded that heme but not iron act as the main source of free radicals in PDT treatment. This is supported by the fact that during PDT ferritin is readily up-regulated, able to bind excess iron formed by the HO-1 action. The combined treatment of photosensitizers with HO-1 inhibitors might increase the effectiveness of PDT in tumor treatment.

  5. δ-Aminolevulinic acid cytotoxic effects on human hepatocarcinoma cell lines

    Directory of Open Access Journals (Sweden)

    del Batlle Alcira M

    2002-03-01

    Full Text Available Abstract Background Acute Intermittent Porphyria is a genetic disorder of heme metabolism, characterized by increased levels of porphyrin precursors, δ-aminolevulinic acid (ALA and porphobilinogen (PBG. ALA has been reported to generate reactive oxygen species and to cause oxidative damage to proteins, subcellular structures and DNA. It is known that oxidative stress can induce apoptosis. The aim of this work was to study the cytotoxic effect of ALA on two hepatocarcinoma cell lines. Results We have determined the impact of ALA on HEP G2 and HEP 3B hepatocarcinoma cell lines survival as measured by the MTT assay. ALA proved to be cytotoxic in both cell lines however; HEP G2 was more sensitive to ALA than HEP 3B. Addition of hemin or glucose diminished ALA cytotoxicity in HEP G2 cells; instead it was enhanced in HEP 3B cells. Because apoptosis is usually associated with DNA fragmentation, the DNA of ALA treated and untreated cells were analyzed. The characteristic pattern of DNA fragmentation ladders was observed in ALA treated cells. To elucidate the mechanisms of ALA induced apoptosis, we examined its effect on p53 expression. No changes in p53 mRNA levels were observed after exposure of both cell lines to ALA for 24 h. CDK2 and CDK4 protein levels were reduced after ALA treatment at physiological concentrations.

  6. Enhanced transdermal delivery of 5-aminolevulinic acid and a dipeptide by iontophoresis.

    Science.gov (United States)

    Krishnan, Gayathri; Roberts, Michael S; Grice, Jeffrey; Anissimov, Yuri G; Benson, Heather A E

    2011-01-01

    Poor skin permeability limits the application of peptides to the skin. Enhanced skin permeation could facilitate the development of new therapies for dermatologic and cosmeceutical applications. The aim of this study was to investigate the application of iontophoresis to the delivery of small peptide model compounds (5-aminolevulinic acid and L-alanine-L-tryptophan) across human skin. Under the conditions tested, iontophoresis increased the in vitro permeability coefficient of ALA.HCl across human epidermis from 7 X 10(-5) cm/h with passive diffusion to 110 x 10(-5) cm/h with iontophoresis. D-Glucose permeation elucidated the iontophoretic electrotransport of ALA.HCl to have contributions of both electrorepulsion and electroosmosis. The L-alanine-L-tryptophan permeability coefficient was increased from 1.5 x 10(-5) cm/h to 35 x 10(-5) cm/h with iontophoretic application. Iontophoretic delivery of the dipeptide increased markedly at lower pH because of an increase in electrorepulsive transport. The study demonstrates that iontophoresis can enhance epidermal permeation of a small peptide and peptide-like drug by up to 15- and 22-fold under the conditions tested.

  7. FERTILIZATION OF VINE BY A 5-AMINOLEVULINIC ACID-BASED FERTILIZER AND ITS PROFITABILITY

    Directory of Open Access Journals (Sweden)

    VLADIMR IMANSK

    2013-03-01

    Full Text Available In this work we investigated the effect of different doses of NPKS fertilizer added into the soil for nutrient contents in the soil, as well as the quantity and quality of grapes. During the vegetation of the vine, we tested the 5-aminolevulinic acid-based fertilizer (ALA. We summarize that higher doses of fertilizer added into soil caused higher amounts of available nutrients. During the vegetation of the vine an increase of ALA had a positive effect on the optimal balance of nutrients. Fertilization also increased the grape-vine yield, with the strongest effect (by 68% observed due to the application of ALA during the vegetation period of the vine. Added fertilizers had a statistically significant influence on decreased sugar concentration in the grape-vine however the addition of fertilizer into the soil, mainly the application of ALA during vegetation of the vine (by 57% had a positive effect on increase of the total content of sugar in the grape-vine, produced on 1 hectare. The year had a significant influence on the economical evaluation.

  8. 5-Aminolevulinic acid-mediated sonosensitization of rat RG2 glioma cells in vitro

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    Krzysztof Bilmin

    2016-10-01

    Full Text Available Sonodynamic therapy (SDT is a promising technique based on the ability of certain substances, called sonosensitizers, to sensitize cancer cells to non-thermal effects of low-energy ultrasound waves, allowing their destruction. Sonosensitization is thought to induce cell death by direct physical effects such as cavitation and acoustical streaming as well as by complementary chemical reactions generating oxygen free radicals. One of the promising sonosensitizers is 5-aminolevulinic acid (ALA which upon selective uptake by cancer cells is metabolized and accumulated as protoporphyrin IX. The objective of the study was to describe ALA-mediated sonodynamic effects in vitro on a rat RG2 glioma cell line. Glioma cells, seeded at the bottom of 96-well plates and incubated with ALA (10 µg/ml for 6 h, were exposed to the sinusoidal US pulses with a resonance frequency of 1 MHz, 1000 µs duration, 0.4 duty-cycle, and average acoustic power varying from 2 W to 6 W. Ultrasound waves were generated by a flat circular piezoelectric transducer with a diameter of 25 mm. Cell viability was determined by MTT assay. Structural cellular changes were visualized with a fluorescence microscope. Signs of cytotoxicity such as a decrease in cell viability, chromatin condensation and apoptosis were found. ALA-mediated SDT evokes cytotoxic effects of low intensity US on rat RG2 glioma cells in vitro . This cell line is indicated for further preclinical assessment of SDT in in vivo conditions.

  9. 5-Aminolevulinic acid-mediated sonosensitization of rat RG2 glioma cells in vitro.

    Science.gov (United States)

    Bilmin, K; Kujawska, T; Secomski, W; Nowicki, A; Grieb, P

    2016-01-01

    Sonodynamic therapy (SDT) is a promising technique based on the ability of certain substances, called sonosensitizers, to sensitize cancer cells to non-thermal effects of low-energy ultrasound waves, allowing their destruction. Sonosensitization is thought to induce cell death by direct physical effects such as cavitation and acoustical streaming as well as by complementary chemical reactions generating oxygen free radicals. One of the promising sonosensitizers is 5-aminolevulinic acid (ALA) which upon selective uptake by cancer cells is metabolized and accumulated as protoporphyrin IX. The objective of the study was to describe ALA-mediated sonodynamic effects in vitro on a rat RG2 glioma cell line. Glioma cells, seeded at the bottom of 96-well plates and incubated with ALA (10 µg/ml) for 6 h, were exposed to the sinusoidal US pulses with a resonance frequency of 1 MHz, 1000 µs duration, 0.4 duty-cycle, and average acoustic power varying from 2 W to 6 W. Ultrasound waves were generated by a flat circular piezoelectric transducer with a diameter of 25 mm. Cell viability was determined by MTT assay. Structural cellular changes were visualized with a fluorescence microscope. Signs of cytotoxicity such as a decrease in cell viability, chromatin condensation and apoptosis were found. ALA-mediated SDT evokes cytotoxic effects of low intensity US on rat RG2 glioma cells in vitro. This cell line is indicated for further preclinical assessment of SDT in in vivo conditions.

  10. Regulation of ion homeostasis by aminolevulinic acid in salt-stressed wheat seedlings

    Science.gov (United States)

    Türk, Hülya; Genişel, Mucip; Erdal, Serkan

    2016-04-01

    Salinity is regarded as a worldwide agricultural threat, as it seriously limits plant development and productivity. Salt stress reduces water uptake in plants by disrupting the osmotic balance of soil solution. In addition, it creates a damaged metabolic process by causing ion imbalance in cells. In this study, we aim to examine the negative effects of 5-aminolevulinic acid (ALA) (20 mg/l) on the ion balance in wheat seedling leaves exposed to salt stress (150 mM). Sodium is known to be highly toxic for plant cells at high concentrations, and is significantly increased by salt stress. However, it can be reduced by combined application of ALA and salt, compared to salt application alone. On the other hand, while the K+/Na+ ratio was reduced by salt stress, ALA application changed this ratio in favor of K+. Manganese, iron, and copper were also able to reduce stress. However, ALA pre-treatment resulted in mineral level increments. Conversely, the stress-induced rise in magnesium, potassium, calcium, phosphorus, zinc, and molybdenum were further improved by ALA application. These data clearly show that ALA has an important regulatory effect of ion balance in wheat leaves.

  11. Dietary supplementation with 5-aminolevulinic acid modulates growth performance and inflammatory responses in broiler chickens.

    Science.gov (United States)

    Sato, K; Matsushita, K; Takahashi, K; Aoki, M; Fuziwara, J; Miyanari, S; Kamada, T

    2012-07-01

    The objective of this study was to investigate the effect of dietary supplementation with 5-aminolevulinic acid (5-ALA) on the immune system, inflammatory response, and growth performance of broiler chickens. The levels of cluster of differentiation 3 (CD3) mRNA in the spleens of chickens gradually increased with dietary 5-ALA concentration, while the expression levels of interleukin (IL)-2 decreased. Mitogen-induced proliferation of splenic mononuclear cells and blood mononuclear cell phagocytosis in chickens fed 0.001 and 0.01% 5-ALA-supplemented diets were significantly greater than in chickens fed a basal diet (control). Plasma thiobarbituric acid reactive substance (TBARS) concentration gradually increased along with 5-ALA supplement concentration. These results provide the first evidence that the use of dietary 0.001 and 0.01% 5-ALA supplementation induces the T-cell immune system via mild oxidative stress in chickens. Three hours after Escherichia coli lipopolysaccharide-induced immune stimulation, the levels of mRNA encoding pro-inflammatory cytokines, such as IL-6 and tumor necrosis factor-like ligand 1A (TL1A), in chickens fed a 0.001% 5-ALA-supplemented diet were significantly lower than those in chickens exposed to other treatments. The plasma caeruloplasmin concentration in chickens fed a 0.001% 5-ALA-supplemented diet was significantly lower than in controls or in chickens fed diets supplemented with other concentrations of 5-ALA 24 h after injection of LPS. In addition, BW at 21 and 50 d of age was significantly higher in chickens fed a 0.001% 5-ALA-supplemented diet than in control chickens. The findings suggest that supplementation of diets with 0.001% 5-ALA could prevent the catabolic changes induced by immunological stimulation. These results show that 5-ALA might be useful as an immunomodulator to stimulate T-cells via mild oxidative stress in growing broiler chickens, thereby improving the growth performance.

  12. Photodynamic therapy using systemic administration of 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode for methicillin-resistant Staphylococcus aureus-infected ulcers in mice.

    Science.gov (United States)

    Morimoto, Kuniyuki; Ozawa, Toshiyuki; Awazu, Kunio; Ito, Nobuhisa; Honda, Norihiro; Matsumoto, Sohkichi; Tsuruta, Daisuke

    2014-01-01

    Bacterial resistance to antibiotics has become a worldwide problem. One potential alternative for bacterial control is photodynamic therapy. 5-aminolevulinic acid is a natural precursor of the photosensitizer protoporphyrin IX. Relatively little is known about the antibacterial efficacy of photodynamic therapy using the systemic administration of 5-aminolevulinic acid; a few reports have shown that 5-aminolevulinic acid exerts photodynamic effects on methicillin-resistant Staphylococcus aureus (MRSA) in vitro. In this study, we evaluated the effectiveness of photodynamic therapy using 5-aminolevulinic acid and a 410-nm wavelength light-emitting diode in vitro and in vivo for the treatment of MRSA. We found that 5-aminolevulinic acid photodynamic therapy with the light-emitting diode had an in-vitro bactericidal effect on MRSA. In vivo, protoporphyrin IX successfully accumulated in MRSA on ulcer surfaces after intraperitoneal administration of 5-aminolevulinic acid to mice. Furthermore, 5-aminolevulinic acid photodynamic therapy accelerated wound healing and decreased bacterial counts on ulcer surfaces; in contrast, vancomycin treatment did not accelerate wound healing. Our findings indicate that 5-aminolevulinic acid photodynamic therapy may be a new treatment option for MRSA-infected wounds.

  13. Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages

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    Cheng J

    2013-02-01

    Full Text Available Jiali Cheng,1,* Xin Sun,1,2,* Shuyuan Guo,1,* Wei Cao,1 Haibo Chen,1 Yinghua Jin,1 Bo Li,1 Qiannan Li,1 Huan Wang,1 Zhu Wang,3 Qi Zhou,3 Peng Wang,3 Zhiguo Zhang,3 Wenwu Cao,3,4 Ye Tian1,21Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People’s Republic of China; 2Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin, People’s Republic of China; 3Laboratory of Photo- and Sono-theranostic Technologies and Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, People’s Republic of China; 4Materials Research Institute, The Pennsylvania State University, University Park, PA, USA*These authors contributed equally to this workBackground: Inflammatory cells exhibit an elevated level of protoporphyrin IX (PpIX after the administration of 5-aminolevulinic acid (ALA. Here, we investigate the sonodynamic effects of ALA-derived PpIX (ALA-PpIX on macrophages, which are the pivotal inflammatory cells in atherosclerosis.Methods and results: Cultured THP-1 macrophages were incubated with ALA. Fluorescence microscope and fluorescence spectrometer detection showed that intracellular PpIX increased with the concentration of ALA in the incubation solution in a time dependent manner; the highest level of intracellular PpIX was observed after 3-hour incubation. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays demonstrated that lower concentrations (less than 2 mM of ALA have no influence on cell viability (more than 90% of cells survived, but sonodynamic therapy (SDT with a low concentration of ALA significantly decreased the survival rate of cells, and the effect was increased with both ALA concentration and ultrasound exposure time. Cell apoptosis and necrosis induced by ALA-mediated SDT (ALA-SDT were measured using

  14. δ氨基酮戊酸光动力疗法对体外培养三株嗜角质真菌杀伤效应的实验研究%Antifungal Effect of Delta-Aminolevulinic Acid Mediated Photodynamic Therapy on Three Strains of Kratinophilic Fungi in Vitro

    Institute of Scientific and Technical Information of China (English)

    黄望强; 史赢; 雷铁池

    2012-01-01

    Objective: To evaluate the killing effect of S-Aminolevulinic acid (ALA) -mediated photody-namic therapy on three strains of keratinophilic fungi in vitro and to investigate its mechanism. Methods: Trichophyton rubrum , Trichophyton mentagrophytes, and Candida albicans were inoculated in Sabouraud glucose peptone, for preparing fungi suspensions. The fungi suspensions were treated with different concentrations of ALA (3, 10, 30, 100, and 300 mmol/L) cultures in DMEM containing 2. 5% fetal calf serum. Confocal fluorescence microscope was used to examine proto-porphyrin IX (PpIX) formation. MTT assay was used to determine the inhibitory rates by different concentrations of ALA-PDT. The ult restructure changes of fungi were observed by transmission electron microscopy after the treatment of 100 mmol/L ALA-PDT. Results: After incubated with 100 mmol/L ALA, PpK was shown as brick-red fluorescent signal in the three stains of fungal inside by confocal laser scanning microscope. There is a positive correlation be-tween the concentration of ALA and the inhibition ratio of three strains of fungi (P<0. 05), but when the concentration of ALA increased to 300 mmol/L, the inhibition rate did not increase significantly. Simple laser and simple ALA treatment had no significant inhibition on fungal growth. The structures of cell wall, cell membrane, and organelles in all the three strains of fungi were destroyed at some extent after 100 mmol/L ALA-PDT treatment. Conclusion: 8-Aminolevulini-cacid-mediated photodynamic treatment have a definite killing effect in these, three strains fungi in vitro, which provides a theoretical basis for treatment of onychomycosis.%目的:探讨δ氨基酮戊酸(ALA)光动力学疗法(PDT)对体外培养的三株嗜角质真菌杀伤效应及作用机制.方法:将红色毛癣菌、须癣毛癣菌、白念珠菌三株标准菌株在沙氏葡萄糖琼脂培养基(SDA)活化培养后制备菌悬液,菌悬液与不同浓度ALA(3,10,30,100,300mmol

  15. Alleviation of salt-induced oxidative damage by 5-aminolevulinic acid in wheat seedlings

    Science.gov (United States)

    Genişel, Mucip; Erdal, Serkan

    2016-04-01

    The aim of this study was to elucidate how 5-aminolevulinic acid (ALA), the precursor of chlorophyll compounds, affects the defence mechanisms of wheat seedlings induced by salt stress. To determine the possible stimulative effects of ALA against salinity, 11-day old wheat seedlings were sprayed with ALA at two different concentrations (10 and 20 mg.l-1) and then stressed by exposure to salt (150 mM NaCl). The salt stress led to significant changes in the antioxidant activity. While guaiacol peroxidase activity decreased, the activities of superoxide dismutase, catalase, and ascorbate peroxidase markedly increased under salt stress. Compared to the salt stress alone, the application of ALA beforehand further increased the activity of these enzymes. This study is the first time the effects of ALA have been monitored with regard to protein content and the isoenzyme profiles of the antioxidant enzymes. Although the salt stress reduced both the soluble protein content and protein band intensities, pre-treating with ALA significantly mitigated these stress-induced reductions. The data for the isoenzyme profiles of the antioxidant enzymes paralleled that of the ALA-induced increases in antioxidant activity. As a consequence of the high antioxidant activity in the seedlings pre-treated with ALA, the stress-induced elevations in the reactive oxygen species, superoxide anion, and hydrogen peroxide contents and lipid peroxidation levels were markedly diminished. Taken together, this data demonstrated that pre-treating with ALA confers resistance to salt stress by modulating the protein synthesis and antioxidant activity in wheat seedlings.

  16. Aminolevulinic Acid-Mediated Photodynamic Therapy Causes Cell Death in MG-63 Human Osteosarcoma Cells.

    Science.gov (United States)

    White, Bradley; Rossi, Vince; Baugher, Paige J

    2016-09-01

    The aim of this study was to test the efficacy of aminolevulinic acid-mediated photodynamic therapy (PDT) against the human osteosarcoma cell line MG-63. Osteosarcoma is the most common type of primary malignant bone tumor diagnosed in the United States among adolescents and children. Treatments for osteosarcoma often result in diminished limb use or amputation. Because ALA-mediated PDT exhibits dual specificity in the context of tumor killing, this therapy could represent a less invasive, but effective, treatment for this disease. To assess ALA dark toxicity in MG-63 cells, cells were incubated with varying concentrations of ALA, and cell viability was determined by crystal violet assay. Protoporphyrin IX (PpIX) accumulation was assessed subsequent to ALA incubation at various concentrations using spectrofluorometry. Cell death subsequent to ALA-PDT was determined by illuminating cells at a wavelength of 635 nm at various light intensities subsequent to ALA incubation. Cell viability was assessed using the MTT assay. ALA dark toxicity was observed only at the highest concentrations of 2, 5, and 10 mM. Maximal PpIX concentration was observed at 0.5 and 1 mM ALA, subsequent to a 24-h incubation. Maximal cell death with minimal light toxicity was observed at 0.5 and 1 mM ALA after illumination with 0.6 and 3 J/cm(2) light. Collectively, our data indicate that ALA-PDT can result in the death of MG-64 human osteosarcoma cells in vitro.

  17. Interference with the Jaffé Method for Creatinine Following 5-Aminolevulinic Acid Administration

    Science.gov (United States)

    Quon, Harry; Grossman, Craig E.; King, Rebecca L.; Putt, Mary; Donaldson, Keri; Kricka, Larry; Finlay, Jarod; Malloy, Kelly; Cengel, Keith A.; Busch, Theresa M.

    2013-01-01

    Background The photosensitizer pro-drug 5-aminolevulinic acid (5-ALA) has been administered systemically for photodynamic therapy. Although several toxicities have been reported, nephrotoxicity has never been observed. Materials and Methods Patients with head and neck mucosal dysplasia have been treated on a phase 1 study of escalating light doses in combination with 60 mg/kg of oral 5-ALA. Serum creatinine was measured with the modified Jaffe method or an enzymatic method in the first 24 hours after 5-ALA. Interference by 5-ALA, as well as by its photosensitizing product protoporphyrin IX, was assessed. Results Among 11 subjects enrolled to date, 9 of 11 had blood chemistries collected within the first 5 hours with 7 demonstrating significant grade 3 creatinine elevations (p=0.030). There was no additional evidence of compromised renal function or increased PDT-induced mucositis. Creatinine levels measured by the Jaffe assay increased linearly as a function of the ex-vivo addition of ALA (p<.0001). The exogenous addition of PpIX did not alter creatinine levels. ALA did not interfere with creatinine levels as measured by an enzymatic assay. A total of 4 of the 11 subjects had creatinine levels prospectively measured by both the Jaffe and the enzymatic assays. Only the Jaffe method demonstrated significant elevations as a function of time after ALA administration. Conclusions The transient increase in creatinine after systematic ALA can be attributed, in part, if not entirely, to interference of ALA in the Jaffe reaction. Alternative assays should be employed in situations calling for monitoring of kidney function after systemic ALA. PMID:21112550

  18. 5-Aminolevulinic acid induced photodynamic inactivation on Staphylococcus aureus and Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Chien-Ming Hsieh

    2014-09-01

    Full Text Available The aim of the present study was to develop a simple and fast screening technique to directly evaluate the bactericidal effects of 5-aminolevulinic acid (ALA-mediated photodynamic inactivation (PDI and to determine the optimal antibacterial conditions of ALA concentrations and the total dosage of light in vitro. The effects of PDI on Staphylococcus aureus and Pseudomonas aeruginosa in the presence of various concentrations of ALA (1.0 mM, 2.5 mM, 5.0 mM, 10.0 mM were examined. All bacterial strains were exponentially grown in the culture medium at room temperature in the dark for 60 minutes and subsequently irradiated with 630 ± 5 nm using a light-emitting diode (LED red light device for accumulating the light doses up to 216 J/cm2. Both bacterial species were susceptible to the ALA-induced PDI. Photosensitization using 1.0 mM ALA with 162 J/cm2 light dose was able to completely reduce the viable counts of S. aureus. A significant decrease in the bacterial viabilities was observed for P. aeruginosa, where 5.0 mM ALA was photosensitized by accumulating the light dose of 162 J/cm2. We demonstrated that the use of microplate-based assays—by measuring the apparent optical density of bacterial colonies at 595 nm—was able to provide a simple and reliable approach for quickly choosing the parameters of ALA-mediated PDI in the cell suspensions.

  19. 5-Aminolevulinic Acid-Based Sonodynamic Therapy Induces the Apoptosis of Osteosarcoma in Mice.

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    Yongning Li

    Full Text Available Sonodynamic therapy (SDT is promising for treatment of cancer, but its effect on osteosarcoma is unclear. This study examined the effect of 5-Aminolevulinic Acid (5-ALA-based SDT on the growth of implanted osteosarcoma and their potential mechanisms in vivo and in vitro.The dose and metabolism of 5-ALA and ultrasound periods were optimized in a mouse model of induced osteosarcoma and in UMR-106 cells. The effects of ALA-SDT on the proliferation and apoptosis of UMR-106 cells and the growth of implanted osteosarcoma were examined. The levels of mitochondrial membrane potential (ΔψM, ROS production, BcL-2, Bax, p53 and caspase 3 expression in UMR-106 cells were determined.Treatment with 5-ALA for eight hours was optimal for ALA-SDT in the mouse tumor model and treatment with 2 mM 5-ALA for 6 hours and ultrasound (1.0 MHz 2.0 W/cm2 for 7 min were optimal for UMR-106 cells. SDT, but not 5-ALA, alone inhibited the growth of implanted osteosarcoma in mice (P<0.01 and reduced the viability of UMR-106 cells (p<0.05. ALA-SDT further reduced the tumor volumes and viability of UMR-106 cells (p<0.01 for both. Pre-treatment with 5-ALA significantly enhanced the SDT-mediated apoptosis (p<0.01 and morphological changes. Furthermore, ALA-SDT significantly reduced the levels of ΔψM, but increased levels of ROS in UMR-106 cells (p<0.05 or p<0.01 vs. the Control or the Ultrasound. Moreover, ALA-SDT inhibited the proliferation of osteosarcoma cells and BcL-2 expression, but increased levels of Bax, p53 and caspase 3 expression in the implanted osteosarcoma tissues (p<0.05 or p<0.01 vs. the Control or the Ultrasound.The ALA-SDT significantly inhibited osteosarcoma growth in vivo and reduced UMR-106 cell survival by inducing osteosarcoma cell apoptosis through the ROS-related mitochondrial pathway.

  20. 5-Aminolevulinic acid-mediated photodynamic therapy for oral cancers and precancers

    Directory of Open Access Journals (Sweden)

    Hsin-Ming Chen

    2012-12-01

    Full Text Available Previous studies have used both systemic and topical 5-aminolevulinic acid (ALA-mediated photodynamic therapy (PDT to treat oral precancers including oral leukoplakia (OL, oral erythroleukoplakia (OEL, and oral verrucous hyperplasia (OVH as well as oral cancers including oral verrucous carcinoma (OVC and oral squamous cell carcinoma (OSCC. Systemic ALA-PDT has been used to treat oral dysplastic lesions and oral cancers with promising clinical outcomes. The efficacy of a regular topical ALA-PDT (fluence rate, 100 mW/cm2; light dose, 100 J/cm2 was tested on an extensive buccal OVC and an enhanced topical ALA-PDT (fluence rate, 200 mW/cm2; light dose, 200 J/cm2 on an early-invasive OSCC; complete regression of the carcinomas was demonstrated after 28 and 18 PDT treatments, respectively. Several previous studies showed relatively good outcomes for OL lesions treated with topical ALA-PDT. However, it was found that the regular topical ALA-PDT is very effective for OVH and OEL lesions but less so for OL lesions. Better PDT outcomes are significantly associated with OVH and OEL lesions with smaller size, pink to red color, epithelial dysplasia, or thinner surface keratin layer. Moreover, the thicker surface keratin layer on the OL lesions is responsible for the relatively poorer PDT outcomes for OL lesions. In addition, both light emitting diode light- and laser light-mediated topical ALA-PDTs are comparative treatment modalities for OVH and OEL lesions. Methotrexate- or vitamin D3-preconditioned prostate or skin carcinoma cells can accumulate more intracellular protoporphyrin IX, resulting in an increased killing of these preconditioned cells by subsequent ALA-PDT. Because chemotherapy can help destroy carcinoma cells and tumor-associated vasculatures and cryotherapy pretreatment may help the diffusion of ALA into lesional epithelial cells, the chemotherapy or cryotherapy-combined topical ALA-PDT may be a new effective PDT alternative for

  1. Evaluation of the risk of liver damage from the use of 5-aminolevulinic acid for intra-operative identification and resection in patients with malignant gliomas

    DEFF Research Database (Denmark)

    Offersen, Cecilie Mørck; Skjoeth-Rasmussen, Jane

    2017-01-01

    BACKGROUND: The clinical efficacy of 5-aminolevulinic acid (5-ALA) for fluorescence-guided surgery of malignant gliomas is evident from several studies; however, as post-operative elevations of liver enzymes have been seen, there is a potential risk of liver damage upon administration. The aim of...

  2. Applications of 5-aminolevulinic acid on the physiological and biochemical characteristics of strawberry fruit during postharvest cold storage

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    Yi Li

    Full Text Available ABSTRACT: The compound 5-aminolevulinic acid (ALA is a key precursor in the biosynthesis of porphyrins, such as chlorophyll, heme and phytochromobilin, and has multiple physiological effects on plants. Varying concentrations of ALA (50mg L-1, 100mg L-1, and 150mg L-1 and water (control were applied to white stage 'Sweet Charlie' strawberry fruit. All ALA treatments delayed senescence and improved the qualities of strawberries fruit during storage. Among the treatments, 150mg L-1 ALA was the most effective dosage concentration. Exogenously applied ALA significantly reduced the decay index, respiration rate, O2 - production rate (O2 -, H2O2 and malondialdehyde (MDA content, increased superoxide dismutase (SOD, ascorbate peroxidase activities (APX, total soluble solids (TSS content, titratable acidity (TA and anthocyanin content during the initial stage of storage. These results supported the pre harvest application of ALA as a beneficial strategy for the prevention of postharvest decay of strawberry fruit.

  3. New proposal for the treatment of viral warts with intralesional injection of 5-aminolevulinic acid photodynamic therapy.

    Science.gov (United States)

    Kim, Jung Eun; Kim, Sun Ji; Hwang, Jong Ik; Lee, Kyung Jin; Park, Hyun Jeong; Cho, Baik Kee

    2012-06-01

    Although photodynamic therapy (PDT) using intralesional injection (ILI) can theoretically enhance the efficacy of the PDT, the effect of ILI-PDT on warts has not been reported in the literature so far. Eight patients with multiple viral warts were enrolled in the study. PDT was performed after the incubation for 1 h, followed by the ILI of aminolevulinic acid (ALA) into the warts. The treatment was repeated at 2-3 week intervals. Fifty percent of patients showed good to cure response. Complete remission was observed in two patients. There was no apparent correlation between the initial severity of warts and the likelihood of response. No one reported severe adverse reaction. The present study suggests that intralesional administration of ALA might be a safe and effective treatment option of thick treatment-resistant warts and can be performed with a shorter incubation period.

  4. 5-aminolevulinic acid-incorporated poly(vinyl alcohol nanofiber-coated metal stent for application in photodynamic therapy

    Directory of Open Access Journals (Sweden)

    Kang DH

    2012-05-01

    Full Text Available Jin Ju Yoo*, Chan Kim*, Chung-Wook Chung, Young-Il Jeong, Dae Hwan KangNational Research and Development Center for Hepatibiliary Disease, Pusan National University Yangsan Hospital, Gyeongnam 626-770, Korea *These authors contributed equally to this work.Background: The study investigated the use of combined photodynamic therapy (PDT and stent placement for the treatment of cholangiocarcinoma (CC. For this purpose, 5-aminolevulinic acid (ALA was incorporated into poly(vinyl alcohol (PVA nanofiber, and coated onto metal stents. Their efficacy was assessed in PDT towards HuCC-T1 CC cells.Methods: Fabrication of ALA-PVA nanofiber, and simultaneous coating onto metal stents, was performed through electrospinning. The dark-toxicity, generation of protoporphyrin IX (PpIX, and PDT effect of ALA and ALA-PVA nanofiber were studied in vitro, using HuCC-T1 CC cells.Results: The ALA-PVA nanofibers were coated onto metal stents less than 1000 nm in diameter. ALA-only displayed marginal cytotoxicity; ALA-PVA nanofiber showed less cytotoxicity. PpIX generation was not sigficantly different between ALA and ALA-PVA nanofiber treatments. PVA itself did not generate PpIX in tumor cells. ALA and ALA-PVA nanofiber displayed a similar PDT effect on tumor cells. Cell viability was decreased, dose-dependently, until ALA concentration reached 100 µg/mL. Necrosis and apoptosis of tumor cells occurred similarly for ALA and ALA- PVA nanofiber treatments.Conclusion: The ALA-PVA nanofiber-coated stent is a promising candidate for therapeutic use with cholangiocarcinoma.Keywords: nanofiber, photodynamic therapy, 5-aminolevulinic acid, poly(vinyl alcohol

  5. [Inhibition rate of gamma-aminolevulinic acid dehydratase activity in erythrocytes as a reliable index for individual workers of low lead exposure].

    Science.gov (United States)

    Hirano, H; Omichi, M; Ohishi, H; Ishikawa, K; Hirashima, N

    1983-09-01

    As the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocytes is decreased by lead exposure, we considered that a net reduction of ALAD activity by lead in blood should be the difference between the activity fully activated with zinc (Zn2+) and dithiothreitol (DTT) and that without activation. The optimal condition of activation of ALAD was found by addition of 0.25 mM of Zn2+ and 10 mM of DTT in the reaction mixture. Judging from our previous results that the amount of inhibition of ALAD activity can be represented as the rate of inhibition and is closely correlated with the dose of lead administered to rabbits, the inhibition rate of ALAD activity and lead content in blood (Pb-B) of lead workers were measured. The scatter diagram obtained from the inhibition rate and lead content in blood has two groups being divided at 50 micrograms/ml of Pb-B. In one group less than 50 micrograms/100 ml of Pb-B, the inhibition rate has been closely related to Pb-B., the regression equation being Y = 1.82 X + 11.7, and the correlation coefficient + 0.926. In another group more than 50 micrograms/100 ml of Pb-B the inhibition rate remained constant at the 90% level. Measurement of the inhibition rate suggests to have practical validity for monitoring lead exposure in workers, and by means of a nomograph lead content in blood can be estimated from the inhibition rate.

  6. Effect of 5-aminolevulinic acid on erythropoiesis: A preclinical in vitro characterization for the treatment of congenital sideroblastic anemia

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Tohru [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Department of Molecular Hematology/Oncology, Tohoku University Graduate School, Sendai (Japan); Okamoto, Koji; Niikuni, Ryoyu [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Takahashi, Kiwamu [SBI Pharmaceuticals Co., Ltd., Tokyo (Japan); Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Ishizawa, Kenichi [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai (Japan); Ichinohasama, Ryo [Department of Hematopathology, Tohoku University Graduate School, Sendai (Japan); Nakamura, Yukio [Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki (Japan); Nakajima, Motowo; Tanaka, Tohru [SBI Pharmaceuticals Co., Ltd., Tokyo (Japan); Harigae, Hideo, E-mail: harigae@med.tohoku.ac.jp [Department of Hematology and Rheumatology, Tohoku University Graduate School, Sendai (Japan); Department of Molecular Hematology/Oncology, Tohoku University Graduate School, Sendai (Japan)

    2014-11-07

    Highlights: • Treatment with ALA induces erythroid differentiation of K562 cells. • Transportation of ALA into erythroid cells occurs predominantly via SLC36A1. • ALA restores defects in ALAS2 in human iPS cell-derived erythroblasts. • ALA may represent a novel therapeutic option for CSA caused by ALAS2 mutations. - Abstract: Congenital sideroblastic anemia (CSA) is a hereditary disorder characterized by microcytic anemia and bone marrow sideroblasts. The most common form of CSA is attributed to mutations in the X-linked gene 5-aminolevulinic acid synthase 2 (ALAS2). ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis. Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects. In a preclinical study, we examined the effects of ALA in human erythroid cells, including K562 cells and human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells. ALA treatment resulted in significant dose-dependent accumulation of heme in the K562 cell line. Concomitantly, the treatment substantially induced erythroid differentiation as assessed using benzidine staining. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed significant upregulation of heme-regulated genes, such as the globin genes [hemoglobin alpha (HBA) and hemoglobin gamma (HBG)] and the heme oxygenase 1 (HMOX1) gene, in K562 cells. Next, to investigate the mechanism by which ALA is transported into erythroid cells, quantitative RT-PCR analysis was performed on previously identified ALA transporters, including solute carrier family 15 (oligopeptide transporter), member (SLC15A) 1, SLC15A2, solute carrier family 36 (proton/amino acid symporter), member (SLC36A1), and solute carrier family 6 (neurotransmitter transporter), member 13 (SLC6A13). Our analysis revealed that SLC36A1 was abundantly

  7. Effect of 5-aminolevulinic acid on erythropoiesis: a preclinical in vitro characterization for the treatment of congenital sideroblastic anemia.

    Science.gov (United States)

    Fujiwara, Tohru; Okamoto, Koji; Niikuni, Ryoyu; Takahashi, Kiwamu; Okitsu, Yoko; Fukuhara, Noriko; Onishi, Yasushi; Ishizawa, Kenichi; Ichinohasama, Ryo; Nakamura, Yukio; Nakajima, Motowo; Tanaka, Tohru; Harigae, Hideo

    2014-11-07

    Congenital sideroblastic anemia (CSA) is a hereditary disorder characterized by microcytic anemia and bone marrow sideroblasts. The most common form of CSA is attributed to mutations in the X-linked gene 5-aminolevulinic acid synthase 2 (ALAS2). ALAS2 is a mitochondrial enzyme, which utilizes glycine and succinyl-CoA to form 5-aminolevulinic acid (ALA), a crucial precursor in heme synthesis. Therefore, ALA supplementation could be an effective therapeutic strategy to restore heme synthesis in CSA caused by ALAS2 defects. In a preclinical study, we examined the effects of ALA in human erythroid cells, including K562 cells and human induced pluripotent stem cell-derived erythroid progenitor (HiDEP) cells. ALA treatment resulted in significant dose-dependent accumulation of heme in the K562 cell line. Concomitantly, the treatment substantially induced erythroid differentiation as assessed using benzidine staining. Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis confirmed significant upregulation of heme-regulated genes, such as the globin genes [hemoglobin alpha (HBA) and hemoglobin gamma (HBG)] and the heme oxygenase 1 (HMOX1) gene, in K562 cells. Next, to investigate the mechanism by which ALA is transported into erythroid cells, quantitative RT-PCR analysis was performed on previously identified ALA transporters, including solute carrier family 15 (oligopeptide transporter), member (SLC15A) 1, SLC15A2, solute carrier family 36 (proton/amino acid symporter), member (SLC36A1), and solute carrier family 6 (neurotransmitter transporter), member 13 (SLC6A13). Our analysis revealed that SLC36A1 was abundantly expressed in erythroid cells. Thus, gamma-aminobutyric acid (GABA) was added to K562 cells to competitively inhibit SLC36A1-mediated transport. GABA treatment significantly impeded the ALA-mediated increase in the number of hemoglobinized cells as well as the induction of HBG, HBA, and HMOX1. Finally, small-interfering RNA

  8. Cystic acne improved by photodynamic therapy with short-contact 5-aminolevulinic acid and sequential combination of intense pulsed light and blue light activation.

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    Melnick, Stuart

    2005-01-01

    Photodynamic therapy with short-contact 5-aminolevulinic acid (Levulan Kerastick, Dusa Pharmaceuticals, Inc.) and activation by intense pulsed light in an initial treatment and blue light in 3 subsequent treatments has resulted in significant improvement in severity of acne, reduction in the number of lesions, improvement in skin texture, and smoothing of scar edges in an Asian patient with severe (class 4) facial cystic acne and scarring.

  9. Optimization of Biomass and 5-Aminolevulinic Acid Production by Rhodobacter sphaeroides ATCC17023 via Response Surface Methodology.

    Science.gov (United States)

    Liu, Shuli; Zhang, Guangming; Li, Jianzheng; Li, Xiangkun; Zhang, Jie

    2016-06-01

    Microbial 5-aminolevulinic acid (ALA) produced from wastewater is considered as potential renewable energy. However, many hurdles are needed to be overcome such as the regulation of key influencing factors on ALA yield. Biomass and ALA production by Rhodobacter sphaeroides was optimized using response surface methodology. The culturing medium was artificial volatile fatty acids wastewater. Three additives were optimized, namely succinate and glycine that are precursors of ALA biosynthesis, and D-glucose that is an inhibitor of ALA dehydratase. The optimal conditions were achieved by analyzing the response surface plots. Statistical analysis showed that succinate at 8.56 mmol/L, glycine at 5.06 mmol/L, and D-glucose at 7.82 mmol/L were the best conditions. Under these optimal conditions, the highest biomass production and ALA yield of 3.55 g/L and 5.49 mg/g-biomass were achieved. Subsequent verification experiments at optimal values had the maximum biomass production of 3.41 ± 0.002 g/L and ALA yield of 5.78 ± 0.08 mg/g-biomass.

  10. The influence of photodynamic therapy (PDT) with δ-aminolevulinic acid (ALA) on J-774A.1 macrophage cell line

    Science.gov (United States)

    Kawczyk-Krupka, Aleksandra; Czuba, Zenon; Ledwon, Aleksandra; Latos, Wojciech; Sliszka, Ewelina; Mianowska, Marta; Krol, Wojciech; Sieron, Aleksander

    2008-02-01

    Introduction. The whole mechanism of the cellular level of tumor destruction by photodynamic therapy (PDT) is still unknown. Despite necrotic and apoptotic ways of cell death, there is a variety of events leading to and magnifying the inactivation of tumor cells. Material and methods. J-774A.1 were incubated with δ-aminolevulinic acid (ALA) at different concentrations (125, 250, 500, 1000 μM) and then irradiated with VIS (400 - 750 nm) at the dose of 5,10 and 30 J/cm2 delivered from the incoherent light source. The effects of the application of ALA-PDT were evaluated on the basis of cell viability, nitric oxide (NO), tumor necrosis factor α- (TNF-α) and interleukin-1β (IL-1β) produced by the J-774A.1 cells. Results. The cell viability (assessed using MTT test) was comparable with control group at 5,10 and 30 J/cm2. At these doses of energy using different concentrations of ALA we have observed that at the higher energy doses, the greater increase of TNF-α release, lowering of the level of IL-1β production and decrease of NO release were observed. There was also observed the dependence of the secretional activity of the cells on the ALA concentrations. Conclusion. The cell viability and production of cytokines depended on ALA concentrations and energy doses of the light. The higher some cytokines' release after PDT could be an additional factor for the complete eradication of tumor.

  11. Effects of 5-aminolevulinic acid photodynamic therapy on TLRs in acne lesions and keratinocytes co-cultured with P. acnes.

    Science.gov (United States)

    Ma, Ying; Chen, Qinyi; Liu, Ye; Wang, Qianqian; Huang, Zheng; Xiang, Leihong

    2016-09-01

    To investigate the effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on the expression of Toll like receptors (TLRs) in human keratinocytes and its role in acne treatment. TLR2 and TLR4 expression in acne lesions before and after ALA-PDT were examined by immunohistochemical assay. Primary keratinocytes were obtained from acne lesions, co-cultured with P. acnes and then treated with ALA-PDT using red or blue LED. Cytokines production were examined by ELISA, TLR2 and TLR4 gene expression by real-time PCR, and TLR2 and TLR4 protein expression by Western-blot assay. The overexpression of TLR2 and TLR4 in acne lesion were detected, which became negative or weaker after ALA-PDT. The infection of P. acnes in keratinocytes could significantly increase the levels of early inflammatory cytokines (e.g. IL-1α, TNF-α and IL-8) (Pkeratinocytes (Pkeratinocytes treated with P. acnes via TLRs pathways. Copyright © 2016. Published by Elsevier B.V.

  12. Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation

    Science.gov (United States)

    Wang, Wenqian; Tabu, Kouichi; Hagiya, Yuichiro; Sugiyama, Yuta; Kokubu, Yasuhiro; Murota, Yoshitaka; Ogura, Shun-ichiro; Taga, Tetsuya

    2017-01-01

    Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs. Among the C6 GSCs, cells with ultralow PpIX fluorescence exhibited dramatically higher tumorigenicity when transplanted into the immune-deficient mouse brain. We further demonstrated that the low PpIX accumulation in the C6 GSCs was enhanced by deferoxamine (DFO)-mediated iron chelation, not by reserpine-mediated inhibition of PpIX-effluxing ABCG2. Finally, we found that the expression level of the gene for heme oxygenase-1 (HO-1), a heme degradation enzyme, was high in C6 GSCs, which was further up-regulated when treated with 5-ALA. Our results provide important new insights into 5-ALA-based PDD of gliomas, particularly photodetection of SP-defined GSCs by iron chelation based on their ALA-PpIX-Heme metabolism. PMID:28169355

  13. Characterization of Three Homoeologous cDNAs Encoding Chloroplast-targeted Aminolevulinic Acid Dehydratase in Common Wheat

    Institute of Scientific and Technical Information of China (English)

    Yu Takenouchi; Haruka Nakajima; Kengo Kanamaru; Shigeo Takumi

    2011-01-01

    In the tetrapyrrole biosynthetic pathway of higher plants,5-aminolevulinic acid (ALA) is metabolized by ALA dehydratase (ALAD).Here,we isolated ALAD1 cDNA from common wheat (Triticum aestivum L.) and its diploid progenitors,and produced transgenic tobacco plants expressing the wheat ALAD1 gene.The ALAD1 genes were highly conserved among wheat relatives,and three homoeologous loci of wheat ALAD1 (TaALAD1) were equally transcribed in common wheat.A transient expression assay of a TaALAD1-GFP (green fluorescent protein) fusion protein suggested that TaALAD1 is localized in chloroplasts.Overexpression of TaALAD1 in transgenic tobacco resulted in a significant increase in ALAD activity in leaves.Moreover,the transgenic tobacco showed vigorous growth and increased survival rate on medium containing ALA at herbicidal concentrations.These results indicate that wheat ALAD1 has catalytic activity in metabolizing ALA in plastids,and that ectopic expression of TaALAD1 in transgenic plants increases their tolerance to ALA application at high concentrations.

  14. Comparative analysis of the effects of CO2 fractional laser and sonophoresis on human skin penetration with 5-aminolevulinic acid.

    Science.gov (United States)

    Choi, J H; Shin, E J; Jeong, K H; Shin, M K

    2017-08-19

    Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm(2) treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration.

  15. Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors.

    Science.gov (United States)

    Ye, Xuying; Yin, Huijuan; Lu, Yu; Zhang, Haixia; Wang, Han

    2016-10-12

    We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3-6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

  16. Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors

    Directory of Open Access Journals (Sweden)

    Xuying Ye

    2016-10-01

    Full Text Available We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA and hematoporphyrin monomethyl ether (HMME to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h and 5.8-fold (3 h higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3–6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

  17. In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

    Science.gov (United States)

    Suzuki, Shigeo; Hikosaka, Kenji; Balogun, Emmanuel O.; Komatsuya, Keisuke; Niikura, Mamoru; Kobayashi, Fumie; Takahashi, Kiwamu; Tanaka, Tohru; Nakajima, Motowo

    2015-01-01

    5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe2+) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug. PMID:26324278

  18. Low-Dose Topical 5-Aminolevulinic Acid Photodynamic Therapy in the Treatment of Different Severity of Acne Vulgaris.

    Science.gov (United States)

    Tao, Shi-Qin; Li, Fei; Cao, Lei; Xia, Ru-Shan; Fan, Hua; Fan, Ying; Sun, Hui; Jing, Cheng; Yang, Li-Jia

    2015-12-01

    The objective of this article is to investigate the effectiveness and safety of photodynamic therapy (PDT) with 3.6 % topical aminolevulinic acid (ALA) and a short incubation time with red light in moderate to severe acne. One hundred and thirty-six patients with moderate to severe acne were treated with 3.6 % topical ALA-PDT for three sessions with an interval of 2 weeks. Patients were evaluated for efficacy and safety on week 2, 4, 6, 8, and 12 after the initial treatment. Most patients showed apparent clearance of acne lesions at the treated site after three sessions. The effective treatment rates were increased after the multiple therapies. The clinical outcomes are the best at 4 weeks after the final treatment. The total effectiveness rate and cure rate of the low-dose ALA-PDT procedure is 92.65 and 47.06 %, respectively. Thirty-one patients and nineteen patients showed apparent exacerbation of acne lesions before the 2nd and 3rd treatment, respectively, but all of them showed good or excellent improvement after a three-course treatment. A few patients showed mild relapse including papules and comedos at 8 weeks after the final treatment. No significant differences are found in the effects of different acne severity and different genders. Adverse reactions are mild and transient. A 3.6 % topical ALA-PDT with a short time incubation with red light is a simple and an effective treatment option for moderate to severe acne with mild side effects in Chinese people.

  19. Diagnostic approach for cancer cells in urine sediments by 5-aminolevulinic acid-based photodynamic detection in bladder cancer.

    Science.gov (United States)

    Miyake, Makito; Nakai, Yasushi; Anai, Satoshi; Tatsumi, Yoshihiro; Kuwada, Masaomi; Onishi, Sayuri; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

    2014-05-01

    Bladder urothelial carcinoma is diagnosed and followed up after transurethral resection using a combination of cystoscopy, urine cytology and urine biomarkers at regular intervals. However, cystoscopy can overlook flat lesions like carcinoma in situ, and the sensitivity of urinary tests is poor in low-grade tumors. There is an emergent need for an objective and easy urinary diagnostic test for the management of bladder cancer. In this study, three different modalities for 5-aminolevulinic acid (ALA)-based photodynamic diagnostic tests were used. We developed a compact-size, desktop-type device quantifying red fluorescence in cell suspensions, named "Cellular Fluorescence Analysis Unit" (CFAU). Urine samples from 58 patients with bladder cancer were centrifuged, and urine sediments were then treated with ALA. ALA-treated sediments were subjected to three fluorescence detection assays, including the CFAU assay. The overall sensitivities of conventional cytology, BTA, NMP22, fluorescence cytology, fluorescent spectrophotometric assay and CFAU assay were 48%, 33%, 40%, 86%, 86% and 87%, respectively. Three different ALA-based assays showed high sensitivity and specificity. The ALA-based assay detected low-grade and low-stage bladder urothelial cells at shigher rate (68-80% sensitivity) than conventional urine cytology, BTA and NMP22 (8-20% sensitivity). Our findings demonstrate that the ALA-based fluorescence detection assay is promising tool for the management of bladder cancer. Development of a rapid and automated device for ALA-based photodynamic assay is necessary to avoid the variability induced by troublesome steps and low stability of specimens.

  20. Clearance of protoporphyrin IX induced by 5-aminolevulinic acid from WiDr human colon carcinoma cells

    Science.gov (United States)

    Juzeniene, Asta; Kaliszewski, Miron; Bugaj, Andrzej; Moan, Johan

    2009-06-01

    5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is the most widely practiced form of PDT in dermatology. One of the advantages of ALA-PDT is that undesirable photosensitization lasts only for 24-48 h. In order to optimize ALA-PDT it is necessary to understand the mechanisms controlling intracellular PpIX clearance (efflux and transformation into heme) in order to decrease protoporphyrin IX (PpIX) clearance rates in the early stages of its production. The aim of this study was to investigate the factors controlling the clearance of intracellular PpIX. Fluorescence spectroscopy was used to study PpIX kinetics in WiDr cells initially treated with ALA. The clearance rate of PpIX in WiDr cells was faster after application of a low concentration of ALA (0.1 mM) than after application of high concentration of ALA (1 mM). PpIX was cleared faster from cells which initially were seeded at low densities than cells seeded at higher densities. The presence of the iron chelator deferoxamine reduced the clearance rate of PpIX, while the presence of ferrous sulfate acted oppositely. The decay rate of PpIX in WiDr cells was faster at higher temperature than at lower. The ferrochelatase activity at pH 7.2 was significantly greater than that at pH 6.7. ALA concentration, application time, cell density, temperature, pH, intracellular iron content, intracellular amount and localization of PpIX are factors controlling PpIX clearance.

  1. Comprehensive analysis of 5-aminolevulinic acid dehydrogenase (ALAD variants and renal cell carcinoma risk among individuals exposed to lead.

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    Dana M van Bemmel

    Full Text Available BACKGROUND: Epidemiologic studies are reporting associations between lead exposure and human cancers. A polymorphism in the 5-aminolevulinic acid dehydratase (ALAD gene affects lead toxicokinetics and may modify the adverse effects of lead. METHODS: The objective of this study was to evaluate single-nucleotide polymorphisms (SNPs tagging the ALAD region among renal cancer cases and controls to determine whether genetic variation alters the relationship between lead and renal cancer. Occupational exposure to lead and risk of cancer was examined in a case-control study of renal cell carcinoma (RCC. Comprehensive analysis of variation across the ALAD gene was assessed using a tagging SNP approach among 987 cases and 1298 controls. Occupational lead exposure was estimated using questionnaire-based exposure assessment and expert review. Odds ratios (OR and 95% confidence intervals (CI were calculated using logistic regression. RESULTS: The adjusted risk associated with the ALAD variant rs8177796(CT/TT was increased (OR = 1.35, 95%CI = 1.05-1.73, p-value = 0.02 when compared to the major allele, regardless of lead exposure. Joint effects of lead and ALAD rs2761016 suggest an increased RCC risk for the homozygous wild-type and heterozygous alleles ((GGOR = 2.68, 95%CI = 1.17-6.12, p = 0.01; (GAOR = 1.79, 95%CI = 1.06-3.04 with an interaction approaching significance (p(int = 0.06. No significant modification in RCC risk was observed for the functional variant rs1800435(K68N. Haplotype analysis identified a region associated with risk supporting tagging SNP results. CONCLUSION: A common genetic variation in ALAD may alter the risk of RCC overall, and among individuals occupationally exposed to lead. Further work in larger exposed populations is warranted to determine if ALAD modifies RCC risk associated with lead exposure.

  2. Topical 5-aminolevulinic acid photodynamic therapy improved refractory acne conglobata and perifolliculitis capitis abscedens et suffodiens rather than hidradenitis suppurativa

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    Linglin Zhang

    2016-01-01

    Full Text Available Acne conglobata (AC, perifolliculitis capitis abscedens et suffodiens (PCAS and hidradenitis suppurativa (HS are uncommon refractory chronic, inflammatory, scarring diseases but cause serious damage to the quality of life. These three diseases are associated with follicular occlusion. Several studies indicated topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT improved follicular occlusion besides acne treatment. So we attempted to apply ALA-PDT to medicine resistant AC, PCAS and HS. Topical ALA-PDT was applied to 10 patients with AC, seven patients with PCAS and three patients with HS for more than three sessions. All the patients completed the dermatology life quality index (DLQI questionnaire and were assessed for the efficacy at the baseline and on two weeks after each treatment. Adverse effects were recorded at each visit. The results showed 25.5% (5/20, two cases of AC and three cases of PCAS of patients achieved excellent improvement after three sessions of PDT and another 60.0% (12/20, eight cases of AC and four cases of PCAS of patients achieved good improvement. 15.0% (3/20, three cases of HS got poor response (< 20% lesions clearance. Another five cases (three cases of AC and two cases of PCAS also achieved excellent response after 5–7 sessions of PDT. We also found that papular/nodular, cyst/abscess showed higher clearance rate than sinus/fistula (88.5%, 86.1% versus 11.1%. DLQI was reduced after three sessions of PDT in AC and PCAS patients rather than HS patients. 5-ALA-PDT could improve refractory AC and PCAS but could not lead to improvement in late stage of HS. The efficacy increased with more treatment sessions.

  3. Blood Lead Level and Δ-Aminolevulinic Acid Dehydratase Activity in Pre-Menopausal and Postmenopausal Women

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    I.R Elezaj

    2012-07-01

    Full Text Available To describe the relationship of blood lead levels (BLL and blood, δ-aminolevulinic acid dehydratase(ALAD activity and haematocrit value(Hct to menopause , were examined 17 pre-or perimenopausal (PreM and 17 postmenopausal women (PosMfrom Prishtina City, the capital ofRepublic Kosovo. The mean age of the PreM women was 28.8 years (21-46, with a mean blood lead level of 1.2 μg/dL (SD=0.583 μg/dL , the mean blood ALAD activity53.2 U/LE (SD= 2.8 U/LE and haematocrit value42.1 % (SD= 4.3 %. The mean age of the PosM women was 53.6 years (43-67, with a mean blood lead level1.9 μg/dL (SD=0.94 μg/dL, the mean blood ALAD activity 44.4 U/LE(SD=7.2 U/LE and haematocrit value 42.1 % ( SD= 4.3 % and 42.2 % (SD=4.4 %. The BPb level of PosM women was significantly higher (P<0.001 in comparison with the BPb level in PreM women. The blood ALAD activity of PosM was significantly inhibited (P<0.002 in comparison with blood ALAD activity in PreM women. The haematocrit values were relatively unchanged. There was established significantly negative correlation between BPb and blood ALAD activity (r=- 0.605; P<0.01 in the PreM women.These results support the hypothesis that release of bone lead stores increases during menopause and constitutes an internal source of exposure possibly associated with adverse health effects on women in menopause transition.

  4. Study on Insecticidal Activities and Effect on Three Kinds of Enzymes by 5- Aminolevulinic Acid on Oxya chinensis

    Institute of Scientific and Technical Information of China (English)

    YIN Kun; MA En-bo; XUE Chun-rong; WU Hai-hua; GUO Ya-ping; ZHANG Jian-zhen

    2008-01-01

    Insecticidal activities and effects on three enzymic activities caused by 5-aminolevulinic acid (ALA) on Oxya chinensis were studied. Fourth-instar nymphs of O. chinensis were treated with different doses of ALA (A 1,250 mM; A2, 450 mM; A3,750 mM; A4, 1 000 mM). Mortality and the activities of acetylcholinesterase (ACHE), glutathione S-transferase (GSTs), and glutathione peroxidase (GPx) were determinated. The mortality of O. chinensis rose with an increasing dose of ALA. The mortality of high-dose treatments A3 and A4 reached 66.19 and 80.21%, respectively. The value of LD50 was 3.61 (3.29-3.93) mg g-1 body weight (95% confidence interval). Biochemical studies showed that the activities of AChE and GPx in the A4 treatment declined by 51.53 and 42.82% in the female, and 42.65 and 43.85% in the male compared to the control, respectively, and the degree of decline reached a significant level at P < 0.05. Meanwhile, the GSTs activities of O. chinensis enhanced with increasing dose of ALA. The GSTs activities of female and male O. chinensis in the A4 treatment remarkably increased by 171.05 and 97.42% compared to the control (P < 0.05). ALA had an obviously toxic effect on O. chinensis. Moreover, ALA caused the photoinactivation of AChE and GPx, which induced nerve transmission blocking and the capability to defend oxidation damage declining. Meanwhile, a high dose of ALA could activate GSTs, which caused a feedback inhibition of the insect to the phototoxic substance.

  5. Inhibition of erythrocytes δ-aminolevulinic acid dehydratase (ALAD) activity in fish from waters affected by lead smelters

    Science.gov (United States)

    Schmitt, Christopher J.; Caldwell, Colleen A.; Olsen, Bill; Serdar, Dave; Coffey, Mike

    2002-01-01

    We assessed the effects on fish of lead (Pb) released to streamsby smelters located in Trail, BC (Canada), E. Helena, MT, Herculaneum, MO, and Glover, MO. Fish were collected by electrofishing from sites located downstream of smelters and from reference sites. Blood from each fish was analyzed for δ-aminolevulinic acid dehydratase (ALAD) activity and hemoglobin (Hb), and samples of blood, liver, or carcass were analyzed for Pb, zinc (Zn), or both. Fish collected downstreamof all four smelters sites had elevated Pb concentrations, decreased ALAD activity, or both relative to their respectivereference sites. At E. Helena, fish from the downstream site also had lower Hb concentrations than fish from upstream. Differences among taxa were also apparent. Consistent with previous studies, ALAD activity in catostomids (Pisces: Catostomidae-northern hog sucker,Hypentelium nigricans;river carpsucker, Carpiodes carpio; largescale sucker, Catostomus macrocheilus; and mountain sucker, C. platyrhynchus) seemed more sensitive to Pb-induced ALADinhibition than the salmonids (Pisces: Salmonidae-rainbow trout,Oncorhynchus mykiss; brook trout,Salvelinus fontinalis) or common carp (Cyprinus carpio). Some of these differences may have resulted from differential accumulation of Zn, which was not measured at all sites. We detected noALAD activity in channel catfish (Ictaluruspunctatus) from either site on the Mississippi River at Herculaneum, MO. Our findings confirmed that Pb is releasedto aquatic ecosystems by smelters and accumulated by fish, andwe documented potentially adverse effects of Pb in fish. We recommend that Zn be measured along with Pb when ALAD activityis used as a biomarker and the collection of at least 10 fish ofa species at each site to facilitate statistical analysis.

  6. A first-principles study of functionalized clusters and carbon nanotubes or fullerenes with 5-Aminolevulinic acid as vehicles for drug delivery

    Science.gov (United States)

    Kia, Majid; Golzar, Maryam; Mahjoub, Kosar; Soltani, Alireza

    2013-10-01

    At present work, we explore the adsorption properties of the 5-Aminolevulinic acid (5ALA) interacting with SWCNTs, C60, and C24 by density functional ab initio (DFT) calculations. It was found that the electronic structure of C60 is more sensitive to the presence of 5ALA in comparison with C24, (5, 5), and (9, 0) SWCNT. Our results demonstrate that the interactions between 5ALA and the nanostructures are chemisorption. The natural bond orbital (NBO) and density of states (DOSs) analyses represent that the nature of 5ALA adsorption on the applied nanostructures is permanently electrostatic rather than covalent.

  7. Improved 5-Aminolevulinic Acid Production with Recombinant Escherichia coli by a Short-term Dissolved Oxygen Shock in Fed-batch Fermentation

    Institute of Scientific and Technical Information of China (English)

    杨俊; 朱力; 傅维琦; 林逸君; 林建平; 岑沛霖

    2013-01-01

    5-Aminolevulinic acid (ALA) is a common precursor for tetrapyrrole compounds in all kinds of organ-isms and has wide applications in agriculture and medicines. In this study, a new strategy, i.e. short-term dissolved oxygen (DO) shock during aerobic fermentation, was introduced to produce 5-aminolevulinic acid with a recombi-nant E. coli. Effects of duration time of DO shock operation on plasmid concentration, intracellular ALA synthase (ALAS) activity and ALA production were investigated in Erlenmeyer shake flasks. The results indicated that both ALAS activity and ALA yield were enhanced in an anaerobic operation of 45 min in the early exponential phase during fermentation, while they decreased when the anaerobic operation time was further increased to 60 min. The DO shock protocol was confirmed with the fed-batch fermentation in a 15 L fermenter and the ALA production achieved 9.4 g·L-1 (72 mmol·L-1), which is the highest yield in the fermentation broth reported up to now.

  8. Aminolevulinic Acid-Mediated Photodynamic Therapy of Human Meningioma: An in Vitro Study on Primary Cell Lines

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    Mustafa El-Khatib

    2015-04-01

    Full Text Available Objective: Five-aminolevulinic acid (5-ALA-induced porphyrins in malignant gliomas are potent photosensitizers. Promising results of ALA-PDT (photodynamic therapy in recurrent glioblastomas have been published. Recently, 5-ALA-induced fluorescence was studied in meningioma surgery. Here, we present an experimental study of ALA-PDT in an in vitro model of primary meningioma cell lines. Methods: We processed native tumor material obtained intra-operatively within 24 h for cell culture. Epithelial membrane antigen (EMA immunohistochemistry was performed after the first passage to confirm that cells were meningioma cells. For 5-ALA-PDT treatment, about 5000 cells per well were seeded in 20 wells of a blank 96-well plate. Each block of 4 wells was inoculated with 150 µL of 0, 25, 50 and 100 µg/mL 5-ALA solutions; one block was used as negative control without 5-ALA and without PDT. Following incubation for 3 h PDT was performed using a laser (635 nm, 18.75 J/cm2. The therapeutic response was analyzed by the water soluble tetrazolium salt (WST-1 cell viability assay 90 min after PDT. Results: 5-ALA-PDT was performed in 14 primary meningioma cell lines. EMA expression was verified in 10 primary cell cultures. The remaining 4 were EMA negative and PDT was without any effect in these cultures. All 10 EMA-positive cell lines showed a significant and dose-dependent decrease in viability rate (p < 0.001. Cell survival at 5-ALA concentrations of 12.5, 25, 50 and 100 μg/mL was 96.5% ± 7.6%, 67.9% ± 29.9%, 24.0% ± 16.7% and 13.8% ± 7.5%, respectively. For the negative controls (no 5-ALA/PDT and ALA/no PDT, the viability rates were 101.72% ± 3.5% and 100.17% ± 3.6%, respectively. The LD50 for 5-ALA was estimated between 25 and 50 µg/mL. Conclusion: This study reveals dose-dependent cytotoxic effects of 5-ALA-PDT on primary cell lines of meningiomas. Either 5-ALA or PDT alone did not affect cell survival. Further efforts are necessary to study the

  9. Safety and Efficacy of 5-Aminolevulinic Acid for High Grade Glioma in Usual Clinical Practice: A Prospective Cohort Study.

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    Pilar Teixidor

    Full Text Available During the last decade, the use of 5-aminolevulinic acid (5-ALA has been steadily increasing in neurosurgery. The study's main objectives were to prospectively evaluate the effectiveness and safety of 5-ALA when used in clinical practice setting on high-grade gliomas' patients.National, multicenter and prospective observational study.authorized conditions of use of 5-ALA.contraindication to 5-ALA, inoperable or partial resected tumors, pregnancy and children. Epidemiological, clinical, laboratory, radiological, and safety data were collected. Effectiveness was assessed using complete resection of the tumor, and progression-free and overall survival probabilities.Between May 2010 and September 2014, 85 patients treated with 5-ALA were included, and 77 were suitable for the effectiveness analysis. Complete resection was achieved in 41 patients (54%. Surgeons considered suboptimal the fluorescence of 5-ALA in 40% of the patients assessed. The median duration of follow-up was 12.3 months. The progression-free survival probability at 6 months was 58%. The median duration overall survival was 14.2 months. Progression tumor risk factors were grade of glioma, age and resection degree; and death risk factors were grade of glioma and gender. No severe adverse effects were reported. At one month after surgery, new or increased neurological morbidity was 6.5%. Hepatic enzymes were frequently increased within the first month after surgery; however, they subsequently normalized, and this was found to have no clinical significance.In clinical practice, the 5-ALA showed a good safety profile, but the benefits related to 5-ALA have not been yet clearly shown. The improved differentiation expected by fluorescence between normal and tumor cerebral tissue was suboptimal in a relevant number of patients; in addition, the expected higher degree of resection was lower than in clinical trials as well as incomplete resection was not identified as a prognostic factor

  10. In vitro skin permeation and retention of 5-aminolevulinic acid ester derivatives for photodynamic therapy.

    Science.gov (United States)

    De Rosa, Fernanda Scarmato; Tedesco, Antônio Cláudio; Lopez, Renata Fonseca Vianna; Pierre, Maria Bernadete Riemma; Lange, Norbert; Marchetti, Juliana Maldonado; Rotta, Jeane Cristina Gomes; Bentley, Maria Vitória Lopes Badra

    2003-04-29

    In photodynamic therapy (PDT), 5-aminiolevulinic acid (5-ALA) applied topically is converted, via the heme cycle, into protoporphyrin IX (PpIX), a photosensitizing agent, which upon excitation with light can induce tumor destruction. Due to its hydrophilic and zwitterionic characteristics, 5-ALA has limited penetration into the skin. More lipophilic 5-ALA ester derivatives are expected to cross stratum corneum more easily than 5-ALA. According to the determination of the partition coefficients of 5-ALA methyl, n-butyl, n-hexyl and n-octyl esters, these compounds showed an increased affinity to the SC, with 5-ALA hexyl ester and 5-ALA-octyl ester having the highest partition coefficients. Our in vitro skin permeation studies demonstrated an increased permeated amount for hexyl-ALA after 6 h of incubation, compared to other esters and 5-ALA. After 6 h, more 5-ALA-hexyl ester and -octyl ester were retained at viable epidermis and dermis than 5-ALA. According to these results, and considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, it can be supposed that topical use of ester derivatives with longer chains (C(6) or C(8)) is an interesting proposal to optimize topical 5-ALA-PDT

  11. Analysis of the role of the Aspergillus niger aminolevulinic acid synthase (hemA) gene illustrates the difference between regulation of yeast and fungal haem- and sirohaem-dependent pathways

    NARCIS (Netherlands)

    Franken, A.C.; Christien Lokman, B.; Ram, A.F.; Hondel, C.A. van den; Weert, S. de; Punt, P.J.

    2012-01-01

    To increase knowledge on haem biosynthesis in filamentous fungi like Aspergillus niger, pathway-specific gene expression in response to haem and haem intermediates was analysed. This analysis showed that iron, 5′-aminolevulinic acid (ALA) and possibly haem control haem biosynthesis mostly via modula

  12. Bi-functional prodrugs of 5-aminolevulinic acid and butyric acid increase erythropoiesis in anemic mice in an erythropoietin-independent manner.

    Science.gov (United States)

    Rephaeli, Ada; Tarasenko, Nataly; Fibach, Eitan; Rozic, Gabriela; Lubin, Ido; Lipovetsky, Julia; Furman, Svetlana; Malik, Zvi; Nudelman, Abraham

    2016-08-25

    Anemia is a major cause of morbidity and mortality worldwide resulting from a wide variety of pathological conditions. In severe cases it is treated by blood transfusions or injection of erythroid stimulating agents, e.g., erythropoietin (Epo), which can be associated with serious adverse effects. Therefore, there is a need to develop new treatment modalities. We recently reported that treatment of erythroleukemic cells with the novel the bi-functional prodrugs of 5-aminolevulinic acid (ALA) and butyric acid (BA), AN233 and AN908, enhanced hemoglobin (Hb) synthesis to a substantially higher level than did ALA and BA individually or their mixture. Herein, we describe that these prodrugs when given orally to mice induced histone deacetylase inhibition in the kidneys, bone marrow and spleen, thus, indicating good penetrability to the tissues. In mice where anemia was chemically induced, treatment with the prodrugs increased the Hb, the number of red blood cells (RBCs) and the percentage of reticulocytes to normal levels. The prodrugs had no adverse effects even after repeated treatment at 100-200mg/kg for 50days. The lack of increased levels of Epo in the blood of mice that were treated with the prodrugs suggests that AN233 and AN908 affected the Hb and RBC levels in an Epo-independent manner. Taken together with our previous studies, we propose that the prodrugs increase globin expression by BA inhibition of histone deacetylase and elevation heme synthesis by ALA. These results support an Epo-independent approach for treating anemia with these prodrugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Constitutive expression of RyhB regulates the heme biosynthesis pathway and increases the 5-aminolevulinic acid accumulation in Escherichia coli.

    Science.gov (United States)

    Li, Fangfang; Wang, Yang; Gong, Kai; Wang, Qian; Liang, Quanfeng; Qi, Qingsheng

    2014-01-01

    In the current study, the small RNA ryhB, which regulates the metabolism of iron in Escherichia coli, was constitutively expressed in engineered E. coli DALA. The resulting strain E. coli DALRA produced 16% more 5-aminolevulinic acid (ALA) than the parent strain E. coli DALA in batch fermentation. Meanwhile, we found that addition of iron in the medium increased heme formation and reduced ALA yield, whereas the presence of iron chelator in the medium decreased heme concentration and increased the ALA production efficiency (ALA yield per OD600). The qRT-PCR analysis showed that the mRNA levels of hemB and hemH were also decreased as well as the known RyhB target genes of acnAB, sdhAB, fumA, and cydAB in E. coli DALRA. These results indicated that small RNA can be used as a tool for regulating ALA accumulation in E. coli.

  14. Improvement of manganese peroxidase production by the hyper lignin-degrading fungus Phanerochaete sordida YK-624 by recombinant expression of the 5-aminolevulinic acid synthase gene.

    Science.gov (United States)

    Hirai, Hirofumi; Misumi, Kenta; Suzuki, Tomohiro; Kawagishi, Hirokazu

    2013-12-01

    The manganese peroxidase (MnP) gene (mnp4) promoter of Phanerochaete sordida YK-624 was used to drive expression of 5-aminolevulinic acid synthase (als), which is a key heme biosynthesis enzyme. The expression plasmid pMnP4pro-als was transformed into P. sordida YK-624 uracil auxotrophic mutant UV-64, and 14 recombinant als expressing-transformants were generated. Average cumulative MnP activities in the transformants were 1.18-fold higher than that of control transformants. In particular, transformants A-14 and A-61 showed significantly higher MnP activity (approximately 2.8-fold) than wild type. RT-PCR analysis indicated that the increased MnP activity was caused by elevated recombinant als expression. These results suggest that the production of MnP is improved by high expression of als.

  15. Promotion by 5-Aminolevulinic Acid of Germination of Pakchoi (Brassica campestris ssp. chinensis var. communis Tsen et Lee) Seeds Under Salt Stress

    Institute of Scientific and Technical Information of China (English)

    Liang-Ju WANG; Wei-Bing JIANG; Hui LIU; Wei-Qin LIU; Lang KANG; Xi-Lin HOU

    2005-01-01

    The seed germination and seedling growth of pakchoi (Brassica campestris ssp. chinensis var.communis Tsen et Lee cv. Hanxiao) were not significantly inhibited until the concentration of NaCl was increased to150 mmol/L. Treatment of pakchoi seeds with exogenous 5-aminolevulinic acid (ALA), at concentrations ranging from 0.01 to 10.00 mg/L, promoted seed germination when seeds were stressed by salinity, whereas levulinic acid (LA), an inhibitor of ALA dehydrase, significantly inhibited seed germination and seedling growth, suggesting that metabolism of ALA into porphyrin compounds was necessary for seed germination and seedling growth. Determination of respiratory rate during seed germination showed that ALA increased seed respiration under both normal conditions and salt stress. Furthermore, salt stress decreased levels of endogenous ALA, as well as heme, in etiolated seedlings. More salt-tolerant cultivars of pakchoi contained higher relative levels of endogenous ALA and heme under conditions of salt stress.These results indicate that salt stress may inhibit the biosynthesis of endogenous ALA and then heme,which is necessary for seed germination, and treatment of seeds with exogenous ALA prior to germination may be associated with the biosynthesis of heme.

  16. Stratum corneum lipids liposomes for the topical delivery of 5-aminolevulinic acid in photodynamic therapy of skin cancer: preparation and in vitro permeation study

    Directory of Open Access Journals (Sweden)

    Bentley M Vitória LB

    2001-08-01

    Full Text Available Abstract Background Photodynamic therapy (PDT using 5-aminolevulinic acid (5-ALA is a skin cancer therapy that still has limitations due to the low penetration of this drug into the skin. We have proposed in this work a delivery system for 5-ALA based on liposomes having lipid composition similar to the mammalian stratum corneum (SCLLs in order to optimize its skin delivery in Photodynamic Therapy (PDT of skin cancers. Methods SCLLs were obtained by reverse phase evaporation technique and size distribution of the vesicles was determinated by photon correlation spectroscopy. In vitro permeation profile was characterized using hairless mouse skin mounted in modified Franz diffusion cell. Results Size exclusion chromatography on gel filtration confirmed vesicle formation. SCLLs obtained by presented a degree of encapsulation of 5-ALA around 5.7%. A distribution of vesicle size centering at around 500 nm and 400 nm respectively for SCLLs and SCLLs containing 5-ALA was found. In vitro 5-ALA permeation study showed that SCLLs preparations presented higher skin retention significantly (p Conclusions The in vitro delivery performance provided by SCLLs lead to consider this systems adequate for the 5-ALA-PDT of skin cancer, since SCLLs have delivered 5-ALA to the target skin layers (viable epidermis + dermis to be treated by topical PDT of skin cancer.

  17. Promotive role of 5-aminolevulinic acid on chromium-induced morphological, photosynthetic, and oxidative changes in cauliflower (Brassica oleracea botrytis L.).

    Science.gov (United States)

    Ahmad, Rehan; Ali, Shafaqat; Hannan, Fakhir; Rizwan, Muhammad; Iqbal, Muhammad; Hassan, Zaidul; Akram, Nudrat Aisha; Maqbool, Saliha; Abbas, Farhat

    2017-03-01

    Chromium (Cr) is among the most toxic pollutants in the environment that adversely affect the living organisms and physiological processes in different plants. The present study investigated the effect of 15 mg L(-1) of 5-aminolevulinic acid (ALA) on morpho-physiological attributes of cauliflower (Brassica oleracea botrytis L.) under different Cr concentrations (0, 10, 100, and 200 μM) in the growth medium. The results showed that Cr stress decreased the growth, biomass, photosynthetic, and gas exchange parameters. Chromium stress enhanced the activities of enzymatic antioxidants, catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD) in response to oxidative stress caused by the elevated levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolyte leakage (EL) in both roots and leaves of cauliflower. Chromium concentrations and total Cr uptake were increased in leaves, stems, and roots with increasing Cr levels in the culture medium. Foliar application of ALA increased the plant growth parameters, biomass, gas exchange parameters, and photosynthetic pigments under Cr stress compared to the treatments without ALA. Foliar application ALA decreased the levels of MDA, EL, and H2O2 while further improved the performance of antioxidant in both leaves and roots compared to only Cr-stressed plant. Chromium concentrations and total Cr uptake were decreased by the ALA application compared to treatments without ALA application. The results of the present study indicated that foliar application of ALA might be beneficial in minimizing Cr uptake and its toxic effects in cauliflower.

  18. Transporter-Mediated Drug Interaction Strategy for 5-Aminolevulinic Acid (ALA-Based Photodynamic Diagnosis of Malignant Brain Tumor: Molecular Design of ABCG2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Toshihisa Ishikawa

    2011-09-01

    Full Text Available Photodynamic diagnosis (PDD is a practical tool currently used in surgical operation of aggressive brain tumors, such as glioblastoma. PDD is achieved by a photon-induced physicochemical reaction which is induced by excitation of protoporphyrin IX (PpIX exposed to light. Fluorescence-guided gross-total resection has recently been developed in PDD, where 5-aminolevulinic acid (ALA or its ester is administered as the precursor of PpIX. ALA induces the accumulation of PpIX, a natural photo-sensitizer, in cancer cells. Recent studies provide evidence that adenosine triphosphate (ATP-binding cassette (ABC transporter ABCG2 plays a pivotal role in regulating the cellular accumulation of porphyrins in cancer cells and thereby affects the efficacy of PDD. Protein kinase inhibitors are suggested to potentially enhance the PDD efficacy by blocking ABCG2-mediated porphyrin efflux from cancer cells. It is of great interest to develop potent ABCG2-inhibitors that can be applied to PDD for brain tumor therapy. This review article addresses a pivotal role of human ABC transporter ABCG2 in PDD as well as a new approach of quantitative structure-activity relationship (QSAR analysis to design potent ABCG2-inhibitors.

  19. The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain

    Directory of Open Access Journals (Sweden)

    Feryal Al-Saber

    2016-01-01

    Full Text Available Type 2 diabetes mellitus is prevalent especially in Gulf countries and poses serious long-term risks to patients. A multifaceted treatment approach can include nutritional supplements with antioxidant properties such as 5-aminolevulinic acid (5-ALA with sodium ferrous citrate (SFC. This prospective, randomized, single-blind, placebo-controlled, dose escalating pilot clinical trial assessed the safety of 5-ALA with SFC at doses up to 200 mg 5-ALA/229.42 mg SFC per day in patients living in Bahrain with type 2 diabetes mellitus that was uncontrolled despite the use of one or more antidiabetic drugs. Fifty-three patients (n=53 from 3 sites at one center were enrolled by Dr. Feryal (Site #01, Dr. Hesham (Site #02, and Dr. Waleed (Site #03 (n=35, 5-ALA-SFC; n=18, placebo. There was no significant difference in incidence of adverse events reported, and the most frequent events reported were gastrointestinal in nature, consistent with the known safety profile of 5-ALA in patients with diabetes. No significant changes in laboratory values and no difference in hypoglycemia between patients receiving 5-ALA and placebo were noted. Overall, the current results support that use of 5-ALA-SFC up to 200 mg per day taken as 2 divided doses is safe in patients taking concomitant oral antidiabetic medications and may offer benefits in the diabetic population. This trial is registered with ClinicalTrials.gov NCT02481141.

  20. Fractionated illumination after topical application of 5-aminolevulinic acid on normal skin of hairless mice: the influence of the dark interval.

    Science.gov (United States)

    de Bruijn, H S; van der Ploeg-van den Heuvel, A; Sterenborg, H J C M; Robinson, D J

    2006-12-01

    We have previously shown that light fractionation during topical aminolevulinic acid based photodynamic therapy (ALA-PDT) with a dark interval of 2h leads to a significant increase in efficacy in both pre-clinical and clinical PDT. However this fractionated illumination scheme required an extended overall treatment time. Therefore we investigated the relationship between the dark interval and PDT response with the aim of reducing the overall treatment time without reducing the efficacy. Five groups of mice were treated with ALA-PDT using a single light fraction or the two-fold illumination scheme with a dark interval of 30 min, 1, 1.5 and 2h. Protoporphyrin IX fluorescence kinetics were monitored during illumination. Visual skin response was monitored in the first seven days after PDT and assessed as PDT response. The PDT response decreases with decreasing length of the dark interval. Only the dark interval of 2h showed significantly more damage compared to all the other dark intervals investigated (Pdark interval used. We conclude that in the skin of the hairless mouse the dark interval cannot be reduced below 2h without a significant reduction in PDT efficacy.

  1. Alleviation of Lead Toxicity by 5-Aminolevulinic Acid Is Related to Elevated Growth, Photosynthesis, and Suppressed Ultrastructural Damages in Oilseed Rape

    Directory of Open Access Journals (Sweden)

    Tian Tian

    2014-01-01

    Full Text Available Lead (Pb is a widely spread pollutant and leads to diverse morphological and structural changes in the plants. In this study, alleviating role of 5-aminolevulinic acid (ALA in oilseed rape (Brassica napus L. was investigated with or without foliar application of ALA (25 mg L−1 in hydroponic environment under different Pb levels (0, 100, and 400 µM. Outcomes stated that plant morphology and photosynthetic attributes were reduced under the application of Pb alone. However, ALA application significantly increased the plant growth and photosynthetic parameters under Pb toxicity. Moreover, ALA also lowered the Pb concentration in shoots and roots under Pb toxicity. The microscopic studies depicted that exogenously applied ALA ameliorated the Pb stress and significantly improved the cell ultrastructures. After application of ALA under Pb stress, mesophyll cell had well-developed nucleus and chloroplast having a number of starch granules. Moreover, micrographs illustrated that root tip cell contained well-developed nucleus, a number of mitochondria, and golgi bodies. These results proposed that under 15-day Pb-induced stress, ALA improved the plant growth, chlorophyll content, photosynthetic parameters, and ultrastructural modifications in leaf mesophyll and root tip cells of the B. napus plants.

  2. No-Needle Jet Intradermal Aminolevulinic Acid Photodynamic Therapy for Recurrent Nodular Basal Cell Carcinoma of the Nose: A Case Report

    Directory of Open Access Journals (Sweden)

    Daniel Barolet

    2011-01-01

    Full Text Available Photodynamic therapy (PDT with aminolevulinic acid (ALA to treat nodular basal cell carcinoma (BCC has been shown to be beneficial. The success rate of ALA-PDT in the treatment of nodular BCC is dependent on optimal penetration of the photosensitizing agent and subsequent PpIX production. To enhance topical delivery of drugs intradermally, a needleless jet injection (NLJI, which employs a high-speed jet to puncture the skin without the side effects of needles, was used in one patient with recurrent BCC of the nose. Photoactivation was then performed using red light emitting diode [CW @ λ 630 nm, irradiance 50 mW/cm2, total fluence 51 J/cm2] for 17 minutes. Excellent cosmesis was obtained. Aside from mild crusting present for six days, no other adverse signs were noted. Clinically, there was no recurrent lesion up two years postintervention. Additional studies in larger samples of subjects are needed to further evaluate this promising technique.

  3. The Safety and Tolerability of 5-Aminolevulinic Acid Phosphate with Sodium Ferrous Citrate in Patients with Type 2 Diabetes Mellitus in Bahrain

    Science.gov (United States)

    Al-Saber, Feryal; Aldosari, Waleed; Alselaiti, Mariam; Khalfan, Hesham; Kaladari, Ahmed; Khan, Ghulam; Harb, George; Rehani, Riyadh; Kudo, Sizuka; Koda, Aya; Tanaka, Tohru

    2016-01-01

    Type 2 diabetes mellitus is prevalent especially in Gulf countries and poses serious long-term risks to patients. A multifaceted treatment approach can include nutritional supplements with antioxidant properties such as 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC). This prospective, randomized, single-blind, placebo-controlled, dose escalating pilot clinical trial assessed the safety of 5-ALA with SFC at doses up to 200 mg 5-ALA/229.42 mg SFC per day in patients living in Bahrain with type 2 diabetes mellitus that was uncontrolled despite the use of one or more antidiabetic drugs. Fifty-three patients (n = 53) from 3 sites at one center were enrolled by Dr. Feryal (Site #01), Dr. Hesham (Site #02), and Dr. Waleed (Site #03) (n = 35, 5-ALA-SFC; n = 18, placebo). There was no significant difference in incidence of adverse events reported, and the most frequent events reported were gastrointestinal in nature, consistent with the known safety profile of 5-ALA in patients with diabetes. No significant changes in laboratory values and no difference in hypoglycemia between patients receiving 5-ALA and placebo were noted. Overall, the current results support that use of 5-ALA-SFC up to 200 mg per day taken as 2 divided doses is safe in patients taking concomitant oral antidiabetic medications and may offer benefits in the diabetic population. This trial is registered with ClinicalTrials.gov NCT02481141.

  4. 提高氨基酮戊酸透皮能力的方法%Methods to improve transdermal delivery of aminolevulinic acid

    Institute of Scientific and Technical Information of China (English)

    石磊; 王秀丽; 王宏伟

    2012-01-01

    氨基酮戊酸光动力治疗在皮肤科领域应用广泛,由于氨基酮戊酸透皮能力低,限制氨基酮戊酸光动力治疗的疗效.氨基酮戊酸衍生物,微针、激光、离子导入和运输载体技术相继被应用于提高氨基酮戊酸的透皮能力,并且取得了一定的效果.它们可通过不同的机制提高氨基酮戊酸透皮的深度和透皮的量,使氨基酮戊酸光动力治疗能更有效地应用于皮肤科领域.%Aminolevulinic acid-based photodynamic therapy (ALA-PDT) has been extensively applied in dermatology.However,the low permeability of ALA across intact skin has limited the efficacy of ALA-PDT.To enhace the percutaneous penetration of ALA,esterified derivatives,microneedles,laser,iontophoresis,delivery vehicles have been used in succession,and some achievements have been made.These methods can increase the transdermal delivery of ALA in terms of depth and quantity by different mechanisms,and indirectly promote the efficacy of ALA-PDT in dermatoses.

  5. Production of uroporphyrinogen III, which is the common precursor of all tetrapyrrole cofactors, from 5-aminolevulinic acid by Escherichia coli expressing thermostable enzymes.

    Science.gov (United States)

    Hibino, Aiko; Petri, René; Büchs, Jochen; Ohtake, Hisao

    2013-08-01

    Uroporphyrinogen III (urogen III) was produced from 5-aminolevulinic acid (ALA), which is a common precursor of all metabolic tetrapyrroles, using thermostable ALA dehydratase (ALAD), porphobilinogen deaminase (PBGD), and urogen III synthase (UROS) of Thermus thermophilus HB8. The UROS-coding gene (hemD₂) of T. thermophilus HB8 was identified by examining the gene product for its ability to produce urogen III in a coupled reaction with ALAD and PBGD. The genes encoding ALAD, PBGD, and UROS were separately expressed in Escherichia coli BL21 (DE3). To inactivate indigenous mesophilic enzymes, the E. coli transformants were heated at 70 °C for 10 min. The bioconversion of ALA to urogen III was performed using a mixture of heat-treated E. coli transformants expressing ALAD, PBGD, and UROS at a cell ratio of 1:1:1. When the total cell concentration was 7.5 g/l, the mixture of heat-treated E. coli transformants could convert about 88 % 10 mM ALA to urogen III at 60 °C after 4 h. Since eight ALA molecules are required for the synthesis of one porphyrin molecule, approximately 1.1 mM (990 mg/l) urogen III was produced from 10 mM ALA. The present technology has great potential to supply urogen III for the biocatalytic production of vitamin B₁₂.

  6. Bucher's indirect comparison of daylight photodynamic therapy with methyl aminolevulinate cream versus diclofenac plus hyaluronic acid gel for the treatment of multiple actinic keratosis.

    Science.gov (United States)

    Calzavara-Pinton, Piergiacomo; Zane, Cristina; Pacou, Maud; Szeimies, Rolf-Markus

    2016-10-01

    Actinic keratosis (AK) is a pre-cancerous condition characterised by patches of thick, scaly skin developing on sun-exposed areas of the body. When multiple AKs develop on severely photodamaged skin, commonly used treatments include photodynamic therapy and diclofenac plus hyaluronic acid gel (DHA). Methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) is an alternative to conventional photodynamic therapy (MAL c-PDT). Trials have indicated that MAL DL-PDT is as effective as MAL c-PDT but reduces treatment-related pain and dermatological side effects. To indirectly compare between MAL DL-PDT and DHA in patients with AK. A total of three randomised trials were collected using a systematic literature review. An adjusted indirect comparison was conducted on complete lesion response rate at 12 weeks. The data indicated that mild lesions, moderate lesions, and mild and moderate lesions treated with MAL DL-PDT were more than four times more likely to undergo a complete response than lesions treated with DHA at 12 weeks, with ORs ranging from 4.23 to 4.81. Results were all statistically significant. This is the first indirect comparison demonstrating the effectiveness of MAL-PDT over DHA for the treatment of AK, and further research is needed to assess the long-term efficacy of these interventions (i.e. six months and beyond), as well as safety and patient-reported outcomes.

  7. Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.

    Science.gov (United States)

    Steluti, Regilene; De Rosa, Fernanda Scarmato; Collett, John; Tedesco, Antônio Cláudio; Bentley, Maria Vitória Lopes Badra

    2005-08-01

    Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations.

  8. Nuclear receptor 5A (NR5A) family regulates 5-aminolevulinic acid synthase 1 (ALAS1) gene expression in steroidogenic cells.

    Science.gov (United States)

    Ju, Yunfeng; Mizutani, Tetsuya; Imamichi, Yoshitaka; Yazawa, Takashi; Matsumura, Takehiro; Kawabe, Shinya; Kanno, Masafumi; Umezawa, Akihiro; Kangawa, Kenji; Miyamoto, Kaoru

    2012-11-01

    5-Aminolevulinic acid synthase 1 (ALAS1) is a rate-limiting enzyme for heme biosynthesis in mammals. Heme is essential for the catalytic activities of P450 enzymes including steroid metabolic enzymes. Nuclear receptor 5A (NR5A) family proteins, steroidogenic factor-1 (SF-1), and liver receptor homolog-1 (LRH-1) play pivotal roles in regulation of steroidogenic enzymes. Recently, we showed that expression of SF-1/LRH-1 induces differentiation of mesenchymal stem cells into steroidogenic cells. In this study, genome-wide analysis revealed that ALAS1 was a novel SF-1-target gene in differentiated mesenchymal stem cells. Chromatin immunoprecipitation and reporter assays revealed that SF-1/LRH-1 up-regulated ALAS1 gene transcription in steroidogenic cells via binding to a 3.5-kb upstream region of ALAS1. The ALAS1 gene was up-regulated by overexpression of SF-1/LRH-1 in steroidogenic cells and down-regulated by knockdown of SF-1 in these cells. Peroxisome proliferator-activated receptor-γ coactivator-1α, a coactivator of nuclear receptors, also strongly coactivated expression of NR5A-target genes. Reporter analysis revealed that peroxisome proliferator-activated receptor-γ coactivator-1α strongly augmented ALAS1 gene transcription caused by SF-1 binding to the 3.5-kb upstream region. Finally knockdown of ALAS1 resulted in reduced progesterone production by steroidogenic cells. These results indicate that ALAS1 is a novel NR5A-target gene and participates in steroid hormone production.

  9. 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Yoshio Terada

    Full Text Available BACKGROUND/AIMS: Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP-based chemotherapy. 5-Aminolevulinic acid (ALA is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI. METHOD: We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E. We divided four groups of rats: control, CDDP only, CDDP + ALA(post;(ALA 10 mg/kg + Fe in drinking water after CDDP, CDDP + ALA(pre & post. RESULT: CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP. CONCLUSION: These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

  10. 5-Aminolevulinic acid protects against cisplatin-induced nephrotoxicity without compromising the anticancer efficiency of cisplatin in rats in vitro and in vivo.

    Science.gov (United States)

    Terada, Yoshio; Inoue, Keiji; Matsumoto, Tatsuki; Ishihara, Masayuki; Hamada, Kazu; Shimamura, Yoshiko; Ogata, Koji; Inoue, Kosuke; Taniguchi, Yoshinori; Horino, Taro; Karashima, Takashi; Tamura, Kenji; Fukuhara, Hideo; Fujimoto, Shimpei; Tsuda, Masayuki; Shuin, Taro

    2013-01-01

    Nephrotoxicity is a frequent and major limitation in cisplatin (CDDP)-based chemotherapy. 5-Aminolevulinic acid (ALA) is widely distributed in animal cells, and it is a precursor of tetrapyrole compounds such as heme that is fundamentally important in aerobic energy metabolism. The aim of this study is to evaluate the protective role of ALA in CDDP-induced acute kidney injury (AKI). We used CDDP-induced AKI rat model and cultured renal tubular cells (NRK-52E). We divided four groups of rats: control, CDDP only, CDDP + ALA(post);(ALA 10 mg/kg + Fe in drinking water) after CDDP, CDDP + ALA(pre & post). CDDP increased Cr up to 6.5 mg/dl, BUN up to 230 mg/dl, and ALA significantly reduced these changes. ALA ameliorates CDDP-induced morphological renal damages, and reduced tubular apoptosis evaluated by TUNEL staining and cleaved caspase 3. Protein and mRNA levels of ATP5α, complex(COX) IV, UCP2, PGC-1α in renal tissue were significantly decreased by CDDP, and ALA ameliorates reduction of these enzymes. In contrast, Heme Oxigenase (HO)-1 level is induced by CDDP treatment, and ALA treatment further up-regulates HO-1 levels. In NRK-52E cells, the CDDP-induced reduction of protein and mRNA levels of mitochondrial enzymes was significantly recovered by ALA + Fe. CDDP-induced apoptosis were ameliorated by ALA + Fe treatment. Furthermore, we evaluated the size of transplantated bladder carcinoma to the rat skin, and ALA did not change the anti cancer effects of CDDP. These data suggested that the protective role of ALA in cisplatin-induced AKI is via protection of mitochondrial viability and prevents tubular apoptosis. Also there are no significant effects of ALA on anticancer efficiency of CDDP in rats. Thus, ALA has the potential to prevent CDDP nephrotoxicity without compromising its anticancer efficacy.

  11. Differential antioxidant defense and detoxification mechanisms in photodynamically stressed rice plants treated with the deregulators of porphyrin biosynthesis, 5-aminolevulinic acid and oxyfluorfen

    Energy Technology Data Exchange (ETDEWEB)

    Phung, Thu-Ha; Jung, Sunyo, E-mail: sjung@knu.ac.kr

    2015-04-03

    This study focuses on differential molecular mechanisms of antioxidant and detoxification systems in rice plants under two different types of photodynamic stress imposed by porphyrin deregulators, 5-aminolevulinic acid (ALA) and oxyfluorfen (OF). The ALA-treated plants with white necrosis exhibited a greater decrease in photochemical quantum efficiency, F{sub v}/F{sub m}, as well as a greater increase in activity of superoxide dismutase, compared to the OF-treated plants. By contrast, the brown necrosis in OF-treated plants resulted in not only more widely dispersed H{sub 2}O{sub 2} production and greater increases in H{sub 2}O{sub 2}-decomposing enzymes, catalase and peroxidase, but also lower ascorbate redox state. In addition, ALA- and OF-treated plants markedly up-regulated transcript levels of genes involved in detoxification processes including transport and movement, cellular homeostasis, and xenobiotic conjugation, with prominent up-regulation of serine/threonine kinase and chaperone only in ALA-treated plants. Our results demonstrate that different photodynamic stress imposed by ALA and OF developed differential actions of antioxidant enzymes and detoxification. Particularly, detoxification system may play potential roles in plant protection against photodynamic stress imposed by porphyrin deregulators, thereby contributing to alleviation of photodynamic damage. - Highlights: • We employ two different types of photodynamic stress, white and brown necrosis. • We examine molecular mechanisms of antioxidative and detoxification systems. • ALA and OF develop differential actions of antioxidant and detoxification systems. • Coordinated mechanism of antioxidants and detoxification works against toxic ROS. • Detoxification system plays critical roles in protection against photodynamic stress.

  12. Effects of exogenous 5-aminolevulinic acid on PIP1 and NIP aquaporin gene expression in seedlings of cucumber cultivars subjected to salinity stress.

    Science.gov (United States)

    Yan, F; Qu, D; Zhao, Y Y; Hu, X H; Zhao, Z Y; Zhang, Y; Zou, Z R

    2014-01-22

    Aquaporins play a direct role in plant water relation under salt stress, but the effects of 5-aminolevulinic acid (ALA) on aquaporin gene expression in salt-treated plants remain unknown. This study investigated the potential effects of exogenous ALA (50 mg/dm3) on aquaporin expression levels under salt stress (75 mM NaCl) in the salt-sensitive (Jinchun No.4) and the relatively salt-tolerant cucumber (Jinyou No.1) seedlings. The expressions of cucumber PIP aquaporin gene (CsPIP1:1) and cucumber NIP aquaporin gene (CsNIP) were analyzed in 20-day-old seedling leaves at 2, 4, 8, 16, and 24 h after ALA treatment. After treatment with saline alone and ALA alone, CsPIP1:1 and CsNIP gene expression levels in the 2 cucumber cultivars increased to maximum at 2 h. The aquaporin gene expression in salt-treated cucumber seedling leaves was considerably higher than that in leaves subjected to exogenous ALA. Further, the aquaporin expression levels in Jinchun No.4 were higher than those in Jinyou No.1, reaching 5.20- and 2-fold induction levels, respectively. After treatment with both ALA and NaCl, the CsNIP gene expression was downregulated in both the cucumber cultivars, while that of CsPIP1:1 decreased at 2 h and then increased to 3.8-fold in Jinchun No.4. In Jinyou No.1, CsPIP1:1 gene expression gradually increased to 2.3-fold at 4 h, followed by a decline in expression. The results indicated that ALA might delay and counteract the upregulated expression of CsPIP1:1 and CsNIP genes in cucumber seedlings under NaCl stress. Thus, salt tolerance of cucumber seedlings might be enhanced by ALA application.

  13. Effects of exogenous 5-aminolevulinic acid on photosynthesis, stomatal conductance, transpiration rate, and PIP gene expression of tomato seedlings subject to salinity stress.

    Science.gov (United States)

    Zhao, Y Y; Yan, F; Hu, L P; Zhou, X T; Zou, Z R; Cui, L R

    2015-06-11

    The effects of exogenous 5-aminolevulinic acid (ALA) on photosynthesis, plant growth, and the expression of two aquaporin genes in tomato seedlings under control and salinity conditions were investigated. Exogenous ALA application significantly improved net photosynthetic rate (Pn), total chlorophyll content, and plant biomass accumulation of tomato seedlings under salinity stress. As revealed by real-time PCR analyses, after treatment with ALA alone, expression of both LePIP1 and LePIP2 in the two tomato cultivars was up-regulated at 2 h and subsequently decreased to normal levels. Under salinity stress, transcript levels of LePIP1 in both leaves and roots of salt-sensitive cultivars (cv. Zhongza No.9) increased significantly and were considerably higher than in cultivars exposed to ALA alone. In contrast, the expression levels of LePIP1 and LePIP2 in cvs. Jinpeng No.1 cultivars were slightly lower under salinity stress than under ALA treatment. In addition, transcript levels of both LePIP1 and LePIP2 in the roots of Jinpeng No. 1 cultivars were considerably lower than those in the roots of Zhongza No. 9 cultivars under salinity stress, regardless of ALA supplementation, implying that Jinpeng No. 1 cultivars had a better capacity to maintain membrane intrinsic protein stability. Further, ALA application distinctly counteracted the up- or down-regulation of LePIP1 and LePIP2 in both cultivars under salinity stress, in accordance with the improvements instomatal conductance, transpiration rate, and Pn of tomato leaves. The results presented here indicate that ALA controls aquaporin expression, thus, presumably ALA regulates water homeostasis and enhances salt tolerance of tomato seedlings.

  14. The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, its current boundaries, and future perspectives: A systematic review.

    Science.gov (United States)

    Mansouri, Alireza; Mansouri, Sheila; Hachem, Laureen D; Klironomos, George; Vogelbaum, Michael A; Bernstein, Mark; Zadeh, Gelareh

    2016-08-15

    5-Aminolevulinic acid (5-ALA) has been approved as an intraoperative adjunct in glioma surgery in Europe, but not North America. A systematic review was conducted to assess the evidence regarding 5-ALA as a surgical adjunct. The MEDLINE, EMBASE, and CENTRAL databases were searched, using terms relevant to "5-ALA" and "high-grade gliomas." Included studies were based on adults aged ≥18 years who underwent surgical resection/biopsy. No language or date limitations were used. Forty-three studies (1830 patients) were identified. Thirty-six were coordinated by European countries, 2 were in the United States, and none were in Canada. One was randomized, 28 were prospective, and 14 were retrospective. Twenty-six studies assessed the utility of 5-ALA as a diagnostic tool, 24 assessed its influence on the extent of resection (EOR), 9 assessed survival, and 22 reported adverse events. 5-ALA had high sensitivity and positive predictive value, whereas its specificity increased with additional adjuncts. The EOR increased with 5-ALA, but only progression-free survival was significantly influenced. Reporting of adverse events was not systematic. The use of 5-ALA improved tumor visualization and thus enabled a greater EOR and perhaps increased survival. However, additional adjuncts may be necessary for maximizing the specificity of resection and patient safety. Additional parameters, such as patient quality of life and health economic analyses, would be informative. Thus, additional systematic collection of prospective evidence may be necessary for the global incorporation of this potentially valuable surgical adjunct into routine practice. Cancer 2016;122:2469-78. © 2016 American Cancer Society. © 2016 American Cancer Society.

  15. Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior.

    Science.gov (United States)

    Fang, Yi-Ping; Huang, Yaw-Bin; Wu, Pao-Chu; Tsai, Yi-Hung

    2009-11-01

    Psoriasis, an inflammatory skin disease, exhibits recurring itching, soreness, and cracked and bleeding skin. Currently, the topical delivery of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is an optional treatment for psoriasis which provides long-term therapeutic effects, is non-toxic and enjoys better compliance with patients. However, the precursor of ALA is hydrophilic, and thus its ability to penetrate the skin is limited. Also, little research has provided a platform to investigate the penetration behavior in disordered skin. We employed a highly potent ethosomal carrier (phosphatidylethanolamine; PE) to investigate the penetration behavior of ALA and the recovery of skin in a hyperproliferative murine model. We found that the application of ethosomes produced a significant increase in cumulative amounts of 5-26-fold in normal and hyperproliferative murine skin samples when compared to an ALA aqueous solution; and the ALA aqueous solution appeared less precise in terms of the penetration mode in hyperproliferative murine skin. After the ethosomes had been applied, the protoporphyrin IX (PpIX) intensity increased about 3.64-fold compared with that of the ALA aqueous solution, and the penetration depth reached 30-80 microm. The results demonstrated that the ethosomal carrier significantly improved the delivery of ALA and the formation of PpIX in both normal and hyperproliferative murine skin samples, and the expression level of tumor necrosis factor (TNF)-alpha was reduced after the ALA-ethosomes were applied to treat hyperproliferative murine skin. Furthermore, the results of present study encourage more investigations on the mechanism of the interaction with ethosomes and hyperproliferative murine skin.

  16. Studies on the metabolism of the Delta9-tetrahydrocannabinol precursor Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) in rat using LC-MS/MS, LC-QTOF MS and GC-MS techniques.

    Science.gov (United States)

    Jung, Julia; Meyer, Markus R; Maurer, Hans H; Neusüss, Christian; Weinmann, Wolfgang; Auwärter, Volker

    2009-10-01

    In Cannabis sativa, Delta9-Tetrahydrocannabinolic acid-A (Delta9-THCA-A) is the non-psychoactive precursor of Delta9-tetrahydrocannabinol (Delta9-THC). In fresh plant material, about 90% of the total Delta9-THC is available as Delta9-THCA-A. When heated (smoked or baked), Delta9-THCA-A is only partially converted to Delta9-THC and therefore, Delta9-THCA-A can be detected in serum and urine of cannabis consumers. The aim of the presented study was to identify the metabolites of Delta9-THCA-A and to examine particularly whether oral intake of Delta9-THCA-A leads to in vivo formation of Delta9-THC in a rat model. After oral application of pure Delta9-THCA-A to rats (15 mg/kg body mass), urine samples were collected and metabolites were isolated and identified by liquid chromatography-mass spectrometry (LC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high resolution LC-MS using time of flight-mass spectrometry (TOF-MS) for accurate mass measurement. For detection of Delta9-THC and its metabolites, urine extracts were analyzed by gas chromatography-mass spectrometry (GC-MS). The identified metabolites show that Delta9-THCA-A undergoes a hydroxylation in position 11 to 11-hydroxy-Delta9-tetrahydrocannabinolic acid-A (11-OH-Delta9-THCA-A), which is further oxidized via the intermediate aldehyde 11-oxo-Delta9-THCA-A to 11-nor-9-carboxy-Delta9-tetrahydrocannabinolic acid-A (Delta9-THCA-A-COOH). Glucuronides of the parent compound and both main metabolites were identified in the rat urine as well. Furthermore, Delta9-THCA-A undergoes hydroxylation in position 8 to 8-alpha- and 8-beta-hydroxy-Delta9-tetrahydrocannabinolic acid-A, respectively, (8alpha-Hydroxy-Delta9-THCA-A and 8beta-Hydroxy-Delta9-THCA-A, respectively) followed by dehydration. Both monohydroxylated metabolites were further oxidized to their bishydroxylated forms. Several glucuronidation conjugates of these metabolites were identified. In vivo conversion of Delta9-THCA-A to Delta9-THC was

  17. Inhibition of VDAC1 prevents Ca²⁺-mediated oxidative stress and apoptosis induced by 5-aminolevulinic acid mediated sonodynamic therapy in THP-1 macrophages.

    Science.gov (United States)

    Chen, Haibo; Gao, Weiwei; Yang, Yang; Guo, Shuyuan; Wang, Huan; Wang, Wei; Zhang, Shuisheng; Zhou, Qi; Xu, Haobo; Yao, Jianting; Tian, Zhen; Li, Bicheng; Cao, Wenwu; Zhang, Zhiguo; Tian, Ye

    2014-12-01

    Ultrasound combined with endogenous protoporphyrin IX derived from 5-aminolevulinic acid (ALA-SDT) is known to induce apoptosis in multiple cancer cells and macrophages. Persistent retention of macrophages in the plaque has been implicated in the pathophysiology and progression of atherosclerosis. Here we investigated the effects of inhibition of voltage-dependent anion channel 1 (VDAC1) on ALA-SDT-induced THP-1 macrophages apoptosis. Cells were pre-treated with VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) disodium salt for 1 h or downregulated VDAC1 expression by small interfering RNA and exposed to ultrasound. Cell viability was assessed by MTT assay, and cell apoptosis along with necrosis was evaluated by Hoechst 33342/propidium iodide staining and flow cytometry. Levels of cytochrome c release was assessed by confocal microscope and Western blot. The levels of full length caspases, caspase activation, and VDAC isoforms were analyzed by Western blot. Intracellular reactive oxygen species generation, mitochondrial membrane permeability, and intracellular Ca(2+) [Ca(2+)]i levels were measured with fluorescent probes. We confirmed that the pharmacological inhibition of VDAC1 by DIDS notably prevented ALA-SDT-induced cell apoptosis in THP-1 macrophages. Additionally, DIDS significantly inhibited intracellular ROS generation and apoptotic biochemical changes such as inner mitochondrial membrane permeabilization, loss of mitochondrial membrane potential, cytochrome c release and activation of caspase-3 and caspase-9. Moreover, ALA-SDT elevated the [Ca(2+)]i levels and it was also notably reduced by DIDS. Furthermore, both of intracellular ROS generation and cell apoptosis were predominately inhibited by Ca(2+) chelating reagent BAPTA-AM. Intriguingly, ALA-treatment markedly augmented VDAC1 protein levels exclusively, and the downregulation of VDAC1 expression by specific siRNA also significantly abolished cell apoptosis. Altogether, these

  18. Arsenic Induced Inhibition of δ-aminolevulinate Dehydratase Activity in Rat Blood and its Response To Meso 2,3-dimercaptosuccinic Acid and Monoisoamyl DMSA

    Institute of Scientific and Technical Information of China (English)

    SMRATI BHADAURIA; SWARAN J.S.FLORA

    2004-01-01

    Objective The objective of this study was to investigate arsenic induced changes in blood δ-aminolevulinic acid dehydratase (ALAD) after in vitro and in vivo exposure to this element and its response to co-administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) either individually or in combination. Methods Rat whole blood was exposed to varying concentrations (0.1, 0.2 and 0.5 mmol/L) of arsenic (Ⅲ) or arsenic (V), to assess their effects on blood ALAD activity. Varying concentrations of MiADMSA and DMSA (0.1, 0.5 and 1.0 mmol/L) were also tried in combination to determine its ability to mask the effect of arsenic induced (0.5 mmol/L) inhibition of blood ALAD in vitro. In vitro and in vivo experiments were also conducted to determine the effects of DMSA and MiADMSA either individually or in combination with arsenic, on blood ALAD activity and blood arsenic concentration. Results In vitro experiments showed significant inhibition of the enzyme activity when 0.1-0.5 mmol/L of arsenic (Ⅲ and V) was used. Treatment with MiADMSA increased ALAD activity when blood was incubated at the concentration of 0.1 mmol/L arsenic (Ⅲ) and 0.1 mmol/L MiADMSA. No effect of 0.1 mmol/L MiADMSA on ALAD activity was noticed when the arsenic concentration was increased to 0.2 and 0.5 mmol/L. Similarly, MiADMSA at a lower concentration (0.1 mmol/L) was partially effective in the turnover of ALAD activity against 0.5 mmol/L arsenic (Ⅲ), but at two higher concentrations (0.5and 1.0 mmol/L) a complete restoration of ALAD activity was observed. DMSA at all the three concentrations (0.1, 0.5 and 1.0 mmol/L) was effective in restoring ALAD activity to the normal value.Conclusions The results thus suggest that arsenic has a distinct effect on ALAD activity. Another important toxicological finding of the present study, based on in vivo experiments further suggests that combined administration of DMSA and MiADMSA could be more beneficial for reducing blood

  19. Effect of cell cycle phase on the sensitivity of SAS cells to sonodynamic therapy using low-intensity ultrasound combined with 5-aminolevulinic acid in vitro.

    Science.gov (United States)

    Li, Nan; Sun, Miao; Wang, Yao; Lv, Yanhong; Hu, Zheng; Cao, Wenwu; Zheng, Jinhua; Jiao, Xiaohui

    2015-08-01

    Sonodynamic therapy (SDT) with 5-aminolevulinic acid (5-ALA) can effectively inhibit various types of tumor in vitro and in vivo. However, the association between the efficacy of SDT and the phase of the cell cycle remains to be elucidated. 5-ALA may generate different quantities of sonosensitizer, protoporphyrin IX (PpIX), in different phases of the cell cycle, which may result in differences in sensitivity to 5-ALA-induced SDT. The present study aimed to investigate the effect of the cell cycle on the susceptibility of SAS cells to SDT following synchronization to different cell cycle phases. These results indicates that the rates of cell death and apoptosis of the SAS cells in the S and G2/M phases were significantly higher following SDT, compared with those in the G1-phase cells and unsynchronized cells, with a corresponding increase in PpIX in the S and G2/M cells. In addition, the expression of caspase-3 increased, while that of B-cell lymphoma (Bcl)-2 decreased markedly in theS and G2/M cells following SDT. Cyclin A was also expressed at higher levels in the S and G2/M cells, compared with the G1-phase cells. SDT also caused a significant upregulation of cyclin A in all phases of the cell cycle, however this was most marked in the S and G2/M cells. It was hypothesized that high expression levels of cyclin A in the S and G2/M cells may promote the induction of caspase-3 and reduce the induction of Bcl-2 by SDT and, therefore, enhance apoptosis. Taken together, these data demonstrated that cells in The S and G2/M phases generate more intracellular PpIX, have higher levels of cyclin A and are, therefore, more sensitive to SDT-induced cytotoxicity. These findings indicate the potential novel approach to preventing the onset of cancer by combining cell-cycle regulators with SDT. This sequential combination therapy may be a simple and cost-effective way of enhancing the effects of SDT in clinical settings.

  20. Safety test of a supplement, 5-aminolevulinic acid phosphate with sodium ferrous citrate, in diabetic patients treated with oral hypoglycemic agents

    Directory of Open Access Journals (Sweden)

    Naohide Yamashita

    2014-09-01

    Full Text Available Objective: This study aimed to examine the safety of 5-aminolevulinic acid phosphate (5-ALA with sodium ferrous citrate (SFC in diabetic patients treated with one or more oral hypoglycemic agents (OHAs. Background: Recent intervention studies performed in the USA and Japan have shown that a nutritional supplement of 5-ALA with SFC efficiently reduced blood glucose levels in pre-diabetic population without any adverse events. Thus, it was anticipated that 5-ALA with SFC may potentially be taken as a beneficial supplement by diabetic patients who were being treated with OHA therapy. Nevertheless, it is important to examine its safety and efficacy in diabetic population. Methods: This study was a prospective single-blinded, randomized, placebo-controlled and parallel-group comparison study. Medically treated diabetic patients between the ages of 30 and 75 were recruited from the Tokyo metropolitan area of Japan and 45 subjects were selected after screening. These subjects were randomly assigned to three groups: daily intake of 15mg 5-ALA, 50mg 5-ALA, and a placebo (n=15, respectively. The supplement or placebo was administered for 12 weeks followed by a four week washout period. The primary endpoint was safety and occurrence of hypoglycemic attack, while the secondary endpoint was changes of fasting blood glucose (FBG and hemoglobin A1c (HbA1c. Results: Adverse events related to 5-ALA with SFC were not observed in all the groups. Abnormalities in blood and urine tests were not observed either. Significant decrease in FBG was not detected in all the groups. However, there was a small but significant decrease in HbA1c at 4 and 8 week in the 15 mg 5-ALA group. Significant decrease in HbA1c was not observed in the 50 mg 5-ALA group, although a tendency to decrease after 4 weeks was apparent. Conclusion: 5-ALA with SFC is a safe and potentially beneficial supplement if taken by diabetic patients treated with OHAs.

  1. Protoporphyrin IX distribution after intra-articular and systemic application of 5-aminolevulinic acid in healthy and arthritic joints

    Science.gov (United States)

    Huettmann, Gereon; Hendrich, Christian; Birngruber, Reginald; Lehnert, Christiane; Seara, Jose; Siebert, Werner E.; Diddens, Heyke C.

    1996-04-01

    Arthroscopic synovectomy, which is limited today to the large joints, is an important early treatment of rheumatoid arthritis (RA). Photodynamic therapy (PDT) is potentially to be a less invasive method of removing the synovial membrane. Therefore, in a rabbit model of RA, the accumulation of the photosensitizer Protoporphyrin IX (PPIX) after intra-articular and systemic application of ALA into arthritic rabbit knee joints was studied in skin, patella, synovial tissue, and meniscus by fluorescence microscopy. PPIX fluorescence was measured in biopsies taken at different times after application of neutral and acid ALA solutions. Significant PPIX fluorescence was observed in the synovial membrane and skin 2 and 4 hours after application. Using intra-articular application, ALA solutions prepared with pH 5.5 were at least as efficient as neutral solutions in sensitizing the synovial membrane. Skin also showed PPIX within 4 hours after application. After 24 hours, a marginal PPIX fluorescence was detected in these tissues. On the other hand, in cartilage and meniscus significant PPIX accumulation was still observed 24 hours after ALA injection. Systemic application of ALA also showed a good accumulation of PPIX. Further experiments are needed to show whether accumulation of the photosensitizer and tissue selectivity are sufficient for a successful treatment of rheumatoid synovitis.

  2. In vitro study of cell death with 5-aminolevulinic acid based photodynamic therapy to improve the efficiency of cancer treatment

    Science.gov (United States)

    Firdous, S.; Nawaz, M.; Ikram, M.; Ahmed, M.

    2012-03-01

    Photodynamic therapy (PDT) is a kind of photochemo therapeutic treatment that exerts its effect mainly through the induction of cell death. Distinct types of cell death may be elicited by different PDT regimes. In this study, efforts are underway to optimize PDT protocols for improved efficacy and combination of all three PDT mechanisms involved in the different human carcinomas cell narcosis. Our in vitro cell culture experiments with 5-aminolevulanic acid (ALA) a clinically approved photiosensitizer (PS) and 635 nm laser light have yielded promising results, as follow: (1) (human cervical cancer (HeLa) cell line incubated, for 18 h, with 30 μg/ml of 5-ALA, treated with laser light dose of 50 J/cm2 can produce 85% of cell killing (2) human larynx carcinoma (Hep2c) cell line incubated, for 7 h, with 55 μg/ml of 5-ALA, treated with laser light dose of 85 J/cm2 can produce 75% of cell killing (3) human liver cancer (HepG2) cell line incubated, for 22-48 h, with 262 μg/ml of 5-ALA, treated with laser light dose of 120 J/cm2 can produce 95% of cell killing (4) human muscle cancer (RD) cell line incubated, for 47 h, with 250 μg/ml of 5-ALA, treated with laser light dose of 80 J/cm2 can produce 76% of cell killing (5) Human embryonic kidney (HEK293T) cell line incu-bated, for 18 h, with 400 μg/ml of 5-ALA, treated with laser light dose of 40 J/cm2 can produce 82% of cell killing confirming the efficacy of photodynamic therapy.

  3. Clinical Effect of 5-aminolevulinic Acid Photodynamic Treating 10 Cases Bowen' s Disease%5-氨基酮戊酸光动力疗法治疗鲍温病10例疗效观察

    Institute of Scientific and Technical Information of China (English)

    熊林; 陆延娜; 万静; 魏亚东; 赵延东

    2012-01-01

    目的 观察5-氨基酮戊酸光动力疗法治疗鲍温病的临床疗效.方法 将20例鲍温病患者分为两组,各10例.治疗组予5-氨基酮戊酸外涂于皮损处,3h后予红光照射20min,能量密度100~120 J/cm2,1次/周,共4周.对照组外涂5-氟尿嘧啶软膏皮损处,2次/d,共4周.结果 治疗组完全缓解率为90.00%,对照组为30.00%,两组间完全缓解率比较,差异有统计学意义(P<0.05).且治疗组均未见严重不良反应,对照组有溃疡及瘢痕等不良反应.结论 5-氨基酮戊酸光动力疗法治疗鲍温病临床疗效较好,且无严重不良反应,值得临床推广应用.%Objective To observe the clinical effect of 5-aminolevulinic acid photodynamic therapy ( ALA-PDT) treating Bowen' s disease. Methods Twonty cases of Bowen' s disease were randomly divided into treatment group and control. Each group has 10 cases. Treatment group: applied 5-aminolevulinic acid (ALA) to the skin lesions, 3 hours later red light irradiated 20min, energy density was 100 ~ 120 J/cm2, one time a week for 4 weeks. Control group: smearing 5-fluorouracil cream(5-Fu ointment) on skin lesions,, twice daily for 4 weeks. Results Completely remission rate was 90. 00% in treatment group and 30. 00% in control. The difference between them had statistical significance(P <0.05). There were no serious side effects in the treatment group, but the control group appeared ulcer, scar and other side effects. Conclusion 5-aminolevulinic acid photodynamic is a good therapeutic method for Bowen' s disease.

  4. Effect of conjugated linoleic acid on fungal delta6-desaturase activity in a transformed yeast system.

    Science.gov (United States)

    Chuang, L T; Thurmond, J M; Liu, J W; Kirchner, S J; Mukerji, P; Bray, T M; Huang, Y S

    2001-02-01

    Conjugated linoleic acid (CLA; 18:2), a group of positional and geometric isomers of linoleic acid (LA; 18:2n-6), has been shown to modulate immune function through its effect on eicosanoid synthesis. This effect has been attributed to a reduced production of n-6 polyunsaturated fatty acid (PUFA), the precursor of eicosanoids. Since delta6-desaturase is the rate-limiting enzyme of the n-6 PUFA production, it is our hypothesis that CLA, which has similar chemical structure to LA, interacts directly with delta6-desaturase. A unique and simple model, i.e., baker's yeast (Saccharomyces cerevisiae) transformed with fungal delta6-desaturase gene, previously established, was used to investigate the direct effect of CLA on delta6-desaturase. This model allows LA to be converted to y-linolenic acid (GLA; 18:3n-6) but not GLA to its metabolite(s). No metabolites of CLA were found in the lipids of the yeast transformed with delta6-desaturase. The inability to convert CLA to conjugated GLA was not due to the failure of yeast cells to take up the CLA isomers. CLA mixture and individual isomers significantly inhibited the activity of delta6-desaturase of the transformed yeast in vivo. Even though its uptake by the yeast was low, CLA c9,t11 isomer was found to be the most potent inhibitor of the four isomers tested, owing to its high inhibitory effect on delta6-desaturase. Since CLA did not cause significant changes in the level of delta6-desaturase mRNA, the inhibition of GLA production could not be attributed to suppression of delta6-desaturase gene expression at the transcriptional level.

  5. Light fractionation does not enhance the efficacy of methyl 5-aminolevulinate mediated photodynamic therapy in normal mouse skin.

    NARCIS (Netherlands)

    Bruijn, H.S. de; Haas, E.R. de; Hebeda, K.M.; Ploeg-van den Heuvel, A. van der; Sterenborg, H.J.C.M.; Neumann, H.A.; Robinson, D.J.

    2007-01-01

    Previous work demonstrated that fractionated illumination using two fractions separated by a dark interval of 2 h, significantly enhanced the clinical efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA). Considering the increasing clinical use of methyl 5-aminolevulinate (MAL) an

  6. The effects of delta1-cortienic acid on skin blanching, pharmacokinetics and stability of loteprednol etabonate.

    Science.gov (United States)

    Wu, W M; Bodor, E T; Howes, J; Bodor, N

    2012-05-01

    The effect of delta1-cortienic acid (delta1-CA) on human skin blanching activity of the soft corticosteroid, loteprednol etabonate (LE), has been studied. Ten volunteers had applied to their forearms a dose of LE ranging from 0.1 to 1 mM, or LE from 0.1 to 1 mM in combination with 2-times the concentration of delta1-CA (0.2 - 2mM). The results indicate that delta1-CA increased LE's effect on human vasoconstriction/skin blanching activity, both in the intensity and duration. This enhancing effect of delta1-CA was also observed in other blanching studies with other corticosteroids, such as hydrocortisone. The enhancement may occur through the displacement of LE bound to transcortin (also known as corticosteroid-binding globulin, or CBG) by delta1-CA as delta1-CA has a higher affinity for CBG than that for glucocorticoid receptor (GR), resulting in more free-LE to act on GR, and increased skin blanching. In rat studies, intravenous injection of delta1-CA (5-50 mg/kg) did not affect the pharmacokinetics of LE (5 mg/kg), indicating that delta1-CA is safe for combined use with LE. In stability studies, the presence of delta1-CA at the same concentrations as LE in aqueous suspension (0.1 and 0.2%) significantly increased the stability of LE. Thus, the combination of delta1-CA with LE serves an enhancing and stabilizing role while not impacting the pharmacokinetic properties of LE.

  7. Comparative study of two routes of administration of 5-aminolevulinic acid (oral and intratumoral via) and their effect on the accumulation of PpIX in tissues in murine model of breast cancer

    Science.gov (United States)

    González-Agüero, G.; Ramón-Gallegos, E.

    2012-10-01

    Protoporphyrin IX (PpIX) is a photosensitizer synthesized from 5-aminolevulinic acid (ALA) that has been used in photodynamic therapy (PDT) as a promising treatment for many types of cancer. In this work it was quantified the accumulation of PpIX in tumors and in different tissues of female mice (nu/nu) inoculated with breast cancer cells. Two routes of administration of ALA: gastric probe and intratumoral injection were used to find optimum time of accumulation and the via that induce the higher quantity of PpIX to improve the efficiency of PDT. The results show that the accumulation of PpIX using the intratumoral via is two times bigger than the oral via in tumors at 8 h of treatment. The concentrations obtained in the different tissues are not physiologically significant.

  8. Synthesis of {delta}-aminolevulic acid. Application to the introduction of carbon-14 and of tritium; Syntheses de l'acide {delta} aminolevulique. Application a l'introduction de carbone 14 et de tritium

    Energy Technology Data Exchange (ETDEWEB)

    Loheac, J. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1966-06-01

    Several new syntheses of {delta} aminolevulic acid ({delta} A.L.A.) have been studied. {sup 14}C-4 {delta} - aminolevulic acid has been obtained from {sup 14}C allylacetic carboxylic acid with a yield of 30 per cent with respect to barium carbonate and with a specific activity of 32 mCi/mM. The {sup 14}C-1 or {sup 14}C-2 {delta}-A.L.A. has been prepared from the {sup 14}C-1 or {sup 14}C-2 acetate with a yield of 55 per cent with respect to the acetate. Finally the tritiated {delta}-A.L.A. has been obtained for the first time by tritiation of ethyl phthalimidodehydrolevulate. (author) [French] Plusieurs syntheses nouvelles de l'acide {delta}-aminolevulique ont ete etudiees. L'acide {delta}-aminolevulique {sup 14}C-4 a ete obtenu a partir d'acide allylacetique carboxylique {sup 14}C, avec un rendement global de 30 pour cent par rapport au carbonate de baryum a une activite specifique de 32 mCi/M. Le {delta}-A.A.L. {sup 14}C-1 ou {sup 14}C-2 a ete obtenu a partir d'acetate {sup 14}C-1 ou {sup 14}C-2 avec un rendement de 55 pour cent par rapport a l'acetate. Enfin le {delta}-A.A.L. tritie a ete obtenu pour la premiere fois par tritiation du phtalimidodehydrolevulate d'ethyle. (auteur)

  9. Tracing the biosynthetic source of essential amino acids in marine turtles using delta13C fingerprints.

    Science.gov (United States)

    Arthur, Karen E; Kelez, Shaleyla; Larsen, Thomas; Choy, C Anela; Popp, Brian N

    2014-05-01

    Plants, bacteria, and fungi produce essential amino acids (EAAs) with distinctive patterns of delta13C values that can be used as naturally occurring fingerprints of biosynthetic origin of EAAs in a food web. Because animals cannot synthesize EAAs and must obtain them from food, their tissues reflect delta13C(EAA) patterns found in diet, but it is not known how microbes responsible for hindgut fermentation in some herbivores influence the delta13C values of EAAs in their hosts' tissues. We examined whether distinctive delta13C fingerprints of hindgut flora are evident in the tissues of green turtles (Chelonia mydas), which are known to be facultative hindgut fermenters. We determined delta13C(EAA) values in tissues of green turtles foraging herbivorously in neritic habitats of Hawaii and compared them with those from green, olive ridley, and loggerhead turtles foraging carnivorously in oceanic environments of the central and southeast Pacific Ocean. Results of multivariate statistical analysis revealed two distinct groups that could be distinguished based on unique delta13C(EAA) patterns. A three-end-member predictive linear discriminant model indicated that delta13C(EAA) fingerprints existed in the tissues of carnivorous turtles that resembled patterns found in microalgae, which form the base of an oceanic food web, whereas herbivorous turtles derive EAAs from a bacterial or seagrass source. This study demonstrates the capacity for delta13C fingerprinting to establish the biosynthetic origin of EAAs in higher consumers, and that marine turtles foraging on macroalgal diets appear to receive nutritional supplementation from bacterial symbionts in their digestive system.

  10. Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid

    DEFF Research Database (Denmark)

    Conti, P; De Amici, M; Bräuner-Osborne, Hans

    2002-01-01

    The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino...

  11. Expression patterns of glial fibrillary acidic protein (GFAP)-delta in epilepsy-associated lesional pathologies

    NARCIS (Netherlands)

    L. Martinian; K. Boer; J. Middeldorp; E.M. Hol; S.M. Sisodiya; W. Squier; E.M.A. Aronica; M. Thom

    2009-01-01

    Aims: Glial fibrillary acidic protein (GFAP)-delta is a novel isoform that differs in its C-terminal sequence from other GFAP isoforms. Previous studies suggest restriction of expression to the subpial layer, subventricular zone and the subgranular zone astrocytes, with an absence in pathological co

  12. Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid

    DEFF Research Database (Denmark)

    Conti, P; De Amici, M; Bräuner-Osborne, Hans

    2002-01-01

    The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino...

  13. Detection of Delta9-tetrahydrocannabinolic acid A in human urine and blood serum by LC-MS/MS.

    Science.gov (United States)

    Jung, Julia; Kempf, Juergen; Mahler, Hellmut; Weinmann, Wolfgang

    2007-03-01

    Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) is the precursor of Delta9-tetrahydrocannabinol (Delta9-THC) in hemp plants. During smoking, the non-psychoactive Delta9-THCA-A is converted to Delta9-THC, the main psychoactive component of marihuana and hashish. Although the decarboxylation of Delta9-THCA-A to Delta9-THC was assumed to be complete--which means that no Delta9-THCA-A should be detectable in urine and blood serum of cannabis consumers--we found Delta9-THCA-A in the urine and blood serum samples collected from police controls of drivers suspected for driving under the influence of drugs (DUID). For LC-MS/MS analysis, urine and blood serum samples were prepared by solid-phase extraction. Analysis was performed with a phenylhexyl column using gradient elution with acetonitrile. For detection of Delta9-THCA-A, the mass spectrometer (MS) (SCIEX API 365 triple-quadrupole MS with TurboIonSpray source) was operated in the multiple reaction monitoring (MRM) mode using the following transitions: m/z357 --> 313, m/z357 --> 245 and m/z357 --> 191. Delta9-THCA-A could be detected in the urine and blood serum samples of several cannabis consumers in concentrations of up to 10.8 ng/ml in urine and 14.8 ng/ml in serum. The concentration of Delta9-THCA-A was below the Delta9-THC concentration in most serum samples, resulting in molar ratios of Delta9-THCA-A/Delta9-THC of approximately 5.0-18.6%. Only in one case, where a short elapsed time between the last intake and blood sampling is assumed, the molar ratio was 18.6% in the serum. This indicates differences in elimination kinetics, which need to be investigated in detail.

  14. Reappraisal of Blood Lead Levels and Relation to Delta-Aminolevulinic Acid Dehydratase, Zinc Protoporphyrin and Urinary ALA Level in Thai Normal Adults and Lead Exposed Workers

    Directory of Open Access Journals (Sweden)

    Watcharachai Rujirojkul

    2008-01-01

    Full Text Available All studied participants of 65 lead-exposed workers and 52 non lead-exposed persons who voluntarily participated and signed consents were interviewed about their working duration, type of work, risk behavior and personal data. Blood and urine samples were drawn for PbB, d-ALAD, ZPP and ALAU analysis respectively. The mean PbB level for workers in lead smelters, 22.4 +/- 17.9 microgram/dl (range 1.3-67.2 microgram/dl was found higher than that for the non-exposed persons (mean = 5.0 +/- 2.4 microgram/dl, range 2.0-13.2 microgram/dl. In relative to previous studies, mean PbB concentration found in the unexposed persons tended to decreased follows the reduced use of leaded gasoline in 1996 in Thailand. A highly significant negative correlation (R2 = 0.86 was observed between PbB concentration and d-ALAD activities among lead exposed persons. Statistical analysis showed that d-ALAD activities significantly decreased (p10 microgram/dl. ZPP measurement is simple and inexpensive, but less sensitive and could be used for screening only in those high lead contaminated persons (PbB>40 microgram/dl. ALAU measurement cannot be served as early biochemical indices of lead exposure both in lead exposed and non-lead exposed persons.

  15. Impact of nitrous acid chemistry on air quality modeling results over the Pearl River Delta region

    Directory of Open Access Journals (Sweden)

    R. Zhang

    2011-05-01

    Full Text Available The impact of nitrous acid chemistry on regional ozone and particulate matter in Pearl River Delta region was investigated using the Community Mutilscale Air Quality modeling system and the CB05 mechanism. Model simulations were conducted for a ten-day period in October 2004. Compared with available observed data, the model performance for NOx, SO2, PM10, and sulfate is reasonably good; however, predictions of HONO are an order of magnitude lower than observed data. The CB05 mechanism contains several homogenous reactions related to nitrous acid. To improve the model performance for nitrous acid, direct emissions, two heterogeneous reactions, and two surface photolysis reactions were incorporated into the model. The inclusion of the additional formation pathways significantly improved simulated nitrous acid compared with observed data. The addition of nitrous acid sources enhance daily maximum 8-h ozone by up to 6 ppb V (8 % and daily mean PM2.5 by up to 17 μg m−3 (12 %. They also affected ozone control strategy in Pearl River Delta region.

  16. Metal Accumulation, Blood δ-Aminolevulinic Acid Dehydratase Activity and Micronucleated Erythrocytes of Feral pigeons (Columba Livia Living Near Former Lead-Zinc Smelter “ Trepça” – Kosovo

    Directory of Open Access Journals (Sweden)

    Elezaj I. R.

    2013-04-01

    Full Text Available The concentration of lead in blood and tibia (Pb, zinc (Zn and cupper (Cu in tibia, blood δ- aminolevulinic acid dehydratase (ALA-D; EC: 4.2.1.24 activity, hematocrit value (Hct and micronuclei frequency (MN of peripheral erythrocytes have been determinated in three different populations of feral pigeons (Columba livia; forma urbana and forma domestica, collected in Mitrovica town (situated close to smelter “Trepça”, down closed in 2000 year and in rural area (Koshare willage . The blood lead level in feral pigeons from Mitrovica (forma urbana was 3 times higher (149.6; 50.5 μg% in comparison with that in feral pigeons from Mitrovica (forma domestica and 27.7 times higher (5.4 μg% in comparison with pigeons from rural area. The Pb concentration of tibia of feral pigeons (froma urbana and forma domestica, from Mitrovica town was significantly higher (P<0.001 in comparison with control. The concentration of Zn in tibia of feral pigeons from Mitrovica town (forma urbana, was significantly higher (P<0.006 in comparison with control. The blood ALA-D activity of feral pigeons from Mitrovica town (forma urbana and froma domestica, was significantly inhibited in comparison with control. The blood ALA-D activity of feral pigeons –forma urbana from Mitrovica town was significantly inhibited (P<0.001 in comparison with the blood ALA-D activity of feral pigeons-forma domestica from Mitrovica town. The erythrocyte MN frequency of feral pigeons from Mitrovica was significantly higher (P <0.001 in comparison with controls. The smelter “Trepça” ten year after closed down pose a threat to the local environment, biota and people’s health.

  17. 5-氨基酮戊酸光动力学疗法在皮肤科的应用进展%Applied advances of 5-aminolevulinic acid photodynamic therapy in dermatology

    Institute of Scientific and Technical Information of China (English)

    张立坤; 竺炯; 张萍

    2012-01-01

    To explore the mechanism and application of photodynamic therapy using aminolevulinic acid (5-ALA) in skin diseases, and provide reference for the rational use in clinic. Summarize the reported articles of mechanism and clinical application of photodynamic therapy in recent ten years, analysis the mechanism in the photodynamic therapy treatment for various skin disease, sort the types of skin disease cured by photodynamic therapy and the side effect related with photodynamic therapy. Photodynamic therapy have good clinical curative effect in skin cancer, erythema scaly skin neoplasms, psoriasis, viral warts, acne, nevus flammeus, etc. and have fewer adverse reactions. Photodynamic therapy is a safe, efficient treatment of psoriasis, and have great application prospects in skin diseases.%探讨5-氨基酮戊酸(ALA)光动力学疗法(PDT)治疗皮肤病的作用原理及应用范围,为临床合理使用ALA-PDT提供参考依据.对近10余年来文献报道的有关PDT研究进展及其临床应用的文献进行总结和分析,综述ALA-PDT治疗各类皮肤病的作用原理和机制,以及ALA-PDT治疗皮肤病的范围,所引起的不良反应.PDT对皮肤肿瘤、红斑鳞屑性皮肤病、人乳头瘤病毒(HPV)感染性皮肤病、痤疮、鲜红斑痣等均有良好的临床效果,不良反应相对较小,在皮肤科有很大的应用前景.

  18. 外源5-氨基乙酰丙酸对红香芋试管苗耐冷性的影响%Effect of Exogenous 5 -aminolevulinic Acid on Cold Tolerance of Taro Plantlets in vitro

    Institute of Scientific and Technical Information of China (English)

    何继红; 蒋芳玲; 李洁英; 吴震

    2012-01-01

    The effects of different concentrations of exogenous 5 - aminolevulinic acid ( ALA) on the cold tolerance and related physiological indexes of taro [ Colocasia esculenta ( L. ) Schott ] plantlets in vitro were studied under the low temperature stress simulated artificially. The results showed that: under short -term (16 h) low temperature stress, the 2 ~20 mg/L exogenous ALA treatment could reduce the damaged degree of taro plantlets in vitro, promote the activities of superoxide dismutase ( SOD) , peroxidase ( POD) , catalase ( CAT) and ascorbic acid peroxidase ( APX) , decrease the production speed of superoxide anion ( · O2 -) and the content of hydrogen peroxide ( H2 O2 ) , suppress the increase in malonaldehyde ( MDA) content and plasma membrane permeability, and strengthen the ability of cell osmoregulation. The above results indicated that the ALA with suitable concentration could enhance the cold tolerance of taro plantlets in vitro, and relieve the injury of low temperature stress to taro test -tube plantlets. The application of 10 mg/L ALA could obtain the best effect.%为探讨外源5 -氨基乙酰丙酸对芋试管苗耐冷性的影响,以红香芋为试材,通过人工模拟低温逆境,研究了不同浓度外源ALA处理下芋试管苗耐冷性相关生理指标的变化.结果表明:短期(16 h)低温胁迫下,添加2~20 mg/L外源ALA可减轻芋试管苗冷害程度,提高超氧化物歧化酶(SOD)、过氧化物酶(POD)、过氧化氢酶(CAT)和抗坏血酸过氧化物酶(APX)活性,降低超氧阴离子(·O2-)产生速率和过氧化氢( H2O2)含量,抑制丙二醛(MDA)含量和质膜透性的上升,同时增强细胞渗透调节能力.以上结果说明,适宜浓度的ALA处理可缓解低温胁迫对芋试管苗的伤害,提高其耐冷性;ALA处理浓度以10 mg/L效果最好.

  19. Cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid (5-ALA) in cervical intraepithelial neoplasia (CIN) II with associated human papillomavirus infection: a comparison of preliminary results.

    Science.gov (United States)

    Bodner, Klaus; Bodner-Adler, Barbara; Wierrani, Franz; Kubin, Andreas; Szölts-Szölts, Josef; Spängler, Babette; Grünberger, Werner

    2003-01-01

    The optimal treatment of preinvasive cervical lesions is still not clear as all surgical techniques cause substantial cervical stroma destruction with the risk of a possible incompetent cervix. Photodynamic therapy can preserve fertility due to selective tissue destruction. The aim of the present study was to compare the efficacy of cold-knife conization versus photodynamic therapy with topical 5-aminolevulinic acid in eradicating cervical intraepithelial neoplasia (CIN) II and associated HPV infection. Eleven HPV-positive non-pregnant women were selected for photodynamic therapy (PDT). To be eligible for this procedure superficial cervical PAP smears as well as colposcopic biopsies performed before therapy had to show CIN II with the lesion involving at least 15% of the cervix and being colposcopically visible. The deep endocervical PAP smear had to show normal endocervical epithelium. The next (following each PDT) 11 HPV-positive women with CIN II treated with cold-knife conization were used as a control group. The cervical sampling for HPV DNA was performed 3 months after conization and PDT. Patients were followed-up for 1 year with cytological smears and colposcopy at the outpatient department of the hospital. Follow-up at three months revealed that HPV was eradicated by both techniques in 73%. After 12 months follow-up, 100 vs. 91% (conization vs. PDT) of the patients were disease-free. No systemic side-effects and no local necrosis, sloughing or scarring occurred due to PDT. One patient treated with PDT presented with a relapsing suspicious PAP smear and an abnormal white colposcopic lesion after application of acetic acid 6 months post-PDT. A subsequent conization was performed and revealed a CIN I lesion. No statistically significant differences concerning HPV eradication (p > 0.05) and recurrence (p > 0.05) could be observed between the two methods. The results presented in this study indicate that topical PDT with 5-ALA is in most cases a successful

  20. SwissProt search result: AK073935 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073935 J033075P19 (P43089) 5-aminolevulinate synthase (EC 2.3.1.37) (5-aminolevul...inic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_PARDE 2e-17 ...

  1. SwissProt search result: AK100689 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100689 J023114D10 (P18079) 5-aminolevulinate synthase (EC 2.3.1.37) (5-aminolevul...inic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_RHOCA 8e-36 ...

  2. SwissProt search result: AK071526 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK071526 J023099J24 (P08080) 5-aminolevulinate synthase (EC 2.3.1.37) (5-aminolevul...inic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_RHIME 2e-40 ...

  3. Inhibitory effect of 5-aminolevulinic acid photodynamic therapy on Candida albicans%5-氨基酮戊酸光动力疗法对白念珠菌抑制效应的实验研究

    Institute of Scientific and Technical Information of China (English)

    梁义; 卢丽明; 陈勇; 尹琦

    2013-01-01

    Objective To evaluate the inhibitory effect of 5-aminolevulinic acid Photodynamic therapy on Candida albicans in vitro. Methods 96-well cell culture plates were used for experimental carriers, and Candida albicans suspension was added to these wells, which were divided into experimental group and four control groups. With He-Ne laser as the excitation source, ALA as photosensitizer, DMSO as penetration enhancer and a solvent, ALA-PDT was performed. Results The growth of Candida albicans was inhibited in experimental group, with MIC of 500 mg/ml (50%). At concentration of 200 mg/ml (20%), ALA began to inhibit the growth of Candida albicans in experimental group, and ALA inhibited the growth of Candida albicans in a concentration-dependent way. The growth of Candida albicans was not inhibited in four control groups, and the CFU of Candida albicans showed no statistically significant difference between the groups. Conclusion ALA-PDT can effectively inhibit the growth of Candida albicans.%目的 评估5-氨基酮戊酸光动力疗法(5-ALA-PDT)在体外对白念珠菌的抑制效应.方法 以96孔细胞培养板为实验载体,加入白念珠菌悬液,分为治疗组和4个对照组,以氦氖激光为激发光源,ALA为光敏剂,使用DMSO作为ALA的溶剂兼穿透增强剂,进行ALA-PDT.结果 治疗组白念珠菌的生长受到抑制,其MIC值为500mg/ml(50%),ALA浓度在200mg/ml(20%)时,开始使治疗组白念珠菌的生长受到抑制,且抑制作用对ALA的浓度呈剂量依赖关系.而对照组中白念珠菌的生长未受到抑制,四组的白念珠菌的CFU数量变化无明显差异.结论 按本实验所使用的方法进行的ALA-PDT能有效地抑制白念珠菌.

  4. Danos ao DNA promovidos por ácido 5-aminolevulínico: possível associação com o desenvolvimento de carcinoma hepatocelular em portadores de porfiria aguda intermitente DNA damage induced by 5-aminolevulinic acid: a possible association with the development of hepatocellular carcinoma in acute intermittent porphyria patients

    Directory of Open Access Journals (Sweden)

    Janice Onuki

    2002-07-01

    Full Text Available 5-Aminolevulinic acid (ALA is a heme precursor accumulated in acute intermittent porphyria (AIP, which might be associated with hepatocellular carcinoma (HCC in symptomatic patients. Under metal catalyzed oxidation, ALA and its cyclic dimerization product, 3,6-dihydropyrazine-2,5-dipropanoic acid, produce reactive oxygen species that damage plasmid and calf thymus DNA bases, increase the steady state level of 8-oxo-7,8-dihydro-2´-deoxyguanosine in liver DNA and promote mitochondrial DNA damage. The final product of ALA, 4,5-dioxovaleric acid (DOVA, is able to alkylate guanine moieties, producing adducts. ALA and DOVA are mutagenic in bacteria. This review shows an up-to-date literature data that reinforce the hypothesis that the DNA damage induced by ALA may be associated with the development of HCC in AIP patients.

  5. In vitro study of 5-aminolevulinic acid-based photodynamic therapy for apoptosis in human cervical HeLa cell line

    Science.gov (United States)

    Atif, M.; Firdous, S.; Khurshid, A.; Noreen, L.; Zaidi, S. S. Z.; Ikram, M.

    2009-12-01

    5-aminolevulanic acid (ALA), belonging among the promising second generation of sensitizers, was evaluated as an inducer of photodamage on HeLa (human cervical adenocarcinoma) cell line. A diode laser (635 nm) was used as a source for initiation of the photodynamic effect. We studied the influence of different incubation times, various concentrations of sensitizer, different irradiation doses and various combinations of sensitizer and light doses on the photodamage of HeLa cells. Viability of cells was determined by means of neutral red assay. The quantitative cellular uptake of ALA sensitizer was done by spectrophotometric measurements. No prominent cytotoxic or phototoxic effects on HeLa were observed due to sensitizer or light doses when studied independently of each other. However phototoxicity evoked by laser irradiated sensitizer was detected in HeLa cell line.

  6. Fluorescence cytology with 5-aminolevulinic acid in EUS-guided FNA as a method for differentiating between malignant and benign lesions (with video).

    Science.gov (United States)

    Ikeura, Tsukasa; Takaoka, Makoto; Uchida, Kazushige; Shimatani, Masaaki; Miyoshi, Hideaki; Kato, Kota; Ohe, Chisato; Uemura, Yoshiko; Kaibori, Masaki; Kwon, A-Hon; Okazaki, Kazuichi

    2015-01-01

    EUS-guided FNA (EUS-FNA) has been increasingly performed to obtain specimens for the pathological evaluation of patients with GI and pancreaticobiliary masses as well as lymphadenopathies of unknown origin. Photodynamic diagnosis by using 5-aminolebulinic acid (ALA) has been reported to be useful for enabling the visual differentiation between malignant and normal tissue in various cancers. To evaluate the diagnostic accuracy of fluorescence cytology with ALA in EUS-FNA. A prospective study. A single center. A total of 28 consecutive patients who underwent EUS-FNA for the pathological diagnosis of a pancreaticobiliary mass lesion or intra-abdominal lymphadenopathy of unknown origin. Patients were orally administered ALA 3 to 6 hours before EUS-FNA. The sample was obtained via EUS-FNA for fluorescence cytology and conventional cytology. A single gastroenterologist performed the fluorescence cytology by using fluorescence microscopy after the procedure, independently of the conventional cytology by pathologists. The accuracy of fluorescence cytology with ALA in the differentiation between benign and malignant lesions by comparing the results of fluorescence cytology with the final diagnosis. Of the 28 patients included in the study, 22 were considered as having malignant lesions and 6 patients as having benign lesions. Fluorescence cytology could correctly discriminate between benign and malignant lesions in all patients. Therefore, both the sensitivity and specificity of fluorescence cytology were 100% in our study. Fluorescence cytology was performed by only 1 gastroenterologist with a small number of patients. Fluorescence cytology with ALA in EUS-FNA may be an effective and simple method for differentiating between benign and malignant lesions. Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  7. Glucose and δ-Aminolevulinic Acid Stimulate the Dark Chlorophyll Synthesis of Rice Seedlings%葡萄糖和δ-氨基酮戊酸促进水稻在黑暗中合成叶绿素

    Institute of Scientific and Technical Information of China (English)

    杨棋明; 蔡慧美; 杨佳豪

    2003-01-01

    This research was to examine if rice (Oryza sativa L.), a monocotyledon of angiosperm, was able to synthesize chlorophyll (Chl) in complete darkness. Five-cm-tall etiolated seedlings of rice were used as starting materials and treated with or without various concentrations of glucose and/or δ-aminolevulinic acid (ALA) in the dark. Leaves harvested at the indicated time were determined for their contents of Chl, protoporphyrin Ⅸ (Proto), Mg-protoporphyrin Ⅸ (Mg-Proto) and protochlorophyllide (Pchlide). The mole percentage of porphyrin was calculated. The Chl content in the etiolated rice seedlings slightly increased from about 2.5 μg/g to 7.5 μg/g within 12 d in the dark, but the total Chl of dark-grown rice increased from 0.36 μg/g to 3.6 μg/g. While the mole percentages of Proto, Mg-Proto and Pchlide in the dark-grown seedlings without any treatment were about 65%, 27.5% and 7.5% at the beginning, respectively, those in the light-grown seedlings were about 42.5%, 35% and 22.5%, respectively. The mole percentage of porphyrin of etiolated seedlings resumed its normal ratio within 2 d after treatment with glucose. While the Chl content of etiolated seedlings grown in culture solution with 3% and 6% glucose increased 2.5 and 4.0 folds, respectively, those with 3% and 6% glucose and 1 mmol/L ALA increased 22 and 24 folds, respectively. It is concluded that angiosperm might be able to synthesize a small amount of Chl in complete darkness, that either glucose or ALA could stimulate dark Chl synthesis in angiosperm, and that a combination of glucose and ALA exhibited an additional effect. It is still unknown and remains to be further explored what is the mechanism of the effect of glucose and ALA on the Chl synthesis of rice in the dark.%本研究检测单子叶被子植物水稻(Oryza sativa L.)在完全黑暗中是否能合成叶绿素.以5 cm高的水稻黄化幼苗为研究材料,在黑暗中用不同浓度的葡萄糖和δ-氨基酮戊酸(δ-aminolevulinic

  8. Examining the Impact of Nitrous Acid Chemistry on Ozone and PM over the Pearl River Delta Region

    Science.gov (United States)

    The impact of nitrous acid (HONO) chemistry on regional ozone and particulate matter in Pearl River Delta region was investigated using the community multiscale air quality (CMAQ) modeling system and the CB05 mechanism. Model simulations were conducted for a ten-day period in Oct...

  9. delta 13C analyses of vegetable oil fatty acid components, determined by gas chromatography--combustion--isotope ratio mass spectrometry, after saponification or regiospecific hydrolysis.

    Science.gov (United States)

    Woodbury, S E; Evershed, R P; Rossell, J B

    1998-05-01

    The delta 13C values of the major fatty acids of several different commercially important vegetable oils were measured by gas chromatography--combustion--isotope ratio mass spectrometry. The delta 13C values obtained were found to fall into two distinct groups, representing the C3 and C4 plants classes from which the oils were derived. The delta 13C values of the oils were measured by continuous flow elemental isotope ratio mass spectrometry and were found to be similar to their fatty acids, with slight differences between individual fatty acids. Investigations were then made into the influence on the delta 13C values of fatty acids of the position occupied on the glycerol backbone. Pancreatic lipase was employed to selectively hydrolyse fatty acids from the 1- and 3-positions with the progress of the reaction being followed by high-temperature gas chromatography in order to determine the optimum incubation time. The 2-monoacylglycerols were then isolated by thin-layer chromatography and fatty acid methyl esters prepared. The delta 13C values obtained indicate that fatty acids from any position on the glycerol backbone are isotopically identical. Thus, whilst quantification of fatty acid composition at the 2-position and measurement of delta 13C values of oils and their major fatty acids are useful criteria in edible oil purity assessment, measurement of delta 13C values of fatty acids from the 2-position does not assist with oil purity assignments.

  10. 氨基酮戊酸光动力疗法对铜绿假单胞菌的杀灭作用的体外研究%Photodynamic inactivation of pseudomonas aeruginosa by 5-aminolevulinic acid in vitro

    Institute of Scientific and Technical Information of China (English)

    成琼辉; 陈年; 欧东; 刘渤; 伍津津; 雷霞

    2014-01-01

    目的:研究氨基酮戊酸(5-aminolevulinic acid,5-ALA)光动力疗法(photodynamic therapy)(ALA-PDT)对铜绿假单胞菌的杀灭作用。方法:以铜绿假单胞菌标准菌株ATCC27853为研究对象,采用ALA为光敏剂,用630nm的红光为光源,按不同的浓度剂量组合分为6组,用细菌涂板法观察细菌浓度,同时利用氯仿萃取法测定照射后48小时的绿脓毒素;结果:仅有光敏剂实验组与对照组(无ALA,无红光)细菌量相比,对铜绿假单胞菌无杀灭作用,仅有红光照射(90J/cm2×40分钟)组有轻度杀菌作用,抑制率为18.9%,而ALA与红光组合的三个ALA-PDT实验组对铜绿假单胞菌均有不同程度的杀菌作用(10nM ALA+90J/cm2红光×20分钟组的抑制率为82.0%,20nM ALA+90J/cm2红光×20分钟组的抑制率为96.4%,而20nM ALA+90J/cm2红光×40分钟组抑制率为100%),ALA-PDT对铜绿假单胞菌的杀灭作用随ALA浓度增高和红光能量增高作用加强;绿脓毒素的量在光动力治疗组也有明显下降,随剂量增加明显下降。结论:ALA-PDT对体外培养的铜绿假单胞菌ATCC27853具有明确的杀灭作用,能减少绿脓毒素分泌,且与剂量相关。%Objective To investigate the effect of 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) on pseudomonas aeruginosa planktonic cells in vitro. Medhods: Pseudomonas aeruginosa standard strain ATCC27853 was used in this study. Pseudomonas aeruginosa was divided into 6 groups according to different dose of ALA and 630nm red light. Spread plate method was used to count the bacteria. The chloroform extraction method was used to detect the exotoxin of Pseudomonas aeruginosa. Results:Compared with blank group, the experimental group with only ALA had no effect to Pseudomonas aeruginosa. But, the experimental group with only red light has mild inhibition (18.9%) to Pseudomonas aeruginosa. Pseudomonas aeruginosa was inhibited in three

  11. Terapêutica fotodinâmica com ácido delta-aminolevulínico em neoplasias queratinocíticas superficiais Photodynamic therapy with delta-aminolevulinic acid for superficial keratinocytic neoplasms

    OpenAIRE

    Renato Marchiori Bakos; Lucio Bakos; Elton Ferlin; Tania Cestari; Tobias Orlandini; Roberto Rezende; Carolina Peukert; Clarissa Berti; Emileine Di Domenico

    2003-01-01

    FUNDAMENTOS: A terapêutica fotodinâmica (TFD) é técnica de tratamento em que são aplicadas, nos tecidos, substâncias fotossensibilizantes, posteriormente ativadas com luzes de comprimentos de onda específicos, com a finalidade de produzir destruição celular, por meio da ação de produtos citotóxicos fotoativados. Tal método tem sido utilizado em diversos tipos de neoplasias cutâneas, com resultados bastante entusiasmadores. OBJETIVOS: Avaliar o efeito de uma única sessão de terapêutica fotodin...

  12. The natural diyne-furan fatty acid EV-086 is an inhibitor of fungal delta-9 fatty acid desaturation with efficacy in a model of skin dermatophytosis.

    Science.gov (United States)

    Knechtle, Philipp; Diefenbacher, Melanie; Greve, Katrine B V; Brianza, Federico; Folly, Christophe; Heider, Harald; Lone, Museer A; Long, Lisa; Meyer, Jean-Philippe; Roussel, Patrick; Ghannoum, Mahmoud A; Schneiter, Roger; Sorensen, Alexandra S

    2014-01-01

    Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need for novel antifungal targets and molecules is thus emerging. Here, we present the identification and characterization of the plant-derived diyne-furan fatty acid EV-086 as a novel antifungal compound. EV-086 has potent and broad-spectrum activity in vitro against Candida, Aspergillus, and Trichophyton spp., whereas activities against bacteria and human cell lines are very low. Chemical-genetic profiling of Saccharomyces cerevisiae deletion mutants identified lipid metabolic processes and organelle organization and biogenesis as targets of EV-086. Pathway modeling suggested that EV-086 inhibits delta-9 fatty acid desaturation, an essential process in S. cerevisiae, depending on the delta-9 fatty acid desaturase OLE1. Delta-9 unsaturated fatty acids-but not saturated fatty acids-antagonized the EV-086-mediated growth inhibition, and transcription of the OLE1 gene was strongly upregulated in the presence of EV-086. EV-086 increased the ratio of saturated to unsaturated free fatty acids and phosphatidylethanolamine fatty acyl chains, respectively. Furthermore, EV-086 was rapidly taken up into the lipid fraction of the cell and incorporated into phospholipids. Together, these findings demonstrate that EV-086 is an inhibitor of delta-9 fatty acid desaturation and that the mechanism of inhibition might involve an EV-086-phospholipid. Finally, EV-086 showed efficacy in a guinea pig skin dermatophytosis model of topical Trichophyton infection, which demonstrates that delta-9 fatty acid desaturation is a valid antifungal target, at least for dermatophytoses.

  13. Regulation of growth, fatty acid composition and delta 6 desaturase expression by dietary lipids in gilthead seabream larvae (Sparus aurata).

    Science.gov (United States)

    Izquierdo, M S; Robaina, Lidia; Juárez-Carrillo, Eduardo; Oliva, V; Hernández-Cruz, Carmen María; Afonso, Juan Manuel

    2008-06-01

    The Delta6 and Delta5 desaturases and elongases show only very limited activity in marine fish, and little is known of the possibility of enhancing Delta6 desaturase gene expression in these fish. The use of plant oils in marine fish diets is limited by their lack of n-3 highly unsaturated fatty acids (HUFA) despite an abundant content of the 18C fatty acid precursor linoleic and alpha-linolenic acids. The objective of the present study was to determine the ability of larval gilthead seabream to utilize vegetable oils and assess the nutritional regulation of Delta6 desaturase gene expression. Seventeen-day-old gilthead seabream larvae were fed during a 17-day period with one of four different microdiets formulated with either sardine fish oil (FO), soybean, rapeseed or linseed oils, respectively, or a fifth diet containing defatted squid meal and linseed oil. Good larval survival and growth, both in terms of total length and body weight, were obtained by feeding the larvae either rapeseed, soybean or linseed oils. The presence of vegetable oils in the diet increased the levels of 20:2n-9 and 20:2n-6, 18:2n-9, 18:3n-6, 20:3n-6 and 20:4n-6, in larvae fed rapeseed and soybean oils in comparison to those fed FO. In addition, a sixfold increase in the relative expression of Delta6 desaturase-like gene was found in larvae fed rapeseed and soybean oils, denoting the nutritional regulation of desaturase activity through its gene expression in this fish species. However, feeding linseed oil did not increase the expression of the Delta6 desaturase gene to such a high extent.

  14. Extensive esterification of adrenal C19-delta 5-sex steroids to long-chain fatty acids in the ZR-75-1 human breast cancer cell line

    Energy Technology Data Exchange (ETDEWEB)

    Poulin, R.; Poirier, D.; Merand, Y.; Theriault, C.; Belanger, A.; Labrie, F.

    1989-06-05

    Estrogen-sensitive human breast cancer cells (ZR-75-1) were incubated with the 3H-labeled adrenal C19-delta 5-steroids dehydroepiandrosterone (DHEA) and its fully estrogenic derivative, androst-5-ene-3 beta,17 beta-diol (delta 5-diol) for various time intervals. When fractionated by solvent partition, Sephadex LH-20 column chromatography and silica gel TLC, the labeled cell components were largely present (40-75%) in three highly nonpolar, lipoidal fractions. Mild alkaline hydrolysis of these lipoidal derivatives yielded either free 3H-labeled DHEA or delta 5-diol. The three lipoidal fractions cochromatographed with the synthetic DHEA 3 beta-esters, delta 5-diol 3 beta (or 17 beta)-monoesters and delta 5-diol 3 beta,17 beta-diesters of long-chain fatty acids. DHEA and delta 5-diol were mainly esterified to saturated and mono-unsaturated fatty acids. For delta 5-diol, the preferred site of esterification of the fatty acids is the 3 beta-position while some esterification also takes place at the 17 beta-position. Time course studies show that ZR-75-1 cells accumulate delta 5-diol mostly (greater than 95%) as fatty acid mono- and diesters while DHEA is converted to delta 5-diol essentially as the esterified form. Furthermore, while free C19-delta 5-steroids rapidly diffuse out of the cells after removal of the precursor (3H)delta 5-diol, the fatty acid ester derivatives are progressively hydrolyzed, and DHEA and delta 5-diol thus formed are then sulfurylated prior to their release into the culture medium. The latter process however is rate-limited, since new steady-state levels of free steroids and fatty acid esters are rapidly reached and maintained for extended periods of time after removal of precursor, thus maintaining minimal concentrations of intracellular steroids.

  15. Summer and winter variations of dicarboxylic acids, fatty acids and benzoic acid in PM2.5 in Pearl Delta River Region, China

    Directory of Open Access Journals (Sweden)

    K. Kawamura

    2010-11-01

    Full Text Available Ground-based PM2.5 samples collected in Pearl River Delta (PRD region during winter and summer (from 14 December 2006 to 28 January 2007 in winter and from 4 July 2007 to 9 August 2007 in summer were analyzed for 30 water-soluble organic species, including dicarboxylic acids, ketocarboxylic acids and dicarbonyls, nine fatty acids, and benzoic acid. Molecular distributions of dicarboxylic acids demonstrated that oxalic acid (C2 was the most abundant species followed by phthalic acid (Ph in PRD region. The concentrations of total dicarboxylic acids ranged from 99 to 1340 ng m−3, with an average of 438 ± 267 ng m−3 in PRD. The concentrations of total ketocarboxylic acids ranged from 0.6 to 207 ng m−3 (43 ± 48 ng m−3 on average while the concentrations of total α-dicarbonyls, including glyoxal and methylglyoxal, ranged from 0.2 to 89 ng m−3, with an average of 11 ± 18 ng m−3 in PRD. The total quantified water-soluble organic carbon (TQWOC accounted for 3.4 ± 2.2% of OC and 14.3 ± 10.3% of water-soluble OC (WSOC. Hexadecanoic acid (C16:0, octadecanoic acid (C18:0 and oleic acid (C18:1 are the three most abundant fatty acids in PRD. The distributions of fatty acids are characterized by a strong even carbon number predominance with a maximum (Cmax at hexadecanoic acid (C16:0. Ratio of C18:1 to C18:0 acts as an indicator for aerosol aging. In PRD, an average of C18:1/C18:0 ratio was 0.53 ± 0.39, suggesting an enhanced photochemical degradation of unsaturated fatty acid. Seasonal variations of the pollutant concentrations were found in the four sampling cities. Higher concentrations of TQWOC were observed in winter (544 ng m−3 than in summer (318 ng m−3. However, the abundances of TQWOC in OC mass were higher in summer (1.8–12.4%, 5.4% on average than in winter (1.1–5.7, 2.6% on average, being consistent with enhanced secondary production of dicarboxylic acids in warmer weather. Spatial variations of water-soluble dicarboxylic

  16. Effect of aminolevulinic acid hydrochloride on the acne model of rabbits' ears%盐酸氨基乙酰丙酸搽剂对实验性兔耳痤疮的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张成梅; 武传涛; 尹志圣; 李春令; 于学慧; 王立; 刘兆平

    2011-01-01

    Objective To investigate the therapeutic effect of aminolevulinic acid (ALA) linimentum on exprimental acne of New Zealand rabbits' ears. Methods Thirty-two healthy adult New Zealand rabbits were used in this experiment. Propionibacterium acnes and oleic acid were administrated to the right inner ears (2 cm× 2 cm range) of the rabbits to establish acne models. Then all the animals were randomly divided into 5 groups, ① the model control group:photodynamics therapy(PDT) was given after solvent was applied in the disease region, once per week for 3 weeks, ②the clindamycin metronidazole acne positive control group: clindamycin metronidazole was smeared in the disease region, 3 times/d for 2 weeks, ③ the retinoid positive control group: retinoid was applied in the disease region, 3 times/d for 2 weeks, ④ the ALA single treatment group: ALA was applied in the disease region, once in the first week, ⑤the ALA repeated treatment group: ALA was applied in the disease region, once per week for 3 weeks, and ⑥the normal control group. The animals in the ALA treatment groups and model control group were protected from light for 3 hours after administration, and then ALA photodynamic therapy(ALA-PDT) was given for 15 min/time. After treatment biopsy, and HE staining, microscopic and histological examination were carried out. Results Statistical resuits and biopsy showed that there was a good therapeutic effect on the rabbits' acne models caused by propionibacterium acnes / oleic acid in the ALA-PDT treatment group ( P <0.01 or P <0.05). The effect in the other two positive treatment groups was also obvious ( P < 0.05 ), and the therapeutic effect in the ALA-PDT repeated treatment group was stronger than in the ALA-PDT single treatment group and the two positive drug groups. Conclusion Repeated ALAPDT treatment has good therapeutic effect on rabbits' acne models caused by pwpionibacterium acnes/oleic acid.%目的 研究盐酸氨基乙酰丙酸(ALA)搽剂对新

  17. {delta}-ALAD activity variations in red blood cells in response to lead accumulation in rock doves (Columba livia)

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, M.; Tejedor, M.C. [Universidad de Alcala de Henares (Spain)

    1992-10-01

    The enzyme {delta}-aminolevulinic acid dehydratase ({delta}-ALAD, E.C. 4.2.1.24), catalyses the second step of the haeme biosynthetic pathway and is required to maintain the haemoglobin and cytochrome content in red cells. {delta}-ALAD is not only found in bone marrow cells, the major site of haeme synthesis, but also in circulating erythrocytes and other tissues. An inverse correlation was found between {delta}-ALAD activity in red blood cells and lead concentration in the blood. The degree of {delta}-ALAD inhibition in erythrocytes has been widely accepted as a standard bioassay to detect acute and chronic lead exposure in humans and in avians. The value of this parameter as an indicator for environmental lead has been often reported in doves and Scanlon. In lead-treated rats, an increase in {delta}-ALAD activity in bone marrow cells and in blood samples was shown by radioimmunoassay at 5 and 9 days after the treatment. Similarly, the amount of {delta}-ALAD seems to be more sensitive to lead in avian species than in mammals, the usefulness of blood {delta}-ALAD activity as an index of lead exposure has already been questioned by Hutton in the pigeon and by Jaffe et al. in humans. The present investigation studied the toxic effects of lead on rock dove red blood cell {delta}-ALAD activity in two situations: in doves treated with lead acetate in the laboratory and in doves exposed to the environment of Alcala de Henares. The final lead blood concentrations were lower in the environmental than in the laboratory doves. {delta}-ALAD activity in bone marrow cells and the relationships between lead accumulation and enzyme activity in red cells, are examined. 20 refs., 5 figs., 1 tab.

  18. Transgenic expression of delta-6 and delta-15 fatty acid desaturases enhances omega-3 polyunsaturated fatty acid accumulation in Synechocystis sp. PCC6803.

    Science.gov (United States)

    Chen, Gao; Qu, Shujie; Wang, Qiang; Bian, Fei; Peng, Zhenying; Zhang, Yan; Ge, Haitao; Yu, Jinhui; Xuan, Ning; Bi, Yuping; He, Qingfang

    2014-03-01

    Polyunsaturated fatty acids (PUFAs), which contain two or more double bonds in their backbone, are the focus of intensive global research, because of their nutritional value, medicinal applications, and potential use as biofuel. However, the ability to produce these economically important compounds is limited, because it is both expensive and technically challenging to separate omega-3 polyunsaturated fatty acids (ω-3 PUFAs) from natural oils. Although the biosynthetic pathways of some plant and microalgal ω-3 PUFAs have been deciphered, current understanding of the correlation between fatty acid desaturase content and fatty acid synthesis in Synechocystis sp. PCC6803 is incomplete. We constructed a series of homologous vectors for the endogenous and exogenous expression of Δ6 and Δ15 fatty acid desaturases under the control of the photosynthesis psbA2 promoter in transgenic Synechocystis sp. PCC6803. We generated six homologous recombinants, harboring various fatty acid desaturase genes from Synechocystis sp. PCC6803, Gibberella fujikuroi and Mortierella alpina. These lines produced up to 8.9 mg/l of α-linolenic acid (ALA) and 4.1 mg/l of stearidonic acid (SDA), which are more than six times the corresponding wild-type levels, at 20°C and 30°C. Thus, transgenic expression of Δ6 and Δ15 fatty acid desaturases enhances the accumulation of specific ω-3 PUFAs in Synechocystis sp. PCC6803. In the blue-green alga Synechocystis sp. PCC6803, overexpression of endogenous and exogenous genes encoding PUFA desaturases markedly increased accumulation of ALA and SDA and decreased accumulation of linoleic acid and γ-linolenic acid. This study lays the foundation for increasing the fatty acid content of cyanobacteria and, ultimately, for producing nutritional and medicinal products with high levels of essential ω-3 PUFAs.

  19. 5-氨基乙酰丙酸介导的光动力学治疗胃癌的实验研究%Effect of photodynamic therapy with 5-aminolevulinic acid on human gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    黄宗海; 周广军; 俞金龙; 厉周; 丁涟沭; 徐如祥; 姜晓丹

    2006-01-01

    目的探讨5-氨基乙酰丙酸(5-ALA)介导的光动力学对人胃癌细胞MGC-803的治疗作用.方法将不同浓度的5-ALA加入细胞培养基中,随之给予相同剂量的激光辐射;之后用固定浓度的5-ALA处理细胞,并给予不同剂量的激光辐射.MTT法测定细胞生存率.结果在相同的辐射剂量下,经0.25、0.5、1.0、2.0、4.0 mmol/L的5-ALA处理的细胞生存率分别为(70.07±5.37)%、(50.04±4.99)%、(34.53±5.30)%、(26.89±4.44)%和23.90%±2.80%,除2.0和4.0 mmol/L5-ALA两组间外,其余各组间具有显著性差异(F=266.39,P<0.001).在相同的5-ALA的浓度下,辐射剂量为6.25、12.5、25.0、50.0、100 J/cm2的细胞生存率分别为(83.50±10.43)%、(67.96±9.23)%、(33.80±8.26)%、(23.31±5.98)%和(14.96±3.50)%,各组之间有显著性差异(F=226.31,P<0.0001).而单用5-ALA处理细胞,对应于其浓度为0.25、0.5、1.0、2.0,和4.0 mmol/L时的细胞生存率分别为(96.46±6.72)%、(97.48±5.27)%、(98.33±6.67)%、(99.47±6.97)%和(95.66±7.72)%,各浓度之间无显著性差异(F=0.79,P=0.5383).单纯激光辐射,其剂量为6.25、12.5、25.0、50.0、100.0 J/cm2时的细胞生存率也无显著性差异(F=0.61,P=0.6551).结论在较低的浓度范围内,5-ALA介导的光动力学治疗对人胃癌MGC-803细胞的杀伤作用随着5-ALA浓度的增加而增加,在较高浓度时则存在饱和现象,杀伤力与光剂量成正比.单纯激光不能产生光动力效应,5-ALA本身对细胞无毒性作用.5-ALA介导的光动力学治疗是很有希望的胃癌治疗方法.%Objective To investigate the effect of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) on MGC-803 human gastric cancer cells in vitro. Methods MGC-803 human gastric cancer cells were treated with 5-ALA at various concentrations followed by laser irradiation. The cells were also treated with 5-ALA at the same concentration before laser exposure at various doses. PDT-induced phototoxicity of the cells was

  20. Urinary delta-ALA: a potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese.

    Science.gov (United States)

    Andrade, Vanda; Mateus, M Luísa; Batoréu, M Camila; Aschner, Michael; dos Santos, A P Marreilha

    2013-09-01

    Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture. Five groups of Wistar rats were treated for 8 days with Pb (5mg/kg), As (60mg/L), Mn (10mg/kg), the 3-metal mixture (same doses of the single metals), and control group. Motor activity was evaluated and 24-h urine collected before and after the treatment. 24-hours (h) after the last dose, the rats were sacrificed and the brains removed for analyses. Delta-ALA and metal levels were determined in brain and urine. Co-treated rats showed a significant (p<0.05) correlation between increased Pb, As, Mn and delta-ALA levels in the brain and decreased motor activity. Delta-ALA-U concentrations were higher in the mixture-treated group than the sum of the delta-ALA-U levels in each single-treated groups and discriminated (p<0.05) between the mixture and untreated rats. Moreover, delta-ALA-U was correlated (p<0.05) with brain delta-ALA levels. These results establish that treatments with this metal mixture exacerbate behavioral dysfunction, increasing most prominently brain Pb levels. This study is the first to establish that delta-ALA-U levels represent a sensitive BM of exposure/neurotoxic effect to this metal mixture.

  1. The davDT operon of Pseudomonas putida, involved in lysine catabolism, is induced in response to the pathway intermediate delta-aminovaleric acid

    DEFF Research Database (Denmark)

    Revelles, O.; Espinosa-Urgel, M.; Molin, Søren;

    2004-01-01

    -aminovaleric acid and then further degraded to glutaric acid via the action of the davDT gene products. We show that the davDT genes form an operon transcribed from a single sigma(70)-dependent promoter. The relatively high level of basal expression from the davD promoter increased about fourfold in response...... to the addition of exogenous lysine to the culture medium. However, the true inducer of this operon seems to be delta-aminovaleric acid because in a mutant unable to metabolize lysine to delta-aminovaleric acid, this compound, but not lysine, acted as an effector. Effective induction of the P. putida P...

  2. Characterization of fatty acid delta-6 desaturase gene in Nile tilapia and heterogenous expression in Saccharomyces cerevisiae.

    Science.gov (United States)

    Tanomman, Supamas; Ketudat-Cairns, Mariena; Jangprai, Araya; Boonanuntanasarn, Surintorn

    2013-10-01

    Fatty acid delta-6 desaturase (fads2)-like gene from Nile tilapia (Oreochromis niloticus) was characterized and designated as oni-fads2. The Oni-FADS2 showed the typical structure of microsomal FADS2. The presence of oni-fads2 transcripts in unfertilized eggs demonstrated the maternal role of Nile tilapia in providing the oni-fads2 transcript in their eggs. In addition, the expression of oni-fads2 was detectable in embryos throughout the hatching stage. Real-time reverse transcription-PCR revealed that oni-fads2 was expressed at a high level in all the brain regions, liver, and testis. Recombinant yeast (RY) was generated by transformation of Saccharomyces cerevisiae with the plasmid containing oni-fads2 driven by the Gal1 promoter (pYoni-fads2). The conspicuous expression of RY was detectable by RT-PCR after induction with galactose for 24h. When RY was induced with galactose, it exhibited 39% and 7% of delta-6 desaturase (∆6) activity toward C18:2n6 and C18:3n3, respectively. Additionally, it displayed 4% of delta-5 desaturase (∆5) activity toward C20:3n6, indicating that Oni-FADS2 had ∆5 and ∆6 bifunction.

  3. Human Influences on the Development of Acid Sulphate Soils in the Pearl River(the Zhujiang) Delta

    Institute of Scientific and Technical Information of China (English)

    LIN

    1996-01-01

    In the Pearl River Delta with more than 1000 years of intensive land reclamation history,the development of acid sulphate soils has been generally limited in terms of their acid potential (pyrite content)and spatial extent.This is attributed to the rapid delta progradation,partially resulted from increasing sediment yield caused by deforestation within the catchment and the empolderment in the estuarine embayment.The empolderment practice accompanied by the clearance of mangroves stopped the upward growth of the pyritic layer on the one hand and limited the vertical accretion of non-pyritic freshwater sediments over the pyritic layer on the one hand and limited the vertical accretion of non-pyritic freshwater sediments over the pyritic estuarine sediments on the other.In such a case,the pyritic layer in the area is frequently thin and of shallow occurrence.Under forced leaching-recharge conditions for the paddy rice cultivation ,the leaching of acid sulphate materials prevails over its production and this leads to a net loss in pyrite oxidation products.Land excavation for fishpond farming accelerates pyrite oxidation due to the direct exposure of the pyrtic sediments to air on the pond bunds.Severe acidification can intensity the environmental degradation of estuarine ecosystems.

  4. Clinical Effect of 5-aminolevulinic Acid Photodynamic Therapy Combined with Carbon Dioxide Laser on Condyloma Acuminatum in Senile Patients%5-氨基酮戊酸光动力联合CO2激光治疗老年尖锐湿疣临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    李灿; 兰长贵; 梅晓锋; 陈伟; 赵静

    2015-01-01

    目的:探讨5-氨基酮戊酸光动力疗法(5-aminolevulinic acid photodynamic therapy ,ALA-PDT)联合CO2激光治疗老年尖锐湿疣的临床疗效。方法选择我院就诊的60例老年尖锐湿疣患者,随机分为治疗组和对照组各30人,对照组仅采用CO2激光去除疣体;治疗组用CO2激光去除疣体,用20%ALA溶液沿疣体周围2cm外敷创面,薄膜封包3小时后用光动力治疗仪距离患处15cm照射20分钟,每周1次,连续3周。治疗结束后两组患者均随访6个月。结果治疗组完成随访27例,对照组完成随访29例。治疗组治愈率为70.37%,对照组治愈率为37.93%,两组治愈率差异具有统计学意义(P<0.05)。结论5-氨基酮戊酸光动力联合CO2激光治疗老年尖锐湿疣治愈率高,复发率低。%Objective To discuss the clinical effect of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with car-bon dioxide laser on condyloma acuminatum in senile patients. Methods 60 senile out-patients with condyloma acuminatum were select-ed and divided randomly into 2 groups:treatment group and control group, 30 in each;carbon dioxide laser was applied in removing the warts of the patients in both groups while ALA-PDT was added to patients in treatment group:external application of 20%ALA liquid was made on the lesions and the round area within 2cm and the lesions were covered with occlusive film for 3 hours, and then were irra-diated by Photodynamic Therapeutic Apparatus with a distance of 15cm from the lesions for 20 minutes, once a week, 3 times in total;follow-up lasted from 6 months in both group. Results 27 patients in treatment group received follow-up while 29 in control group;the cure rate in treatment group was 70.37%while 37.93%in control group, the difference was of statistical significance (P<0.05). Conclu-sions 5-aminolevulinic acid photodynamic therapy (ALA-PDT) combined with carbon dioxide laser is of high cure rate and low reoccur

  5. Angiopoietin-like 4 mediates PPAR delta effect on lipoprotein lipase-dependent fatty acid uptake but not on beta-oxidation in myotubes.

    Directory of Open Access Journals (Sweden)

    Marius R Robciuc

    Full Text Available Peroxisome proliferator-activated receptor (PPAR delta is an important regulator of fatty acid (FA metabolism. Angiopoietin-like 4 (Angptl4, a multifunctional protein, is one of the major targets of PPAR delta in skeletal muscle cells. Here we investigated the regulation of Angptl4 and its role in mediating PPAR delta functions using human, rat and mouse myotubes. Expression of Angptl4 was upregulated during myotubes differentiation and by oleic acid, insulin and PPAR delta agonist GW501516. Treatment with GW501516 or Angptl4 overexpression inhibited both lipoprotein lipase (LPL activity and LPL-dependent uptake of FAs whereas uptake of BSA-bound FAs was not affected by either treatment. Activation of retinoic X receptor (RXR, PPAR delta functional partner, using bexarotene upregulated Angptl4 expression and inhibited LPL activity in a PPAR delta dependent fashion. Silencing of Angptl4 blocked the effect of GW501516 and bexarotene on LPL activity. Treatment with GW501516 but not Angptl4 overexpression significantly increased palmitate oxidation. Furthermore, Angptl4 overexpression did not affect the capacity of GW501516 to increase palmitate oxidation. Basal and insulin stimulated glucose uptake, glycogen synthesis and glucose oxidation were not significantly modulated by Angptl4 overexpression. Our findings suggest that FAs-PPARdelta/RXR-Angptl4 axis controls the LPL-dependent uptake of FAs in myotubes, whereas the effect of PPAR delta activation on beta-oxidation is independent of Angptl4.

  6. Cholic acid is accumulated spontaneously, driven by membrane Delta pH, in many lactobacilli

    NARCIS (Netherlands)

    Kurdi, P; van Veen, HW; Tanaka, H; Mierau, [No Value; Konings, WN; Tannock, GW; Tomita, F; Yokota, A

    2000-01-01

    Many lactobacilli from various origins were found to apparently lack cholic acid extrusion activity. Cholic acid was accumulated spontaneously, driven by the transmembrane proton gradient. Accumulation is a newly identified kind of interaction between intestinal microbes and unconjugated bile acids

  7. One-step synthesis of delta-MnO2 nanoparticles using ascorbic acid and their scavenging properties to Pb(II), Zn(II) and methylene blue

    NARCIS (Netherlands)

    Wang, M.X.; Pang, P.; Koopal, L.K.; Qiu, G.H.; Wang, Y.; Liu, F.

    2014-01-01

    To obtain delta-MnO2 particles with a large specific surface area, MnO2 was synthesized in an ice-water bath using ascorbic acid (AA) to reduce KMnO4. At pH 3 and 5 and KMnO4/AA molar ratios of 8/1 and 10/1, nanoparticles of delta-MnO2 were produced. The specific surface areas (SSAs) of the samples

  8. Spatial distribution and partition of perfluoroalkyl acids (PFAAs) in rivers of the Pearl River Delta, southern China.

    Science.gov (United States)

    Liu, Baolin; Zhang, Hong; Xie, Liuwei; Li, Juying; Wang, Xinxuan; Zhao, Liang; Wang, Yanping; Yang, Bo

    2015-08-15

    This study investigated the occurrence of perfluoroalkyl acids (PFAAs) in surface water from 67 sampling sites along rivers of the Pearl River Delta in southern China. Sixteen PFAAs, including perfluoroalkyl carboxylic acids (PFCAs, C5-14, C16 and C18) and perfluoroalkyl sulfonic acids (PFSAs, C4, C6, C8 and C10) were determined by high performance liquid chromatography-negative electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS). Total PFAA concentrations (∑ PFAAs) in the surface water ranged from 1.53 to 33.5 ng·L(-1) with an average of 7.58 ng·L(-1). Perfluorobutane sulfonic acid (PFBS), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS) were the three most abundant PFAAs and on average accounted for 28%, 16% and 10% of ∑ PFAAs, respectively. Higher concentrations of ∑ PFAAs were found in the samples collected from Jiangmen section of Xijiang River, Dongguan section of Dongjiang River and the Pearl River flowing the cities which had very well-developed manufacturing industries. PCA model was employed to quantitatively calculate the contributions of extracted sources. Factor 1 (72.48% of the total variance) had high loading for perfluorohexanoic acid (PFHxA), perfluoropentanoic acid (PFPeA), PFBS and PFOS. For factor 2 (10.93% of the total variance), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUdA) got high loading. The sorption of PFCAs on suspended particulate matter (SPM) increased by approximately 0.1 log units for each additional CF2 moiety and that on sediment was approximately 0.8 log units lower than the SPM logKd values. In addition, the differences in the partition coefficients were influenced by the structure discrepancy of absorbents and influx of fresh river water. These data are essential for modeling the transport and environmental fate of PFAAs.

  9. Soil knowledge for farmers, farmer knowledge for soil scientists : the case of acid sulphate soils in the Mekong delta, Viet Nam

    NARCIS (Netherlands)

    Mensvoort, van M.E.F.

    1996-01-01


    Half the Mekong delta in Vietnam, i.e. around 2 million hectares, suffers soil related problems due to acid sulphate soils. These soils generate sulphuric acid due to the oxidation of pyrite after aeration. Pyrite is most easily formed in tidal swamps. Human interference through land

  10. Soil knowledge for farmers, farmer knowledge for soil scientists. The case of acid sulphate soils in the Mekong delta, Viet Nam.

    NARCIS (Netherlands)

    Mensvoort, van M.E.F.

    1996-01-01

    Half the Mekong delta in Vietnam, i.e. around 2 million hectares, suffers soil related problems due to acid sulphate soils. These soils generate sulphuric acid due to the oxidation of pyrite after aeration. Pyrite is most easily formed in tidal swamps. Human interference through land drainage is the

  11. Effective management for acidic pollution in the canal network of the Mekong Delta of Vietnam: a modeling approach.

    Science.gov (United States)

    Phong, Ngo Dang; Hoanh, Chu Thai; Tuong, To Phuc; Malano, Hector

    2014-07-01

    Acidic pollution can cause severe environmental consequences annually in coastal areas overlain with acid sulfate soils (ASS). A water quality model was used as an analytical tool for exploring the effects of water management options and other interventions on acidic pollution and salinity in Bac Lieu, a coastal province of the Mekong Delta. Fifty eight percent of the provincial area is covered by ASS, and more than three-fourths (approximately 175,000 ha) are used for brackish-water shrimp culture. Simulations of acid water propagation in the canal network indicate that the combination of opening the two main sluices along the East Sea of the study area at high tide for one day every week in May and June and widening the canals that connect these sluices to the West Sea allows for adequate saline water intake and minimizes the acidic pollution in the study area. On the other hand, canal dredging in the freshwater ASS area should be done properly as it can create severe acidic pollution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Improvement of bioinsecticides production through mutagenesis of Bacillus thuringiensis by u.v. and nitrous acid affecting metabolic pathways and/or delta-endotoxin synthesis.

    Science.gov (United States)

    Ghribi, D; Zouari, N; Jaoua, S

    2004-01-01

    The present work aimed to obtain bioinsecticide over-producing mutants through classical mutagenesis of vegetative cells of Bacillus thuringiensis (Bt) by using u.v. and nitrous acid, and to evidence the involvement of cell metabolism in delta-endotoxin synthesis. Vegetative cells of Bt were treated by nitrous acid (0.17 mg ml(-1)) or exposed to u.v. rays (emitted at a wave length of 240 nm). The isolated survivors were screened on the basis of the production of delta-endotoxins and biomass in glucose and/or in gruel-based media at two aeration conditions. Bioinsecticide over-producing mutants were obtained with high frequencies because random mutations were shown to affect cell metabolism at different pathways related to the regulation of delta-endotoxin synthesis. Classical mutagenesis of Bt cells lead to the isolation of a large variety of delta-endotoxin over-producing mutants that could be classified into six groups based on the location of the mutations, particularly in metabolism pathways and delta-endotoxin synthesis. High frequencies of delta-endotoxin over-producing mutants of Bt could be obtained through classical mutagenesis of vegetative cells. This should contribute to a significant reduction of production and utilization costs of Bt bioinsecticides.

  13. Low-dose methotrexate enhances aminolevulinate-based photodynamic therapy in skin carcinoma cells in vitro and in vivo.

    Science.gov (United States)

    Anand, Sanjay; Honari, Golara; Hasan, Tayyaba; Elson, Paul; Maytin, Edward V

    2009-05-15

    To improve treatment efficacy and tumor cell selectivity of delta-aminolevulinic acid (ALA)-based photodynamic therapy (PDT) via pretreatment of cells and tumors with methotrexate to enhance intracellular photosensitizer levels. Skin carcinoma cells, in vitro and in vivo, served as the model system. Cultured human SCC13 and HEK1 cells, normal keratinocytes, and in vivo skin tumor models were preconditioned with methotrexate for 72 h and then incubated with ALA for 4 h. Changes in protoporphyrin IX (PpIX) levels and cell survival after light exposure were assessed. Methotrexate preconditioning of monolayer cultures preferentially increased intracellular PpIX levels 2- to 4-fold in carcinoma cells versus normal keratinocytes. Photodynamic killing was synergistically enhanced by the combined therapy compared with PDT alone. Methotrexate enhancement of PpIX levels was achieved over a broad methotrexate concentration range (0.0003-1.0 mg/L; 0.6 nmol/L-2 mmol/L). PpIX enhancement correlated with changes in protein expression of key porphyrin pathway enzymes, approximately 4-fold increase in coproporphyrinogen oxidase and stable or slightly decreased expression of ferrochelatase. Differentiation markers (E-cadherin, involucrin, and filaggrin) were also selectively induced by methotrexate in carcinoma cells. In vivo relevance was established by showing that methotrexate preconditioning enhances PpIX accumulation in three models: (a) organotypic cultures of immortalized keratinocytes, (b) chemically induced skin tumors in mice; and (c) human A431 squamous cell tumors implanted subcutaneously in mice. Combination therapy using short-term exposure to low-dose methotrexate followed by ALA-PDT should be further investigated as a new combination modality to enhance efficacy and selectivity of PDT for epithelial carcinomas.

  14. PPAR{delta} is a fatty acid sensor, which enhances mitochondrial oxidation in insulin

    DEFF Research Database (Denmark)

    Ravnskjaer, Kim; Frigerio, Francesca; Boergesen, Michael;

    2010-01-01

    against adverse effects on GSIS associated with prolonged fatty acid exposure. The presented results indicate that the nuclear receptor PPARdelta is a fatty acid sensor that adapts beta-cell mitochondrial function to long-term changes in unsaturated fatty acid levels. As maintenance of mitochondrial...... is the PPAR subtype expressed at the highest level in insulinoma cells and rat pancreatic islets. Furthermore, PPARdelta displays high transcriptional activity and acts in pronounced synergy with RXR. Interestingly, unsaturated fatty acids mimic the effects of synthetic PPARdelta agonists. Using sh......RNA-mediated knockdown we demonstrate that the ability of unsaturated fatty acids to stimulate fatty acid metabolism is dependent on PPARdelta. Activation of PPARdelta increases the fatty acid oxidation potential in INS-1E beta-cells, enhances glucose-stimulated insulin secretion (GSIS) from islets, and protects GSIS...

  15. Stoichiometry of expressed alpha(4)beta(2)delta gamma-aminobutyric acid type A receptors depends on the ratio of subunit cDNA transfected.

    Science.gov (United States)

    Wagoner, Kelly R; Czajkowski, Cynthia

    2010-05-07

    The gamma-aminobutyric acid type A receptor (GABA(A)R) is the target of many depressants, including benzodiazepines, anesthetics, and alcohol. Although the highly prevalent alphabetagamma GABA(A)R subtype mediates the majority of fast synaptic inhibition in the brain, receptors containing delta subunits also play a key role, mediating tonic inhibition and the actions of endogenous neurosteroids and alcohol. However, the fundamental properties of delta-containing GABA(A)Rs, such as subunit stoichiometry, are not well established. To determine subunit stoichiometry of expressed delta-containing GABA(A)Rs, we inserted the alpha-bungarotoxin binding site tag in the alpha(4), beta(2), and delta subunit N termini. An enhanced green fluorescent protein tag was also inserted into the beta(2) subunit to shift its molecular weight, allowing us to separate subunits using SDS-PAGE. Tagged alpha(4)beta(2)delta GABA(A)Rs were expressed in HEK293T cells using various ratios of subunit cDNA, and receptor subunit stoichiometry was determined by quantitating fluorescent alpha-bungarotoxin bound to each subunit on Western blots of surface immunopurified tagged GABA(A)Rs. The results demonstrate that the subunit stoichiometry of alpha(4)beta(2)delta GABA(A)Rs is regulated by the ratio of subunit cDNAs transfected. Increasing the ratio of delta subunit cDNA transfected increased delta subunit incorporation into surface receptors with a concomitant decrease in beta(2) subunit incorporation. Because receptor subunit stoichiometry can directly influence GABA(A)R pharmacological and functional properties, considering how the transfection protocols used affect subunit stoichiometry is essential when studying heterologously expressed alpha(4)beta(2)delta GABA(A)Rs. Successful bungarotoxin binding site tagging of GABA(A)R subunits is a novel tool with which to accurately quantitate subunit stoichiometry and will be useful for monitoring GABA(A)R trafficking in live cells.

  16. Awareness and Use of Folic Acid among Women in the Lower Mississippi Delta

    Science.gov (United States)

    Robbins, James M.; Hopkins, Sarah E.; Mosley, Bridget S.; Casey, Patrick H.; Cleves, Mario A.; Hobbs, Charlotte A.

    2006-01-01

    Context: National and state efforts to increase folic acid awareness and use may not be reaching large segments of the population. Purpose: This study examines folic acid awareness and use among women of childbearing age in a representative, economically at-risk rural sample and identifies factors that influence awareness and use. Methods: A…

  17. Integrated soil and water management in acid sulphate soils. Balancing agricultural production and environmental requirements in the Mekong Delta, Viet Nam.

    NARCIS (Netherlands)

    Le Quang Minh,

    1996-01-01

    The objectives of this study in the Mekong delta, Vietnam, were: (1) to obtain a better understanding of the effects of soil physical properties and flow types on solute transport in ASS emphasing aluminum; (2) to quantify environmental hazards resulting from amelioration activities in acid sulphate

  18. Phosphate solubilization and acid phosphatase activity of Serratia sp. isolated from mangrove soil of Mahanadi river delta, Odisha, India

    Directory of Open Access Journals (Sweden)

    B.C. Behera

    2017-06-01

    Full Text Available Phosphorus is an essential element for all life forms. Phosphate solubilizing bacteria are capable of converting phosphate into a bioavailable form through solubilization and mineralization processes. Hence in the present study a phosphate solubilizing bacterium, PSB-37, was isolated from mangrove soil of the Mahanadi river delta using NBRIP-agar and NBRIP-BPB broth containing tricalcium phosphate as the phosphate source. Based on phenotypic and molecular characterization, the strain was identified as Serratia sp. The maximum phosphate solubilizing activity of the strain was determined to be 44.84 μg/ml, accompanied by a decrease in pH of the growth medium from 7.0 to 3.15. During phosphate solubilization, various organic acids, such as malic acid (237 mg/l, lactic acid (599.5 mg/l and acetic acid (5.0 mg/l were also detected in the broth culture through HPLC analysis. Acid phosphatase activity was determined by performing p-nitrophenyl phosphate assay (pNPP of the bacterial broth culture. Optimum acid phosphatase activity was observed at 48 h of incubation (76.808 U/ml, temperature of 45 °C (77.87 U/ml, an agitation rate of 100 rpm (80.40 U/ml, pH 5.0 (80.66 U/ml and with glucose as a original carbon source (80.6 U/ml and ammonium sulphate as a original nitrogen source (80.92 U/ml. Characterization of the partially purified acid phosphatase showed maximum activity at pH 5.0 (85.6 U/ml, temperature of 45 °C (97.87 U/ml and substrate concentration of 2.5 mg/ml (92.7 U/ml. Hence the present phosphate solubilizing and acid phosphatase production activity of the bacterium may have probable use for future industrial, agricultural and biotechnological application.

  19. Bile acid deoxycholate induces differential subcellular localisation of the PKC isoenzymes beta 1, epsilon and delta in colonic epithelial cells in a sodium butyrate insensitive manner.

    Science.gov (United States)

    Looby, Eileen; Long, Aideen; Kelleher, Dermot; Volkov, Yuri

    2005-05-10

    Elevated levels of bile acids have been implicated in the abnormal morphogenesis of the colonic epithelium thus contributing to colorectal cancer (CRC). Alternatively sodium butyrate (NaB) produced by anaerobic fermentation of dietary fibre is regarded as being protective against colon cancer. Bile acids such as deoxycholic acid (DCA) are thought to mediate some of their actions by differentially activating protein kinase C (PKC). We examined the effects of DCA on the subcellular localisation of PKC-beta(1), -epsilon and -delta and whether these responses could be modulated by NaB. HCT116 cells endogenously express PKC-epsilon and -delta but not PKC-beta. DCA treatment results in endogenous PKC-epsilon translocation but not PKC-delta after 1 hr. To study the subcellular localisation of PKC isoforms in response to DCA in real time, PKC-beta(1), PKC-epsilon and PKC-delta functionally intact green fluorescent protein (GFP) fusion constructs were used. Stimulation with 300 microM DCA induces rapid translocation of PKC-beta(1)-GFP and PKC-epsilon-GFP but not PKC-delta-GFP from the cytosol to the plasma membrane in 15 min. Interestingly, pretreatment with 4mM NaB does not modify the response of the PKC isoenzymes to DCA as PKC-beta(1)-GFP and PKC-epsilon-GFP translocates to the plasma membrane in 15 min whereas PKC-delta-GFP localisation remains unaltered. Immunofluorescence shows that PKC-beta(1)-GFP and PKC-epsilon-GFP cells treated with DCA colocalise with the cytoskeletal elements actin and tubulin adjacent to the plasma membrane. Our findings demonstrate that the differential activation of the PKC isoenzymes by DCA may be of critical importance for the functional responses of colonic epithelial cells. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.

  20. [Distribution Characteristics and Risk Assessment of Phthalic Acid Esters in Agricultural Products Around the Pearl River Delta. South China].

    Science.gov (United States)

    Li, Bin; Wu, Shan; Liang, Jin-ming; Deng, Jie-fan; Wang, Ke; Liang, Wen-li; Zeng, Cai-ming; Peng, Si-qing; Zhang, Tian-bin; Yang, Guo-yi

    2016-01-15

    In order to investigate and assess the distribution of pathalic acid easters (PAEs) in agricultural products from typical areas of the Pearl River Delta, South China, 131 agricultural products were sampled for determination of 6 PAEs priority pollutants classified by the U. S. EPA by GC-FID. The results showed that the total contents of the PAEs (sigma PAEs) in agricultural products samples ranged from nd to 79.86 mg x kg(-1) and the mean value was 2.84 mg x kg(-1), with the detected ratio of 98.5%. The average concentrations of sigma PAEs in different types of agricultural products were ordered by vegetables (3.03 mg x kg(-1)) > rice (2.52 mg x kg(-1)) > fruits (1.26 mg x kg(-1)). The mean concentration of PAEs distributed in the four typical cities of the Pearl River Delta, and decreased in the sequence of Zhuhai (6.53 mg x kg(-1)) > Dongguan (2.59 mg x kg(-1)) > Huizhou (1.53 mg x kg(-1)) > Zhongshan (1.12 mg x kg(-1)). Di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP) and di-n-octyl phthalate (DnOP) contributed more than 90. 8% of the total PAEs in samples, and were the main components of PAEs in agricultural products from the Pearl River Delta, with higher percentage contents and detected ratio. Meanwhile, the average concentrations of sigma PAEs in cabbage mustard, lettuce occurred in Zhuhai and Dongguan cities, followed by lettuce and leaf lettuce in the corresponding DEHP from Zhuhai city, both exceeded the suggested standards in U.S.A. and Europe and were of high health risk. There were significant differences among 14 various vegetables in the contents of the 6 PAEs compounds, and the sigma PAEs contents in cabbage mustard and lettuce as part of leafy vegetables were higher than those in other vegetables, while the lowest were detected in flowering cabbage and edible amaranth. Therefore, the type of vegetables and its growing environment exposed to the atmosphere and soil were the main factors that significantly affected their accumulation of

  1. High-performance liquid chromatographic determination of delta9-tetrahydrocannabinol and the corresponding acid in hemp containing foods with special regard to the fluorescence properties of delta9-tetrahydrocannabinol.

    Science.gov (United States)

    Zoller, O; Rhyn, P; Zimmerli, B

    2000-03-03

    A solvent programmed reversed-phase HPLC method with UV detection for the determination of delta9-tetrahydrocannabinol (THC) and delta9-tetrahydrocannabinolic acid A (THCA-A) in foods containing parts of hemp such as edible oil, herb-teas (infusion), herbal hemp or hempseed is presented. The THC peak is also detected by fluorescence. The detection limits with UV detection are 0.01 ng for THC and 0.05 ng for THCA-A and with fluorescence detection 0.1 ng for THC. The relative standard deviation under repeatability conditions of the chromatographic procedure is about 0.5% and that of the over-all analytical procedure for THC in vegetable oils 2% (concentration range of 10-100 mg/kg).

  2. 5-氨基酮戊酸光动力疗法治疗中、重度痤疮的疗效观察%The Study of Clinical Efficacy on 5-Aminolevulinic acid-photodynamic Therapy in Treatment of Moderate and Severe Acne

    Institute of Scientific and Technical Information of China (English)

    黄咏梅

    2013-01-01

    目的 观察5%5-氨基酮戊酸光动力疗法治疗中、重度痤疮的临床疗效和安全性.方法 将60例中、重度痤疮患者随机分为治疗组和对照组.治疗组根据患者皮损面积配制易透皮吸收的5%5-氨基酮戊酸凝胶外敷于皮损处,避光1h后,戴护目镜,红光照射20min,每周治疗1次,共4次.对照组仅采用红光照射,隔日治疗1次,共14次.每次治疗前进行疗效观察及不良反应记录,两组患者均在治疗4周后,进行疗效判定,随访6个月.结果 治疗组5%5-氨基酮戊酸光动力疗法(ALA-PDT)治疗4次后有效率为93.33%,对照组为73.33%,两组差异有统计学意义(P<0.05).结论 5%5-氨基酮戊酸光动力疗法治疗中重度痤疮安全、有效,疗效优于单用红光.%Objective To evaluate the efficacy and safety of 5-aminolevulinic acid-photodynamic(ALA-PDT)on patients with moderate and severe acne.Methods Sixty patients were randomly divided into treatment group and control group.5%5-aminolevulinic acid-mediated photodynamic gel,which was prepared to be easily absorbed according to the extent of skin lesions,was external application to the patients in treatment group.After 1 hour away from light,those patients received a treatment for 20 minutes' red laser irradiation wearing goggles once a week,which lasted 4 weeks in all.In control group,only a treatment of red laser irradiation on every other day was applied,which were a total of 14 times treatment.The efficacy was evaluated 4weeks later.All patients were observed and recorded the therapeutic and side effects before every treatment,and were followed up for 6 months.Results The total effective rate of two groups was 93.33%and 73.33%respectively after 4-week treatment.There were obvious statistics differences of efficacy between ALA-PDT and red laser only(P<0.05).Conclusion ALA-PDT which is effective and safe in treatment of moderate and severe acne surpassed the red laser irradiation only.

  3. 5-aminolevulinic acid-mediated photodynamic therapy combined with CO2 laser therapy in treatment of condyloma acuminatum%5-氨基酮戊酸光动力疗法联合二氧化碳激光治疗尖锐湿疣的疗效观察

    Institute of Scientific and Technical Information of China (English)

    顾俊瑛; 史玉玲; 李秀丽; 李晓建; 刘至昱; 高飞

    2011-01-01

    目的 比较5-氨基酮戊酸光动力疗法(5-aminolevulinic acid-mediated photodynamic therapy,ALA-PDT)和二氧化碳( CO2)激光治疗尖锐湿疣(CA)的临床疗效.方法 将同济大学附属第十人民医院皮肤科2010年4月至2010年12月就治的111例尖锐湿疣患者分为3组,第一组为特殊部位(尿道口、系带或宫颈部位)的疣体患者,共17例,单用ALA-PDT治疗;余94例患者随机分为两组,每组47例,分别采用ALA-PDT联合CO2激光治疗和单一CO2激光治疗.ALA-PDT每周治疗1次,3次为1个疗程.CO2激光治疗根据疣体大小一次或分次清除疣体.3组患者治疗结束后每1、2、3个月分别电话随访一次.结果 单用ALA-PDT组一个疗程结束后的清除率为93.4%(16/17),3个月后总复发率为11.8%(2/17).联合治疗组和CO2激光单一治疗组3个月后的总复发率分别为14.9%(7/47)和55.3%(26/47),差异有统计学意义(x2=16.857,P<0.001).结论 ALA-PDT联合CO2激光治疗CA疗效确切,复发率低;ALA-PDT可有效治疗特殊部位的疣体,临床适用范围广.%Objective To evaluate the efficacy of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) combined with CO2 laser therapy in treatment of condyloma acuminatum. Methods One hundred and eleven patients with condyloma acuminatum admitted from April to December 2010 were enrolled in the study. Seventeen cases whose condylomas are at urethral orifice, vinculum or cervix uteri were treated with ALA-PDT alone. Other 94 cases were randomly assigned into two groups with 47 in each, who were treated by ALA-PDT combined with CO2 laser therapy or CO2 laser alone, respectively. Results The clearance rate was 93. 4% (16/17) and the relapse rate was 11.8% (2/17) in patients treated with ALA-PDT alone. The relapse rates of ALA-PDT combined with CO2 laser and CO2 laser alone were 14. 9% (7/47 ) and 55. 3% (26/47 ) , respectively (x2 = 16. 857, P < 0. 001). Conclusion ALA-PDT is effective in treatment of condyloma

  4. EFFECT OF ACIDITY ON DELTA 7 STIGMASTENOL CONTENT OF PALESTINIAN OLIVE OIL

    Directory of Open Access Journals (Sweden)

    Jihad M. Quasem

    2012-01-01

    Full Text Available Olive oil quality is a term influenced by many factors. Δ7 Stigmastenol is a new criteria used to determine olive oil quality especially its purity from adulteration with other types of seeds oil. Δ7 Stigmastenol-acidity correlation were investigated through studying the effect of the literature’s highlighted factors, namely; Olive fly infection, the land topographic and the preservation of olive before pressing. In this study,13 olive samples were collected and analyzed from different areas in Palestine to study the factors that affect Δ7 Stigmastenol in Olive Oil. This study starts on October 2007 and ends on July 2008. The results obtained were very interesting and varied between having positive Δ7 Stigmastenol-acidity correlation as in case of infection mode factors and preservation of olive fruit before pressing negative Δ7 Stigmastenol-acidity correlation for other factors as found to the land topographic factors. Further studies are needed to investigate the correlation between acidity and other factors.

  5. Effect of 5-aminolevulinic acid-mediated photodynamic therapy on human gastric cancer xenografts in nude mice in vivo%5-氨基乙酰丙酸介导的光动力学对裸鼠人胃癌移植瘤的治疗作用

    Institute of Scientific and Technical Information of China (English)

    周广军; 黄宗海; 俞金龙; 厉周; 丁涟沭

    2008-01-01

    Objective To investigate the effect of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) on human gastric cancer xenografts in vivo and to explore its potential tumoreidal mechanism. Methods Cultured MGC-803 human gastric cancer cells were injected below the skins of the nude mice to develop the tumor model. The tumor-bearing nude mice were examined under the Leica LT-9MACIMSYSPULS to detect the fluorescence. The tumor volume of day 1, 3, 7, 14, 21 after treatment were measured, and its histological changes were also studied. The tissues of the tumors in nude mice of the control group, light group, 5-ALA group and PDT group were examined with the electron microscope and apoptosis was detected by TUNEL assay. Results The tumor model was successfully developed. The tumor in the nude mice emited the red fluorescence under the Leica LT-9MACIMSYSPULS. The tumor volumes were (0.189±0.010)cm3, (0.183±0.011)cm3, (0.185±0.019) cm3, (0.182±0.015)cm3 for the control group, light group, 5-ALA group, PDT group, respectively at day 1 after treatment, while at day 3, (0.294±0.010)cm3, (0.280±0.013)cm3, (0.278±0.016)cm3, (0.183±0.014)cm3;at day 7, (0.409±0.016)cm3, (0.411±0.009)cm3, (0.407±0.015)cm3, (0.221±0.008)cm3;at day 14, (0.970±0.055)cm3 (0.976±0.054)cm3, (0.981±0.032)cm3, (0.318±0.005)cm3;at day 21, (1.495±0.059)cm3, (1.513±0.057)cm3, ( 1.524±0.063)cm3, (0.446±0.042)cm3(F=1003.086, P=0.000). The histology demonstrated that most tumor blood vessels were congested and necrosis developed after PDT while not in the control group, light group and 5-ALA group. Necrosis and apoptosis were observed in the cells of the tumors of the PDT group examined by TUNEL and electron microscope while not in the cells of the tumors of the other groups. Conclusions 5-aminolevulinic acid-mediated photodynamic therapy (PDT) can induce injury to human gastric cancer xenografts and inhibit the tumor growth while light only and 5-ALA only can not. 5-aminolevulinic

  6. Hemp oil ingestion causes positive urine tests for delta 9-tetrahydrocannabinol carboxylic acid.

    Science.gov (United States)

    Costantino, A; Schwartz, R H; Kaplan, P

    1997-10-01

    A hemp oil product (Hemp Liquid Gold) was purchased from a specialty food store. Fifteen milliliters was consumed by seven adult volunteers. Urine samples were taken from the subjects before ingestion and at 8, 24, and 48 h after the dose was taken. All specimens were screened by enzyme immunoassay with SYVA EMIT II THC 20, THC 50, and THC 100 kits. The tetrahydrocannabinol carboxylic acid (THCA) concentration was determined on all samples by gas chromatography-mass spectrometry (GC-MS) (5). A total of 18 postingestion samples were submitted. Fourteen of the samples screened above the 20-ng cutoff, seven were above the 50-ng cutoff, and two screened greater than the 100-ng cutoff. All of the postingestion samples showed the presence of THCA by GC-MS.

  7. Efficacies of cryotherapy plus 5-aminolevulinic acid-photodynamic therapy in patients with condyloma acuminatum and nursing experiences%冷冻联合5-氨基酮戊酸光动力治疗尖锐湿疣的临床疗效观察和护理体会

    Institute of Scientific and Technical Information of China (English)

    段颖; 黄英

    2015-01-01

    用冷冻联合5-氨基酮戊酸光动力(ALA-PDT)和单独光动力两种方法治疗65例尖锐湿疣患者.冷冻时动作轻柔,深度适中,光动力治疗时敷药、照光护理细致、全面,出现不良反应者给予康复新液湿敷和抗生素软膏.联合组先冷冻2次,再经ALA-PDT治疗1~3次,单独治疗组经ALA-PDT治疗1~4次,所有患者均给予1次ALA-PDT巩固治疗.联合组治愈率83% (29/35),复发率17%(6/35);光动力组治愈率70%(21/30),复发率30%(9/30).冷冻联合光动力疗法是一种实用、疗效更好、复发率更低的治疗方法,治疗时全面、细致、舒适的护理能保证临床疗效,减少复发和治疗的不适感.%A total of 65 patients of condyloma acuminatum (CA) received cryotherapy plus 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) or ALA-PDT alone.During cryotherapy,handling was gentle with a moderate depth.The nursing of PDT was both meticulous and comprehensive.Patients with adverse reactions received Kangfuxin liquid for wet packing and topical antibiotic ointment.The combination group received cryotherapy for 2 sessions and then PDT for 1-3 sessions while PDT was administered for 1-4 sessions in single PDT group.Then all patients received PDT once for consolidation therapy.For groups 1 and 2,the effective rates were 83% and 70% and the recurrent rates 17% and 30% respectively.Cryotherapy plus ALA-PDT is feasible for CA and it offers better efficacies and lower recurrent rates.And comprehensive,meticulous and comfortable nursing may achieve clinical efficacies,reduce the recurrent rate and minimize discomforts during treatment.

  8. Direct influence of C-terminally substituted amino acids in the Dmt-Tic pharmacophore on delta-opioid receptor selectivity and antagonism.

    Science.gov (United States)

    Balboni, Gianfranco; Salvadori, Severo; Guerrini, Remo; Negri, Lucia; Giannini, Elisa; Bryant, Sharon D; Jinsmaa, Yunden; Lazarus, Lawrence H

    2004-07-29

    A series of 17 analogues were developed on the basis of the general formula H-Dmt-Tic-NH-CH(R)-R' (denotes chirality; R = charged, neutral, or aromatic functional group; R' = -OH or -NH(2)). These compounds were designed to test the following hypothesis: the physicochemical properties of third-residue substitutions C-terminal to Tic in the Dmt-Tic pharmacophore modify delta-opioid receptor selectivity and delta-opioid receptor antagonism through enhanced interactions with the mu-opioid receptor. The data substantiate the following conclusions: (i) all compounds had high receptor affinity [K(i)(delta) = 0.034-1.1 nM], while that for the mu-opioid receptor fluctuated by orders of magnitude [K(i)(mu) = 15.1-3966 nM]; (ii) delta-opioid receptor selectivity [K(i)(mu)/K(i)(delta)] declined 1000-fold from 22,600 to 21; (iii) a C-terminal carboxyl group enhanced selectivity but only as a consequence of the specific residue; (iv) amidated, positive charged residues [Lys-NH(2) (6), Arg-NH(2) (7)], and a negatively charged aromatic residue [Trp-OH (11)] enhanced mu-opioid affinity [K(i)(mu) = 17.0, 15.1, and 15.7 nM, respectively], while Gly-NH(2) (8), Ser-NH(2) (10), and His-OH (12) were nearly one-tenth as active; and (v) D-isomers exhibited mixed effects on mu-opioid receptor affinity (2' 1 microM) except H-Dmt-Tic-Glu-NH(2) (3), which was a partial delta-opioid receptor agonist (IC(50) = 2.5 nM). Thus, these C-terminally extended analogues indicated that an amino acid residue containing a single charge, amino or guanidino functionality, or aromatic group substantially altered the delta-opioid receptor activity profile (selectivity and antagonism) of the Dmt-Tic pharmacophore, which suggests that the C-terminal constituent plays a major role in determining opioid receptor activity as an "address domain".

  9. PM2.5 acidity at a background site in the Pearl River Delta region in fall-winter of 2007-2012.

    Science.gov (United States)

    Fu, Xiaoxin; Guo, Hai; Wang, Xinming; Ding, Xiang; He, Quanfu; Liu, Tengyu; Zhang, Zhou

    2015-04-09

    Based on field observations and thermodynamic model simulation, the annual trend of PM2.5 acidity and its characteristics on non-hazy and hazy days in fall-winter of 2007-2012 in the Pearl River Delta region were investigated. Total acidity ([H(+)](total)) and in-situ acidity ([H(+)](in-situ)) of PM2.5 significantly decreased (F-test, p 0.6), NH4NO3 was most likely formed via homogenous reaction. When the acidity was high (R ≤ 0.6), the gas-phase formation of NH4NO3 was inhibited, and the proportion of NO3(-) produced via heterogeneous reaction of N2O5 became significant.

  10. The analysis of delta9-tetrahydrocannabinol and metabolite in whole blood and 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid in urine using disposable pipette extraction with confirmation and quantification by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Schroeder, Jennifer L; Marinetti, Laureen J; Smith, Roy K; Brewer, William E; Clelland, Brandi L; Morgan, Stephen L

    2008-10-01

    Essential to forensic laboratories is the desire to find a more sensitive, rapid method of analyzing Delta9-tetrahydrocannabinol (THC) and metabolite in biological specimens. Disposable pipette extraction (DPX) is a valuable method in extracting THC and 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid (THCc) in blood and THCc in urine. Less waste and solvent usage; smaller specimen volume; clean chromatograms; and utilization of lowcost equipment and consumables were achieved using this method. Differing from traditional solid-phase extraction devices, DPX uses loosely packed sorbent allowing thorough mixing with the specimen without requiring vacuum for elution. Prior to extraction, urine specimens were hydrolyzed and proteins precipitated from blood. Specimen volume requirements were 1 mL of blood and 0.2 mL of urine. The limits of quantitation for THC and THCc in blood were 1 and 2 ng/mL, respectively, and 3 ng/mL for THCc in urine. With R2 values > or = 0.99, blood calibration curves were linear from 1 to 200 ng/mL and 2 to 500 ng/mL for THC and THCc, respectively, with urine THCc linear from 3 to 2000 ng/mL.

  11. Advances in the treatment of skin diseases with δ-aminolevulinic acid-based photodynamic therapy%δ-氨基酮戊酸光动力学疗法治疗皮肤病的研究进展

    Institute of Scientific and Technical Information of China (English)

    夏育民; 徐世正

    2008-01-01

    δ-氨基酮戊酸光动力学疗法是一种非创伤性局部治疗技术,可特异性杀死病变细胞.近年研究表明,该疗法对靶细胞某些生物学特征的影响是重要作用机制之一.除非色素细胞性皮肤恶性肿瘤外,δ-氨基酮戊酸光动力学疗法的适应症逐渐扩展至癌前病变、病毒疣、痤疮、结缔组织病、光化性疾病等范围.升高温度、促溶剂、金属离子螫合物、电离子导入、脂质体载体等因素可促进其疗效.%δ-aminolevulinic acid(ALA)-based photodynamic therapy(PDT)is a noninvasive topical treatment choice that can selectively kill target cells.One important mechanism for its therapeutic effect is to intluence some biological characteristics of target cells.Besides nonpigment cell malignant tumors of skin,ALA-PDT could be used in the treatment of premalignant lesions,viral warts,acne,connective tissue diseases,actinic skin diseases,and SO on.Appropriate higher temperature,cosolvents,metal chelating agents.iontoplaoretic delivery and liposome vector may enhance the therapeutic efrect of ALA-PDT.

  12. Early Performance of Duong Mandarin (Citrus reticulata Blanco on Three Rootstock under Acid Sulfate Soil Fields at Mekong Delta of Vietnam

    Directory of Open Access Journals (Sweden)

    Khoe Thi Le

    2016-01-01

    Full Text Available Abstract About 1.6 billion hectare area of acid sulfate soils is at Mekong Delta of Vietnam, and Duong mandarin fruits are valued for the fresh market due to the easy peeling, attractive flavor, and health and nutritional properties; thereby, the investigation on early performance of Duong mandarin on three rootstock under acid sulfate soil fields (pH below 4 at Mekong Delta of Vietnam was undertaken from 2009 to 2012 for determination of the most promising scion stock combination of Duong mandarin, which introduced to growers for expanding citrus production to increase in income of farmers, and helping to use the sustainable and efficient land resource at acid sulfate soil region of Mekong Delta. Primary results showed that Duong mandarin grafted on Mat orange, Tau lemon and Carrizo citrange were significant differenence in vegetative parameters, fruit yield and quality. It proved that Duong mandarin trees grafted on Tau lemon were better growth and development on acid sulfate soil fields with below 4 pH in soil and water suspension of 1:2.5 ratio as compared to those grafted on Mat orange and Carrizo citrange rootstocks; whereby, that induced trees with 171.48 cm height, 6.65 m3 canopy volume and 51.84 mm trunk diameter, 1.08 scion/ stock ratio in third year after growing. Moreover, Duong mandarin trees grafted on Tau lemon were with spreading growth performance. In regarding to fruit yield and quality, Duong mandarin trees grafted on Tau lemon produced highest fruit yield of 9.21 kg per tree per year in third year after planting, and fruit with 115.30g weight, 8.85 brix juice, thinner and somewhat easy peel rind. 

  13. Effect of sodium fluoride on adrenal gland of rabbit. I. Studies on ascorbic acid and delta 5-3beta hydroxysteroid dehydrogenase activity

    Energy Technology Data Exchange (ETDEWEB)

    Rao, K.; Susheela, A.K.

    1979-04-01

    Rabbits were given 50 mg sodium fluoride/kg body weight through the intragastric route every 24 hours for a total period of 200 days. The left adrenal gland was removed and its total weight recorded. Adrenal glands from rabbits sacrificed at varying intervals for other investigative purposes were also collected and their weights recorded. The data indicate a significant rise in the total weight of the gland. Both ascorbic acid and steroid dehydrogenase (Delta 5-3Beta hydroxysteroid dehydrogenase) were localized in the adrenal gland by histochemical methods. The results indicate that, in rabbits exposed to NaF, a reduction in ascorbic acid content as well as a depletion of steroid dehydrogenase activity occurs especially at the zona glomerulosa. The significance of the increase in weight of the gland to the reduction of the ascorbic acid content and steroid dehydrogenase activity is discussed. 15 references, 4 figures.

  14. The yin and yang of 15-lipoxygenase-1 and delta-desaturases: Dietary omega-6 linoleic acid metabolic pathway in prostate

    Directory of Open Access Journals (Sweden)

    Kelavkar Uddhav

    2006-03-01

    Full Text Available Abstract One of the major components in high-fat diets (Western diet is the omega (ω, n-6 polyunsaturated fatty acid (PUFA called linoleic acid (LA. Linoleic acid is the precursor for arachidonic acid (AA. These fatty acids are metabolized to an array of eicosanoids and prostaglandins depending upon the enzymes in the pathway. Aberrant expression of the catabolic enzymes such as cyclooxygenases (COX-1 and/or -2 or lipoxygenases (5-LO, 12-LO, 15-LO-1, and 15-LO-2 that convert PUFA either AA and/or LA to bioactive lipid metabolites appear to significantly contribute to the development of PCa. However, PUFA and its cellular interactions in PCa are poorly understood. We therefore examined the mRNA levels of key enzymes involved in the LA and AA pathways in 18 human donor (normal prostates compared to 60 prostate tumors using the Affymetrix U95Av2 chips. This comparative (normal donor versus prostate cancer study showed that: 1 the level of 15-LO-1 expression (the key enzyme in the LA pathway is low (P P P = 0.001, elongase (P = 0.16 and 15-lipoxygenase-2 (15-LO-2, P = 0.74 are higher in donor (normal prostates, and 2 Contrary to the observation in the normal tissues, significantly high levels of only 15-LO-1; whereas low levels of delta-6 desaturase, elongase, delta-5 desaturase and 15-LO-2 respectively, were observed in PCa tissues. Although the cyclooxygenase (COX-1 and COX-2 mRNA levels were high in PCa, no significant differences were observed when compared in donor tissues. Our study underscores the importance of promising dietary intervention agents such as the omega-3 fatty acids as substrate competitors of LA/AA, aimed primarily at high 15-LO-1 and COX-2 as the molecular targets in PCa initiation and/or progression.

  15. How closely do the delta(13)C values of Crassulacean Acid metabolism plants reflect the proportion of CO(2) fixed during day and night?

    Science.gov (United States)

    Winter, Klaus; Holtum, Joseph A M

    2002-08-01

    The extent to which Crassulacean acid metabolism (CAM) plant delta(13)C values provide an index of the proportions of CO(2) fixed during daytime and nighttime was assessed. Shoots of seven CAM species (Aloe vera, Hylocereus monocanthus, Kalanchoe beharensis, Kalanchoe daigremontiana, Kalanchoe pinnata, Vanilla pauciflora, and Xerosicyos danguyi) and two C(3) species (teak [Tectona grandis] and Clusia sp.) were grown in a cuvette, and net CO(2) exchange was monitored for up to 51 d. In species exhibiting net dark CO(2) fixation, between 14% and 73.3% of the carbon gain occurred in the dark. delta(13)C values of tissues formed inside the cuvette ranged between -28.7 per thousand and -11.6 per thousand, and correlated linearly with the percentages of carbon gained in the light and in the dark. The delta(13)C values for new biomass obtained solely during the dark and light were estimated as -8.7 per thousand and -26.9 per thousand, respectively. For each 10% contribution of dark CO(2) fixation integrated over the entire experiment, the delta(13)C content of the tissue was, thus, approximately 1.8 per thousand less negative. Extrapolation of the observations to plants previously surveyed under natural conditions suggests that the most commonly expressed version of CAM in the field, "the typical CAM plant," involves plants that gain about 71% to 77% of their carbon by dark fixation, and that the isotopic signals of plants that obtain one-third or less of their carbon in the dark may be confused with C(3) plants when identified on the basis of carbon isotope content alone.

  16. Allergic contact dermatitis to methyl aminolevulinate after photodynamic therapy in 9 patients.

    Science.gov (United States)

    Hohwy, Thomas; Andersen, Klaus Ejner; Sølvsten, Henrik; Sommerlund, Mette

    2007-11-01

    This report describes 9 patients who developed allergic contact dermatitis to methyl aminolevulinate used for photodynamic therapy (PDT). The risk of developing contact allergy to methyl aminolevulinate in PDT treated patients was calculated to 1% after an average of 7 treatments (range 2-21).

  17. Allergic contact dermatitis to methyl aminolevulinate after photodynamic therapy in 9 patients

    DEFF Research Database (Denmark)

    Hohwy, Thomas; Andersen, Klaus Ejner; Sølvsten, Henrik;

    2007-01-01

    This report describes 9 patients who developed allergic contact dermatitis to methyl aminolevulinate used for photodynamic therapy (PDT). The risk of developing contact allergy to methyl aminolevulinate in PDT treated patients was calculated to 1% after an average of 7 treatments (range 2...

  18. Observational $\\Delta\

    CERN Document Server

    Hernández, Antonio García; Monteiro, Mário J P F G; Suárez, Juan Carlos; Reese, Daniel R; Pascual-Granado, Javier; Garrido, Rafael

    2015-01-01

    Delta Scuti ($\\delta$ Sct) stars are intermediate-mass pulsators, whose intrinsic oscillations have been studied for decades. However, modelling their pulsations remains a real theoretical challenge, thereby even hampering the precise determination of global stellar parameters. In this work, we used space photometry observations of eclipsing binaries with a $\\delta$ Sct component to obtain reliable physical parameters and oscillation frequencies. Using that information, we derived an observational scaling relation between the stellar mean density and a frequency pattern in the oscillation spectrum. This pattern is analogous to the solar-like large separation but in the low order regime. We also show that this relation is independent of the rotation rate. These findings open the possibility of accurately characterizing this type of pulsator and validate the frequency pattern as a new observable for $\\delta$ Sct stars.

  19. 5-Aminolevulinic acid fluorescence-guided surgery for spinal meningioma.

    Science.gov (United States)

    Muroi, Carl; Fandino, Javier; Coluccia, Daniel; Berkmann, Sven; Fathi, Ali-Reza; Landolt, Hans

    2013-01-01

    Fluorescence-guided surgery for cranial meningioma has been reported to be useful. There are no reports about spinal cases using this technique. We report on a meningioma of the cervical spine for which fluorescence-guided surgery was used. A 78-year-old female patient with a meningioma located in the cervical spine underwent surgery using fluorescence guidance. After complete removal of the meningioma and removal and coagulation of the dural attachment (equal to Simpson grade II resection), a fluorescence-positive remnant could be identified and successfully removed. The remnant was found to harbor meningioma tissue on histological examination. Fluorescence-guided microsurgery is helpful in achieving a total resection of spinal meningiomas, and might therefore reduce the risk of recurrence. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy.

    Science.gov (United States)

    Ishizuka, Masahiro; Abe, Fuminori; Sano, Yuki; Takahashi, Kiwamu; Inoue, Katsushi; Nakajima, Motowo; Kohda, Takeo; Komatsu, Naoki; Ogura, Shun-ichiro; Tanaka, Tohru

    2011-03-01

    Early detection and intervention are needed for optimal outcomes in cancer therapy. Improvements in diagnostic technology, including endoscopy, photodynamic diagnosis (PDD), and photodynamic therapy (PDT), have allowed substantial progress in the treatment of cancer. 5-Aminolevulinic acid (ALA) is a natural, delta amino acid biosynthesized by animal and plant mitochondria. ALA is a precursor of porphyrin, heme, and bile pigments, and it is metabolized into protoporphyrin IX (PpIX) in the course of heme synthesis. PpIX preferentially accumulates in tumor cells resulting in a red fluorescence following irradiation with violet light and the formation of singlet oxygen. This reaction, utilized to diagnose and treat cancer, is termed ALA-induced PDD and PDT. In this review, the biological significance of heme metabolites, the mechanism of PpIX accumulation in tumor cells, and the therapeutic potential of ALA-induced PDT alone and combined with hyperthermia and immunotherapy are discussed.

  1. Effects of exogenous 5-aminolevulinic acid on chlorophyll fluorescence characteristics and energy dissipation of Sarcandra glabra under drought stress%外源5-氨基乙酰丙酸对干旱胁迫下草珊瑚叶绿素荧光特性及能量分配的影响

    Institute of Scientific and Technical Information of China (English)

    张春平; 何平; 袁凤刚; 喻泽莉; 杜丹丹; 韦品祥; 胡世俊

    2012-01-01

    Objective To study the effects of drought stress on chlorophyll fluorescence characteristics and energy dissipation of Sarcandra glabra and get the method of alleviating drought stress, so as to provide theoretical basis against drought in planting. Methods Several physiological indexes of S. Glabra treated by 5-aminolevulinic acid (ALA) under drought stress (PEG-6000 at the concentration of 15%) were measured, such as the contents of photosynthetic pigment, chlorophyll fluorescence parameters, and energy parameters. Results Exogenous ALA obviously increased the content of chlorophyll and carotenoids, enhanced the maximum fluorescence (Fm), photochemical efficiency of photosystem II (PSII, Fv/Fm), potential photochemical efficiency (Fv/Fo), photochemical efficiency (Fv'/Fmr), PSII actual photochemical efficiency (OPSII), photochemical quenching coefficient (qP), electronic transfer rate (ETR), and photochemistry rate (PCR), as well as significnatly decreased the level of minimum fluorescence (Fo), non-photochemical quenching (NPQ) coefficient, and heat dissipation rate (HDR). The proportion of ALA absorbed light in photochemistry (P) was increased, the fraction of antenna pigment heat dissipation (D) and excess energy (£) for NPQ was decreased. The fraction of P was the main pathway for excessive energy dissipation. ALA could promote the redistribution of energy reasonablely. Conclusion Exogenous ALA (100 mg/L) could significantly reduce the dissipation of excess excitation energy, improve the photochemical electron transport efficiency,and efficiently protect leaf blade of S. Glabra from PSII damage under drought stress. ALA could obviously promote the droughtresistance of S. Glabra plantlet.%目的 探讨干旱胁迫对草珊瑚叶绿素荧光特性及能量分配的影响,找到延缓干旱胁迫的方法,为抗旱栽培提供理论依据.方法 考察15% PEG-6000模拟干旱胁迫条件下,经过不同浓度5-氨基乙酰丙酸(ALA)和不同时间处理后

  2. A study on clinical efifcacy of two kinds of concentration of 5-Aminolevulinic acid photodynamic therapy in treatment of moderate to severe acne%两种浓度5-氨基酮戊酸光动力疗法治疗中重度痤疮疗效观察

    Institute of Scientific and Technical Information of China (English)

    刘海波; 王雪松

    2016-01-01

    目的:探讨两种浓度5-氨基酮戊酸光动力疗法(ALA-PDT)治疗中重度痤疮的有效性及安全性。方法:将68例中重度痤疮患者随机分为两组:低浓度组:31例,给予5%ALA-PDT治疗;高浓度组:37例,给予10%ALA-PDT治疗,两组均每2周治疗1次,共治疗3次。在治疗后第2、4、6周对两组患者进行疗效判断和比较,同时记录治疗过程中出现的不良反应。结果:31例接受5%ALA-PDT治疗的患者经3次治疗后,总有效率87.10%;37例接受10%ALA-PDT治疗的患者经3次治疗后,总有效率为94.59%,两组疗效相比无统计学意义(P>0.05)。结论:5%ALA封包组与10%ALA封包组疗效相比无统计学意义,但低浓度组红斑、水肿、色素沉着等不良反应小。%Objective To study the safety and efifcacy of two kinds of concentrations of 5-aminolevulinic acid photodynamic therapy (5-ALA-PDT) in the treatment of moderate to severe acne. Methods 68 patients with moderate to severe acne were randomly divided into two groups:31 cases in low concentration group were treated with 5%5-ALA followed by red laser irradiation with a photodynamic therapy device;37 patients in high concentration group were treated with 10%5-ALA followed by red laser irradiation with a photodynamic therapy device. Patients in both groups were treated once every two weeks, 3 times totally. The patients were followed up 2, 4, and 6 weeks after the treatment, the therapeutic effects in two groups were compared and the adverse reactions were recorded. Results After 3 times treatments, the total effective rates of low and high concentration groups were respectively 87.1%and 94.59%. There was no signiifcant difference between the two groups (P>0.05). Conclusion The clinical efifcacy has no signiifcant difference between 5%5-ALA group and 10%5-ALA group, but the cases with adverse reactions in 5%5-ALA group, such as erythema, oedema, hyperpigmentation, were less.

  3. Effects of Foliar Spraying 5 - Aminolevulinic Acid on Growth, Photosynthesis and Yield of Tomato under Shade Conditions%叶面喷施5-氨基乙酰丙酸对遮阴条件下番茄生长、光合特性和产量的影响

    Institute of Scientific and Technical Information of China (English)

    郭晓青; 李超汉; 李青竹; 李霞; 李衍素; 于贤昌

    2011-01-01

    为明确喷施外源5-氨基乙酰丙酸(ALA)对弱光条件下番茄生长发育的影响,以“金丰盛冠”番茄为材料,研究了叶面喷施ALA(0.06 g/m2)对遮阴条件下番茄植株形态、叶绿素含量、光合特性及产量的影响.结果表明,遮阴处理使番茄植株高度增加,茎粗减小,叶片净光合速率(Pn)、气孔导度(Gs)、羧化效率(CE)、表观量子效率(AQY)、光补偿点(LCP)和产量降低,胞间二氧化碳浓度(Ci)、CO2补偿点(CCP)和叶绿索含量升高.遮阴环境下,叶面喷施ALA使番茄叶片Pn、Gs、CE、AQY、LCP和产量的降低幅度及Ci、CCP的升高幅度减小,并提高了叶绿素的含量,但对植株形态的影响不显著.叶面喷施ALA对80%遮阴下番茄生长、光合特性和产量的影响较小.表明在遮阴导致的弱光环境下,叶面喷施ALA能在一定程度上提高番茄叶片的光合能力,提高产量,并在一定范围内缓解遮阴对番茄生长造成的不利影响.%To make clear the influence of 5 - aminolevulinic acid ( ALA ) on the growth and development of tomato under weak light, the plant height, stem diameter, photosynthesis characteristics, chlorophyll content and yield of tomato were investigated after sprayed 0.06 g/m2 ALA. The results showed that the stem diameter, net photosynthetic rate (Pn), stomatal conductance (Gs), carboxylation efficiency (CE) , apparent quantum yield ( AQY) , the light compensation point ( LCP) and yield of tomato were decreased by shadingtreatment. On the contrary, the intercellular CO2 concentration ( Ci) and CO2 compensation point ( CCP) , chlorophyll content and plant height of tomato increased. Compared with spraying water, the decrease range of Pn, Gs, CE, AQY, LCP and yield and the increase range of Ci and CCP were relatively smaller after sprayed ALA under shade conditions, while the chlorophyll content increased. The foliar application of ALA had little influence on the tomato growth, photosynthesis

  4. Evolution of cyclizing 5-aminolevulinate synthases in the biosynthesis of actinomycete secondary metabolites: outcomes for genetic screening techniques.

    Science.gov (United States)

    Petříčková, Kateřina; Chroňáková, Alica; Zelenka, Tomáš; Chrudimský, Tomáš; Pospíšil, Stanislav; Petříček, Miroslav; Krištůfek, Václav

    2015-01-01

    A combined approach, comprising PCR screening and genome mining, was used to unravel the diversity and phylogeny of genes encoding 5-aminolevulinic acid synthases (ALASs, hemA gene products) in streptomycetes-related strains. In actinomycetes, these genes were believed to be directly connected with the production of secondary metabolites carrying the C5N unit, 2-amino-3-hydroxycyclopent-2-enone, with biological activities making them attractive for future use in medicine and agriculture. Unlike "classical" primary metabolism ALAS, the C5N unit-forming cyclizing ALAS (cALAS) catalyses intramolecular cyclization of nascent 5-aminolevulinate. Specific amino acid sequence changes can be traced by comparison of "classical" ALASs against cALASs. PCR screening revealed 226 hemA gene-carrying strains from 1,500 tested, with 87% putatively encoding cALAS. Phylogenetic analysis of the hemA homologs revealed strain clustering according to putative type of metabolic product, which could be used to select producers of specific C5N compound classes. Supporting information was acquired through analysis of actinomycete genomic sequence data available in GenBank and further genetic or metabolic characterization of selected strains. Comparison of 16S rRNA taxonomic identification and BOX-PCR profiles provided evidence for numerous horizontal gene transfers of biosynthetic genes or gene clusters within actinomycete populations and even from non-actinomycete organisms. Our results underline the importance of environmental and evolutionary data in the design of efficient techniques for identification of novel producers.

  5. SwissProt search result: AK107303 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107303 002-126-C11 (O94069) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_CANAL 6e-20 ...

  6. SwissProt search result: AK120617 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK120617 J013152B12 (P07997) 5-aminolevulinate synthase, nonspecific, mitochondrial... precursor (EC 2.3.1.37) (5-aminolevulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) (ALAS-H) HEM1_CHICK 4e-33 ...

  7. SwissProt search result: AK069723 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069723 J023027A08 (Q92403) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_AGABI 6e-32 ...

  8. SwissProt search result: AK065537 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065537 J013026J17 (Q7RVY5) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_NEUCR 4e-21 ...

  9. SwissProt search result: AK069007 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK069007 J023001A14 (Q7RVY5) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_NEUCR 6e-28 ...

  10. SwissProt search result: AK100991 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100991 J023146D11 (P13195) 5-aminolevulinate synthase, nonspecific, mitochondrial... precursor (EC 2.3.1.37) (5-aminolevulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) (ALAS-H) HEM1_RAT 1e-23 ...

  11. SwissProt search result: AK073935 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK073935 J033075P19 (Q92403) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_AGABI 9e-26 ...

  12. SwissProt search result: AK107303 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107303 002-126-C11 (Q9XS79) 5-aminolevulinate synthase, nonspecific, mitochondria...l precursor (EC 2.3.1.37) (5-aminolevulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) (ALAS-H) HEM1_DELLE 2e-23 ...

  13. SwissProt search result: AK067765 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK067765 J013120O07 (Q63147) 5-aminolevulinate synthase, erythroid-specific, mitoch...ondrial precursor (EC 2.3.1.37) (5-aminolevulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) (ALAS-E) HEM0_RAT 3e-22 ...

  14. SwissProt search result: AK107303 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107303 002-126-C11 (P38092) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_EMENI 1e-18 ...

  15. SwissProt search result: AK065537 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK065537 J013026J17 (P13196) 5-aminolevulinate synthase, nonspecific, mitochondrial... precursor (EC 2.3.1.37) (5-aminolevulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) (ALAS-H) HEM1_HUMAN 3e-22 ...

  16. SwissProt search result: AK107303 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK107303 002-126-C11 (P26505) 5-aminolevulinate synthase (EC 2.3.1.37) (5-aminolevu...linic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_AGRRD 9e-29 ...

  17. SwissProt search result: AK100689 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100689 J023114D10 (P13195) 5-aminolevulinate synthase, nonspecific, mitochondrial... precursor (EC 2.3.1.37) (5-aminolevulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) (ALAS-H) HEM1_RAT 4e-29 ...

  18. SwissProt search result: AK103411 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK103411 J033128F03 (O14092) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_SCHPO 6e-23 ...

  19. SwissProt search result: AK100991 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK100991 J023146D11 (P09950) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_YEAST 1e-18 ...

  20. SwissProt search result: AK105851 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK105851 001-203-G09 (P08080) 5-aminolevulinate synthase (EC 2.3.1.37) (5-aminolevu...linic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_RHIME 7e-28 ...

  1. SwissProt search result: AK071526 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK071526 J023099J24 (P13196) 5-aminolevulinate synthase, nonspecific, mitochondrial... precursor (EC 2.3.1.37) (5-aminolevulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) (ALAS-H) HEM1_HUMAN 1e-32 ...

  2. SwissProt search result: AK241034 [KOME

    Lifescience Database Archive (English)

    Full Text Available AK241034 J065058O11 (O94069) 5-aminolevulinate synthase, mitochondrial precursor (EC 2.3.1.37) (5-aminolev...ulinic acid synthase) (Delta-aminolevulinate synthase) (Delta-ALA synthetase) HEM1_CANAL 4e-32 ...

  3. Fractional laser-assisted delivery of methyl aminolevulinate

    DEFF Research Database (Denmark)

    Haak, Christina S; Farinelli, William A; Tam, Joshua

    2012-01-01

    Pretreatment of skin with ablative fractional lasers (AFXL) enhances the uptake of topical photosensitizers used in photodynamic therapy (PDT). Distribution of photosensitizer into skin layers may depend on depth of laser channels and incubation time. This study evaluates whether depth of intrade...... of intradermal laser channels and incubation time may affect AFXL-assisted delivery of methyl aminolevulinate (MAL).......Pretreatment of skin with ablative fractional lasers (AFXL) enhances the uptake of topical photosensitizers used in photodynamic therapy (PDT). Distribution of photosensitizer into skin layers may depend on depth of laser channels and incubation time. This study evaluates whether depth...

  4. Effects of fish oil and starch added to a diet containing sunflower-seed oil on dairy goat performance, milk fatty acid composition and in vivo delta9-desaturation of [13C]vaccenic acid.

    Science.gov (United States)

    Bernard, Laurence; Mouriot, Julien; Rouel, Jacques; Glasser, Frédéric; Capitan, Pierre; Pujos-Guillot, Estelle; Chardigny, Jean-Michel; Chilliard, Yves

    2010-08-01

    The potential benefits on human health have prompted an interest in developing nutritional strategies for specifically increasing rumenic acid (RA) in ruminant milk. The aims of the present study were to (i) compare two dietary treatments with lipid supplements on milk yield and composition, (ii) measure the in vivo delta9-desaturation of vaccenic acid (VA) to RA using 13C-labelled VA and (iii) determine the effect of the dietary treatments on this variable. Treatments were 90 g sunflower-seed oil (SO) per d or 60 g sunflower-seed oil and 30 g fish oil per d plus additional starch (SFO), in a grassland hay-based diet given to eight Alpine goats in a 2 x 2 cross-over design with 21 d experimental periods. Milk yield and composition were similar between treatments. Goats fed SFO had higher milk 6 : 0-16 : 0 concentration, lower milk sigmaC18 concentrations and showed no effect on milk VA and RA, compared with SO. At the end of the experiment, intravenous injection of 1.5 g [13C]VA followed by measurements of milk lipid 13C enrichment showed that in vivo 31.7 and 31.6 % of VA was delta9-desaturated into milk RA in the caprine with the SO and SFO treatments, respectively. The expression of genes encoding for delta9-desaturase (or stearoyl-CoA desaturase; SCD1, SCD5) in mammary tissues and four milk delta9-desaturation ratios were similar between treatments. In conclusion, the present study provides the first estimates of in vivo endogenous synthesis of RA (63-73 % of milk RA) from VA in goats, and shows no difference between the two lipid supplements compared.

  5. Delta robot

    NARCIS (Netherlands)

    Herder, J.L.; Van der Wijk, V.

    2010-01-01

    The invention relates to a delta robot comprising a stationary base (2) and a movable platform (3) that is connected to the base with three chains of links (4,5,6), and comprising a balancing system incorporating at least one pantograph (7) for balancing the robot's center of mass, wherein the at le

  6. Delta robot

    NARCIS (Netherlands)

    Herder, J.L.; Van der Wijk, V.

    2010-01-01

    The invention relates to a delta robot comprising a stationary base (2) and a movable platform (3) that is connected to the base with three chains of links (4,5,6), and comprising a balancing system incorporating at least one pantograph (7) for balancing the robot's center of mass, wherein the at le

  7. Delta1-pyrroline-5-carboxylic acid formed by proline dehydrogenase from the Bacillus subtilis ssp. natto expressed in Escherichia coli as a precursor for 2-acetyl-1-pyrroline.

    Science.gov (United States)

    Huang, Tzou-Chi; Huang, Yi-Wen; Hung, Hui-Ju; Ho, Chi-Tang; Wu, Mei-Li

    2007-06-27

    Proline dehydrogenase (PRODH) catalyzes the biosynthesis of Delta1-pyrroline-5-carboxylic acid (P5C). The Bacillus subtilis subsp. natto gene for the proline dehydrogenase (BnPRODH) was cloned and expressed in Escherichia coli. Nucleotide sequence analysis of the clone revealed an open-reading frame that encodes 302 amino acid polypeptide with a calculated molecular mass of 34.5 kDa. The deduced amino acid sequence showed sequence similarity to bacterial PRODH and PutA of E. coli. The BnPRODH gene was cloned into pET21b and was expressed at a high level in E. coli BL21(DE3). The expressed protein was purified by using nickel ion affinity column chromatography to homogeneity before characterization. The purified recombinant BnPRODH was used to produce P5C. Model system composed of P5C and methylglyoxal was set up to study the formation of 2-acetyl-1-pyrroline. Our data showed that P5C, derived from the conversion of l-proline by the purified recombinant PRODH, might react directly with methylglyoxal to form 2-AP. P5C/methylglyoxal pathway represents the first report of a biological mechanism by which 2-AP may be synthesized in vitro by PRODH.

  8. Identification of atherosclerosis using aminolevulinic gold nanoparticle assay in fecal specimens

    Science.gov (United States)

    Gonçalves, Karina de O.; da Silva, Mônica N.; Courrol, Lilia C.

    2015-06-01

    The atheromatous plaques exhibit an accumulation of protoporphyrin IX, or PpIX, which is transferred to the feces. In this work it was associated a precursor of the PpIX, the 5-aminolevulinic acid, ALA, with gold nanoparticles (ALA:AuNps). The objective was verify the possibility to use ALA:AuNPs as a diagnosis agent for atherosclerosis. ALA:AuNps were synthesized mixing ALA with Tetrachloroauric(III) acid in miliQ water solution followed by photoreduction with light from a Xenon lamp. A total of 22 Male New Zealand rabbits were divided into 3 groups: control group (CG) where animals received normal diet, control group with ALA (CGALA ) and Experimental Group with ALA:AuNPs ( EGALAAu ) in which the animals received a diet with 1% cholesterol. Measurements of the emission intensity of extracted porphyrins from the feces in the region between 575 and 725 nm were done. An increase in the feces porphyrin emission after ALA and ALA:AuNPs administration was observed.

  9. Precipitation Chemistry and Occurrence of Acid Rain over the Oil-Producing Niger Delta Region of Nigeria

    Directory of Open Access Journals (Sweden)

    John Kanayo Chukwu Nduka

    2010-01-01

    Full Text Available This study investigated the nitrate, sulfate, total dissolved solid (TDS, electrical conductivity, total hardness (TH, and bicarbonates of rainwater samples collected from Warri and Port Harcourt between April–June, July–August, and September–October of 2005 and 2006 to depict onset of rainy season, mid-rainy season, and end of rainy season for the two major crude oil–producing cities of the Niger Delta region of Nigeria (although Port Harcourt is also noted for non-oil manufacturing industries. The same was done in Awka, a non-oil producing city in the hinterland of southeastern Nigeria. In each of the cities, rain samples were collected from three points in a triangular equilibrium using a clean plastic basin fastened to a table 2 m above ground level and 115 m away from tall buildings and trees. The parameters were determined after filtering, using their respective standard methods. Averages of 1.50, 1.81, 1.13 and 2.14, 1.50, 1.86 mg/l of nitrate for April–June, July–August, and September–October were recorded for Warri in 2005 and 2006, respectively. While 15.21, 3.23, 22.31 and 20.89, 9.96, and 14.27 mg/l were recorded in Port Harcourt. Sulfate levels for Warri and Port Harcourt for the same periods are follows: 1.38, 1.88, 1.06, 1.50, 1.43, 1.50 and 2.64, 1.15, 5.88, 4.73, 1.90, 1.55 mg/l, respectively. Nitrate levels were higher than sulfate. Other parameters include TDS (5.44, 4.79, 3.30 and 7.63, 3.69, 2.56 mg/l for Warri in 2005 and 2006; 12.57, 2.07, 25.214 and 28.87, 6.73, 7.80 mg/l for Port Harcourt for the same periods. Other parameters also varied in that order for the 2 years in same cities. Crude oil exploration and gas flaring in the Niger Delta, and multiplicity of cottage industries in Awka, impacted on the inorganic ion pollution of the rainwater. This may have public health implications in the region.

  10. 5-氨基乙酰丙酸介导的光动力学作用对胃癌细胞MKN-45增殖与凋亡作用的研究%Effect of 5-aminolevulinic acid mediated photodynamic therapy on proliferation and apoptosis of gastric cancer cell line MKN-45

    Institute of Scientific and Technical Information of China (English)

    王晓龙; 魏军; 程立文; 张骞; 闫鹏; 王贵玉

    2016-01-01

    Objective To explore the 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy (PDT) for proliferation and apoptosis of gastric cancer cell line MKN-45.Methods The human gastric cancer cell line MKN-45 was cultured in vitro.The MTT method was used to detect fixed lighting processing (laser radiation dose fixed for 25.00 J/cm2,5-ALA photosensitizer concentrations were 0 mmol/L,0.25 mmol/L,0.50 mmol/L,1.00 mmol/L,2.00 mmol/L),fixed photosensitizer concentration treatment (5-ALA photosensitizer concentrations fixed to 1.00 mmol/L,laser radiation dose were 0 J/cm2,6.25 J/cm2,12.50 J/cm2,25.00 J/cm2,50.00 J/cm2,100.00 J/cm2) of the cell apoptosis rate,and then fixed 5-ALA photosensitizer 1 mmol/L and selected the control group,5-ALA group,pure illumination group and PDT group.The promoting effect on cell apoptosis was determined by MTT,electron microscope and flow cytometry.The activity of human gastric cancer cells MKN-45 apoptosis related proteins p65 and the downstream gene regulatory protein bcl-2,bax,caspase-3 and caspase-9 were detected by using Western blot method.Results When laser radiation dose was fixed,5-ALA photosensitizer concentrations in promoting gastric cancer cell apoptosis was positively related to the dominant (P < 0.01).When 5-ALA photosensitizer concentration was fixed,laser radiation dose effect had no longer dominant after 25.00 J/cm2 positive correlation (P =0.613).When 5-ALA photosensitizer concentration was fixed in 1 mmol/L,compared to control group,5-ALA group and pure illumination group,the inhibition of the MKN-45 cell proliferation in PDT group was more apparently,apoptosis rate increased obviously,signal pathways in cell apoptosis protein involved in the NF-kappa B p65 expression was reduced,the downstream gene regulation of target protein bcl-2,caspase-3 and caspase-9 expression were reduced,and bax protein expression was increased.Conclusions 5-ALA mediated photodynamic has a strong inhibitory effect on the growth of gastric

  11. Characterization of three novel desaturases involved in the delta-6 desaturation pathways for polyunsaturated fatty acid biosynthesis from Phytophthora infestans.

    Science.gov (United States)

    Sun, Quanxi; Liu, Jiang; Zhang, Qin; Qing, Xiaohe; Dobson, Gary; Li, Xinzheng; Qi, Baoxiu

    2013-09-01

    Phytophthora infestans is the causative agent of potato blight that resulted in the great famine in Ireland in the nineteenth century. This microbe can release large amounts of the C20 very long-chain polyunsaturated fatty acids arachidonic acid (ARA; 20:4Δ(5, 8, 11, 14)) and eicosapentaenoic acid (EPA; 20:5Δ(5, 8, 11, 14, 17)) upon invasion that is known to elicit a hypersensitive response to their host plant. In order to identify enzymes responsible for the biosynthesis of these fatty acids, we blasted the recently fully sequenced P. infestans genome and identified three novel putatively encoding desaturase sequences. These were subsequently functionally characterized by expression in Saccharomyces cerevisiae and confirmed that they encode desaturases with Δ12, Δ6 and Δ5 activity, designated here as PinDes12, PinDes6 and PinDes5, respectively. This, together with the combined fatty acid profiles and a previously identified Δ6 elongase activity, implies that the ARA and EPA are biosynthesized predominantly via the Δ6 desaturation pathways in P. infestans. Elucidation of ARA and EPA biosynthetic mechanism may provide new routes to combating this potato blight microbe directly or by means of conferring resistance to important crops.

  12. Tuning the degradation rate of calcium phosphate cements by incorporating mixtures of polylactic-co-glycolic acid microspheres and glucono-delta-lactone microparticles.

    Science.gov (United States)

    Sariibrahimoglu, Kemal; An, Jie; van Oirschot, Bart A J A; Nijhuis, Arnold W G; Eman, Rhandy M; Alblas, Jacqueline; Wolke, Joop G C; van den Beucken, Jeroen J J P; Leeuwenburgh, Sander C G; Jansen, John A

    2014-11-01

    Calcium phosphate cements (CPCs) are frequently used as synthetic bone graft materials in view of their excellent osteocompatibility and clinical handling behavior. Hydroxyapatite-forming CPCs, however, degrade at very low rates, thereby limiting complete bone regeneration. The current study has investigated whether degradation of apatite-forming cements can be tuned by incorporating acid-producing slow-resorbing poly(D,L-lactic-co-glycolic) acid (PLGA) porogens, fast-resorbing glucono-delta-lactone (GDL) porogens, or mixtures thereof. The physicochemical, mechanical, and degradation characteristics of these CPC formulations were systematically analyzed upon soaking in phosphate-buffered saline (PBS). In parallel, various CPC formulations were implanted intramuscularly and orthotopically on top of the transverse process of goats followed by analysis of the soft tissue response and bone ingrowth after 12 weeks. In vitro degradation of GDL was almost completed after 2 weeks, as evidenced by characterization of the release of gluconic acid, while PLGA-containing CPCs released glycolic acid throughout the entire study (12 weeks), resulting in a decrease in compression strength of CPC. Extensive in vitro degradation of the CPC matrix was observed upon simultaneous incorporation of 30% PLGA-10% GDL. Histomorphometrical evaluation of the intramuscularly implanted samples revealed that all CPCs exhibited degradation, accompanied by an increase in capsule thickness. In the in vivo goat transverse process model, incorporation of 43% PLGA, 30% PLGA-5% GDL, and 30% PLGA-10% GDL in CPC significantly increased bone formation and resulted in higher bone height compared with both 10% GDL and 20% GDL-containing CPC samples.

  13. Amino acid sequence of the oligomycin sensitivity-conferring protein (OSCP) of beef-heart mitochondria and its homology with the delta-subunit of the F1-ATPase of Escherichia coli.

    Science.gov (United States)

    Ovchinnikov, Y A; Modyanov, N N; Grinkevich, V A; Aldanova, N A; Trubetskaya, O E; Nazimov, I V; Hundal, T; Ernster, L

    1984-01-23

    The complete amino acid sequence of the oligomycin sensitivity-conferring protein (OSCP) of beef-heart mitochondria is reported. The protein contains 190 amino acids and has a molecular mass of 20 967. Its structure is characterized by a concentration of charged amino acids in the two terminal segments (N 1-77 and C 128-190) of the protein, whereas its central region is more hydrophobic. The earlier reported homology of the protein with the delta-subunit of E. coli F1, based on the terminal amino acid sequences of OSCP, is further substantiated.

  14. Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease.

    Science.gov (United States)

    Cheng, Jeffrey B; Jacquemin, Emmanuel; Gerhardt, Marie; Nazer, Hisham; Cresteil, Danièle; Heubi, James E; Setchell, Kenneth D R; Russell, David W

    2003-04-01

    The 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase (C(27) 3beta-HSD) is a membrane-bound enzyme of the endoplasmic reticulum that catalyzes an early step in the synthesis of bile acids from cholesterol. Subjects with autosomal recessive mutations in the encoding gene, HSD3B7, on chromosome 16p11.2-12 fail to synthesize bile acids and develop a form of progressive liver disease characterized by cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract. The gene encoding the human C(27) 3beta-HSD enzyme was isolated previously, and a 2-bp deletion in exon 6 of HSD3B7 was identified in a well characterized subject with this disorder. Here, we report a molecular analysis of 15 additional patients from 13 kindreds with C(27) 3beta-HSD deficiency. Twelve different mutations were identified in the HSD3B7 gene on chromosome 16p11.2-12. Ten mutations were studied in detail and shown to cause complete loss of enzyme activity and, in two cases, alterations in the size or amount of the transcribed mRNA. Mutations were inherited in homozygous form in 13 subjects from 10 families and compound heterozygous form in four subjects from three families. We conclude that a diverse spectrum of mutations in the HSD3B7 gene underlies this rare form of neonatal cholestasis.

  15. Long-term melatonin administration reduces hyperinsulinemia and improves the altered fatty-acid compositions in type 2 diabetic rats via the restoration of Delta-5 desaturase activity.

    Science.gov (United States)

    Nishida, Shigeru; Segawa, Toshiko; Murai, Ichiro; Nakagawa, Shigeki

    2002-01-01

    The objective of this study was to investigate the effect of long-term melatonin administration on plasma levels of triglycerides, insulin and leptin, and on the fatty-acid metabolism of plasma and hepatic lipids in type 2 diabetic rats. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus, were divided into two groups: one untreated (n=6), and one implanted with time-releasing melatonin pellets (1.1 mg/day for 30 wk) under the abdominal skin (n=6). Age-matched Long-Evans Tokushima Otsuka (LETO) rats (n=6) were used as healthy controls. The untreated diabetic rats had the increased plasma levels of triglycerides, cholesterol, insulin and leptin at 35 wk, as compared with the healthy control rats (n=6). The diabetic rats also had augmented ratios of 20:3n-6/20:4n-6 fatty acids, owing to diminished activity of Delta-5 desaturase, an insulin-permissive enzyme, in the liver. Melatonin administration to OLETF rats reduced the hypertriglyceridemia (-39%, P melatonin-releasing pellet thus resulted in improved lipid metabolism in diabetic rats, probably through restored insulin resistance.

  16. Metal binding by humic acids isolated from water hyacinth plants (Eichhornia crassipes [Mart.] Solm-Laubach: Pontedericeae) in the Nile Delta, Egypt

    Energy Technology Data Exchange (ETDEWEB)

    Ghabbour, Elham A.; Davies, Geoffrey; Lam, Y.-Y.; Vozzella, Marcy E

    2004-10-01

    Humic acids (HAs) are animal and plant decay products that confer water retention, metal and organic solute binding functions and texture/workability in soils. HAs assist plant nutrition with minimal run-off pollution. Recent isolation of HAs from several live plants prompted us to investigate the HA content of the water hyacinth (Eichhornia crassipes [Mart.] Solm-Laubach: Pontedericeae), a delicately flowered plant from Amazonian South America that has invaded temperate lakes, rivers and waterways with devastating economic effects. Hyacinth thrives in nutrient-rich and polluted waters. It has a high affinity for metals and is used for phytoremediation. In this work, HAs isolated from the leaves, stems and roots of live water hyacinth plants from the Nile Delta, Egypt were identified by chemical and spectral analysis and by comparison with authentic soil and plant derived HAs. Similar carbohydrate and amino acid distributions and tight metal binding capacities of the HAs and their respective plant components suggest that the presence of HAs in plants is related to their metal binding properties.

  17. An insect with a delta-12 desaturase, the jewel wasp Nasonia vitripennis, benefits from nutritional supply with linoleic acid

    Science.gov (United States)

    Brandstetter, Birgit; Ruther, Joachim

    2016-06-01

    The availability of linoleic acid (LA; C18:2∆9,12) is pivotal for animals. While vertebrates depend on a nutritional supply, some invertebrates, including the parasitic wasp Nasonia vitripennis, are able to synthesize LA from oleic acid (OA; C18:1∆9). This raises the question as to whether these animals nevertheless benefit from the additional uptake of LA with the diet. LA plays an important role in the sexual communication of N. vitripennis because males use it as a precursor for the synthesis of an abdominal sex pheromone attracting virgin females. We reared hosts of N. vitripennis that were fed diets enriched in the availability of stearic acid (SA: C18:0), OA or LA. N. vitripennis males developing on the different host types clearly differed in both the fatty acid composition of their body fat and sex pheromone titres. Males from LA-enriched hosts had an almost fourfold higher proportion of LA and produced significantly more sex pheromone than males from SA (2.2-fold) and OA (1.4-fold) enriched hosts, respectively. Our study demonstrates that animals being able to synthesize important nutrients de novo may still benefit from an additional supply with their diet.

  18. Oxidative Profile and δ-Aminolevulinate Dehydratase Activity in Healthy Pregnant Women with Iron Supplementation.

    Science.gov (United States)

    De Lucca, Leidiane; Rodrigues, Fabiane; Jantsch, Letícia B; Neme, Walter S; Gallarreta, Francisco M P; Gonçalves, Thissiane L

    2016-05-03

    An oxidative burst occurs during pregnancy due to the large consumption of oxygen in the tissues and an increase in metabolic demands in response to maternal physiological changes and fetal growth. This study aimed to determine the oxidative profile and activity of δ-aminolevulinate dehydratase (δ-ALA-D) in pregnant women who received iron supplementation. Oxidative stress parameters were evaluated in 25 pregnant women with iron supplementation, 25 pregnant women without supplementation and 25 non-pregnant women. The following oxidative stress parameters were evaluated: thiobarbituric acid reactive substances (TBARS), protein thiol groups (P-SH), non-protein thiol levels (NP-SH), vitamin C levels, catalase and δ-ALA-D activity. Markers of oxidative stress and cell damage, such as TBARS in plasma were significantly higher in pregnant women without supplementation. Levels of P-SH, NP-SH and δ-ALA-D activity were significantly lower in pregnant women without supplementation compared to non-pregnant and pregnant women with supplementation, while vitamin C levels were significantly lower in pregnant women without supplementation when compared to non-pregnant women. The increase in the generation of oxidative species and decrease of antioxidants suggest the loss of physiological oxidative balance during normal pregnancy, which was not observed in pregnant women with iron supplementation, suggesting a protective effect of iron against oxidative damage.

  19. Synthesis and characterization of proton conductive CaZr{sub 0.90}In{sub 0.10}O{sub 3-{delta}} by a citric acid complexation method

    Energy Technology Data Exchange (ETDEWEB)

    Han Jinduo [Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 DingXi Road, Shanghai 200050 (China); Wen Zhaoyin, E-mail: zywen@mail.sic.ac.c [Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 DingXi Road, Shanghai 200050 (China); Zhang Jingchao; Xu Xiaohe; Gu Zhonghua; Liu Yu [Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 DingXi Road, Shanghai 200050 (China)

    2010-12-15

    A citric acid complexation method is applied to synthesize CaZr{sub 0.90}In{sub 0.10}O{sub 3-{delta}}. TG-DSC, XRD, SEM, linear shrinkage and the complex impedance method are conducted to investigate the physical and protonic conduction properties of CaZr{sub 0.90}In{sub 0.10}O{sub 3-{delta}}. The results show that the citrate method is a favorable way to produce high purity nano-CaZr{sub 0.90}In{sub 0.10}O{sub 3-{delta}} powders suitable for fabricating dense ceramics at lower temperature. In addition, the protonic conduction tests indicate that the total, bulk and grain boundary conductivities of the ceramics are much higher than those of the ceramics fabricated from the powders synthesized by the conventional solid-state reaction method.

  20. Hair analysis for Delta9-tetrahydrocannabinolic acid A--new insights into the mechanism of drug incorporation of cannabinoids into hair.

    Science.gov (United States)

    Auwärter, Volker; Wohlfarth, Ariane; Traber, Jessica; Thieme, Detlef; Weinmann, Wolfgang

    2010-03-20

    Differentiation between external contamination and incorporation of drugs or their metabolites from inside the body via blood, sweat or sebum is a general issue in hair analysis and of high concern when interpreting analytical results. In hair analysis for cannabinoids the most common target is Delta9-tetrahydrocannabinol (THC), sometimes cannabidiol (CBD) and cannabinol (CBN) are determined additionally. After repeated external contamination by cannabis smoke these analytes are known to be found in hair even after performing multiple washing steps. A widely accepted strategy to unequivocally prove active cannabis consumption is the analysis of hair extracts for the oxidative metabolite 11-nor-9-carboxy-THC (THC-COOH). Although the acidic nature of this metabolite suggests a lower rate of incorporation into the hair matrix compared to THC, it is not fully understood up to now why hair concentrations of THC-COOH are generally found to be much lower (mostly <10 pg/mg) than the corresponding THC concentrations. Delta9-Tetrahydrocannabinolic acid A (THCA A) is the preliminary end product of the THC biosynthesis in the cannabis plant. Unlike THC it is non-psychoactive and can be regarded as a 'precursor' of THC being largely decarboxylated when heated or smoked. The presented work shows for the first time that THCA A is not only detectable in blood and urine of cannabis consumers but also in THC positive hair samples. A pilot experiment performed within this study showed that after oral intake of THCA A on a regular basis no relevant incorporation into hair occurred. It can be concluded that THCA A in hair almost exclusively derives from external contamination e.g. by side stream smoke. Elevated temperatures during the analytical procedure, particularly under alkaline conditions, can lead to decarboxylation of THCA A and accordingly increase THC concentrations in hair. Additionally, it has to be kept in mind that in hair samples tested positive for THCA A at least a

  1. Evolution of cyclizing 5-aminolevulinate synthases in the biosynthesis of actinomycete secondary metabolites: Outcomes for genetic screening techniques

    Directory of Open Access Journals (Sweden)

    Katerina ePetrickova

    2015-08-01

    Full Text Available A combined approach, comprising PCR screening and genome mining, was used to unravel the diversity and phylogeny of genes encoding 5-aminolevulinic acid synthases (ALASs, hemA gene products in streptomycetes-related strains. In actinomycetes, these genes were believed to be directly connected with the production of secondary metabolites carrying the C5N unit, 2-amino-3-hydroxycyclopent-2-enone, with biological activities making them attractive for future use in medicine and agriculture. Unlike classical primary metabolism ALAS, the C5N unit-forming cALAS (cyclizing ALAS catalyses intramolecular cyclization of nascent 5-aminolevulinate. Specific amino acid sequence changes can be traced by comparison of classical ALASs against cALASs. PCR screening revealed 226 hemA gene-carrying strains from 1,500 tested, with 87 % putatively encoding cALAS. Phylogenetic analysis of the hemA homologues revealed strain clustering according to putative type of metabolic product, which could be used to select producers of specific C5N compound classes. Supporting information was acquired through analysis of actinomycete genomic sequence data available in GeneBank and further genetic or metabolic characterization of selected strains. Comparison of 16S rRNA taxonomic identification and BOX-PCR profiles provided evidence for numerous horizontal gene transfers of biosynthetic genes or gene clusters within actinomycete populations and even from non-actinomycete organisms. Our results underline the importance of environmental and evolutionary data in the design of efficient techniques for identification of novel producers.

  2. 氨基酮戊酸光动力疗法对鲜红斑痣动物模型鸡冠的影响%Effects of aminolevulinic acid-based photodynamic therapy on chicken combs, an animal model for port wine stains

    Institute of Scientific and Technical Information of China (English)

    王娇; 黄熙

    2015-01-01

    目的:探讨外用氨基酮戊酸光动力疗法(ALA-PDT)对鲜红斑痣(PWS)动物模型鸡冠的作用和治疗鲜红斑痣的可行性。方法80只莱亨鸡随机分为10组:空白对照组、单纯 ALA 组、单纯激光75 J/cm2组、100 J/cm2组、150 J/cm2、200 J/cm2组,ALA-PDT 75 J/cm2组、100 J/cm2组、150 J/cm2组、200 J/cm2组。单纯激光组仅给予630 nm 红光照射,ALA-PDT 组外用 ALA 后给予红光照射。干预14 d、28 d 分别取材,观察鸡冠形态学、组织学变化,计算毛细血管减少率和血管内皮细胞凋亡情况。结果外用 ALA-PDT 75 J/cm2、100 J/cm2、150 J/cm2和200 J/cm2组鸡冠实验区域颜色变淡,光镜下真皮毛细血管数目减少、管径变小,部分血管内皮细胞凋亡;毛细血管减少率分别为33.53%±4.89%、52.02%±2.77%、67.48%±5.58%、88.96%±2.47%;凋亡指数分别为:63.44±1.09、88.50±6.11、94.32±3.67、113.76±10.57,与其余各组分别比较,均 P <0.01;血管内皮细胞凋亡深度分别为:201.19μm ±0.33μm、266.15μm ±1.02μm、546.09μm ±2.45μm、766.37μm ±1.08μm,各组间两两比较,均 P <0.01。结论外用 ALA-PDT 对鸡冠毛细血管有明显损伤,损伤程度和深度与红光能量密度相关;诱导血管内皮细胞凋亡可能是其治疗机制之一。%Objective To investigate the effects of aminolevulinic acid-based photodynamic therapy(ALA-PDT) on chicken combs, an animal model for port wine stains (PWS), and to explore the feasibility of PWS treatment with ALA-PDT. Methods A total of 80 leghorns were randomly and equally divided into 10 groups: blank control group receiving no treatment, ALA group treated with ALA alone, four single laser groups irradiated with 630-nm red laser at 75, 100, 150 and 200 J/cm2 respectively, four ALA-PDT groups pretreated with ALA followed by 630-nm red laser radiation at 75, 100, 150 and 200 J/cm2 respectively. An area sized 1 cm × 1 cm were marked at one side

  3. Concentration and source identification of polycyclic aromatic hydrocarbons and phthalic acid esters in the surface water of the Yangtze River Delta, China

    Institute of Scientific and Technical Information of China (English)

    Lifei Zhang; Liang Dong; Lijun Ren; Shuangxin Shi; Li Zhou; Ting Zhang; Yeru Huang

    2012-01-01

    The pollution from polycyclic aromatic hydrocarbons (PAHs) and phthalic acid esters (PAEs) in the surface water of the rapidly urbanized Yangtze River Delta region was investigated.Fourteen surface water samples were collected in June 2010.Water samples were liquid-liquid extracted using methylene chloride and analyzed by gas chromatography-mass spectrometry.Concentrations of PAHs and PAEs ranged 12.9-638.1 ng/L and 61-28550 ng/L,respectively.Fluoranthene,naphthalene,pyrene,phenanthrene,di-2-ethylhexyl phthalate,and di-n-butyl phthalate were the most abundant compounds in the samples.The water samples were moderately Polluted with benzo[a]pyrene according to China's environmental quality standard for surface water.The two highest concentrations of PAHs and PAEs occurred in samples from Taihu Lake,Wuxi City and the western section of Yangchenghu Lake.Potential sources of Pollution at S7 were petroleum combustion and the plastics industry,and at Yangchenghu Lake were petroleum combustion and domestic waste.Pollution in samples from the Beijing-Hangzhou Grand Canal originated from diesel engines.There were no obvious sources of pollution for the other water samples.These results can be used as reference levels for future monitoring programs of pollution from PAHs and PAEs.

  4. Factors responsible for rapid dissipation of acidic herbicides in the coastal lagoons of the Camargue (Rhône River Delta, France).

    Science.gov (United States)

    Al Housari, Fadi; Höhener, Patrick; Chiron, Serge

    2011-01-01

    This study was aimed at investigating which processes cause acidic herbicides (e.g., bentazone, MCPA and dichlorprop) to rapidly disappear in the lagoons of the Rhône delta, which are peculiar brackish and shallow aquatic environments. The use of the model MASAS (Modeling of Anthropogenic Substances in Aquatic Systems) revealed that sorption, sedimentation, volatilization, flushing and abiotic hydrolysis had a minor role in the attenuation of the investigated herbicides. Laboratory scale biodegradation and photodegradation studies were conducted to better assess the significance of these two processes in the natural attenuation of herbicides in brackish (lagoons) waters with respect to fresh waters (canals draining paddy fields). Herbicide biodegradation rates were significantly lower in lagoon water than in canal water. Consequently, photodegradation was the main dissipation route of all investigated herbicides. The contribution of indirect photolysis was relevant for MCPA and dichlorprop while direct photolysis dominated for bentazone removal. There is a need to further investigate the identity of phototransformation products of herbicides in lagoons.

  5. Simultaneous quantification of delta-9-THC, THC-acid A, CBN and CBD in seized drugs using HPLC-DAD.

    Science.gov (United States)

    Ambach, Lars; Penitschka, Franziska; Broillet, Alain; König, Stefan; Weinmann, Wolfgang; Bernhard, Werner

    2014-10-01

    An HPLC-DAD method for the quantitative analysis of Δ(9)-tetrahydrocannabinol (THC), Δ(9)-tetrahydrocannabinolic acid-A (THCA-A), cannabidiol (CBD), and cannabinol (CBN) in confiscated cannabis products has been developed, fully validated and applied to analyse seized cannabis products. For determination of the THC content of plant material, this method combines quantitation of THCA-A, which is the inactive precursor of THC, and free THC. Plant material was dried, homogenized and extracted with methanol by ultrasonication. Chromatographic separation was achieved with a Waters Alliance 2695 HPLC equipped with a Merck LiChrospher 60 RP-Select B (5μm) precolumn and a Merck LiChroCart 125-4 LiChrospher 60 RP-Select B (5μm) analytical column. Analytes were detected and quantified using a Waters 2996 photo diode array detector. This method has been accepted by the public authorities of Switzerland (Bundesamt für Gesundheit, Federal Office of Public Health), and has been used to analyse 9092 samples since 2000. Since no thermal decarboxylation of THCA-A occurs, the method is highly reproducible for different cannabis materials. Two calibration ranges are used, a lower one for THC, CBN and CBD, and a higher one for THCA-A, due to its dominant presence in fresh plant material. As provider of the Swiss proficiency test, the robustness of this method has been tested over several years, and homogeneity tests even in the low calibration range (1%) show high precision (RSD≤4.3%, except CBD) and accuracy (bias≤4.1%, except CBN).

  6. PM{sub 2.5} acidity at a background site in the Pearl River Delta region in fall-winter of 2007–2012

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Xiaoxin [Guangzhou Institute of Geochemistry, Chinese Academy of Sciences (China); Department of Civil and Environmental Engineering, Hong Kong Polytechnic University, Hong Kong (China); Shenzhen Research Institute, Hong Kong Polytechnic University (China); Guo, Hai, E-mail: ceguohai@polyu.edu.hk [Department of Civil and Environmental Engineering, Hong Kong Polytechnic University, Hong Kong (China); Shenzhen Research Institute, Hong Kong Polytechnic University (China); Wang, Xinming, E-mail: wangxm@gig.ac.cn [Guangzhou Institute of Geochemistry, Chinese Academy of Sciences (China); Ding, Xiang; He, Quanfu; Liu, Tengyu; Zhang, Zhou [Guangzhou Institute of Geochemistry, Chinese Academy of Sciences (China)

    2015-04-09

    Highlights: • 24-h PM{sub 2.5} samples were collected in fall-winter of 2007–2012. • The annual reduction trends of [H{sup +}]{sub total} and [H{sup +}]{sub in-situ} of PM{sub 2.5} was −32 ± 1.5 and −9 ± 1.7 nmol m{sup −3}, respectively. • On hazy days, the concentration of OM showed significant enhancement when [H{sup +}]{sub in-situ} ranged from 85 to 240 nmol m{sup −3}. • [H{sup +}]{sub in-situ} presented a close relationship with NO{sub 3}{sup −} formation mechanisms in low and high acidity of PM{sub 2.5}. - Abstract: Based on field observations and thermodynamic model simulation, the annual trend of PM{sub 2.5} acidity and its characteristics on non-hazy and hazy days in fall-winter of 2007–2012 in the Pearl River Delta region were investigated. Total acidity ([H{sup +}]{sub total}) and in-situ acidity ([H{sup +}]{sub in-situ}) of PM{sub 2.5} significantly decreased (F-test, p < 0.05) at a rate of −32 ± 1.5 nmol m{sup −3} year{sup −1} and −9 ± 1.7 nmol m{sup −3} year{sup −1}, respectively. The variation of acidity was mainly caused by the change of the PM{sub 2.5} component, i.e., the decreasing rates of [H{sup +}]{sub total} and [H{sup +}]{sub in-situ} due to the decrease of sulfate (SO{sub 4}{sup 2−}) exceeded the increasing rate caused by the growth of nitrate (NO{sub 3}{sup −}). [H{sup +}]{sub total}, [H{sup +}]{sub in-situ} and liquid water content on hazy days were 0.9–2.2, 1.2–3.5 and 2.0–3.0 times those on non-hazy days, respectively. On hazy days, the concentration of organic matter (OM) showed significant enhancement when [H{sup +}]{sub in-situ} increased (t-test, p < 0.05), while this was not observed on non-hazy days. Moreover, when the acidity was low (i.e., R = [NH{sub 4}{sup +}]/(2 × [SO{sub 4}{sup 2−}] + [NO{sub 3}{sup −}]) > 0.6), NH{sub 4}NO{sub 3} was most likely formed via homogenous reaction. When the acidity was high (R ≤ 0.6), the gas-phase formation of NH{sub 4}NO{sub 3} was

  7. Delta III—an evolutionary delta growth

    Science.gov (United States)

    Arvesen, R. J.; Simpson, J. S.

    1996-03-01

    In order to remain competitive in the future and expand the McDonnell Douglas Aerospace market share, MDA has developed an expendable launch system strategy that devices cost-effective launch systems from the Delta II with a growth vehicle configuration called Delta III. The Delta III evolves from the Delta II launch system through development of a larger payload fairing (4-meter diameter), new cryogenically propelled upper stage, new first stage fuel tank, and larger strap-on solid rocket motors. We are developing the Delta III using Integrated Product Development Teams that capitalize on the experience base that has led us to a world record breaking mission success of 49 consecutive Delta II missions. The Delta III first-launch capability is currently planned for the spring of 1998 in support of our first spacecraft customer, Hughes Space and Communications International.

  8. Automated extraction of 11-nor-delta9-tetrahydrocannabinol carboxylic acid from urine samples using the ASPEC XL solid-phase extraction system.

    Science.gov (United States)

    Langen, M C; de Bijl, G A; Egberts, A C

    2000-09-01

    The analysis of 11-nor-delta9-tetrahydrocannabinol-carboxylic acid (THCCOOH, the major metabolite of cannabis) in urine with gas chromatography and mass spectrometry (GC-MS) and solid-phase extraction (SPE) sample preparation is well documented. Automated SPE sample preparation of THCCOOH in urine, although potentially advantageous, is to our knowledge poorly investigated. The objective of the present study was to develop and validate an automated SPE sample-preparation step using ASPEC XL suited for GC-MS confirmation analysis of THCCOOH in urine drug control. The recoveries showed that it was not possible to transfer the protocol for the manual SPE procedure with the vacuum manifold to the ASPEC XL without loss of recovery. Making the sample more lipophilic by adding 1 mL 2-propanol after hydrolysis to the urine sample in order to overcome the problem of surface adsorption of THCCOOH led to an extraction efficiency (77%) comparable to that reached with the vacuum manifold (84%). The reproducibility of the automated SPE procedure was better (coefficient of variation 5%) than that of the manual procedure (coefficient of variation 12%). The limit of detection was 1 ng/mL, and the limit of quantitation was 4 ng/mL. Precision at the 12.5-ng/mL level was as follows: mean, 12.4 and coefficient of variation, 3.0%. Potential carryover was evaluated, but a carryover effect could not be detected. It was concluded that the proposed method is suited for GC-MS confirmation urinalysis of THCCOOH for prisons and detoxification centers.

  9. Coencapsulation of oxygen carriers and glucose oxidase in polyelectrolyte complex capsules for the enhancement of D-gluconic acid and delta-gluconolactone production.

    Science.gov (United States)

    Bucko, Marek; Gemeiner, Peter; Vikartovská, Alica; Mislovicová, Danica; Lacík, Igor; Tkác, Ján

    2010-04-01

    A novel encapsulated oxidative biocatalyst comprising glucose oxidase (GOD) coencapsulated with oxygen carriers within polyelectrolyte complex capsules was developed for the production of D-gluconic acid and delta-gluconolactone. The capsules containing immobilized GOD were produced by polyelectrolyte complexation with sodium alginate (SA) and cellulose sulfate (CS) as polyanions, poly(methylene-co-guanidine) (PMCG) as the polycation, CaCl(2) as the gelling agent and NaCl as the antigelling agent (GOD-SA-CS/PMCG capsules). Poly(dimethylsiloxane) (PDMS) and an emulsion of n-dodecane (DOD) or perfluorodecaline (PFD) with PDMS were used as the oxygen carriers and MnO(2) was used as a hydrogen peroxide decomposition catalyst. Water-soluble PDMS was found to act as both an oxygen carrier and an emulsifier of water-insoluble DOD and PFD. Stable microcapsules could be produced with concentrations of up to 4% (w/w) of PDMS, 10% (w/w) of DOD and PFD, and 25% (w/w) of MnO(2) in the polyanion solution of SA and CS. Roughly a two-fold increase in the GOD activity from 21.0+/-1.1 to 38.4+/-2.0 U*g(-1) and product space-time yields (STY) from 44.3+/-2.0 to 83.4+/-3.4 g*H*day(-1) could be achieved utilizing coencapsulated oxygen carriers compared to GOD encapsulated in the absence of oxygen carriers. This enhanced production does not significantly depend on the selected oxygen carrier under the conditions used in this study.

  10. The Delta 2 launcher

    Science.gov (United States)

    Ousley, Gilbert W., Sr.

    1991-12-01

    The utilization of the Delta 2 as the vehicle for launching Aristoteles into its near Sun synchronous orbit is addressed. Delta is NASA's most reliable launch vehicle and is well suited for placing the present Aristoteles spacecraft into a 400 m circular orbit. A summary of some of the Delta 2 flight parameters is presented. Diagrams of a typical Delta 2 two stage separation are included along with statistics on delta reliability and launch plans.

  11. Activation of PPAR{delta} up-regulates fatty acid oxidation and energy uncoupling genes of mitochondria and reduces palmitate-induced apoptosis in pancreatic {beta}-cells

    Energy Technology Data Exchange (ETDEWEB)

    Wan, Jun; Jiang, Li; Lue, Qingguo; Ke, Linqiu [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China); Li, Xiaoyu [State Key Laboratory of Oral Diseases, Sichuan University, No. 14, 3rd Section, Renmin South Road, Chengdu, Sichuan 610041 (China); Tong, Nanwei, E-mail: buddyjun@hotmail.com [Department of Endocrinology, West China Hospital of Sichuan University, 37 Guoxue Lane, Chengdu, Sichuan 610041 (China)

    2010-01-15

    Recent evidence indicates that decreased oxidative capacity, lipotoxicity, and mitochondrial aberrations contribute to the development of insulin resistance and type 2 diabetes. The goal of this study was to investigate the effects of peroxisome proliferator-activated receptor {delta} (PPAR{delta}) activation on lipid oxidation, mitochondrial function, and insulin secretion in pancreatic {beta}-cells. After HIT-T15 cells (a {beta}-cell line) were exposed to high concentrations of palmitate and GW501516 (GW; a selective agonist of PPAR{delta}), we found that administration of GW increased the expression of PPAR{delta} mRNA. GW-induced activation of PPAR{delta} up-regulated carnitine palmitoyltransferase 1 (CPT1), long-chain acyl-CoA dehydrogenase (LCAD), pyruvate dehydrogenase kinase 4 (PDK4), and uncoupling protein 2 (UCP2); alleviated mitochondrial swelling; attenuated apoptosis; and reduced basal insulin secretion induced by increased palmitate in HIT cells. These results suggest that activation of PPAR{delta} plays an important role in protecting pancreatic {beta}-cells against aberrations caused by lipotoxicity in metabolic syndrome and diabetes.

  12. Vitamin D as a potential enhancer of aminolevulinate-based photodynamic therapy for nonmelanoma skin cancer

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay; Atanaskova, Natasha; Wilson, Clara

    2010-02-01

    Vitamin D3 (Vit D3) is a hormone essential for normal bone and cardiovascular health, and may participate in preventing nonmelanoma skin cancers (NMSC). Calcitriol (1,25 dihydroxyD3) is the active form of the hormone. We showed previously that calcitriol is a potent inducer of protoporphyrin IX (PpIX) in skin keratinocytes grown in organotypic cultures. Here, we investigated the ability of Vit D3 to enhance PpIX levels within skin tumors in vivo. Squamous tumors, generated by chemical carcinogenesis in mice, were pretreated for 3 days with topical calcitriol. Then 5-aminolevulinic acid (5-ALA) was applied topically, and PpIX levels were measured by noninvasive fluorimetry and in biopsied tissue. Calcitriol pretreatment resulted in a 3 to 4-fold elevation of PpIX in tumors, relative to no pretreatmen, providing significantly more photosensitizer available for tumor destruction. For deep tumors, topical calcitriol may not penetrate sufficiently. Therefore we explored whether systemic Vit D3, given short-term (3 days), might elevate PpIX within NMSC in a deep tumor model (subcutaneously-implanted A431 human squamous carcinoma cells). Defined amounts of calcitriol were injected into the mice for 3 d, followed by systemic 5-ALA, tissue biopsy, and confocal microscopic measurement of PpIX in frozen tissues. PpIX was clearly elevated after systemically delivered calcitriol. More work is needed, but if the amount of calcitriol required to elevate PpIX levels proves to be small, then the approach may ultimately prove attractive. Since most Americans are currently Vitamin D deficient, a small increase in calcitriol might be possible without risk of hypercalcemia.

  13. Enzymatic synthesis oF L-tryptophan from D,L-2-amino-delta2-thiazoline-4-carboxylic acid and indole by Pseudomonas sp. TS1138 L-2-amino-delta2-thiazoline-4-carboxylic acid hydrolase, S-carbamyl-L-cysteine amidohydrolase, and Escherichia coli L-tryptophanase.

    Science.gov (United States)

    Du, J; Duan, J J; Zhang, Q; Hou, J; Bai, F; Chen, N; Bai, G

    2012-01-01

    L-Tryptophan (L-Trp) is an essential amino acid. It is widely used in medical, health and food products, so a low-cost supply is needed. There are 4 methods for L-Trp production: chemical synthesis, extraction, enzymatic synthesis, and fermentation. In this study, we produced a recombinant bacterial strain pET-tnaA of Escherichia coli which has the L-tryptophanase gene. Using the pET-tnaA E. coli and the strain TS1138 of Pseudomonas sp., a one-pot enzymatic synthesis of L-Trp was developed. Pseudomonas sp. TS1138 was added to a solution of D,L-2-amino-delta2-thiazoline-4-carboxylic acid (DL-ATC) to convert it to L-cysteine (L-Cys). After concentration, E. coli BL21 (DE 3) cells including plasmid pET-tnaA, indole, and pyridoxal 5'-phosphate were added. At the optimum conditions, the conversion rates of DL-ATC and L-Cys were 95.4% and 92.1%, respectively. After purifying using macroporous resin S8 and NKA-II, 10.32 g of L-Trp of 98.3% purity was obtained. This study established methods for one-pot enzymatic synthesis and separation of L-Trp. This method of producing L-Trp is more environmentally sound than methods using chemical synthesis, and it lays the foundations for industrial production of L-Trp from DL-ATC and indole.

  14. DNA polymerase III accessory proteins. I. holA and holB encoding delta and delta'.

    Science.gov (United States)

    Dong, Z; Onrust, R; Skangalis, M; O'Donnell, M

    1993-06-05

    The genes encoding the delta and delta' subunits of the 10-subunit Escherichia coli replicase, DNA polymerase III holoenzyme, have been identified and sequenced. The holA gene encoding delta is located downstream of rlpB at 15.2 min and predicts a 38.7 kda protein. The holB gene encoding delta' is located at 24.3 min and predicts a 36.9-kDa protein. Hence the delta and delta' subunits are unrelated proteins encoded by separate genes. The genes have been used to express and purify delta and delta' in quantity. The predicted amino acid sequence of delta' is homologous to the sequences of the tau and gamma subunits revealing a large amount of structural redundancy within the holoenzyme.

  15. Role of melatonin in modulation of oxidative stress induced by delta-

    Directory of Open Access Journals (Sweden)

    El-Sawi, MR, Badawy, ME and El-Gharieb, NM.

    2007-09-01

    Full Text Available Backgrounds: Delta-aminolevulinic acid (ALA is a heme precursor that accumulates in acute intermittent porphyria (AIP due to enzymatic deficiencies in the heme biosynthetic pathway, its accumulation has been associated with several symptoms because it works as an endogenous source of reactive oxygen species, which can exert oxidative damage to cell structures. The present work was designed to examine the ability of melatonin, a well known antioxidant and a free radical scavenger secreted from the pineal gland, to revert ALA-promoted damage in brain, liver and kidney of rats. Results: The present data demonstrated that chronically ALA-treated rats (40 mg / kg body wt day after day for 14 days exhibited very highly significant increases in malondialdehyde (MDA and protein carbonyl (PC whereas the level of glutathione (GSH was significantly diminished in the tissue homogenates of all tested organs (brain, kidney & liver. Among antioxidant enzymes, superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GSH-Rd, glutathione-S-transferase (GST activities were significantly diminished by ALA treatment. Intraperitoneal injection of melatonin (10 mg / kg body weight, every day for 14 consecutive days significantly ameliorated all the tested parameters. Melatonin moderately increased SOD, CAT, GSH-Rd and GST activities, thereby counteracting the oxidative stress induced by ALA. Nevertheless, exogenous ALA caused a strong net rise in MDA and PC and a significant decrease in GSH when given together with ALA, melatonin antagonized these effects and largely protected the integrity of tissue structures. From the present data, the protection of melatonin against ALA oxidative stress is obviously, so it is well recommended to use melatonin in patients suffering from symptoms related to ALA accumulation

  16. Allergic contact dermatitis to methyl aminolevulinate (Metvix) cream used in photodynamic therapy.

    Science.gov (United States)

    Harries, Matthew J; Street, Gill; Gilmour, Elizabeth; Rhodes, Lesley E; Beck, Michael H

    2007-02-01

    Topical photodynamic therapy (PDT) is increasingly used in the treatment of superficial skin malignancies including actinic keratosis, Bowen's disease and superficial basal cell carcinoma. Contact allergy to the prodrug is rarely reported. We report a case of allergic contact dermatitis to methyl aminolevulinate cream used in PDT.

  17. Delta Plaza kohvik = Delta Plaza cafe

    Index Scriptorium Estoniae

    2010-01-01

    Tallinnas Pärnu mnt 141 asuva kohviku Delta Plaza sisekujundusest. Sisearhitektid Tiiu Truus ja Marja Viltrop (Stuudio Truus OÜ). Tiiu Truusi tähtsamate tööde loetelu. Büroohoone Delta Plaza arhitektid Marika Lõoke ja Jüri Okas (AB J. Okas & M. Lõoke)

  18. Delta Plaza kohvik = Delta Plaza cafe

    Index Scriptorium Estoniae

    2010-01-01

    Tallinnas Pärnu mnt 141 asuva kohviku Delta Plaza sisekujundusest. Sisearhitektid Tiiu Truus ja Marja Viltrop (Stuudio Truus OÜ). Tiiu Truusi tähtsamate tööde loetelu. Büroohoone Delta Plaza arhitektid Marika Lõoke ja Jüri Okas (AB J. Okas & M. Lõoke)

  19. Integrated soil and water management in acid sulphate soils : balancing agricultural production and environmental requirements in the Mekong Delta, Viet Nam

    NARCIS (Netherlands)

    Le, Q.M.

    1996-01-01


    The objectives of this study in the Mekong delta, Vietnam, were: (1) to obtain a better understanding of the effects of soil physical properties and flow types on solute transport in ASS emphasing aluminum; (2) to quantify environmental hazards resulting from amelioration activities in

  20. Isolation of Delta9-THCA-A from hemp and analytical aspects concerning the determination of Delta9-THC in cannabis products.

    Science.gov (United States)

    Dussy, Franz E; Hamberg, Cornelia; Luginbühl, Marco; Schwerzmann, Thomas; Briellmann, Thomas A

    2005-04-20

    A simple procedure based on a common silica gel column chromatography for the isolation of Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) from hemp in a multi-milligram scale is presented. Further, the decarboxylation reaction of Delta9-THCA-A to the toxicologically active Delta9-tetrahydrocannabinol (Delta9-THC) at different analytical and under-smoking conditions is investigated. Maximal conversion in an optimised analytical equipment yields about 70% Delta9-THC. In the simulation of the smoking process, only about 30 % of the spiked substance could be recovered as Delta9-THC.

  1. Differentiation of Boc-protected alpha,delta-/delta,alpha- and beta,delta-/delta,beta-hybrid peptide positional isomers by electrospray ionization tandem mass spectrometry.

    Science.gov (United States)

    Raju, G; Ramesh, V; Srinivas, R; Sharma, G V M; Shoban Babu, B

    2010-06-01

    Two new series of Boc-N-alpha,delta-/delta,alpha- and beta,delta-/delta,beta-hybrid peptides containing repeats of L-Ala-delta(5)-Caa/delta(5)-Caa-L-Ala and beta(3)-Caa-delta(5)-Caa/delta(5)-Caa-beta(3)-Caa (L-Ala = L-alanine, Caa = C-linked carbo amino acid derived from D-xylose) have been differentiated by both positive and negative ion electrospray ionization (ESI) ion trap tandem mass spectrometry (MS/MS). MS(n) spectra of protonated isomeric peptides produce characteristic fragmentation involving the peptide backbone, the Boc-group, and the side chain. The dipeptide positional isomers are differentiated by the collision-induced dissociation (CID) of the protonated peptides. The loss of 2-methylprop-1-ene is more pronounced for Boc-NH-L-Ala-delta-Caa-OCH(3) (1), whereas it is totally absent for its positional isomer Boc-NH-delta-Caa-L-Ala-OCH(3) (7), instead it shows significant loss of t-butanol. On the other hand, second isomeric pair shows significant loss of t-butanol and loss of acetone for Boc-NH-delta-Caa-beta-Caa-OCH(3) (18), whereas these are insignificant for its positional isomer Boc-NH-beta-Caa-delta-Caa-OCH(3) (13). The tetra- and hexapeptide positional isomers also show significant differences in MS(2) and MS(3) CID spectra. It is observed that 'b' ions are abundant when oxazolone structures are formed through five-membered cyclic transition state and cyclization process for larger 'b' ions led to its insignificant abundance. However, b(1)(+) ion is formed in case of delta,alpha-dipeptide that may have a six-membered substituted piperidone ion structure. Furthermore, ESI negative ion MS/MS has also been found to be useful for differentiating these isomeric peptide acids. Thus, the results of MS/MS of pairs of di-, tetra-, and hexapeptide positional isomers provide peptide sequencing information and distinguish the positional isomers.

  2. Porphyrin biodistribution in UV-exposed murine skin after methyl- and hexyl-aminolevulinate incubation

    DEFF Research Database (Denmark)

    Togsverd-Bo, Katrine; Lerche, Catharina M; Philipsen, Peter A

    2012-01-01

    Topical photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is a well-established treatment for precancerous skin lesions and non-melanoma skin cancer. Treatment outcomes are less effective for thick than for superficial lesions, which are presumed to be due to insufficient Pp......IX biodistribution in tumour tissue. Hexyl-aminolevulinate (HAL) is a more lipophilic photosensitizer precursor than MAL and may penetrate the skin to a greater depth and more homogeneously. We compared HAL- and MAL-induced PpIX accumulation in specific skin compartments using concentrations of 2%, 6% and 20% HAL...... and MAL on long-term UV-irradiated mouse skin. Furthermore, 20% HAL and 20% MAL were applied to non-irradiated skin. Porphyrin fluorescence was measured by fluorescence microscopy in selected skin regions: the epidermis, superficial dermis, deep dermis and sebaceous gland epithelium down to a depth of 1...

  3. Urticaria after methyl aminolevulinate photodynamic therapy in a patient with nevoid basal cell carcinoma syndrome.

    Science.gov (United States)

    Wolfe, Christopher M; Green, W Harris; Hatfield, H Keith; Cognetta, Armand B

    2012-11-01

    Methyl aminolevulinate photodynamic therapy (MAL-PDT) is utilized in several countries for the treatment of basal cell carcinoma, but allergic sensitization has been reported by the manufacturer. To the best of our knowledge, we report the first case of urticaria following MAL-PDT in a patient with nevoid basal cell carcinoma syndrome. Prophylactic use of antihistamines may allow continued use of MAL-PDT in this setting.

  4. A 10-Year Retrospective Analysis of Methyl Aminolevulinate Photodynamic Therapy Consultation at the Hospital de Braga

    OpenAIRE

    Brito, C; Resende, C.; Oliveira, P.

    2016-01-01

    Introduction Photodynamic therapy (PDT) is a well-established treatment for actinic keratosis (AK), basal cell carcinoma (BCC), and Bowen’s disease (BD). The object of this study was to describe the results of a retrospective analysis of patients treated with methyl aminolevulinate PDT (MAL-PDT) with red light, over the past decade at the Hospital de Braga (Braga, Portugal). Methods This study is based on the retrospective analysis of the clinical records of patients treated with MAL-PDT from...

  5. Oxidative Profile and δ-Aminolevulinate Dehydratase Activity in Healthy Pregnant Women with Iron Supplementation

    OpenAIRE

    Leidiane De Lucca; Fabiane Rodrigues; Letícia B. Jantsch; Neme, Walter S.; Gallarreta, Francisco M. P.; Gonçalves, Thissiane L.

    2016-01-01

    An oxidative burst occurs during pregnancy due to the large consumption of oxygen in the tissues and an increase in metabolic demands in response to maternal physiological changes and fetal growth. This study aimed to determine the oxidative profile and activity of δ-aminolevulinate dehydratase (δ-ALA-D) in pregnant women who received iron supplementation. Oxidative stress parameters were evaluated in 25 pregnant women with iron supplementation, 25 pregnant women without supplementation and 2...

  6. Reduced aminolevulinate dehydrase activity in rats with functional renal failure induced by cyclosporin A.

    Science.gov (United States)

    Fontanellas, A; Herrero, J A; Enríquez de Salamanca, R

    1997-01-01

    Patients with chronic failure evidence various abnormalities in heme metabolism, primarily erythrocyte aminolevulinate dehydrase hypoactivity and increased plasma and erythrocyte porphyrin levels. Such abnormalities have also been observed in animals with both acute and chronic experimental renal failure. The aim of this work was to study these parameters of porphyrin metabolism in an experimental model of functional renal failure. A group of 11 male Wistar rats received 13 doses (25 mg/kg body weight/day) of cyclosporin A. Serum creatinine did not vary, but the blood urea nitrogen levels increased and a significant decrease in the creatinine clearance was observed. The drug also caused a marked decrease in the erythrocyte aminolevulinate dehydrase activity, a slight reduction of the hematocrit value, and increased levels of blood porphyrins. The plasma of treated rats showed capacity to inhibit aminolevulinate dehydrase activity when incubated in vitro with erythrocytes from control rats. Porphyrin metabolism remained unchanged in the liver. The daily diuresis was significantly decreased in the cyclosporin as compared to the control group; however, the porphyrinuria showed no changes. The derangements in the erythrocyte heme biosynthesis pathway observed in patients with chronic renal failure are reproducible in an experimental model of cyclosporin A-induced functional renal failure.

  7. Delta-ALA-mediated fluorescence spectroscopy of gastrointestinal tumors: comparison of in vivo and in vitro results

    Science.gov (United States)

    Vladimirov, B.; Borisova, E.; Avramov, L.

    2007-06-01

    The limitations of standard endoscopy for detection of dysplastic changes of mucosa are significant challenge and initiate development of new photodiagnostic techniques, additional to diagnostic possibilities of standard endoscopic equipment. One of the most widely examined optical modalities is the laser- or light-induced fluorescence spectroscopy (LIFS), because of its rapid and highly sensitive response to early biochemical and morphological changes in biological tissues. In the recent study delta-aminolevulinic acid/protoporphyrin IX is used as fluorescent marker for dysplasia and tumor detection in esophagus and stomach. The δ -ALA is administered per os six hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from in vivo tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Mucosa autofluorescence lies at 450-600 nm region. The fluorescence of PpIX is clearly pronounced at the 630-710 nm region. Deep minima in the tumor fluorescence signals are observed in the region 540-575 nm, related to hemoglobin re-absorption. Such high hemoglobin content is an indication of the tumors vascularization and it is clearly pronounced in all dysplastic and tumor sites investigated. After formalin conservation for in vitro samples hemoglobin absorption is strongly reduced that increases mucous fluorescence signal in green-yellow spectral region. Simultaneously the maxima at 635 nm and 720 nm are reduced.

  8. The efficacy of monoisoamyl ester of dimercaptosuccinic acid in chronic experimental arsenic poisoning in mice.

    Science.gov (United States)

    Flora, S J S; Kannan, G M; Pant, B P; Jaiswal, D K

    2003-01-01

    The therapeutic efficacy of monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new monoester of 2,3-dimercaptosuccinic acid on arsenic induced oxidative stress in liver and kidneys, alterations in hematopoietic system and depletion of arsenic burden was assessed, in mice. Three different doses of MiADMSA (25, 50 or 100 mg/kg) for five consecutive days were administered in chronically arsenic exposed mice (10 ppm in drinking water for six months). Oral administration of MiADMSA particularly at a dose of 50 mg/kg, produced relatively more pronounced beneficial effects on the inhibited blood delta-aminolevulinic acid dehydratase (ALAD), biochemical variables indicative of hepatic and renal oxidative stress and depletion of arsenic concentration in blood, liver and kidneys, compared with intraperitoneal administration of the drug. The treatment with MiADMSA although, produced essential metals imbalance which could be a restrictive factor for the possible therapeutic use of this compound in chronic arsenic poisoning and thus require further exploration.

  9. Delta hedging strategies comparison

    DEFF Research Database (Denmark)

    De Giovanni, Domenico; Ortobelli, S.; Rachev, S.T.

    2008-01-01

    In this paper we implement dynamic delta hedging strategies based on several option pricing models. We analyze different subordinated option pricing models and we examine delta hedging costs using ex-post daily prices of S&P 500. Furthermore, we compare the performance of each subordinated model ...

  10. Horizontal Symmetries $\\Delta(150)$ and $\\Delta(600)$

    CERN Document Server

    Lam, C S

    2013-01-01

    Using group theory of mixing to examine all finite subgroups of SU(3) with an order less than 512, we found recently that only the group $\\Delta(150)$ can give rise to a correct reactor angle $\\th_{13}$ of neutrino mixing without any free parameter. It predicts $\\sin^22\\th_{13}=0.11$ and a sub-maximal atmospheric angle with $\\sin^22\\th_{23}=0.94$, in good agreement with experiment. The solar angle $\\th_{12}$, the CP phase $\\d$, and the neutrino masses $m_i$ are left as free parameters. In this article we provide more details of this case, discuss possible gain and loss by introducing right-handed symmetries, and/or valons to construct dynamical models. A simple model is discussed where the solar angle agrees with experiment, and all its mixing parameters can be obtained from the group $\\Delta(600)$ by symmetry alone. The promotion of $\\Delta(150)$ to $\\Delta(600)$ is on the one hand analogous to the promotion of $S_3$ to $S_4$ in the presence of tribimaximal mixing, and on the other hand similar to the extens...

  11. Clinical studies of combined photodynamic therapy using 5-fluorouracil and methyl-aminolevulinate in patients at high risk for squamous cell carcinoma

    Science.gov (United States)

    Maytin, Edward V.; Lohser, Sara; Tellez, Alejandra; Wene, Lauren; Ishak, Rim; Anand, Sanjay

    2013-03-01

    Photodynamic therapy (PDT) using aminolevulinic acid or its methyl ester, methyl-aminolevulinate (MAL), is an increasingly recognized approach for treating squamous neoplasia of the skin. Advantages of MAL-PDT include its ability to cover broad diseased areas (field treatment), and to do multiple sessions with little-to-no risk of scarring or mutagenesis. MAL-PDT is especially valuable in certain populations at high risk for skin cancer, including Caucasian patients with extensive solar damage, and organ transplant recipients (OTR) who take immunosuppressive drugs to prevent graft rejection. The latter group has a 65-200 fold increased risk of developing squamous cell carcinoma (SCC), a major cause of mortality. Therapeutic options for those patients, other than frequent surgeries, are very limited. Topical 5-Fluorouracil (5-FU), frequently prescribed in normal patients for pre-SCC of the skin, is only minimally effective in the OTR group. MAL-PDT, however, has ~40% efficacy for pre-SCC in OTR patients. Based upon our preclinical studies in mouse tumor models, which showed that preconditioning with 5-FU can drive higher accumulation of target protoporphyins (PpIX), we proposed a rational combination regimen of 5-FU and MAL-PDT in humans. A clinical trial was designed to test the hypothesis that a combination of 5-FU followed by MAL-PDT will elevate PpIX levels and achieve better clinical outcomes in high-risk OTR patients. Primary endpoints include PpIX levels and biochemical markers (p53) measured noninvasively and in skin biopsies. Lesion clearance and recurrence (via photographs and clinical exam) are secondary endpoints. Ongoing results of this clinical trial are presented.

  12. Molecular dynamics analysis of the structural and dynamic properties of the functionally enhanced hepta-variant of mouse 5-aminolevulinate synthase.

    Science.gov (United States)

    Na, Insung; DeForte, Shelly; Stojanovski, Bosko M; Ferreira, Gloria C; Uversky, Vladimir N

    2017-01-09

    Heme biosynthesis, a complex, multistage, and tightly controlled process, starts with 5-aminolevulinate (ALA) production, which, in metazoa and certain bacteria, is a reaction catalyzed by 5-aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate (PLP)-dependent enzyme. Functional aberrations in ALAS are associated with several human diseases. ALAS can adopt open and closed conformations, with segmental rearrangements of a C-terminal, 16-amino acid loop and an α-helix regulating accessibility to the ALAS active site. Of the murine erythroid ALAS (mALAS2) forms previously engineered to assess the role of the flexible C-terminal loop versus mALAS2 function one stood out due to its impressive gain in catalytic power. To elucidate how the simultaneously introduced seven mutations of this activity-enhanced variant affected structural and dynamic properties of mALAS2, we conducted extensive molecular dynamics simulation analysis of the dimeric forms of wild-type mALAS2, hepta-variant and Rhodobacter capsulatus ALAS (aka R. capsulatus HemA). This analysis revealed that the seven simultaneous mutations in the C-terminal loop, which extends over the active site of the enzyme, caused the bacterial and murine proteins to adopt different conformations. Specifically, a new β-strand in the mutated 'loop' led to interaction with two preexisting β-strands and formation of an anti-parallel three-stranded β-sheet, which likely endowed the murine hepta-variant a more 'stable' open conformation than that of wild-type mALAS2, consistent with a kinetic mechanism involving a faster closed-to-open conformation transition and product release for the mutated than wild-type enzyme. Further, the dynamic behavior of the mALAS2 protomers was strikingly different in the two dimeric forms.

  13. 氨基酮戊酸光动力疗法抑制成纤维细胞生长因子10诱导的HaCaT细胞过度角化及增殖的机制研究%Mechanisms underlying the inhibitory effects of aminolevulinic acid-based photodynamic therapy on fibroblast growth factor 10-induced excessive cornification and proliferation of HaCaT cells

    Institute of Scientific and Technical Information of China (English)

    易飞; Maya Valeska Gozali; 张家安; 周炳荣; 骆丹; 张丽超; 王申; 刘娟; 吴红巾

    2015-01-01

    目的 探讨氨基酮戊酸光动力疗法(ALA-PDT)对成纤维细胞生长因子10(FGF-10)诱导的HaCaT细胞过度角化及增殖的作用及其机制.方法 将培养的HaCaT细胞分为4组:空白对照组(无任何处理),FGF-10组(加入FGF-10孵育24 h),ALA-PDT组(ALA孵育24 h后红光照射),FGF-10+ ALA-PDT组(FGF-10孵育24 h后,再加ALA孵育24 h,红光照射).用CCK-8法检测各组细胞增殖活性,Western印迹法检测K1、K6、K16及角质形成细胞生长因子受体(KGFR)的含量,ELISA法检测各组细胞上清液中白细胞介素1α(IL-1α)蛋白表达,免疫荧光检测各组细胞KGFR和K6蛋白表达水平.统计学分析采用析因设计的方差分析和单因素方差分析.结果 析因分析显示,ALA-PDT和FGF-10对HaCaT细胞增殖无交互作用(F交互=1.369,P=0.276),FGF-10对HaCaT细胞增殖有促进作用(FFGF-10=20.853,P<0.05),而ALA-PDT有抑制作用(FALA-PDT=24.822,P< 0.05).与空白对照组细胞增殖活性(A值为0.924±0.024)比较,FGF-10组(1.233±0.099)显著升高(P<0.05),而ALA-PDT组(0.718±0.107)显著降低(P<0.05),FGF-10+ ALA-PDT组(0.901±0.014)较FGF-10组显著降低(P<0.05).Western印迹法显示,FGF-10可促进K1、K6、K16蛋白和KGFR的表达(均P<0.05),而ALA-PDT抑制这些蛋白的表达(均P< 0.05),FGF-10+ ALA-PDT组K1、K6、K16和KGFR的相对表达量与FGF-10组比较均显著降低(均P< 0.05).ELISA法显示,FGF-10会增加HaCaT细胞IL-1α蛋白分泌(P<0.05),但ALA-PDT对其没有影响(P=0.467).此外,免疫荧光检测显示,FGF-10增加HaCaT细胞K6和KGFR免疫荧光强度(P<0.05),而ALA-PDT降低K6和KGFR免疫荧光强度(P<0.05),FGF-10+ ALA-PDT组K6和KGFR免疫荧光强度显著低于FGF-10组(P<0.05).结论 ALA-PDT能抑制FGF-10诱导的HaCaT细胞过度角化及增殖,其机制与下调K1、K6、K16、KGFR及IL-1α有关.%Objective To evaluate the inhibitory effects of aminolevulinic acid-based photodynamic therapy (ALA-PDT) on fibroblast growth factor

  14. Conversion of the bifunctional 8-oxoguanine/beta-delta apurinic/apyrimidinic DNA repair activities of Drosophila ribosomal protein S3 into the human S3 monofunctional beta-elimination catalyst through a single amino acid change.

    Science.gov (United States)

    Hegde, V; Kelley, M R; Xu, Y; Mian, I S; Deutsch, W A

    2001-07-20

    The Drosophila S3 ribosomal protein has important roles in both protein translation and DNA repair. In regards to the latter activity, it has been shown that S3 contains vigorous N-glycosylase activity for the removal of 8-oxoguanine residues in DNA that leaves baseless sites in their places. Drosophila S3 also possesses an apurinic/apyrimidinic (AP) lyase activity in which the enzyme catalyzes a beta-elimination reaction that cleaves phosphodiester bonds 3' and adjacent to an AP lesion in DNA. In certain situations, this is followed by a delta-elimination reaction that ultimately leads to the formation of a single nucleotide gap in DNA bordered by 5'- and 3'-phosphate groups. The human S3 protein, although 80% identical to its Drosophila homolog and shorter by only two amino acids, has only marginal N-glycosylase activity. Its lyase activity only cleaves AP DNA by a beta-elimination reaction, thus further distinguishing itself from the Drosophila S3 protein in lacking a delta-elimination activity. Using a hidden Markov model analysis based on the crystal structures of several DNA repair proteins, the enzymatic differences between Drosophila and human S3 were suggested by the absence of a conserved glutamine residue in human S3 that usually resides at the cleft of the deduced active site pocket of DNA glycosylases. Here we show that the replacement of the Drosophila glutamine by an alanine residue leads to the complete loss of glycosylase activity. Unexpectedly, the delta-elimination reaction at AP sites was also abrogated by a change in the Drosophila glutamine residue. Thus, a single amino acid change converted the Drosophila activity into one that is similar to that possessed by the human S3 protein. In support of this were experiments executed in vivo that showed that human S3 and the Drosophila site-directed glutamine-changed S3 performed poorly when compared with Drosophila wild-type S3 and its ability to protect a bacterial mutant from the harmful effects of

  15. Menhaden oil, but not safflower or soybean oil, aids in restoring the polyunsaturated fatty acid profile in the novel delta-6-desaturase null mouse

    Directory of Open Access Journals (Sweden)

    Monteiro Jessica

    2012-05-01

    Full Text Available Abstract Background Polyunsaturated fatty acids (PUFA have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA and α-linolenic acid (ALA, have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid. Objective The aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids. Methodology Liver and serum phospholipid (PL fatty acid composition was examined in D6KO and wild type mice fed i 10% safflower oil diet (SF, LA rich ii 10% soy diet (SO, LA+ALA or iii 3% menhaden oil +7% SF diet (MD, HUFA rich for 28 days (n = 3-7/group. Results Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice. Conclusions Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

  16. Comparative effects of sulfuric and nitric acid rain on litter decomposition and soil microbial community in subtropical plantation of Yangtze River Delta region.

    Science.gov (United States)

    Liu, Xin; Zhang, Bo; Zhao, Wenrui; Wang, Ling; Xie, Dejin; Huo, Wentong; Wu, Yanwen; Zhang, Jinchi

    2017-12-01

    Acid rain is mainly caused by dissolution of sulfur dioxide and nitrogen oxides in the atmosphere, and has a significant negative effect on ecosystems. The relative composition of acid rain is changing gradually from sulfuric acid rain (SAR) to nitric acid rain (NAR) with the rapidly growing amount of nitrogen deposition. In this study, we investigated the impact of simulated SAR and NAR on litter decomposition and the soil microbial community over four seasons since March 2015. Results first showed that the effects of acid rain on litter decomposition and soil microbial were positive in the early period of the experiment, except for SAR on soil microbes. Second, soil pH with NAR decreased more rapidly with the amount of acid rain increased in summer than with SAR treatments. Only strongly acid rain (both SAR and NAR) was capable of depressing litter decomposition and its inhibitory effect was stronger on leaf than on fine root litter. Meanwhile, NAR had a higher inhibitory effect on litter decomposition than SAR. Third, in summer, autumn and winter, PLFAs were negatively impacted by the increased acidity level resulting from both SAR and NAR. However, higher acidity level of NAR (pH=2.5) had the strongest inhibitory impact on soil microbial activity, especially in summer. In addition, Gram-negative bacteria (cy19:0) and fungi (18:1ω9) were more sensitive to both SAR and NAR, and actinomycetes was more sensitive to SAR intensity. Finally, soil total carbon, total nitrogen and pH were the most important soil property factors affecting soil microbial activity, and high microbial indices (fungi/bacteria) with high soil pH. Our results suggest that the ratio of SO4(2-) to NO3(-) in acid rain is an important factor which could affect litter decomposition and soil microbial in subtropical forest of China. Copyright © 2017. Published by Elsevier B.V.

  17. On the width of N-Delta and Delta-Delta states

    CERN Document Server

    Niskanen, J A

    2016-01-01

    It is seen by a coupled-channel calculation that in the two-baryon N-Delta or Delta-Delta system the width of the state is greatly diminished due to the relative kinetic energy of the two baryons, since the internal energy of the particles, available for pionic decay, is smaller. A similar state dependent effect arises from the centrifugal barrier in N-Delta or Delta-Delta systems with non-zero orbital angular momentum. The double-Delta width can become even smaller than the free width of a single Delta. This has some bearing to the interpretation of the d'(2380) resonance recently discovered at COSY.

  18. Clinical, histological, and immunohistochemical markers of resistance to Methyl-aminolevulinate Photodynamic therapy in Bowen's disease.

    Science.gov (United States)

    Gracia-Cazaña, T; Salazar, N; Vera-Álvarez, J; Aguilera, J; López-Navarro, N; Herrera-Ceballos, E; González, S; Juarranz, Á; Gilaberte, Y

    2017-09-08

    Bowen's disease (BD) is an intraepidermic squamous cell carcinoma (SCC), which principally appears on photoexposed areas.(1) Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) is an excellent option for the treatment of BD (strength of recommendation, A; quality of evidence, 1). However, despite good response rates, some tumors prove non-responsive due to primary or acquired resistance.(2) The present study sought to identify clinical, histological, and molecular variables implicated in the response to MAL-PDT in BD. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. A terapia fotodinâmica com ácido 5-aminolevulínico como modalidade de tratamento para neoplasias cutâneas não-melanoma Topical 5-aminolevulinic acid photodynamic therapy as a treatment modality for nonmelanoma skin cancer

    Directory of Open Access Journals (Sweden)

    Lília Bernardini Antunes de Felício

    2008-08-01

    Full Text Available FUNDAMENTOS: A terapia fotodinâmica baseia-se na associação de fonte de luz e fotossensibilizador para destruir seletivamente as células. OBJETIVO: Avaliar os efeitos imediatos e tardios, a resposta clínica e os resultados estéticos da terapia fotodinâmica com ácido 5-aminolevulínico em neoplasias cutâneas não-melanoma. MÉTODOS: Trinta e quatro lesões, sendo 19 disceratoses de Bowen e 15 carcinomas basocelulares, foram submetidas à aplicação tópica e oclusiva do ácido 5-aminolevulínico a 20%, por seis horas, e posteriormente a sessão única de laser de diodo (630nm. RESULTADOS: Foram registrados: sensação de queimação durante as sessões; eritema, edema e erosões, nas primeiras 72 horas; cicatrização em média de quatro semanas; resultados estéticos variáveis de excelentes a bons. Aos três meses, a resposta clínica foi de 91,2%, sendo reduzida, aos 18 meses, para 73,3%, de modo similar tanto para disceratose de Bowen (72,2% quanto para carcinoma basocelular (75%. Foi evidenciada relação de tendência linear entre a redução da freqüência da resposta clínica e o aumento da dimensão das neoplasias cutâneas não-melanoma (pBACKGROUND: Photodynamic therapy is based on the association of a light source and photosensitizer in order to selectively destroy cells. OBJECTIVE: To evaluate the short and long-term effects, clinical response, and cosmetic outcome of the photodynamic therapy with 5-aminolaevulinic acid for non-melanoma skin cancer. METHODS: TThirty-four non-melanoma skin cancer - 19 Bowen’s diseases and 15 basal cell carcinomas, were submitted to a single 6-hour topical and occlusive application of 20% 5-aminolaevulinic acid, and were later exposed to 630 nm diode laser single session. RESULTS: Burning sensation during the session; erythema, edema and erosions in the first 72 hours; healing process after 4 weeks on average and excellent or good cosmetic results were observed. After 3 months, tumor

  20. geomorphology_delta

    Data.gov (United States)

    California Department of Resources — Surficial geology of the Delta area of California by Brian Atwater of the U.S. Geological Survey. Source maps are from the USGS publication MF-1401. This digital...

  1. Delta-Reliability

    OpenAIRE

    Eugster, P.; Guerraoui, R.; Kouznetsov, P.

    2001-01-01

    This paper presents a new, non-binary measure of the reliability of broadcast algorithms, called Delta-Reliability. This measure quantifies the reliability of practical broadcast algorithms that, on the one hand, were devised with some form of reliability in mind, but, on the other hand, are not considered reliable according to the ``traditional'' notion of broadcast reliability [HT94]. Our specification of Delta-Reliability suggests a further step towards bridging the gap between theory and...

  2. Vitamin D Combined with Aminolevulinate (ALA)-Mediated Photodynamic Therapy (PDT) for Human Psoriasis: A Proof-of-Principle Study.

    Science.gov (United States)

    Maytin, Edward V; Honari, Golara; Khachemoune, Amor; Taylor, Charles R; Ortel, Bernhard; Pogue, Brian W; Sznycer-Taub, Nathaniel; Hasan, Tayyaba

    2012-09-01

    We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis.

  3. Developing management packages for acid sulphate soils based on farmer and expert knowledge : field study in the Mekong Delta, Viet Nam

    NARCIS (Netherlands)

    Quang Tri, Le

    1996-01-01


    Effective interaction of farmers' expertise and expert knowledge has been a special point of attention for this study. The objectives of the study were to describe the process of interaction between farmers and experts in improving the use of acid sulphate soils and to point out difficult

  4. Developing management packages for acid sulphate soils based on farmer and expert knowledge. Field study in the Mekong Delta, Viet Nam.

    NARCIS (Netherlands)

    Le Quang Tri,

    1996-01-01

    Effective interaction of farmers' expertise and expert knowledge has been a special point of attention for this study. The objectives of the study were to describe the process of interaction between farmers and experts in improving the use of acid sulphate soils and to point out difficulties encount

  5. {\\delta}M Formalism

    CERN Document Server

    Talebian-Ashkezari, Alireza; Abolhasani, Ali Akbar

    2016-01-01

    We study the evolution of the "non-perturbative" metric perturbations in a Bianchi background in the long-wavelength limit. By applying the gradient expansion to the equations of motion we exhibit a generalized "Separate Universe" approach to the cosmological perturbation theory. Having found this consistent separate universe picture, we introduce the "{\\delta}M formalism" for calculating the evolution of the tensor perturbations in anisotropic inflation models in almost similar way as the so-called {\\delta}N formula for the super-horizon dynamics of the curvature perturbations. Likewise its ancestor, {\\delta}N formalism, this new method can substantially reduce the amount of calculations related to the evolution of the tensor modes.

  6. The Niger Delta Crisis

    African Journals Online (AJOL)

    chifaou.amzat

    2013-09-28

    Sep 28, 2013 ... lions de barils par jour à environ 1 million au plus fort de la crise du Delta ... (JTF) between 13 May 2009 and 4 October 2009 (the deadline for embrac- ..... He had just ended his welcome address as the occasion's chairman.

  7. Fractionated PDT with 5-aminolevulinic acid: effective, cost effective, and patient friendly

    Science.gov (United States)

    de Vijlder, Hannah C.; Middelburg, Tom A.; de Bruijn, Henriette S.; Robinson, Dominic J.; Neumann, H. A. Martino; de Haas, Ellen R. M.

    2009-06-01

    PDT with ALA and MAL is established as a relatively effective treatment for non-melanoma skin cancer and premalignancies. PDT is often repeated, because a single treatment gives poor long term results. Preclinical studies showed that ALA-PDT applying a fractionated illumination scheme with a small first light fraction and a second larger light fraction separated by a dark interval of two hours resulted in a significant increase in efficacy. Whereas the efficacy was not enhanced by fractionating MAL-PDT, indicating that ALA-PDT mechanism is not the same as MAL-PDT mechanism. The increase in efficacy using fractionated PDT was confirmed clinically. A randomized comparative clinical study comparing fractionated ALA-PDT versus non-fractionated ALA-PDT in the treatment of superficial basal cell carcinoma showed a significant higher response rate in the lesions treated with fractionated ALA-PDT after a follow-up of one year ( pMAL-PDT treatments separated by one week), both reducing direct and indirect costs and the burden to the patient.

  8. Raman spectroscopy of bladder tissue in the presence of 5-aminolevulinic acid

    NARCIS (Netherlands)

    Grimbergen, M. C. M.; van Swol, C. F. P.; van Moorselaar, Rj. A.; Uff, J.; Mahadevan-Jansen, A.; Stone, N.

    2009-01-01

    Raman spectroscopy has the ability to provide differential diagnosis of different cancers with high sensitivity and specificity. A major limitation in its clinical application is the weak nature of Raman signal, which inhibits scanning large surface areas of tissues. In bladder cancer diagnosis, flu

  9. OPTIMIZATIONS FOR 5-AMINOLEVULINIC ACID BASED PHOTODYNAMIC THERAPY IN PURGING LEUKEMIA CELL HL60

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Photodynamictherapy(PDT),whichinvolves administrationofatumorlocalizing photosensiti zingagentthatmayrequiremetabolizingsynthesis(i.e.,aprodrug),followedbyactivationofthea gentbylightofaspecificwavelength.Thistherapy resultsinasequenceofphotochemicalandphotobio logicprocessthatcausesirreversiblephotodamageto tumortissue.SeveralphotosensitizersinPDThavesofar beenappliedtoeradicateresidualtumorcellsinau tograftsandtoreducecontaminationoftumorcells inhemopathy[1-3].However,alltheexogenous photosensitizershavea...

  10. Effects of 5-aminolevulinic acid-mediated sonodynamic therapy on macrophages

    OpenAIRE

    Cheng J; Sun X; Guo S; Chen H.; Jin Y; Li B; Li Q; Wang H; Wang Z.; Zhou Q; Wang P; Zhang Z; Cao W.; Tian Y

    2013-01-01

    Jiali Cheng,1,* Xin Sun,1,2,* Shuyuan Guo,1,* Wei Cao,1 Haibo Chen,1 Yinghua Jin,1 Bo Li,1 Qiannan Li,1 Huan Wang,1 Zhu Wang,3 Qi Zhou,3 Peng Wang,3 Zhiguo Zhang,3 Wenwu Cao,3,4 Ye Tian1,21Division of Cardiology, the First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, Harbin, People’s Republic of China; 2Division of Pathophysiology, the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Minist...

  11. Increased brain edema following 5-aminolevulinic acid mediated photodynamic in normal and tumor bearing rats

    Science.gov (United States)

    Hirschberg, Henry; Angell-Petersen, Even; Spetalen, Signe; Mathews, Marlon; Madsen, Steen J.

    2007-02-01

    Introduction: Failure of treatment for high grade gliomas is usually due to local recurrence at the site of surgical resection indicating that a more aggressive form of local therapy, such as PDT, could be of benefit. PDT causes damage to both tumor cells as well as cerebral blood vessels leading to degradation of the blood brain barrier with subsequent increase of brain edema. The increase in brain edema following ALA-PDT was evaluated in terms of animal survival, histopatological changes in normal brain and tumor tissue and MRI scanning. The effect of steroid treatment, to reduce post-treatment PDT induced edema, was also examined. Methods:Tumors were established in the brains of inbred BD-IX and Fisher rats. At various times following tumor induction the animals were injected with ALA ip. and four hours later light treatment at escalating fluences and fluence rates were given. Nontumor bearing control animals were also exposed to ALA-PDT in a similar manner to evaluate damage to normal brain and degree of blood brain barrier (BBB) disruption. Results: Despite a very low level of PpIX production in normal brain, with a 200:1 tumor to normal tissue selectivity ratio measured at a distance of 2 mm from the tumor border, many animals succumbed shortly after treatment. A total radiant energy of 54 J to non-tumor bearing animals resulted in 50% mortality within 5 days of treatment. Treatment of tumor bearing animals with moderate fluence levels produced similar brain edema compared to higher fluence levels. ALA PDT in nontumor bearing animals produced edema that was light dose dependent. PDT appeared to open the BBB for a period of 24-48 hrs after which it was restored. The addition of post operative steroid treatment reduced the incident of post treatment morbidity and mortality. Conclusions: T2 and contrast enhanced T1 MRI scanning proved to be a highly effective and non-evasive modality in following the development of the edema reaction and the degree and time course of BBB dysfunction thus allowing the use of fewer animals.

  12. Estimation of measurement uncertainty for the quantification of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid and its glucuronide in urine using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Kim, Jin Young; Kwon, Woonyong; Kim, Hee Seung; Suh, Sungill; In, Moon Kyo

    2014-04-01

    Recently, the estimation of the measurement uncertainty has become a significant issue in the quality control of forensic drug testing. In the present study, the uncertainty of the measurement was calculated for the quantification of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and its glucuronide conjugate (THC-COOH-glu) in urine using liquid chromatography-tandem mass spectrometry. The procedure was based on liquid-liquid extraction of a volume of urine (800 µL) with ethyl acetate. The sources of uncertainty were identified and classified into four major categories as follows: standard preparation, calibration curve, method precision and bias. The overall contribution of combined standard uncertainty on THC-COOH increased in the order of standard preparation (0.9%), method precision (10.4%), calibration curve (30.3%) and bias (58.4%) and, while calibration curve (53.0%) and bias (40.4%) gave the bigger contributions to the combined standard uncertainty for THC-COOH-glu than method precision and standard preparation, which accounted for 6.3 and 0.3%, respectively. The reliability of a measurement was expressed by stating the expanded uncertainty of the measurement result at 95% confidence level. The concentrations of THC-COOH and THC-COOH-glu in the urine sample with their expanded uncertainties were 10.20 ± 1.14 ng/mL and 25.42 ± 5.01 ng/mL, respectively.

  13. The relation between methyl aminolevulinate concentration and inflammation after photodynamic therapy in healthy volunteers

    DEFF Research Database (Denmark)

    Fabricius, Susanne; Lerche, Catharina Margrethe; Philipsen, Peter Alshede;

    2013-01-01

    Inflammation and pain are well known adverse-effects in photodynamic therapy (PDT). There is currently a tendency towards introducing lower concentrations of the photosensitizer than used in the standard treatment for various indications. The aim of this study was to investigate whether reduced...... concentrations of methyl aminolevulinate (MAL) can reduce inflammation (erythema) during PDT treatment. We measured the formation of protoporphyrin IX (PpIX) using fluorescence and monitored both erythema and pain during and after PDT treatment with conventional 16% MAL and threee reduced concentrations of 2, 0.......75, and 0.25% in twenty-four healthy volunteers. We found that lowering the MAL concentration reduced PpIX fluorescence and erythema after PDT treatment. There was a strong correlation (R(2) = 0.70) between the PpIX fluorescence and erythema after treatment. A further increase in erythema after PDT...

  14. Daylight photodynamic therapy with methyl-aminolevulinate for the treatment of actinic cheilitis.

    Science.gov (United States)

    Fai, Dario; Romanello, Eugenio; Brumana, Marta Benedetta; Fai, Carlotta; Vena, Gino Antonio; Cassano, Nicoletta; Piaserico, Stefano

    2015-01-01

    Actinic cheilitis (AC) is a common premalignant condition that requires an effective treatment to reduce the risk of malignant transformation. Photodynamic therapy (PDT) has been recently added to the armamentarium available for AC treatment. Daylight PDT (D-PDT) is a novel PDT modality in which the activation of the topical photosensitizer is induced by the exposure to natural daylight instead of artificial light sources without preliminary occlusion. This simplified procedure was found to be more tolerated as compared to conventional PDT. We report our preliminary experience on the use of D-PDT using methyl-aminolevulinate cream in 10 patients with refractory AC of the lower lip. Patients received two consecutive D-PDT sessions with an interval of 7-14 days. At 3 months after therapy, a complete response was observed in seven patients, with sustained results in five patients over an observational period of 6-12 months. Treatment was well tolerated.

  15. Responses to hexyl 5-aminolevulinate-induced photodynamic treatment in rat bladder cancer model

    Science.gov (United States)

    Arum, Carl-Jørgen; Gederas, Odrun; Larsen, Eivind; Randeberg, Lise; Zhao, Chun-Mei

    2010-02-01

    OBJECTIVES: In this study, we evaluated histologically the effects of hexyl 5-aminolevulinateinduced photodynamic treatment in the AY-27 tumor cell induced rat bladder cancer model. MATERIAL & METHODS: The animals (fischer-344 female rats) were divided into 2 groups, half of which were orthotopically implanted with 400,000 syngeniec AY-27 urothelia1 rat bladder cancer cells and half sham implanted. 14 days post implantation 6 rats from each group were treated with hexyl 5-aminolevulinate-induced photodynamic treatment (8mM HAL and light fluence of 20 J/cm2). Additional groups of animals were only given HAL instillation, only light treatment, or no treatment. All animals were sacrificed 7 days after the PDT/only HAL/only light or no treatment. Each bladder was removed, embedded in paraffin and stained with hematoxylin, eosin, and saferin for histological evaluation at high magnification for features of tissue damage by a pathologist blinded to the sample source. RESULTS: In all animals that were AY-27 implanted and not given complete PDT treatment, viable tumors were found in the bladder mucosa and wall. In the animals treated with complete HAL-PDT only 3 of 6 animals had viable tumor. In the 3 animals with viable tumor it was significantly reduced in volume compared to the untreated animals. It was also noted that in the PDT treated animals there was a significantly increased inflammatory response (lymphocytic and mononuclear cell infiltration) in the peri-tumor area compared to implanted animals without complete HAL-PDT. CONCLUSION: Our results suggest that hexyl 5-aminolevulinate-induced photodynamic treatment in a rat bladder cancer model involves both direct effects on cell death (necrosis and apoptosis) and indirect effects to evoke the host immune-response, together contributing to tumor eradication.

  16. DELTAS: A new Global Delta Sustainability Initiative (Invited)

    Science.gov (United States)

    Foufoula-Georgiou, E.

    2013-12-01

    Deltas are economic and environmental hotspots, food baskets for many nations, home to a large part of the world population, and hosts of exceptional biodiversity and rich ecosystems. Deltas, being at the land-water interface, are international, regional, and local transport hubs, thus providing the basis for intense economic activities. Yet, deltas are deteriorating at an alarming rate as 'victims' of human actions (e.g. water and sediment reduction due to upstream basin development), climatic impacts (e.g. sea level rise and flooding from rivers and intense tropical storms), and local exploration (e.g. sand or aggregates, groundwater and hydrocarbon extraction). Although many efforts exist on individual deltas around the world, a comprehensive global delta sustainability initiative that promotes awareness, science integration, data and knowledge sharing, and development of decision support tools for an effective dialogue between scientists, managers and policy makers is lacking. Recently, the international scientific community proposed to establish the International Year of Deltas (IYD) to serve as the beginning of such a Global Delta Sustainability Initiative. The IYD was proposed as a year to: (1) increase awareness and attention to the value and vulnerability of deltas worldwide; (2) promote and enhance international and regional cooperation at the scientific, policy, and stakeholder level; and (3) serve as a launching pad for a 10-year committed effort to understand deltas as complex socio-ecological systems and ensure preparedness in protecting and restoring them in a rapidly changing environment. In this talk, the vision for such an international coordinated effort on delta sustainability will be presented as developed by a large number of international experts and recently funded through the Belmont Forum International Opportunities Fund. Participating countries include: U.S., France, Germany, U.K., India, Japan, Netherlands, Norway, Brazil, Bangladesh

  17. Gamma-delta T lymphocytes and 25-hydroxy vitamin D levels as key factors in autoimmunity and inflammation: the case of zoledronic acid-induced acute phase reaction.

    Science.gov (United States)

    De Santis, M; Cavaciocchi, F; Ceribelli, A; Crotti, C; Generali, E; Fabbriciani, G; Selmi, C; Massarotti, M

    2015-04-01

    Zoledronic acid (ZA) infusion for osteoporosis is frequently associated with the onset of an acute phase reaction (APR) secondary to the activation of γδ T cell receptor (TCR) lymphocytes (γδ T cells) and to low vitamin D levels, similar to what is observed in chronic inflammation and autoimmunity. In this study we investigated whether the phenotype of γδ T cells is associated with APR and 25-OH vitamin D (25-OHvD) levels. For flow-cytometry analysis, peripheral blood samples were obtained from 52 osteoporotic women prior to 5 mg ZA intravenous infusion and from nine women (five with APR) one week later. Twenty-six/52 (50%) patients reported APR and APR+ cases had a higher percentage of central memory Th1-like γδ T cells. One week after ZA infusion, APR was associated with a decreased percentage of central memory Th1-like γδ T cells, an increase in the percentage and activation of effector memory Th1-like γδ T cells, and an increase in Th17-like γδ T cells. Lower 25-OHvD levels were significantly associated with APR, but no correlation was found between 25-OHvD level and γδ T cell percentage or subsets. In conclusion, patients experiencing APR related to ZA infusion have lower 25-OHvD levels and we suggest that the higher percentage of central memory Th1-like γδ T cells and the expansion of effector memory Th1-like and Th17-like γδ T cells are associated with the occurrence of APR.

  18. Do cytochromes function as oxygen sensors in the regulation of nitrate reductase biosynthesis?

    Science.gov (United States)

    MacGregor, C H; Bishop, C W

    1977-01-01

    The observation that oxygen represses nitrate reductase biosynthesis in a hemA mutant grown aerobically with or without delta-aminolevulinic acid indicates that cytochromes are not responsible for nitrate reductase repression in aerobically grown cells. PMID:326768

  19. Transgenic expression of salmon delta-5 and delta-6 desaturase in zebrafish muscle inhibits the growth of Vibrio alginolyticus and affects fish immunomodulatory activity.

    Science.gov (United States)

    Wang, Yi-Da; Peng, Kuan-Chieh; Wu, Jen-Leih; Chen, Jyh-Yih

    2014-08-01

    Marine fish are an important nutritional source for highly polyunsaturated fatty acids (PUFAs). PUFA biosynthesis requires the following key enzymes: delta-4 (Δ-4) desaturase, delta-5 (Δ-5) desaturase, delta-6 (Δ-6) desaturase, delta-5 (Δ-5) elongase, and delta-6 (Δ-6) elongase. The effect of overexpressing delta-5 desaturase and/or delta-6 desaturase in zebrafish muscle has not previously been reported. Herein, we investigated the effects of these proteins on antibacterial and immunomodulatory activity in transgenic zebrafish infected with Vibrio alginolyticus. Overexpression of delta-5 and delta-6 desaturase enhanced antibacterial activity at 4 and 12 h after injection of bacteria into muscle, as compared to controls. Furthermore, expression of immune-related genes (IL-1β, IL-22, and TNF-α) was observed to be altered in transgenic fish after 4 h of bacterial infection, resulting in a significant decrease in the inflammatory response, as compared to control fish. These results demonstrate that muscle-specific expression of transgenic desaturases in zebrafish not only enhance PUFA production, but also enhance antibacterial and anti-inflammatory activity. Overall, these results identify delta-5 and delta-6 desaturase as novel candidate genes for use in aquaculture, to enhance both disease resistance and fish oil production.

  20. Timelike gamma* N -> Delta form factors and Delta Dalitz decay

    CERN Document Server

    Ramalho, G

    2012-01-01

    We extend a covariant model, tested before in the spacelike region for the physical and lattice QCD regimes, to a calculation of the gamma* N -> Delta reaction in the timelike region, where the square of the transfered momentum, q^2, is positive (q^2>0). We estimate the Dalitz decay Delta -> Ne+e- and the Delta distribution mass distribution function. The results presented here can be used to simulate the NN -> NNe+e- reactions at moderate beam kinetic energies.

  1. Delta II commercial space transportation

    Science.gov (United States)

    Meyers, J. F.

    1988-07-01

    Delta II is an upgraded variant of the Delta family of launch vehicles that has been in use by NASA since 1960. Among the design improvements incorporated by Delta II is a cryogenic-propellant second stage, a 2.89-m diameter satellite-protecting nose fairing, graphite/epoxy solid rocket motor cases, and 12:1 main engine expansion nozzle. The manufacturer/operator offers Delta II customers a dedicated, single satellite launch capability fully tailored to the given spacecraft's unique mission requirements.

  2. Expression profiling of peroxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissue microarray.

    Science.gov (United States)

    Higashiyama, Hiroyuki; Billin, Andrew N; Okamoto, Yuji; Kinoshita, Mine; Asano, Satoshi

    2007-05-01

    Peroxisome proliferator-activated receptor-delta (PPAR-delta) is known as a transcription factor involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in several tissues, such as skeletal muscle, liver and adipose tissues. In this study, to elucidate systemic physiological functions of PPAR-delta, we examined the tissue distribution and localization of PPAR-delta in adult mouse tissues using tissue microarray (TMA)-based immunohistochemistry. PPAR-delta positive signals were observed on variety of tissues/cells in multiple systems including cardiovascular, urinary, respiratory, digestive, endocrine, nervous, hematopoietic, immune, musculoskeletal, sensory and reproductive organ systems. In these organs, PPAR-delta immunoreactivity was generally localized on the nucleus, although cytoplasmic localization was observed on several cell types including neurons in the nervous system and cells of the islet of Langerhans. These expression profiling data implicate various physiological roles of PPAR-delta in multiple organ systems. TMA-based immunohistochemistry enables to profile comprehensive protein localization and distribution in a high-throughput manner.

  3. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia

  4. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia wh

  5. Peat compaction in deltas : implications for Holocene delta evolution

    NARCIS (Netherlands)

    van Asselen, S.|info:eu-repo/dai/nl/304838101

    2010-01-01

    Many deltas contain substantial amounts of peat, which is the most compressible soil type. Therefore, peat compaction potentially leads to high amounts of subsidence in deltas. The main objective of this research was to quantify subsidence due to peat compaction in Holocene fluvial-deltaic settings

  6. Phenotypic expressions of CCR5-Delta 32/Delta 32 homozygosity

    NARCIS (Netherlands)

    Nguyen, GT; Carrington, M; Beeler, JA; Dean, M; Aledort, LM; Blatt, PM; Cohen, AR; DiMichele, D; Eyster, ME; Kessler, CM; Konkle, B; Leissinger, C; Luban, N; O'Brien, SJ; Goedert, JJ; O'Brien, TR

    1999-01-01

    Objective: As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-Delta 32/Delta 32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Design: Study subjects were white homosexual men or men with hemophilia wh

  7. Positive response of a recurrent keloid scar to topical methyl aminolevulinate-photodynamic therapy.

    Science.gov (United States)

    Nie, Zhuxiang; Bayat, Ardeshir; Behzad, Farhad; Rhodes, Lesley E

    2010-12-01

    A 36-year-old Caucasian female of Iranian origin presented with a persistently raised dermal lesion under her chin, confirmed histologically to be a keloid scar. There was a 4-year history of a negative response to a range of conventional treatments including topical silicone gel sheets, steroid creams, steroid injections and surgical excision. In view of treatment failure and an in vitro study indicating a positive effect of photodynamic therapy (PDT)on keloid fibroblasts, we treated our patient's lesion with five sessions of methyl aminolevulinate photodynamic therapy (MAL-PDT) over a period of 5 months. Following this treatment regime, her keloid scar had considerably reduced in size and become flattened.The surface of the keloid also became smooth, with attenuation in erythema at the margin as well as an improvement in the colour of the scar, which was better matched to the surrounding skin. There was no recurrence at 1-year follow-up and this treatment resulted in an overall acceptable cosmetic outcome. This case report presents PDT as a potential treatment option for persistent keloid lesions unresponsive to conventional scar modulation therapies and suggests a need for further research in this area.

  8. Acne treatment by methyl aminolevulinate photodynamic therapy with red light vs. intense pulsed light.

    Science.gov (United States)

    Hong, Jong Soo; Jung, Jae Yoon; Yoon, Ji Young; Suh, Dae Hun

    2013-05-01

    Various methods of photodynamic therapy (PDT) for acne have been introduced. However, comparative studies among them are still needed. We performed this study to compare the effect of methyl aminolevulinate (MAL) PDT for acne between red light and intense pulsed light (IPL). Twenty patients were enrolled in this eight-week, prospective, split-face study. We applied MAL cream over the whole face with a three-hour incubation time. Then patients were irradiated with 22 J/cm(2) of red light on one-half of the face and 8-10 J/cm(2) of IPL on the other half during each treatment session. We performed three treatment sessions at two-week intervals and followed-up patients until four weeks after the last session. Inflammatory and non-inflammatory acne lesions were reduced significantly on both sides. The red light side showed a better response than the IPL side after the first treatment. Serious adverse effects after treatment were not observed. MAL-PDT with red light and IPL are both an effective and safe modality in acne treatment. Red light showed a faster response time than IPL. After multiple sessions, both light sources demonstrated satisfactory results. We suggest that reducing the total dose of red light is desirable when performing MAL-PDT in Asian patients with acne compared with Caucasians.

  9. Aminolevulinate dehydrogenase polymorphisms did not modified lead serum and memory relationship

    Directory of Open Access Journals (Sweden)

    Lantip Rujito

    2012-12-01

    Full Text Available Background Lead accumulation in the blood widely known affecting the formation of heme and oxygen transport processes in vital organs, Leading to organ failure including the brain synapses. Lead affinity has been recognized influenced by constitutional genotype of aminolevulinate dehydrogenase (ALAD, which encodes for heme synthesis. This research aimed to determine the relationship between plumbum (Pb and short term memory on each ALAD gene genotyping (ALAD 1-1, ALAD 1-2 or ALAD 2-2 in gas station workers. Methods Seventy six probands from gas station workers were recruited to participate in this research. Each probands was carried out ALAD genotyping using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method, lead serum level using atomic absorbent spectrophotometer (AAS, and short term memory was measurement by intelligence structure test (IST. Results Proportion of d ALAD 1-1, 1-2, and 2-2 were 91.8%, 8.2% and 0% respectively. Lead serum showed 15.84 ppb in homozygous 1-1, and 20.79 ppb in heterozygous. Short term memory in the probands varied from 85 until 117, with average in 99.71. There was significant negative relationship between lead serum and short term memory (r=-0.24; p=0.038. However, we could not find any significant correlation in each d ALAD genotypes. Conclusion The d ALAD genotypes did not modified the relationship between serum lead level and short term memory in gas station workers.

  10. Identification of regulatory sequences in the gene for 5-aminolevulinate synthase from rat.

    Science.gov (United States)

    Braidotti, G; Borthwick, I A; May, B K

    1993-01-15

    The housekeeping enzyme 5-aminolevulinate synthase (ALAS) regulates the supply of heme for respiratory cytochromes. Here we report on the isolation of a genomic clone for the rat ALAS gene. The 5'-flanking region was fused to the chloramphenicol acetyltransferase gene and transient expression analysis revealed the presence of both positive and negative cis-acting sequences. Expression was substantially increased by the inclusion of the first intron located in the 5'-untranslated region. Sequence analysis of the promoter identified two elements at positions -59 and -88 bp with strong similarity to the binding site for nuclear respiratory factor 1 (NRF-1). Gel shift analysis revealed that both NRF-1 elements formed nucleoprotein complexes which could be abolished by an authentic NRF-1 oligomer. Mutagenesis of each NRF-1 motif in the ALAS promoter gave substantially lowered levels of chloramphenicol acetyltransferase expression, whereas mutagenesis of both NRF-1 motifs resulted in the almost complete loss of expression. These results establish that the NRF-1 motifs in the ALAS promoter are critical for promoter activity. NRF-1 binding sites have been identified in the promoters of several nuclear genes encoding mitochondrial proteins concerned with oxidative phosphorylation. The present studies suggest that NRF-1 may co-ordinate the supply of mitochondrial heme with the synthesis of respiratory cytochromes by regulating expression of ALAS. In erythroid cells, NRF-1 may be less important for controlling heme levels since an erythroid ALAS gene is strongly expressed and the promoter for this gene apparently lacks NRF-1 binding sites.

  11. Aminolevulinate dehydrogenase polymorphisms did not modified lead serum and memory relationship

    Directory of Open Access Journals (Sweden)

    Lantip Rujito

    2015-12-01

    Full Text Available BACKGROUND Lead accumulation in the blood widely known affecting the formation of heme and oxygen transport processes in vital organs, Leading to organ failure including the brain synapses. Lead affinity has been recognized influenced by constitutional genotype of aminolevulinate dehydrogenase (ALAD, which encodes for heme synthesis. This research aimed to determine the relationship between plumbum (Pb and short term memory on each ALAD gene genotyping (ALAD 1-1, ALAD 1-2 or ALAD 2-2 in gas station workers. METHODS Seventy six probands from gas station workers were recruited to participate in this research. Each probands was carried out ALAD genotyping using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP method, lead serum level using atomic absorbent spectrophotometer (AAS, and short term memory was measurement by intelligence structure test (IST. RESULTS Proportion of δ ALAD 1-1, 1-2, and 2-2 were 91.8%, 8.2% and 0% respectively. Lead serum showed 15.84 ppb in homozygous 1-1, and 20.79 ppb in heterozygous. Short term memory in the probands varied from 85 until 117, with average in 99.71. There was significant negative relationship between lead serum and short term memory (r=-0.24; p=0.038. However, we could not find any significant correlation in each δ ALAD genotypes. CONCLUSION The δ ALAD genotypes did not modified the relationship between serum lead level and short term memory in gas station workers.

  12. Liver δ-Aminolevulinate Dehydratase Activity is Inhibited by Neonicotinoids and Restored by Antioxidant Agents

    Directory of Open Access Journals (Sweden)

    Elisa Sauer

    2014-11-01

    Full Text Available Neonicotinoids represent the most used class of insecticides worldwide, and their precursor, imidacloprid, is the most widely marketed. The aim of this study was to evaluate the effect of imidacloprid on the activity of hepatic δ-aminolevulinate dehydratase (δ-ALA-D, protective effect of potential antioxidants against this potential effect and presence of chemical elements in the constitution of this pesticide. We observed that δ-ALA-D activity was significantly inhibited by imidacloprid at all concentrations tested in a dose-dependent manner. The IC50 value was obtained and used to evaluate the restoration of the enzymatic activity. δ-ALA-D inhibition was completely restored by addition of dithiotreitol (DTT and partly by ZnCl2, demonstrating that the inhibition occurs by oxidation of thiol groups and by displacement of the Zn (II, which can be explained by the presence of chemical elements found in the constitution of pesticides. Reduced glutathione (GSH had the best antioxidant effect against to δ-ALA-D inhibition caused by imidacloprid, followed by curcumin and resveratrol. It is well known that inhibition of the enzyme δ-ALA-D may result in accumulation of its neurotoxic substrate (δ-ALA, in this line, our results suggest that further studies are needed to investigate the possible neurotoxicity induced by neonicotinoids and the involvement of antioxidants in cases of poisoning by neonicotinoids.

  13. $\\Delta$-N Electromagnetic Transition

    CERN Document Server

    Loan, M

    1999-01-01

    The EM ratio for a free Delta electromagnetic transition is discussed within the frame work of nonrelativistic approach. Such an approach gives a good account of data for a free Delta but is less important for an intrinsically relativistic nuclear many body problem.

  14. Mida pakub Delta? / Teele Kurm

    Index Scriptorium Estoniae

    Kurm, Teele

    2011-01-01

    Politsei- ja Piirivalveamet võtab kasutusele ühise Siseministeeriumi infotehnoloogia- ja arenduskeskuse ning Webmedia AS koostööna loodud dokumendihaldussüsteemi Delta. Kust sai Delta oma nime? Projekti "Dokumendihaldussüsteemi juurutamine Siseministeeriumi haldusalas" eesmärgid

  15. Delta Electroproduction in 12-C

    Energy Technology Data Exchange (ETDEWEB)

    Steven McLauchlan

    2003-01-31

    The Delta-nucleus potential is a crucial element in the understanding of the nuclear system. Previous electroexcitation measurements in the delta region reported a Q2 dependence of the delta mass indicating that this potential is dependent on the momentum of the delta. Such a dependence is not observed for protons and neutrons in the nuclear medium. This thesis presents the experimental study of the electroexcitation of the delta resonance in 12C, performed using the high energy electron beam at the Thomas Jefferson National Accelerator Facility, and the near 4(pie) acceptance detector CLAS that enables the detection of the full reaction final state. Inclusive, semi inclusive, and exclusive cross sections were measured with an incident electron beam energy of 1.162GeV over the Q2 range 0.175-0.475 (GeV/c)2. A Q2 dependence of the delta mass was only observed in the exclusive measurements indicating that the delta-nucleus potential is affected by the momentum of the delta.

  16. Mida pakub Delta? / Teele Kurm

    Index Scriptorium Estoniae

    Kurm, Teele

    2011-01-01

    Politsei- ja Piirivalveamet võtab kasutusele ühise Siseministeeriumi infotehnoloogia- ja arenduskeskuse ning Webmedia AS koostööna loodud dokumendihaldussüsteemi Delta. Kust sai Delta oma nime? Projekti "Dokumendihaldussüsteemi juurutamine Siseministeeriumi haldusalas" eesmärgid

  17. Mackenzie River Delta, Canada

    Science.gov (United States)

    2007-01-01

    The Mackenzie River in the Northwest Territories, Canada, with its headstreams the Peace and Finley, is the longest river in North America at 4241 km, and drains an area of 1,805,000 square km. The large marshy delta provides habitat for migrating Snow Geese, Tundra Swans, Brant, and other waterfowl. The estuary is a calving area for Beluga whales. The Mackenzie (previously the Disappointment River) was named after Alexander Mackenzie who travelled the river while trying to reach the Pacific in 1789. The image was acquired on August 4, 2005, covers an area of 55.8 x 55.8 km, and is located at 68.6 degrees north latitude, 134.7 degrees west longitude. The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  18. DELTA 3D PRINTER

    Directory of Open Access Journals (Sweden)

    ȘOVĂILĂ Florin

    2016-07-01

    Full Text Available 3D printing is a very used process in industry, the generic name being “rapid prototyping”. The essential advantage of a 3D printer is that it allows the designers to produce a prototype in a very short time, which is tested and quickly remodeled, considerably reducing the required time to get from the prototype phase to the final product. At the same time, through this technique we can achieve components with very precise forms, complex pieces that, through classical methods, could have been accomplished only in a large amount of time. In this paper, there are presented the stages of a 3D model execution, also the physical achievement after of a Delta 3D printer after the model.

  19. Sex pheromone biosynthesis in the processionary moth Thaumetopoea pityocampa by delta-13 desaturation.

    Science.gov (United States)

    Arsequell, G; Fabriàs, G; Camps, F

    1990-01-01

    In vivo treatments of female sex pheromone glands of the processionary moth, Thaumetopoea pityocampa, with mass-labeled fatty acids showed that (Z)-13-hexadecen-11-ynyl acetate, the main sex pheromone component, is biosynthesized from palmitic acid by the combined action of delta-11 and delta-13 desaturases. The involvement of this unusual delta-13 has been proven by application of [16,16,16-2H3] [1,2-13C2]-hexadecanoic acid to the glands with a resultant incorporation of all labeled atoms into the pheromone and each one of the corresponding intermediates. These results seem to exclude alternative biosynthetic pathways, such as chain shortening and elongation combined with delta-11 desaturation. The delta-11 desaturase responsible for the formation of the triple bond in both the 11-hexadecynoyl and (Z)-13-hexadecen-11-ynoyl intermediates is also an unusual enzyme not previously reported in lepidopteran sex pheromone biosynthesis.

  20. Potent delta-opioid receptor agonists containing the Dmt-Tic pharmacophore.

    Science.gov (United States)

    Balboni, Gianfranco; Salvadori, Severo; Guerrini, Remo; Negri, Lucia; Giannini, Elisa; Jinsmaa, Yunden; Bryant, Sharon D; Lazarus, Lawrence H

    2002-12-01

    Conversion of delta-opioid receptor antagonists containing the 2',6'-dimethyl-L-tyrosine (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) pharmacophore into potent delta-agonists required a third heteroaromatic nucleus, such as 1H-benzimidazole-2-yl (Bid) and a linker of specified length both located C-terminally to Tic in the general formula H-Dmt-Tic-NH-CH(R)-R'. The distance between Tic and Bid is a determining factor responsible for the acquisition of delta agonism (2, 2', 3, 4, 6) or delta antagonism (8). Compounds containing a C-terminal Ala (1, 1'), Asp (5), or Asn (7) with an amide (1, 1', 5) or free acid group (7) served as delta-antagonist controls lacking the third heteroaromatic ring. A change in chirality of the spacer (2, 2') or inclusion of a negative charge via derivatives of Asp (4, 6) resulted in potent delta agonism and moderate mu agonism, although delta-receptor affinity decreased about 10-fold for 4 while mu affinity fell by over 2 orders of magnitude. Repositioning of the negative charge in the linker altered activity: H-Dmt-Tic-NH-CH(CH(2)-Bid)COOH (6) maintained high delta affinity (K(i) = 0.042 nM) and delta agonism (IC(50) = 0.015 nM), but attachment of the free acid group to Bid [H-Dmt-Tic-NH-CH(2)-Bid(CH(2)-COOH) (9)] reconstituted delta antagonism (K(e) = 0.27 nM). The data demonstrate that a linker separating the Dmt-Tic pharmacophore and Bid, regardless of the presence of a negative charge, is important in the acquisition of opioids exhibiting potent delta agonism and weak mu agonism from a parent delta antagonist.

  1. WORLD DELTAS AND THEIR EVOLUTION

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    In August 1998, an international symposium on the world deltas was held in New Orleans, Louisiana, USA. This symposium attracted discussion about more than 25 deltas from around the world with emphasis placed on those that are most densely populated and impacted by humans. Keynote papers printed details about the physical, biological, engineering and socioeconomic aspects of six deltas including the Mississippi, Nile, Ganges-Brahmaputra, Rhine-Meuse, Changjiang and Po. The main purpose of this symposium was to inform scientists, engineers and decision-makers about information that is currently available and to provide them a basis for working in such environments.

  2. Dynamical Casimir effect with $\\delta-\\delta^{\\prime}$ mirrors

    CERN Document Server

    Silva, Jeferson Danilo L; Alves, Danilo T

    2016-01-01

    We calculate the spectrum and the total rate of created particles for a real massless scalar field in $1+1$ dimensions, in the presence of a partially transparent moving mirror simulated by a Dirac $\\delta-\\delta^{\\prime}$ point interaction. We show that, strikingly, a partially reflecting mirror can produce a larger number of particles in comparison with a perfectly reflecting one. In the limit of a perfect mirror, our formulas recover those found in the literature for the Robin boundary condition.

  3. 5-Aminolevulinate production by Escherichia coli containing the Rhodobacter sphaeroides hemA gene

    Energy Technology Data Exchange (ETDEWEB)

    Van Der Werf, M.J. [Michigan State Univ., East Lansing, MI (United States); Zeikus, J.G. [Michigan State Univ., East Lansing, MI (United States)]|[MBI International, Lansing, MI (United States)

    1996-10-01

    The Rhodobacter sphaeroides hemA gene codes for 5-aminolevulinate (ALA) synthase. This enzyme catalyzes the pyridoxal phosphate-dependent condensation of succinyl coenzyme A and glycine-forming ALA. The R. sphaeroides hemA gene in the pUC18/19 vector system was transformed into Escherichia coli. The effects of both genetic and physiological factors on the expression of ALA synthase and the production of ALA were studied. ALA synthase activity levels were maximal when hemA had the same transcription direction as the lac promoter. The distance between the lac promoter and hemA affected the expression of ALA synthase on different growth substrates. The E. coli host strain used had an enormous effect on the ALA synthase activity level and on the production of ALA, with E. coli DH1 being best suited. The ALA synthase activity level was also dependent on the carbon source. Succinate, L-malate, fumarate, and L-aspartate gave the highest levels of ALA synthase activity, while the use of lactose as a carbon source resulted in a repression of ALA synthase. After growth on succinate, ALA synthase represented {approx}5% of total cellular protein. The ALA synthase activity level was also dependent on the pH of the medium, with maximal activity occurring at pH 6.5. ALA production by whole cells was limited by the availability of glycine, and the addition of 2 g of glycine per liter to the growth medium increased the production of ALA fivefold, to 2.25 mM. In recombinant E. coli extracts, up to 22 mM ALA was produced from succinate, glycine, and ATP. 58 refs., 4 figs., 7 tabs.

  4. Low-dose Methotrexate Enhances Aminolevulinate-based Photodynamic Therapy in Skin Carcinoma Cells In-vitro and In-vivo

    Science.gov (United States)

    Anand, Sanjay; Honari, Golara; Hasan, Tayyaba; Elson, Paul; Maytin, Edward V.

    2009-01-01

    Purpose To improve treatment efficacy and tumor cell selectivity of δ-aminolevulinic acid (ALA)-based photodynamic therapy (PDT), via pretreatment of cells and tumors with methotrexate (MTX) to enhance intracellular photosensitizer levels. Experimental Design Skin carcinoma cells, in-vitro and in-vivo, served as the model system. Cultured human SCC13 and HEK1 cells, normal keratinocytes, and in-vivo skin tumor models (see below) were preconditioned with MTX for 72 h, then incubated with ALA for 4 h. Changes in PpIX levels and in cell survival after light exposure were assessed. Results MTX-preconditioning of monolayer cultures preferentially raised intracellular PpIX levels 2- to 4-fold in carcinoma cells versus normal keratinocytes. Photodynamic killing was synergistically enhanced by the combined therapy, compared to PDT alone. MTX enhancement of PpIX levels was achieved over a broad MTX concentration range (0.0003 – 1.0 mg/L; 0.6 nM – 2 mM). PpIX enhancement correlated with changes in protein expression of key porphyrin pathway enzymes, i.e. ~4-fold increase in coproporphyrinogen oxidase, and stable or slightly decreased expression of ferrochelatase. Differentiation markers (E-cadherin, involucrin, filaggrin) were also selectively induced by MTX in carcinoma cells. In-vivo relevance was established by showing that MTX preconditioning enhances PpIX accumulation in three models: (1) organotypic cultures of immortalized keratinocytes; (2) chemically-induced skin tumors in mice; and (3) human A431 squamous cell tumors implanted subcutaneously in mice. Conclusion Combination therapy using short-term exposure to low-dose MTX followed by ALA-PDT should be further investigated as a new combination modality to enhance efficacy and selectivity of PDT for epithelial carcinomas. PMID:19447864

  5. PARAMETRIC DESIGN OF DELTA ROBOT

    Directory of Open Access Journals (Sweden)

    Mert Gürgen

    2016-09-01

    Full Text Available This article describes a sophisticated determination and presentation of a workspace volume for a delta robot, with consideration of its kinematic behavior. With the help of theoretical equations, optimization is performed with the aid of the stiffness and dexterity analysis. Theoretical substructure is coded in Matlab and three-dimensional (3D data for delta robot are developed in computer-aided design (CAD environment. In later stages of the project, both 3D and theoretical data are linked together and thus, with the changing design parameter of the robot itself, the Solidworks CAD output adapts and regenerates output with a new set of parameters. To achieve an optimum workspace volume with predefined parameters, a different set of robot parameters are iterated through design optimization in Matlab, and the delta robot design is finalized and illustrated in the 3D CAD environment, Solidworks. This study provides a technical solution to accomplish a generic delta robot with optimized workspace volume.

  6. [Primary structure of delta-latroinsectotoxin from venom of the Latrodectus mactans tredecimguttatus spider].

    Science.gov (United States)

    Dulubova, I E; Khvoshchev, M V; Krasnoperov, V G; Galkina, T G; Pluzhnikov, K A; Volkova, T M; Grishin, E V

    1996-01-01

    The structural gene of delta-latroinsectotoxin was cloned and its nucleotide sequence was determined. The gene contains an open reading frame of 3642 bp. The deduced amino acid sequence is homologous to the sequences of latrotoxins studied earlier.

  7. The clinical efficacy of topical methyl-aminolevulinate photodynamic therapy in moderate to severe actinic keratoses of the face and scalp.

    NARCIS (Netherlands)

    Kleinpenning, M.M.; Kerkhof, P.C.M. van de; Gerritsen, M.J.P.

    2010-01-01

    INTRODUCTION: Since actinic keratoses (AKs) often appear in areas with field cancerization, photodynamic therapy (PDT) may have significant advantages over the standard treatment options. Objectives: Clinical efficacy of PDT with topical methyl aminolevulinate (MAL-PDT) in field cancerization was ev

  8. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial.

    NARCIS (Netherlands)

    Morton, C.; Horn, M.; Leman, J.; Tack, B.; Bedane, C.; Tjioe, M.; Ibbotson, S.; Khemis, A.; Wolf, P.

    2006-01-01

    OBJECTIVE: To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ. DESIGN: Randomized, placebo-controlled study, with follow-up at 3 and 1

  9. Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment

    DEFF Research Database (Denmark)

    Rubel, D M; Spelman, L; Murrell, D F

    2014-01-01

    BACKGROUND: Daylight photodynamic therapy (DL-PDT) of actinic keratosis (AK) has shown preliminary efficacy and safety results comparable to conventional photodynamic therapy (c-PDT), using methyl aminolevulinate (MAL) cream. OBJECTIVES: To demonstrate the efficacy and safety of DL-PDT vs. c...

  10. Influence des contraintes édaphiques sur la nutrition minérale, le développement et la production du cocotier (Cocos nucifera L.) dans des sols sulfatés acides salés ou non salés du delta du Mékong : effet améliorant d'un apport de phosphate naturel

    OpenAIRE

    Diep, Thi My Hanh

    1994-01-01

    La production d'huile végétale est un enjeu économique majeur au Viet Nam. Cependant, l'extension de la culture du cocotier à des sols sulfatés acides ou sulfatés acides salés, carencés en phosphore et en calcium, a entraîné une chute importante de la production par comparaison aux sols alluviaux. Ces carences ont été confirmées par le diagnostic foliaire mais aussi racinaire. Les potentiels hydriques élevés montrent que le cocotier ne souffre pas de stress hydrique dans le delta du Mékong mê...

  11. Student Difficulties with the Dirac Delta Function

    CERN Document Server

    Wilcox, Bethany R

    2014-01-01

    The Dirac delta function is a standard mathematical tool used in multiple topical areas in the undergraduate physics curriculum. While Dirac delta functions are usually introduced in order to simplify a problem mathematically, students often struggle to manipulate and interpret them. To better understand student difficulties with the delta function at the upper-division level, we examined responses to traditional exam questions and conducted think-aloud interviews. Our analysis was guided by an analytical framework that focuses on how students activate, construct, execute, and reflect on the Dirac delta function in physics. Here, we focus on student difficulties using the delta function to express charge distributions in the context of junior-level electrostatics. Challenges included: invoking the delta function spontaneously, constructing two- and three-dimensional delta functions, integrating novel delta function expressions, and recognizing that the delta function can have units.

  12. Evaluation of the Dmt-Tic pharmacophore: conversion of a potent delta-opioid receptor antagonist into a potent delta agonist and ligands with mixed properties.

    Science.gov (United States)

    Balboni, Gianfranco; Guerrini, Remo; Salvadori, Severo; Bianchi, Clementina; Rizzi, Daniela; Bryant, Sharon D; Lazarus, Lawrence H

    2002-01-31

    Analogues of the 2',6'-dimethyl-L-tyrosine (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) pharmacophore were prepared to test the hypothesis that a "spacer" and a third aromatic center in opioid peptides are required to convert a delta-antagonist into ligands with delta-agonist or with mixed delta-antagonist/mu-agonist properties. Potent delta-agonists and bifunctional compounds with high delta- and mu-opioid receptor affinities were obtained by varying the spacer length [none, NH-CH(2), NH-CH(2)-CH(2), Gly-NH-CH(2)] and C-terminal aromatic nucleus [1H-benzimidazole-2-yl, phenyl (Ph) and benzyl groups]. C-terminal modification primarily affected mu-opioid receptor affinities, which increased maximally 1700-fold relative to the prototype delta-antagonist H-Dmt-Tic-NH(2) and differentially modified bioactivity. In the absence of a spacer (1), the analogue exhibited dual delta-agonism (pEC(50), 7.28) and delta-antagonism (pA(2), 7.90). H-Dmt-Tic-NH-CH(2)-1H-benzimidazole-2-yl (Bid) (2) became a highly potent delta-agonist (pEC(50), 9.90), slightly greater than deltorphin C (pEC(50), 9.56), with mu-agonism (pE(50), 7.57), while H-Dmt-Tic-Gly-NH-CH(2)-Bid (4) retained potent delta-antagonism (pA(2), 9.0) but with an order of magnitude less mu-agonism. Similarly, H-Dmt-Tic-Gly-NH-Ph (5) had nearly equivalent high delta-agonism (pEC(50), 8.52) and mu-agonism (pEC(50), 8.59), while H-Dmt-Tic-Gly-NH-CH(2)-Ph (6) whose spacer was longer by a single methylene group exhibited potent delta-antagonism (pA(2), 9.25) and very high mu-agonism (pEC(50), 8.57). These data confirm that the distance between the Dmt-Tic pharmacophore and a third aromatic nucleus is an important criterion in converting Dmt-Tic from a highly potent delta-antagonist into a potent delta-agonist or into ligands with mixed delta- and mu-opioid properties.

  13. {Delta}I = 3/2 and {Delta}S = 2 Hyperon decays in chiral perturbation theory

    Energy Technology Data Exchange (ETDEWEB)

    He, X.G. [University of Melbourne, Parkville, VIC (Australia). School of Physics; Valencia, G. [Iowa State University, Ames, Iowa (United States). Department of Physics and Astronomy

    1997-05-01

    We study the| {Delta}I| = 3/2 and |{Delta}S| = 2 amplitudes for hyperon decays of the form B {yields} B`{pi} at lowest order in chiral perturbation theory. At this order, the {Delta}I = 3/2 amplitudes depend on only one constant. We extract the value of this constant from experiment and find a reasonable description of these processes within experimental errors. The same constant determines the {Delta}S = 2 transitions which, in the standard model, are too small to be observed. We find that new physics with parity odd {Delta}S = 2 interactions can produce observable rates in hyperon decays while evading the bounds from K{sup 0} - K-bar{sup 0} mixing. (authors) 10 refs., 3 tabs.

  14. Reactive versus anticipative adaptive management of Deltas: The Sacramento-San Joaquin Delta and the Rhine-Meuse Delta compared

    NARCIS (Netherlands)

    Vlieg, T.J.; Zandvoort, M.

    2013-01-01

    In this paper Californian Adaptive Management (AM) and Dutch Adaptive Delta Management (ADM) are compared. The concepts are introduced in a policy context to deal with prevailing types of uncertainty in water management in the Californian Sacramento-San Joaquin Delta and the Dutch Rhine-Meuse Delta

  15. Facts About Delta Pi Epsilon

    Science.gov (United States)

    Delta Pi Epsilon Journal, 1976

    1976-01-01

    The article discusses the purpose and structure of Delta Pi Epsilon and the general qualifications for membership. Service projects and publications, research awards, timely facts, the year of each chapter's origination, national presidents, and executive secretaries for the last 40 years are listed. (BP)

  16. Hydrological and Climatic Significance of Martian Deltas

    Science.gov (United States)

    Di Achille, G.; Vaz, D. A.

    2017-10-01

    We a) review the geomorphology, sedimentology, and mineralogy of the martian deltas record and b) present the results of a quantitative study of the hydrology and sedimentology of martian deltas using modified version of terrestrial model Sedflux.

  17. Yellow River Delta Faces a Historic Opportunity

    Institute of Scientific and Technical Information of China (English)

    Li Zhen

    2010-01-01

    @@ China's State Council has endorsed the Development Plan of an Efficient Eco-Economic Zone at Yellow River Delta. The plan is meant to create a more ecologically sustainable economic zone along the river delta.

  18. Yellow River Delta Faces a Historic Opportunity

    Institute of Scientific and Technical Information of China (English)

    Li Zhen

    2011-01-01

    @@ China's State Council has endorsed the Development Plan of an Efficient Eco-Economic Zone at Yellow River Delta.The plan is meant to create a more ecologically sustainable economic zone along the river delta.

  19. On the modelling of river delta formation

    NARCIS (Netherlands)

    Geleynse, N.

    2013-01-01

    This thesis presents approaches to the modelling of river delta formation. In particular, it provides results of numerical stratigraphic-morphodynamic modelling of river delta formation under various environmental forcings.

  20. Adaptive delta management: Roots and branches

    NARCIS (Netherlands)

    Timmermans, J.S.; Haasnoot, M.; Hermans, L.M.; Kwakkel, J.H.; Rutten, M.M.; Thissen, W.A.H.

    2015-01-01

    Deltas are generally recognized as vulnerable to climate change and therefore a salient topic in adaptation science. Deltas are also highly dynamic systems viewed from physical (erosion, sedimentation, subsidence), social (demographic), economic (trade), infrastructures (transport, energy, metropoli

  1. Delta Vegetation and Land Use [ds292

    Data.gov (United States)

    California Department of Resources — Vegetation and land use are mapped for the approximately 725,000 acres constituting the Legal Delta portion of the Sacramento and San Joaquin River Delta area....

  2. Limited junctional diversity of V delta 5-J delta 1 rearrangement in multiple sclerosis patients.

    Science.gov (United States)

    Nowak, J S; Michałowska-Wender, G; Januszkiewicz, D; Wender, M

    1997-01-01

    T-cell receptor (TCR) delta gene repertoire, as assessed by V delta-J delta rearrangements, has been analyzed in nine multiple sclerosis (MS) cases and in 30 healthy individuals by seminested PCR technique. Among the V delta-J delta junctional diversities studied, the most striking result has been observed in V delta 5-J delta 1 rearrangement. The detection of repeated V delta 5-J delta 1 nucleotide sequences in all analyzed clones from seven out of nine patients studied proved the monoclonal nature of gamma delta T-cells with V delta 5-J delta 1 rearrangement. The clonal nature of this rearrangement proved by PAGE and sequencing analysis may suggest an antigen-driven expansion of gamma delta T cells and argues for a significant role of gamma delta T-cells with V delta 5-J delta 1 rearrangement in MS pathogenesis. However, it cannot be excluded that clonal expansion of these lymphocytes may represent secondary change to central nervous system damage.

  3. Reflections on Development Strategy of Pearl River Delta: In Comparison with Yangtze River Delta

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    <正>1. A comparison between Pearl River Delta and Yangtze River Delta 1.1 Basic conditions 1.1.1 Location, area and scope Located in the southeast of Guangdong Province, the Pearl River Delta (PRD) as an economic zone is a compound delta

  4. Synthesis of novel analogues of the delta opioid ligand SNC-80 using AlCl3-promoted aminolysis.

    Science.gov (United States)

    Barn, D R; Bom, A; Cottney, J; Caulfield, W L; Morphy, J R

    1999-05-03

    Two focused libraries of delta opioid ligands were synthesised using AlCl3 facilitated aminolysis. Several compounds were identified with DOR binding affinities higher or similar to SNC-80. A novel acyclic derivative of SNC-80 produced antinociception in the acetic acid abdominal constriction test, which is at least partially mediated via the delta-opioid receptor.

  5. Quantitative fluorescence using 5-aminolevulinic acid–induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

    Science.gov (United States)

    Valdés, Pablo A.; Jacobs, Valerie; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Paulsen, Keith D.; Roberts, David W.

    2015-01-01

    OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were

  6. Ral GTPase interacts with the N-terminal in addition to the C-terminal region of PLC-delta1.

    Science.gov (United States)

    Grujic, Ognjen; Bhullar, Rajinder P

    2009-06-12

    Previously, we have shown that RalA, a calmodulin (CaM)-binding protein, binds to the C2 region in the C-terminal of PLC-delta1, and increases its enzymatic activity. Since PLC-delta1 contains a CaM-like region in its N-terminus, we have investigated if RalA can also bind to the N-terminus of PLC-delta1. Therefore, we created a GST-PLC-delta1 construct consisting of the first 294 amino acids of PLC-delta1 (GST-PLC-delta1(1-294)). In vitro binding experiments confirmed that PLC-delta1(1-294) was capable of binding directly to RalA. W-7 coupled to polyacrylamide beads bound pure PLC-delta1, demonstrating that PLC-delta1 contains a CaM-like region. Competition assays with W-7, peptides representing RalA and the newly identified RalB CaM-binding regions, or the IQ peptide from PLC-delta1 were able to inhibit RalA binding to PLC-delta1(1-294). This study demonstrates that there are two binding sites for RalA in PLC-delta1 and provides further insight into the role of Ral GTPase in the regulation of PLC-delta1 function.

  7. Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis.

    Science.gov (United States)

    Cotter, P D; May, A; Li, L; Al-Sabah, A I; Fitzsimons, E J; Cazzola, M; Bishop, D F

    1999-03-01

    X-linked sideroblastic anemia (XLSA) in four unrelated male probands was caused by missense mutations in the erythroid-specific 5-aminolevulinate synthase gene (ALAS2). All were new mutations: T647C, C1283T, G1395A, and C1406T predicting amino acid substitutions Y199H, R411C, R448Q, and R452C. All probands were clinically pyridoxine-responsive. The mutation Y199H was shown to be the first de novo XLSA mutation and occurred in a gamete of the proband's maternal grandfather. There was a significantly higher frequency of coinheritance of the hereditary hemochromatosis (HH) HFE mutant allele C282Y in 18 unrelated XLSA hemizygotes than found in the normal population, indicating a role for coinheritance of HFE alleles in the expression of this disorder. One proband (Y199H) with severe and early iron loading coinherited HH as a C282Y homozygote. The clinical and hematologic histories of two XLSA probands suggest that iron overload suppresses pyridoxine responsiveness. Notably, reversal of the iron overload in the Y199H proband by phlebotomy resulted in higher hemoglobin concentrations during pyridoxine supplementation. The proband with the R452C mutation was symptom-free on occasional phlebotomy and daily pyridoxine. These studies indicate the value of combined phlebotomy and pyridoxine supplementation in the management of XLSA probands in order to prevent a downward spiral of iron toxicity and refractory anemia.

  8. Co-administration of monoisoamyl dimercaptosuccinic acid and Moringa oleifera seed powder protects arsenic-induced oxidative stress and metal distribution in mice.

    Science.gov (United States)

    Mishra, Deepshikha; Gupta, Richa; Pant, S C; Kushwah, Pramod; Satish, H T; Flora, S J S

    2009-02-01

    Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geo-environmental disasters to date. Chelation therapy with chelating agents is considered to be the best known treatment against arsenic poisoning; however, they are compromised with certain serious drawbacks/side-effects. Efficacy of combined administration of Moringa oleifera (M. oleifera) (English: Drumstick tree) seed powder, a herbal extract, with a thiol chelator monoisoamyl DMSA (MiADMSA) post-arsenic exposure in mice was studied. Mice were exposed to 100 ppm arsenic in drinking water for 6 months, followed by 10-days treatment with M. oleifera seed powder (500 mg/kg, orally through gastric gavage, once daily), MiADMSA (50 mg/kg, intraperitoneally, once daily) either individually or in combination. Arsenic exposure caused significant decrease in blood glutathione, delta-aminolevulinic acid dehydratase (ALAD), accompanied by increased production of reactive oxygen species in blood and soft tissues. Significant inhibition of superoxide dismutase, catalase, and glutathione peroxidase activities in tissues (liver in particular) along with significant increase in thiobarbituric acid reactive substances and metallothionein levels in arsenic intoxicated mice was also noted. Combined administration of MiADMSA with M. oleifera proved better than all other treatments in the recovery of most of the above parameters accompanied by more pronounced depletion of arsenic. The results suggest that concomitant administration of M. oleifera during chelation treatment with MiADMSA might be a better treatment option than monotherapy with the thiol chelator in chronic arsenic toxicity.

  9. What is $\\Delta m^2_{ee}$ ?

    CERN Document Server

    Parke, Stephen

    2016-01-01

    The current short baseline reactor experiments, Daya Bay and RENO (Double Chooz) have measured (or are capable of measuring) an effective $\\Delta m^2$ associated with the atmospheric oscillation scale of 0.5 km/MeV in electron anti-neutrino disappearance. In this paper, I compare and contrast the different definitions of such an effective $\\Delta m^2$ and argue that the simple, L/E independent, definition given by $\\Delta m^2_{ee} \\equiv \\cos^2 \\theta_{12} \\Delta m^2_{31}+ \\sin^2 \\theta_{12} \\Delta m^2_{32}$, i.e. "the $\

  10. Periodicity in Delta-modulated feedback control

    Institute of Scientific and Technical Information of China (English)

    Xiaohua XIA; Guanrong CHEN; Rudong GAI; Alan S. I. ZINOBER

    2008-01-01

    The Delta-modulated feedback control of a linear system introduces nonlinearity into the system through switchings between two input values. It has been found that Delta-modulation gives rise to periodic orbits. The existence of periodic points of all orders of Sigma-Delta modulation with "leaky" integration is completely characterized by some interesting groups of polynomials with "sign" coefficients. The results are naturally generalized to Sigma-Delta modulations with multiple delays, Delta-modulations in the "downlink", unbalanced Delta-modulations and systems with two-level quantized feedback. Further extensions relate to the existence of periodic points arising from Delta-modulated feedback control of a stable linear system in an arbitrary direction, for which some necessary and sufficient conditions are given.

  11. Entendiendo Delta desde las Humanidades

    OpenAIRE

    José Calvo Tello

    2016-01-01

    Stylometry is one of the research areas in greater development within Digital Humanities. However, few studies have worked until recently with texts in Spanish and even less so from Spanish-speaking countries. The aim of this paper is to present in Spanish, and without prior statistical knowledge from the reader, one of the main methods used in stylometry, the measure of textual distance Burrows’ Delta. This paper explains this measure using a very small corpus of proverbs and then checks the...

  12. Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): current clinical and development status

    Science.gov (United States)

    Marcus, Stuart L.; Sobel, Russel S.; Golub, Allyn L.; Carroll, Ronald L.; Lundahl, Scott L.; Shulman, D. Geoffrey

    1996-04-01

    Exogenous provision of ALA to many tissues results in the accumulation of sufficient quantities of the endogenous photosensitizer protoporphyrin IX, (PpIX), to produce a photodynamic effect. Therefore, ALA may be considered the only current PDT agent in clinical development which is a biochemical precursor of a photosensitizer. Topical ALA application, followed by exposure to activating light (ALA PDT), has been reported effective for the treatment of a variety of dermatologic diseases including cutaneous T-cell lymphoma, superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses, and is also being examined for treatment of acne and hirsutism. PpIX induced by ALA application also may serve as a fluorescence detection marker for photodiagnosis (PD) of malignant and pre- malignant conditions of the urinary bladder and other organs. Local internal application of ALA has also been used for selective endometrial ablation in animal model systems and is beginning to be examined in human clinical studies. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer, various gastrointestinal cancers, and the condition known as Barrett's esophagus. This brief paper reviews the current clinical and development status of ALA PDT.

  13. The effects of visual fluorescence marking induced by 5-aminolevulinic acid for endoscopic diagnosis of urinary bladder cancer

    Science.gov (United States)

    Daniltchenko, Dmitri I.; Koenig, Frank; Schnorr, Dietmar; Valdman, Alexander; Al-Shukri, Salman; Loening, Stefan A.

    2003-10-01

    During cystoscopy procedure, fluorescence diagnostics induced by 5-ALA improves visual detection of the bladder cancer. Macroscopic ALA-fluorescence allows visualizing of small flat tumors, carcinoma in situ, true neoplasm margins and dysplasias of the bladder. Following ALA instillation, cystoscopy has been performed under both standard and blue light illumination. Totally, 153 biopsies have been carried out at 53 patients with suspicion of bladder cancer. The results were compared to ALA-fluorescence data. In 13% of the patients, bladder cancer and dysplasia were found out in addition, due to red fluorescence. The sensitivity and specificity of ALA-fluorescence technique aggregated 96% and 52% respectively. The sensitivity and specificity of 5-ALA-fluorescent detection exceeded standard endoscopy under white light on 20%. The new method does not exclude a false positive and a false negative fluorescent luminescence. The ALA-based fluorescence detection system enhances the diagnosis of malignant/dysplastic bladder lesions significantly.

  14. Treatment of Sweat gland carcinoma with Topical Aminolevulinic Acid Photodynamic therapy: An effective treatment method to improve surgical outcomes.

    Science.gov (United States)

    He, Xian; Yang, Yadong; Yang, Yang; Wang, Yuanyuan; Wang, Wensheng; Song, Yanying; Zeng, Yongfang; Yang, Yunchuan; Zhang, Xingcun; Li, Guoling; Gao, Yang; Lu, Yuangang

    2017-03-01

    Sweat gland carcinoma is an extremely rare skin cancer, which is hard to diagnose and completely resect without causing functional and cosmetic problems. Moreover, the high rate of recurrence is hard to handle in the treatment of sweat gland carcinoma. Photodynamic therapy is a novel treatment protocol which can selectively destroy tumor cells with good functional and cosmetic outcomes. This is a case about a 53 years old patient with sweat gland carcinoma on his right foot, which received surgery and photodynamic therapy. There is no recurrence one year after treatment of surgery and photodynamic therapy. Excision combined with photodynamic therapy during operation is a promising strategy towards tumors which are hard to resect thoroughly and have a high risk of recurrence. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Treatment of hidradenitis suppurativa with intralesional photodynamic therapy with 5-aminolevulinic acid and 630nm laser beam.

    Science.gov (United States)

    Suárez Valladares, María Jesús; Eiris Salvado, Noemi; Rodríguez Prieto, Manuel Angel

    2017-03-01

    Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease with multiple treatment options that have been used with mixed results. To evaluate the effectiveness, safety and tolerability of intralesional photodynamic therapy (I-PDT) in the management of HS. Also, to assess the effect of this technique on the different areas treated. Case series of 38 HS patients treated with I-PDT between 2011-2015 following a standardized protocol to assess response at the treated areas RESULTS: 29 patients achieved a complete response, while persistence was noted on 8 cases and only 1 suffered a recurrence. Difference between basal (median 28.5) and final (0) Hidradenitis Severity Score showed a significant reduction of 24.5 points (ptreatment option for localized HS lesions, achieving a high rate of remission with an adequate maintenance of response i and few complications. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  16. Induced Protoporphyrin IX Accumulation by the δ-Aminolevulinic Acid in Bacteria and its Potential Use in the Photodynamic Therapy

    Science.gov (United States)

    Brígido-Aparicio, Cyntiha; Ramón-Gallegos, Eva; Arenas-Huertero, Francisco Jesús; Uribe-Hernández, Raúl

    2008-08-01

    The increasing incident of resistant strains to antibiotic has encouraged the search of new antibacterial treatments, such as the photodynamic therapy. In recent years, photodynamic therapy has demonstrated being a good technology for the treatment of recurrent bacteria infection. PDT presents a hopeful approach to eliminate Gram positive and negative bacteria in immunological compromised patients. This therapy uses a laser in combination with a photosensibilizer in presence of intracellular molecular oxygen. The process generates an effect of phototoxicity in bacterial cells. The aim of this work was to determine the in vitro conditions to accumulate PpIX in effective concentrations in Staphylococcus aureus ATCC25923 and Streptococcus pyogenes, which are responsible of human cutaneous diseases. A cellular suspension of both strains was prepared in TSB to obtain growth in Log-phase, then, the suspensions were adjusted to a final concentration of 2.61×108 cells/mL. The strains were exposed to increasing concentrations from 0 to 160μg/mL of δ-ALA in order to determinate the concentration that induces the biggest accumulation of PpIX. PpIX was measured using the Piomelli method modified for bacteria. The concentration selected was 40 mg/mL of ALA. It was found that in basal concentration of δ-ALA (0 μg/mL) both strains accumulated similar amount of PpIX. In concentrations of 5 mg/mL of δ-ALA it was observed a significant (p<0.001) increment in PpIX concentration. Finally it was realized a kinetic to determinate the optimal accumulation over the time at 0, 5, 10, 15 and 30 min, and 1, 2, 4, 8, 16 and 32 h. It was found that the ideal time for PDT application, in both strains, was 24 h because in smaller times there was not statistically significant difference. The S. aureus ATCC25923 accumulated significantly the biggest concentration of PpIX with regard to S. pyogenes. In conclusion, it was found that the optimal conditions to apply PDT will be to expose both strains to 40 mg/mL of ALA and to irradiate at 24 h after the exposition.

  17. Human urinary excretion profile after smoking and oral administration of ( sup 14 C)delta 1-tetrahydrocannabinol

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, E.; Gillespie, H.K.; Halldin, M.M. (BMC, Uppsala (Sweden))

    1990-05-01

    The urinary excretion profiles of delta 1-tetrahydrocannabinol (delta 1-THC) metabolites have been evaluated in two chronic and two naive marijuana users after smoking and oral administration of ({sup 14}C)delta 1-THC. Urine was collected for five days after each administration route and analyzed for total delta 1-THC metabolites by radioactivity determination, for delta 1-THC-7-oic acid by high-performance liquid chromatography, and for cross-reacting cannabinoids by the EMIT d.a.u. cannabinoid assay. The average urinary excretion half-life of {sup 14}C-labeled delta 1-THC metabolites was calculated to be 18.2 +/- 4.9 h (+/- SD). The excretion profiles of delta 1-THC-7-oic acid and EMIT readings were similar to the excretion profile of {sup 14}C-labeled metabolites in the naive users. However, in the chronic users the excretion profiles of delta 1-THC-7-oic acid and EMIT readings did not resemble the radioactive excretion due to the heavy influence from previous Cannabis use. Between 8-14% of the radioactive dose was recovered in the urine in both user groups after oral administration. Lower urinary recovery was obtained both in the chronic and naive users after smoking--5 and 2%, respectively.

  18. Challenges, Approaches and Experiences from Asian Deltas and the Rhine-Meuse Delta : Regional Training Workshop on Delta Planning and Management

    NARCIS (Netherlands)

    Wosten, J.H.M.; Douven, W.; Long Phi, H.; Fida Abdullah Khan, M.

    2013-01-01

    River delta's, like the Mekong Delta (Vietnam), Ganges-Brahmaputra Delta (Bangladesh), Ayeyarwady Delta (Myanmar), Nile (Egypt) and Ciliwung Delta (Indonesia) are developing rapidly and are characterised by large-scale urbanisation and industrialization processes. They are facing serious planning ch

  19. Deformation characteristics of {delta} phase in the delta-processed Inconel 718 alloy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, H.Y., E-mail: haiyanzhang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Zhang, S.H., E-mail: shzhang@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Cheng, M. [Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Li, Z.X. [Beijing Institute of Aeronautica1 Materials, Beijing 100095 (China)

    2010-01-15

    The hot working characteristics of {delta} phase in the delta-processed Inconel 718 alloy during isothermal compression deformation at temperature of 950 deg. C and strain rate of 0.005 s{sup -1}, were studied by using optical microscope, scanning electron microscope and quantitative X-ray diffraction technique. The results showed that the dissolution of plate-like {delta} phase and the precipitation of spherical {delta} phase particles coexisted during the deformation, and the content of {delta} phase decreased from 7.05 wt.% to 5.14 wt.%. As a result of deformation breakage and dissolution breakage, the plate-like {delta} phase was spheroidized and transferred to spherical {delta} phase particles. In the center with largest strain, the plate-like {delta} phase disappeared and spherical {delta} phase appeared in the interior of grains and grain boundaries.

  20. Cloning and characterization of a delta-6 desaturase encoding gene from Nannochloropsis oculata

    Institute of Scientific and Technical Information of China (English)

    MA Xiaolei; YU Jianzhong; ZHU Baohua; PAN Kehou; PAN Jin; YANG Guanpin

    2011-01-01

    A gene (NANOC-D6D) encoding a desaturase that removes two hydrogen atoms from fatty acids at delta 6 position was isolated from a eDNA library of Nannochloropsis oculata (Droop)D. J. Hibberd (Eustigmatophyceae). The unicellular marine microalga N. oculata synthesizes rich long chain polyunsaturated fatty acids (LCPUFAs), including eicosapentaenoic acid (20:5n-3, EPA).The deduced protein contains 474 amino acids that fold into 4 trans-membrane domains. The neighbor-joining phylogenetic tree indicates that NANOC-D6D is phylogenetically close to the delta-6 fatty acid desaturase of marine microalgae such as Glossomastix chrysoplasta, Thalassiosira pseudonana, and Phaeodactylum tricornutum. The gene was expressed in Saccharomyces cerevisiae INVSc1 to verify the substrate specificity of NANOC-D6D. Our results suggest that the recombinant NANOC-D6D simultaneously desaturates linoleic acid (LA) and α-linolenic acid (ALA).

  1. Cloning and characterization of a delta-6 desaturase encoding gene from Nannochloropsis oculata

    Science.gov (United States)

    Ma, Xiaolei; Yu, Jianzhong; Zhu, Baohua; Pan, Kehou; Pan, Jin; Yang, Guanpin

    2011-03-01

    A gene ( NANOC-D6D) encoding a desaturase that removes two hydrogen atoms from fatty acids at delta 6 position was isolated from a cDNA library of Nannochloropsis oculata (Droop) D. J. Hibberd (Eustigmatophyceae). The unicellular marine microalga N. oculata synthesizes rich long chain polyunsaturated fatty acids (LCPUFAs), including eicosapentaenoic acid (20:5n-3, EPA). The deduced protein contains 474 amino acids that fold into 4 trans-membrane domains. The neighbor-joining phylogenetic tree indicates that NANOC-D6D is phylogenetically close to the delta-6 fatty acid desaturase of marine microalgae such as Glossomastix chrysoplasta, Thalassiosira pseudonana, and Phaeodactylum tricornutum. The gene was expressed in Saccharomyces cerevisiae INVScl to verify the substrate specificity of NANOC-D6D. Our results suggest that the recombinant NANOC-D6D simultaneously desaturates linoleic acid (LA) and α-linolenic acid (ALA).

  2. Migration in Deltas: An Integrated Analysis

    Science.gov (United States)

    Nicholls, Robert J.; Hutton, Craig W.; Lazar, Attila; Adger, W. Neil; Allan, Andrew; Arto, Inaki; Vincent, Katharine; Rahman, Munsur; Salehin, Mashfiqus; Sugata, Hazra; Ghosh, Tuhin; Codjoe, Sam; Appeaning-Addo, Kwasi

    2017-04-01

    Deltas and low-lying coastal regions have long been perceived as vulnerable to global sea-level rise, with the potential for mass displacement of exposed populations. The assumption of mass displacement of populations in deltas requires a comprehensive reassessment in the light of present and future migration in deltas, including the potential role of adaptation to influence these decisions. At present, deltas are subject to multiple drivers of environmental change and often have high population densities as they are accessible and productive ecosystems. Climate change, catchment management, subsidence and land cover change drive environmental change across all deltas. Populations in deltas are also highly mobile, with significant urbanization trends and the growth of large cities and mega-cities within or adjacent to deltas across Asia and Africa. Such migration is driven primarily by economic opportunity, yet environmental change in general, and climate change in particular, are likely to play an increasing direct and indirect role in future migration trends. The policy challenges centre on the role of migration within regional adaptation strategies to climate change; the protection of vulnerable populations; and the future of urban settlements within deltas. This paper reviews current knowledge on migration and adaptation to environmental change to discern specific issues pertinent to delta regions. It develops a new integrated methodology to assess present and future migration in deltas using the Volta delta in Ghana, Mahanadi delta in India and Ganges-Brahmaputra-Meghna delta across India and Bangladesh. The integrated method focuses on: biophysical changes and spatial distribution of vulnerability; demographic changes and migration decision-making using multiple methods and data; macro-economic trends and scenarios in the deltas; and the policies and governance structures that constrain and enable adaptation. The analysis is facilitated by a range of

  3. Casimir force between $\\delta-\\delta^{\\prime}$ mirrors transparent at high frequencies

    CERN Document Server

    Braga, Alessandra N; Alves, Danilo T

    2016-01-01

    We investigate, in the context of a real massless scalar field in $1+1$ dimensions, models of partially reflecting mirrors simulated by Dirac $\\delta-\\delta^{\\prime}$ point interactions. In the literature, these models do not exhibit full transparency at high frequencies. In order to provide a more realistic feature for these models, we propose a modified $\\delta-\\delta^{\\prime}$ point interaction that enables to achieve full transparency in the limit of high frequencies. Taking this modified $\\delta-\\delta^{\\prime}$ model into account, we investigate the Casimir force, comparing our results with those found in the literature.

  4. Evolving deltas: Conceptualising coevolution with engineered interventions

    Science.gov (United States)

    Welch, Amy; Nicholls, Robert; Lazar, Attila

    2017-04-01

    Mid to low latitude deltas have been populated for thousands of years due to their fertile soil and coastal location. This has led to an alteration in the land cover of deltas to primary agriculture and dense rural settlements and more recently, major cities and megacities have developed on or adjacent to many deltas. Deltas may be prosperous in terms of their outputs and services; however, they are also susceptible to many hazards due to their location and low-lying nature. Hazards include storm surges, fluvial flooding and erosion of both coastal and riverine areas, as well as subsidence, relative sea-level rise and pollution. This can have severe impacts on the delta, its population and its services. Therefore engineered interventions have been used for some time to protect the population and the valuable land from the consequences of hazards. Coevolution can be described as a feedback loop between nature and humans: each has an effect on how the other behaves and hence this inter-dependence interaction continues. Therefore the natural evolution of the delta interacts with engineered interventions, such as promoting accelerated subsidence over time, necessitating further adaptation. The deltaic landscape and associated livelihoods are thus the result of this co-evolution process between natural delta processes and engineered interventions. This presentation will identify and discuss various drivers and consequences of large scale engineered interventions, comparing and contrasting the management approaches taken in five populated deltas (Ganges-Brahmaputra-Meghna, Yangtze, Rhine-Meuse-Scheldt, Mekong and Nile). The type of engineered intervention and management approaches had a direct effect on the coevolution of deltas, with each of the deltas being at different stages in terms of extent of coevolution. A qualitative timeline of the typical steps of coevolution between the human system and the delta system of the studied deltas was produced. The major

  5. Delta hepatitis agent: structural and antigenic properties of the delta-associated particle.

    Science.gov (United States)

    Bonino, F; Hoyer, B; Shih, J W; Rizzetto, M; Purcell, R H; Gerin, J L

    1984-01-01

    Delta agent (delta) was serially passaged to a second and third hepatitis B surface antigen (HBsAg) carrier chimpanzee, using as inoculum the peak delta antigen (delta Ag) serum of an animal previously infected with human serum. The characteristics of serially transmitted delta Ag were similar to those described in first-passage animals. It was consistently detected before the development of anti-delta, in association with a 35- to 37-nm subpopulation of HBsAg particles and a unique low-molecular-weight (5.5 X 10(5)) RNA. RNase susceptibility of the delta-associated RNA and release of delta Ag activity upon treatment of delta-associated particles with detergent revealed that this particle is organized into a virion-like form with the RNA and delta Ag as internal components within a coat of HBsAg. Surface determinants of the delta-associated particle other than HBsAg were not detected by radioimmunoprecipitation experiments, using sera of humans and chimpanzees convalescent from delta hepatitis. The HBsAg-associated particle is the "candidate agent" of delta hepatitis. Images PMID:6698598

  6. The Niger Delta Amnesty Program

    Directory of Open Access Journals (Sweden)

    Benjamin A. Okonofua

    2016-06-01

    Full Text Available The armed conflict between militias and government forces in Nigeria’s Niger Delta region has spanned for more than two decades, defying all solutions. A disarmament, demobilization, and reintegration (DDR program was established in August 2015 in effort to end the violence and has remained in place. It is a radically different approach from past approaches that displayed zero tolerance to all political challenges to oil production or the allocation of oil profits. The approach appeared to be immediately successful in that it forced a ceasefire, engaged militants in planned programs to rehabilitate and reintegrate them into civilian society, and opened up the oil wells (many of which had been shut due to the crisis with the effect of increasing government revenue, which depends 85% on oil exports. Yet, few studies have attempted to understand the dynamics within the country that are responsible for the design and implementation of this broad policy shift or to understand whether and how the current initiative is able to end the conflict and institute peace beyond the short term. This study, therefore, is important because it provides a critical perspective that anticipates and explains emerging issues with the Niger Delta Amnesty Program, which have implications for DDR adaptation and implementation all over the world. Ultimately, the research demonstrates how the DDR program both transforms the Niger Delta conflict and becomes embroiled in intense contestations not only about the mechanism for transforming the targeted population but also whether and how the program incorporates women who are being deprioritized by the program.

  7. Analysis and Synthesis of Delta Operator Systems

    CERN Document Server

    Yang, Hongjiu; Shi, Peng; Zhao, Ling

    2012-01-01

    This book is devoted to analysis and design on delta operator systems. When sampling is fast, a dynamical system will become difficult to control, which can be seen in wide real world applications. Delta operator approach is very effective to deal with fast sampling systems. Moreover, it is easy to observe and analyze the control effect with different sampling periods in delta operator systems. The framework of this book has been carefully constructed for delta operator systems to handle sliding mode control, time delays, filter design, finite frequency and networked control. These problems indeed are especially important and significant in automation and control systems design. Through the clear framework of the book, readers can easily go through the learning process on delta operator systems via a precise and comfortable learning sequence. Following this enjoyable trail, readers will come out knowing how to use delta operator approach to deal with control problems under fast sampling case. This book should...

  8. Delta Clipper - Design for supportability

    Science.gov (United States)

    Smiljanic, Ray R.; Conrad, Charles; Spaulding, Ed; Gisburne, Don

    1993-07-01

    The 'Delta Clipper' Single Stage Rocket Technology (SSRT) currently under development in the DC-X program will implement reliability-centered maintenance and support, involving on-equipment/off-equipment two-level maintenance, a logistics and spares pipeline, and a minimization of 'blue suit' skill-level personnel. Attention is given to the range of SSRT features that are to be validated via the DC-X test program; these prominently involve LRUs replaceability and accessibility, standardization and interchangeability, and 'aircraft-like' automated data collection.

  9. Climate change and the Delta

    Science.gov (United States)

    Dettinger, Michael; Anderson, Jamie; Anderson, Michael L.; Brown, Larry R.; Cayan, Daniel; Maurer, Edwin P.

    2016-01-01

    Anthropogenic climate change amounts to a rapidly approaching, “new” stressor in the Sacramento–San Joaquin Delta system. In response to California’s extreme natural hydroclimatic variability, complex water-management systems have been developed, even as the Delta’s natural ecosystems have been largely devastated. Climate change is projected to challenge these management and ecological systems in different ways that are characterized by different levels of uncertainty. For example, there is high certainty that climate will warm by about 2°C more (than late-20th-century averages) by mid-century and about 4°C by end of century, if greenhouse-gas emissions continue their current rates of acceleration. Future precipitation changes are much less certain, with as many climate models projecting wetter conditions as drier. However, the same projections agree that precipitation will be more intense when storms do arrive, even as more dry days will separate storms. Warmer temperatures will likely enhance evaporative demands and raise water temperatures. Consequently, climate change is projected to yield both more extreme flood risks and greater drought risks. Sea level rise (SLR) during the 20th century was about 22cm, and is projected to increase by at least 3-fold this century. SLR together with land subsidence threatens the Delta with greater vulnerabilities to inundation and salinity intrusion. Effects on the Delta ecosystem that are traceable to warming include SLR, reduced snowpack, earlier snowmelt and larger storm-driven streamflows, warmer and longer summers, warmer summer water temperatures, and water-quality changes. These changes and their uncertainties will challenge the operations of water projects and uses throughout the Delta’s watershed and delivery areas. Although the effects of climate change on Delta ecosystems may be profound, the end results are difficult to predict, except that native species will fare worse than invaders. Successful

  10. Effect of an oxygen pressure injection (OPI) device on the oxygen saturation of patients during dermatological methyl aminolevulinate photodynamic therapy.

    Science.gov (United States)

    Blake, E; Allen, J; Thorn, C; Shore, A; Curnow, A

    2013-05-01

    Methyl aminolevulinate photodynamic therapy (MAL-PDT) (a topical treatment used for a number of precancerous skin conditions) utilizes the combined interaction of a photosensitizer (protoporphyrin IX (PpIX)), light of the appropriate wavelength, and molecular oxygen to produce singlet oxygen and other reactive oxygen species which induce cell death. During treatment, localized oxygen depletion occurs and is thought to contribute to decreased efficacy. The aim of this study was to investigate whether an oxygen pressure injection (OPI) device had an effect on localized oxygen saturation levels and/or PpIX fluorescence of skin lesions during MAL-PDT. This study employed an OPI device to apply oxygen under pressure to the skin lesions of patients undergoing standard MAL-PDT. Optical reflectance spectrometry and fluorescence imaging were used to noninvasively monitor the localized oxygen saturation and PpIX fluorescence of the treatment area, respectively. No significant changes in oxygen saturation were observed when these data were combined for the group with OPI and compared to the group that received standard MAL-PDT without OPI. Additionally, no significant difference in PpIX photobleaching or clinical outcome at 3 months between the groups of patients was observed, although the group that received standard MAL-PDT demonstrated a significant increase (pMAL-PDT. Further investigation is therefore required to find a more effective method of MAL-PDT enhancement.

  11. Long-term follow-up of metil aminolevulinate (MAL)-PDT in difficult-to-treat cutaneous Bowen's disease.

    Science.gov (United States)

    Cavicchini, Stefano; Serini, Stefano Maria; Fiorani, Roberta; Girgenti, Valentina; Ghislanzoni, Massimo; Sala, Francesco

    2011-08-01

    Bowen's disease (BD) is a form of intraepidermal squamous cell carcinoma, which is clinically characterized by gradually enlarging, well-demarcated erythematous plaques with irregular borders and surface crusting or scaling, affecting primarily the elderly. BD often presents with lesions difficult to treat with standard therapy as surgery, cryosurgery, or 5-fluorouracil (5-FU) for the risk of significantly poor cosmetic outcome, failure rate, and adverse events, related mainly to the age of the patients. Topical PDT with methyl aminolevulinate (MAL) represents a valid and approved therapy for BD lesions in many cases, especially for lesions located at poor healing sites or for large patches of disease, due to its high efficacy coupled with good tolerability and tissue-sparing attitude. In this study, we sought to investigate the efficacy, safety, and cosmetic outcome of MAL-PDT in a series of patients with BD lesions which were challenging to treat for clinical, surgical, and patient-related reasons, such as size of the lesion, difficult surgical approach for anatomical sites, or age of patients and request of the best cosmetic result. We also performed a long-term follow-up to assess recurrence rates and eventual late-onset adverse events.

  12. From Natural to Design River Deltas

    Science.gov (United States)

    Giosan, Liviu

    2016-04-01

    Productive and biologically diverse, deltaic lowlands attracted humans since prehistory and may have spurred the emergence of the first urban civilizations. Deltas continued to be an important nexus for economic development across the world and are currently home for over half a billion people. But recently, under the double whammy of sea level rise and inland sediment capture behind dams, they have become the most threatened coastal landscape. Here I will address several deceptively simple questions to sketch some unexpected answers using example deltas from across the world from the Arctic to the Tropics, from the Danube to the Indus, Mississippi to Godavari and Krishna, Mackenzie to Yukon. What is a river delta? What is natural and what is not in a river delta? Are the geological and human histories of a delta important for its current management? Is maintaining a delta the same to building a new one? Can we design better deltas than Nature? These answers help us see clearly that survival of deltas in the next century depends on human intervention and is neither assured nor simple to address or universally applicable. Empirical observations on the hydrology, geology, biology and biochemistry of deltas are significantly lagging behind modeling capabilities endangering the applicability of numerical-based reconstruction solutions and need to be ramped up significantly and rapidly across the world.

  13. Charged current weak electroproduction of $\\Delta$ resonance

    CERN Document Server

    Alvarez-Ruso, L; Vacas, M J V

    1998-01-01

    We study the weak production of $\\Delta$ (i.e. $e^{-} + p \\to \\Delta^{0}+ energy range corresponding to the Mainz and TJNAF electron accelerators. The differential cross sections $\\sigma(\\theta)$ are found to be of the order of $ 10^{-39}$ cm$^2$/sr, over a range of angles which increases with energy. The possibility of observing these reactions with the high luminosities available at these accelerators, and studying the weak N-$\\Delta$ transition form factors through these reactions is discussed. The production cross section of N$^*(1440)$ in the kinematic region of $\\Delta$ production is also estimated and found to be small.

  14. Delta Semantics Defined By Petri Nets

    DEFF Research Database (Denmark)

    Jensen, Kurt; Kyng, Morten; Madsen, Ole Lehrmann

    This report is identical to an earlier version of May 1978 except that Chapter 5 has been revised. A new paper: "A Petri Net Definition of a System Description Language", DAIMI, April 1979, 20 pages, extends the Petri net model to include a data state representing the program variables. Delta...... and the possibility of using predicates to specify state changes. In this paper a formal semantics for Delta is defined and analysed using Petri nets. Petri nets was chosen because the ideas behind Petri nets and Delta concide on several points. A number of proposals for changes in Delta, which resulted from...

  15. SNC 80 and related delta opioid agonists.

    Science.gov (United States)

    Calderon, S N; Coop, A

    2004-01-01

    The discovery of the selective delta (delta) opioid agonists SNC 80 and BW373U86, which possess a diarylmethylpiperazine structure unique among opioids, was a major advance in the field of delta-opioid ligands. Much research has been performed to uncover the structure-activity relationships (SAR) of this class of ligands and also to compare the diarylmethylpiperazines with the traditional morphinan-based delta opioids. This review focuses on the development of the SAR of this unique series of ligands, and discusses questions which remain unanswered.

  16. Follow-up of the delta4 to delta16 trans-18:1 isomer profile and content in French processed foods containing partially hydrogenated vegetable oils during the period 1995-1999. Analytical and nutritional implications.

    Science.gov (United States)

    Wolff, R L; Combe, N A; Destaillats, F; Boué, C; Precht, D; Molkentin, J; Entressangles, B

    2000-08-01

    A survey of the total content of trans-18:1 acids and their detailed profile in French food lipids was conducted in 1995-1996, and 1999. For this purpose, 37 food items were chosen from their label indicating the presence of partially hydrogenated vegetable oils (PHVO) in their ingredients. The content as well as the detailed profile of these isomers was established by a combination of argentation thin-layer chromatography and gas liquid chromatography (GLC) on long polar capillary columns. With regard to the mean trans-18:1 acid contents of extracted PHVO, a significant decrease was observed between the two periods, i.e., from 26.9 to 11.8% of total fatty acids. However, only minor differences were noted in the mean relative distribution profiles of individual trans-18:1 isomers with ethylenic bonds between positions delta4 and delta16 for the two periods. The predominant isomer was delta9-18:1 (elaidic) acid, in the wide range 15.2-46.1% (mean, 27.9+/-7.2%) of total trans-18:1 acids, with the delta10 isomer ranked second, with a mean of 21.3% (range, 11.6 to 27.4%). The content of the unresolved delta6 to delta8 isomer group was higher than the delta11 isomer (vaccenic acid), representing on average 17.5 and 13.3%, respectively. Other isomers delta4, delta5, delta12, delta13/delta14, delta15, and delta16, were less than 10% each: 1.0, 1.6, 7.4, 7.1, 1.8, and 1.0%, respectively. However, considering individual food items, it was noted that none of the extracted PHVO were identical to one another, indicating a considerable diversity of such fats available to the food industry. A comparison of data for French foods with similar data recently established for Germany indicates that no gross differences occur in PHVO used by food industries in both countries. Estimates for the absolute mean consumption of individual isomers from ruminant fats and PHVO are made for the French population and compared to similarly reconstructed hypothetical profiles for Germany and North

  17. $\\Delta$ decay in nuclear medium

    CERN Document Server

    Jain, B K; Kundu, Bijoy

    1996-01-01

    Proton-nucleus collisions, where the beam proton gets excited to the delta resonance and then decays to p\\pi ^+, either inside or outside the nuclear medium, are studied. Cross-sections for various kinematics for the (p,p' \\pi ^+) reaction between 500 MeV and 1 GeV beam energy are calculated to see the effects of the nuclear medium on the propagation and decay of the resonance. The cross-sections studied include proton energy spectra in coincidence with the pion, four momentum transfer distributions, and the invariant p\\pi^+ mass distributions. We find that the effect of the nuclear medium on these cross-sections mainly reduces their magnitudes. Comparing these cross-sections with those considering the decay of the delta outside the nucleus only, we further find that at 500 MeV the two sets of cross-sections have large differences, while by 1 GeV the differences between them become much smaller.

  18. Ambulant photodynamic therapy of superficial malignomas with 5-ALA in combination with folic acid and use of noncoherent light.

    Science.gov (United States)

    Jindra, R H; Kubin, A; Kolbabek, H; Alth, G; Dobrowsky, W

    1999-01-01

    This study reports our first results of ambulant photodynamic treatment with 5-aminolevulinic acid (5-ALA) in combination with folic acid and subsequent illumination with a noncoherent light source. The compound was topically applied to avoid total body skin sensitivity which occurs in the case of systemic administration. If no therapeutic response could be proved, we added folic acid to 5-ALA for a further treatment attempt. Illumination was performed by broad band red thermic light to also excitate reaction products with absorption bands located near to that of the sensitizer. As a result, we observed a response in all cases, however, in some cases only after the addition of folic acid.

  19. Comparative assessment of the vulnerability and resilience of deltas : extended version with 14 deltas : synthesis report

    NARCIS (Netherlands)

    Bucx, T.; Driel, van W.F.; Boer, de H.; Graas, S.; Langenberg, V.; Marchand, M.; Guchte, van de C.

    2014-01-01

    Worldwide, deltas host dense populations and are important centres of agricultural and industrial production, and economic activity. Many deltas are areas of great ecological importance as well, featuring wetlands of high and unique biodiversity. Deltas are vulnerable to changes by natural forces an

  20. $\\Delta I=4$ and $\\Delta I=8$ bifurcations in rotational bands of diatomic molecules

    CERN Document Server

    Bonatsos, Dennis; Lalazissis, G A; Drenska, S B; Minkov, N; Raychev, P P; Roussev, R P; Bonatsos, Dennis

    1996-01-01

    It is shown that the recently observed $\\Delta I=4$ bifurcation seen in superdeformed nuclear bands is also occurring in rotational bands of diatomic molecules. In addition, signs of a $\\Delta I=8$ bifurcation, of the same order of magnitude as the $\\Delta I=4$ one, are observed both in superdeformed nuclear bands and rotational bands of diatomic molecules.

  1. INFLUENCE OF THE DELTA-DELTA-MESON COUPLING ON NUCLEON AND DELTA PROPERTIES IN NUCLEAR-MATTER

    NARCIS (Netherlands)

    DEJONG, F; MALFLIET, R

    1994-01-01

    We introduce a scalar and a vector DELTADELTA-meson vertex in the relativistic Dirac-Brueckner model for nuclear matter and investigate the consequences. We find small effects on the effective nucleon properties. The effects in the DELTA sector are more profound, although the DELTA is still effectiv

  2. Electromagnetic excitation of the Delta(1232) resonance

    Energy Technology Data Exchange (ETDEWEB)

    V. Pascalutsa; M. Vanderhaeghen; Shin Nan Yang

    2006-09-05

    We review the description of the lowest-energy nucleon excitation--the Delta(1232)-resonance. Much of the recent effort has been focused on the precision measurements of the nucleon to Delta transition by means of electromagnetic probes. We review the results of those measurements and confront them with the state-of-the-art calculations based on chiral effective-field theories (EFT), lattice QCD, and QCD-inspired models. Some of the theoretical approaches are reviewed in detail. In particular, we describe the chiral EFT of QCD in the energy domain of the Delta-resonance, and its applications to the electromagnetic nucleon-to-Delta transition (gamma N Delta). We also describe the recent dynamical and unitary-isobar models of pion electroproduction which are extensively used in the extraction of the gamma* N Delta form factors from experiment. Furthermore, we discuss the link of the gamma* N Delta form factors to generalized parton distributions (GPDs), as well as the predictions of perturbative QCD for these transition form factors. The present status of understanding the Delta-resonance properties and the nature of its excitation is summarized.

  3. Structure and replication of hepatitis delta virus

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Unidade de Biologia Molecular, Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, ... molecules of both delta antigens (Ryu et al., 1993). This ..... Glenn JS, Watson JA, Havel CM, White JO (1992). ... HDV RNA encoding the large delta antigen cannot replicate. J. Gen.

  4. Generalised CP and $\\Delta (96)$ Family Symmetry

    CERN Document Server

    Ding, Gui-Jun

    2014-01-01

    We perform a comprehensive study of the $\\Delta (96)$ family symmetry combined with the generalised CP symmetry $H_{\\rm{CP}}$. We investigate the lepton mixing parameters which can be obtained from the original symmetry $\\Delta (96)\\rtimes H_{\\rm{CP}}$ breaking to different remnant symmetries in the neutrino and charged lepton sectors, namely $G_{\

  5. Delta Blues Scholarship and Imperialist Nostalgia.

    Science.gov (United States)

    Nye, William P.

    When Delta blues are considered to be "folk music," the genre is inextricably tied to the neocolonial, sharecropping system of cotton production characteristic of the Mississippi Delta region between the Civil War and World War II. "Imperialist nostalgia," then, arises in accounts which pay primary and positive tribute to blues…

  6. The delta opioid receptor tool box.

    Science.gov (United States)

    Vicente-Sanchez, Ana; Segura, Laura; Pradhan, Amynah A

    2016-12-03

    In recent years, the delta opioid receptor has attracted increasing interest as a target for the treatment of chronic pain and emotional disorders. Due to their therapeutic potential, numerous tools have been developed to study the delta opioid receptor from both a molecular and a functional perspective. This review summarizes the most commonly available tools, with an emphasis on their use and limitations. Here, we describe (1) the cell-based assays used to study the delta opioid receptor. (2) The features of several delta opioid receptor ligands, including peptide and non-peptide drugs. (3) The existing approaches to detect delta opioid receptors in fixed tissue, and debates that surround these techniques. (4) Behavioral assays used to study the in vivo effects of delta opioid receptor agonists; including locomotor stimulation and convulsions that are induced by some ligands, but not others. (5) The characterization of genetically modified mice used specifically to study the delta opioid receptor. Overall, this review aims to provide a guideline for the use of these tools with the final goal of increasing our understanding of delta opioid receptor physiology.

  7. Entendiendo Delta desde las Humanidades

    Directory of Open Access Journals (Sweden)

    José Calvo Tello

    2016-05-01

    Full Text Available Stylometry is one of the research areas in greater development within Digital Humanities. However, few studies have worked until recently with texts in Spanish and even less so from Spanish-speaking countries. The aim of this paper is to present in Spanish, and without prior statistical knowledge from the reader, one of the main methods used in stylometry, the measure of textual distance Burrows’ Delta. This paper explains this measure using a very small corpus of proverbs and then checks the results in a corpus of Spanish novels. Both data and Python scripts are available to the community through GitHub, commented step by step so that you can play and visualize each step.

  8. Jiaxing: Delicacy of the Yangtze River Delta

    Institute of Scientific and Technical Information of China (English)

    WUXINYI; WANGNAN

    2004-01-01

    THE yangtze River Delta,where the Yangtzc River crosses China's east coast,has one of the country's most dynamic economies.In 1976Jcan Gottmann.a french geographer,called shanghai and its neighboring Yangtze River Delta the world's "sixth largest megalopolis." The Yangtze River Delta has 15 cities. Its territory accounts for one percent of China's total, 5.8 percent of hthe population, and 19.5 percent of the national GDP.In terms of both aggregate economy and growth speed, the Delta currently leads China and could likely be the "enginc" of the world's future economic growth. Located at the juncition of Shanghai Jiangsu and Zhejiang, Jiaxing City holds a central economic belt. It is within 100 kilometers of Shanghai, Hangzhou and Suzhou. In 200 and 2003, Jiaxing's GDP growth rate was first in Zhejiang Province and second among the 1.5 Delta cities.

  9. In Vivo Non-Invasive Evaluation of Actinic Keratoses Response to Methyl-Aminolevulinate-Photodynamic Therapy (MAL-PDT) by Reflectance Confocal Microscopy

    OpenAIRE

    Marina Venturini; Arianna Zanca; Piergiacomo Calzavara-Pinton

    2014-01-01

    Photodynamic therapy (PDT) with methyl-aminolevulinate (MAL) is an approved non-invasive treatment option for actinic keratoses (AKs). In vivo reflectance confocal microscopy (RCM) is a non-invasive tool for real-time imaging of epidermis and superficial dermis in vivo that has been previously reported to facilitate the in vivo evaluation of skin lesions, including AKs. The aim of this study was to investigate the use of in vivo RCM in evaluating AKs response to MAL-PDT. For this reason a tot...

  10. Characterization of rapeseed (Brassica napus) oils by bulk C, O, H, and fatty acid C stable isotope analyses.

    Science.gov (United States)

    Richter, Eva Katharina; Spangenberg, Jorge E; Kreuzer, Michael; Leiber, Florian

    2010-07-14

    Rapeseed ( Brassica napus ) oils differing in cultivar, sites of growth, and harvest year were characterized by fatty acid concentrations and carbon, hydrogen, and oxygen stable isotope analyses of bulk oils (delta(13)C(bulk), delta(2)H(bulk), delta(18)O(bulk) values) and individual fatty acids (delta(13)C(FA)). The delta(13)C(bulk), delta(2)H(bulk), and delta(18)O(bulk) values were determined by continuous flow combustion and high-temperature conversion elemental analyzer-isotope ratio mass spectrometry (EA/IRMS, TC-EA/IRMS). The delta(13)C(FA) values were determined using gas chromatography--combustion-isotope ratio mass spectrometry (GC/C/IRMS). For comparison, other C(3) vegetable oils rich in linolenic acid (flax and false flax oils) and rich in linoleic acid (poppy, sunflower, and safflower oils) were submitted to the same chemical and isotopic analyses. The bulk and molecular delta(13)C values were typical for C(3) plants. The delta(13)C value of palmitic acid (delta(13)C(16:0)) and n-3 alpha-linolenic acid (delta(13)C(18:3n-3)) differed (p oils. Also within species, significant differences of delta(13)C(FA) were observed (p oil differed between cultivars (p oil and specific fatty acid stable isotope analysis might be useful in tracing dietary lipids differing in their origin.

  11. Characterization of the fatty acyl elongase (elovl) gene family, and hepatic elovl and delta-6 fatty acyl desaturase transcript expression and fatty acid responses to diets containing camelina oil in Atlantic cod (Gadus morhua).

    Science.gov (United States)

    Xue, Xi; Feng, Charles Y; Hixson, Stefanie M; Johnstone, Kim; Anderson, Derek M; Parrish, Christopher C; Rise, Matthew L

    2014-09-01

    For aquaculture to become sustainable, there is a need to substitute fish oil [FO, rich in ω3 long chain polyunsaturated fatty acids (LC-PUFA) such as 20:5ω3 (EPA) and 22:6ω3 (DHA)] in aquafeed with plant oils such as camelina oil [CO, rich in C18 PUFA such as 18:3ω3 (ALA) and 18:2ω6 (LNA)]. The LC-PUFA are essential components in fish diets for maintaining optimal health, physiology and growth. However, most marine fish including Atlantic cod are inefficient at producing LC-PUFA from shorter chain precursors. Since elovl genes encode enzymes that play key roles in fatty acid biosynthesis, we hypothesized that they may be involved in Atlantic cod responses to diets rich in 18:3ω3 and 18:2ω6. Ten members of the cod elovl gene family were characterized at the mRNA level. RT-PCR was used to study constitutive expression of elovl transcripts in fifteen tissues. Some transcripts (e.g. elovl5) were ubiquitously expressed, while others had tissue-specific expression (e.g. elovl4a in brain and eye). Cod fed a CO-containing diet (100% CO replacement of FO and including solvent-extracted fish meal) had significantly lower weight gain, with significant up-regulation of elovl5 and fadsd6 transcripts in the liver as shown by QPCR analysis, compared with cod on a FO control diet after a 13-week trial. Multivariate statistical analyses (SIMPER and PCA) indicated that high 18:3ω3 and/or low ω3 LC-PUFA levels in the liver were associated with the up-regulation of elovl5 and fadsd6, which are involved in LC-PUFA biosynthesis in cod.

  12. Influence of different organic fertilizers on quality parameters and the delta(15)N, delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of orange fruit (Citrus sinensis L. Osbeck).

    Science.gov (United States)

    Rapisarda, Paolo; Camin, Federica; Fabroni, Simona; Perini, Matteo; Torrisi, Biagio; Intrigliolo, Francesco

    2010-03-24

    To investigate the influence of different types of fertilizers on quality parameters, N-containing compounds, and the delta(15)N, delta(13)C, delta(2)H, delta (34)S, and delta(18)O values of citrus fruit, a study was performed on the orange fruit cv. 'Valencia late' (Citrus sinensis L. Osbeck), which was harvested in four plots (three organic and one conventional) located on the same farm. The results demonstrated that different types of organic fertilizers containing the same amount of nitrogen did not effect important changes in orange fruit quality parameters. The levels of total N and N-containing compounds such as synephrine in fruit juice were not statistically different among the different treatments. The delta(15)N values of orange fruit grown under fertilizer derived from animal origin as well as from vegetable compost were statistically higher than those grown with mineral fertilizer. Therefore, delta(15)N values can be used as an indicator of citrus fertilization management (organic or conventional), because even when applied organic fertilizers are of different origins, the natural abundance of (15)N in organic citrus fruit remains higher than in conventional ones. These treatments also did not effect differences in the delta(13)C, delta(2)H, delta(34)S, and delta(18)O values of fruit.

  13. Identifying hazards associated with lava deltas

    Science.gov (United States)

    Poland, Michael P.; Orr, Tim R.

    2014-01-01

    Lava deltas, formed where lava enters the ocean and builds a shelf of new land extending from the coastline, represent a significant local hazard, especially on populated ocean island volcanoes. Such structures are unstable and prone to collapse—events that are often accompanied by small explosions that can deposit boulders and cobbles hundreds of meters inland. Explosions that coincide with collapses of the East Lae ‘Apuki lava delta at Kīlauea Volcano, Hawai‘i, during 2005–2007 followed an evolutionary progression mirroring that of the delta itself. A collapse that occurred when the lava–ocean entry was active was associated with a blast of lithic blocks and dispersal of spatter and fine, glassy tephra. Shortly after delta growth ceased, a collapse exposed hot rock to cold ocean water, resulting in an explosion composed entirely of lithic blocks and lapilli. Further collapse of the delta after several months of inactivity, by which time it had cooled significantly, resulted in no recognizable explosion deposit. Seaward displacement and subsidence of the coastline immediately inland of the delta was measured by both satellite and ground-based sensors and occurred at rates of several centimeters per month even after the lava–ocean entry had ceased. The anomalous deformation ended only after complete collapse of the delta. Monitoring of ground deformation may therefore provide an indication of the potential for delta collapse, while the hazard associated with collapse can be inferred from the level of activity, or the time since the last activity, on the delta.

  14. Synthesis and conformational analysis of muramic acid delta-lactam structures and their 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl) derivatives, characteristic of bacterial spore peptidoglycan.

    Science.gov (United States)

    Keglević, D; Kojić-Prodić, B; Banić, Z; Tomić, S; Puntarec, V

    1993-03-17

    1,6-Anhydro-4-O-benzyl-beta-muramic acid 1',2-lactam (2) was prepared by reduction of 1,6-anhydro-2-azido-4-O-benzyl-2-deoxy-3-O-[(R)-1- methoxycarbonylethyl]-beta-D-glucopyranose (1) followed by cyclisation. Debenzylation of 2 (-->3) and glycosylation of HO-4 with 3,4,6-tri-O-acetyl-2- deoxy-2-phthalimido-beta-D-glucopyranosyl chloride afforded 75% of a beta-(1-->4)-linked disaccharide derivative (7). Removal of the Phth group from 7, then acetylation, and O-deacetylation yielded 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-amino-1,6-anhydro-3-O- [(R)- 1-carboxyethyl]-2-deoxy-beta-D-glucopyranose 1',2-lactam (10) Acetolysis of the 1,6-anhydro ring in the 4-acetate (4) of 3 and the 3',4',6'-triacetate (9) of 10, with saponification of the products 5 and 11, afforded 2-amino-3-O- [(R)-1-carboxyethyl]-2-deoxy-D-glucopyranose 1',2-lactam (6) and 4-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-2-amino-3- O-[(R)-1-carboxyethyl]-2-deoxy-beta-D-glucopyranose 1',2-lactam (12), respectively. The structure of 12 corresponds to that of the disaccharide unit characteristic of the glycan chains of bacterial spore peptidoglycan. 1H NMR spectroscopy indicated that the beta-D-glucopyranose ring in the 1,6-anhydro 1',2-lactam derivatives adopts the BO,3 conformation. On cleavage of the 1,6-anhydro ring by acetolysis, the D-glucopyranose ring adopts the 4C1 conformation. X-ray analysis of 2, 4, and 5 confirmed the proposed structures. Molecular mechanics and molecular dynamics simulations were used to follow the transformation of the BO,3 conformation of the D-glucopyranose ring via transition states to the 4C1 form.

  15. Proof of cannabis administration by sensitive detection of 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid in hair using selective methylation and application of liquid chromatography- tandem and multistage mass spectrometry.

    Science.gov (United States)

    Thieme, Detlef; Sachs, Hans; Uhl, Michael

    2014-01-01

    The identification of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in hair represents an exceptional forensic analytical challenge due to low target concentrations in a complex matrix. Several dedicated techniques [gas chromatography-negative chemical ionization-tandem mass spectrometry (GC-NCI-MS/MS) or GC-GC-MS couplings] were specifically introduced into forensic toxicology aiming to a selective and sensitive identification of THCCOOH in hair. The combination of liquid-chromatography (LC) and MS/MS gained an outstanding relevance in forensic toxicology (including the detection of cannabinoids). However, its application to hair matrix is characterized by a lack of specificity which is due to the unspecific decarboxylation as most abundant fragmentation reaction. Therefore, various chemical modifications of the carboxyl and/or phenolic hydroxyl groups were examined to improve the selectivity. The selective methylation of the 9-carboxyl-group proved to be the most efficient derivatization procedure. Hair extracts were redissolved in acetonitrile and after addition of few milligrams of solid sodium carbonate derivatized with 25 μL methyl iodide. The resulting THC-9-carboxymethylester was separated by conventional reverse phase LC and selectively detected using negative electrospray ionization by recording the fragmentation reactions 357➔325 and 357➔297. Resulting limits of quantification were below 100 fg/mg. A further significant improvement was achieved by application of the multistage MS3 fragmentation 357➔325➔297. To verify the validity of this procedure, a systematic quantitative comparison of THCCOOH concentrations in hair with data from a well established GC-NCI-MS/MS technique was performed. Both techniques proved to be in good accordance (R(2)=0.647, p = <0.001) and equally suitable for hair testing of THCCOOH. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Studies on mu and delta opioid receptor selectivity utilizing chimeric and site-mutagenized receptors.

    Science.gov (United States)

    Wang, W W; Shahrestanifar, M; Jin, J; Howells, R D

    1995-01-01

    Opioid receptors are members of the guanine nucleotide binding protein (G protein)-coupled receptor family. Three types of opioid receptors have been cloned and characterized and are referred to as the delta, kappa and mu types. Analysis of receptor chimeras and site-directed mutant receptors has provided a great deal of information about functionally important amino acid side chains that constitute the ligand-binding domains and G-protein-coupling domains of G-protein-coupled receptors. We have constructed delta/mu opioid receptor chimeras that were express in human embryonic kidney 293 cells in order to define receptor domains that are responsible for receptor type selectivity. All chimeric receptors and wild-type delta and mu opioid receptors displayed high-affinity binding of etorphine (an agonist), naloxone (an antagonist), and bremazocine (a mixed agonist/antagonist). In contrast, chimeras that lacked the putative first extracellular loop of the mu receptor did not bind the mu-selective peptide [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO). Chimeras that lacked the putative third extracellular loop of the delta receptor did not bind the delta-selective peptide, [D-Ser2,D-Leu5]enkephalin-Thr (DSLET). Point mutations in the putative third extracellular loop of the wild-type delta receptor that converted vicinal arginine residues to glutamine abolished DSLET binding while not affecting bremazocine, etorphine, and naltrindole binding. We conclude that amino acids in the putative first extracellular loop of the mu receptor are critical for high-affinity DAMGO binding and that arginine residues in the putative third extracellular loop of the delta receptor are important for high-affinity DSLET binding. Images Fig. 3 PMID:8618916

  17. Delta Electroproduction in 12-C

    Energy Technology Data Exchange (ETDEWEB)

    McLauchlan, Steven [Univ. of Glasgow, Scotland (United Kingdom)

    2003-01-01

    The Δ-nucleus potential is a crucial element in the understanding of the nuclear system. Previous electroexcitation measurements in the delta region reported a Q2 dependence of the Δ mass indicating that this potential is dependent on the momentum of the Δ. Such a dependence is not observed for protons and neutrons in the nuclear medium. This thesis presents the experimental study of the electroexcitation of the Δ resonance in 12C, performed using the high energy electron beam at the Thomas Jefferson National Accelerator Facility, and the near 4π acceptance detector CLAS that enables the detection of the full reaction final state. Inclusive, semi inclusive, and exclusive cross sections were measured with an incident electron beam energy of 1.162GeV over the Q2 range 0.175-0.475 (GeV/c)2. A Q2 dependence of the Δ mass was only observed in the exclusive measurements indicating that the Δ-nucleus potential is affected by the momentum of the Δ.

  18. Novel diazabicycloalkane delta opioid agonists.

    Science.gov (United States)

    Loriga, Giovanni; Lazzari, Paolo; Manca, Ilaria; Ruiu, Stefania; Falzoi, Matteo; Murineddu, Gabriele; Bottazzi, Mirko Emilio Heiner; Pinna, Giovanni; Pinna, Gérard Aimè

    2015-09-01

    Here we report the investigation of diazabicycloalkane cores as potential new scaffolds for the development of novel analogues of the previously reported diazatricyclodecane selective delta (δ) opioid agonists, as conformationally constrained homologues of the reference δ agonist (+)-4-[(αR)-α((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80). In particular, we have simplified the diazatricyclodecane motif of δ opioid agonist prototype 1a with bridged bicyclic cores. 3,6-diazabicyclo[3.1.1]heptane, 3,8-diazabicyclo[3.2.1]octane, 3,9-diazabicyclo[3.3.1]nonane, 3,9-diazabicyclo[4.2.1]nonane, and 3,10-diazabicyclo[4.3.1]decane were adopted as core motifs of the novel derivatives. The compounds were synthesized and biologically assayed as racemic (3-5) or diastereoisomeric (6,7) mixtures. All the novel compounds 3-7 showed δ agonism behaviour and remarkable affinity to δ receptors. Amongst the novel derivatives, 3,8-diazabicyclo[3.2.1]octane based compound 4 evidenced improved δ affinity and selectivity relative to SNC80. Published by Elsevier Ltd.

  19. Damped Oscillator with Delta-Kicked Frequency

    Science.gov (United States)

    Manko, O. V.

    1996-01-01

    Exact solutions of the Schrodinger equation for quantum damped oscillator subject to frequency delta-kick describing squeezed states are obtained. The cases of strong, intermediate, and weak damping are investigated.

  20. Delta-nucleus dynamics: proceedings of symposium

    Energy Technology Data Exchange (ETDEWEB)

    Lee, T.S.H.; Geesaman, D.F.; Schiffer, J.P. (eds.)

    1983-10-01

    The appreciation of the role in nuclear physics of the first excited state of the nucleon, the delta ..delta..(1232), has grown rapidly in the past decade. The delta resonance dominates nuclear reactions induced by intermediate energy pions, nucleons, and electromagnetic probes. It is also the most important non-nucleonic degree of freedom needed to resolve many fundamental problems encountered in the study of low-energy nuclear phenomena. Clearly, a new phase of nuclear physics has emerged and conventional thinking must be extended to account for this new dimension of nuclear dynamics. The most challenging problem we are facing is how a unified theory can be developed to describe ..delta..-nucleus dynamics at all energies. In exploring this new direction, it is important to have direct discussions among researchers with different viewpoints. Separate entries were prepared for the 49 papers presented. (WHK)

  1. in the Niger Delta of Nigeria

    African Journals Online (AJOL)

    suggestions as policy options for the resolution of the armed conflict in the. Niger Delta ... indiscriminate use of lethal weapons by local militias, the cumulative effect of which is the ... of many 'child' soldiers in local conflicts or wars nowadays.

  2. Contemporary depositional environments of the Omo delta.

    Science.gov (United States)

    Butzer, K W

    1970-05-02

    Geomorphological and sedimentological studies of depositional environments of the modern Omo River delta and floodplain are essential to an understanding of the Pliocene to Pleistocene Mursi, Nkalabong and Kibish Formations of the Lower Omo Basin (southwestern Ethiopia).

  3. Legal Delta Boundary, 2001, DWR [ds586

    Data.gov (United States)

    California Department of Resources — The original topographic maps containing the drawn delta border were scanned from the Department of Water Resources. Images were registered to 1:24,000 USGS DRG's in...

  4. Cackling Canada goose nesting populations, Yukon Delta

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — Number of potential territories, number of cackling Canada Goose nests, and percent occupancy of available territories from CCG plots on the Yukon Delta National...

  5. Water quality in the Okavango Delta

    African Journals Online (AJOL)

    2010-03-12

    Mar 12, 2010 ... water and sediments in the Okavango Delta published between 2000 and 2010. Despite the shortage ... Their interactions with light, water, dissolved nutrients and suspended solids ...... temporal remote sensing. Int. J. Remote ...

  6. California Black Rail - Central Delta [ds17

    Data.gov (United States)

    California Department of Resources — Results of taped-call black rail surveys of in-stream habitat within certain waterways in the central Sacramento / San Joaquin Delta during 1992 and 1993. TIME...

  7. Propagator for the double delta potential

    Energy Technology Data Exchange (ETDEWEB)

    Cacciari, Ilaria [Istituto di Fisica Applicata ' Nello Carrara' , CNR, via Madonna del Piano 10, 50019 Sesto Fiorentino, Florence (Italy); Moretti, Paolo [Istituto dei Sistemi Complessi, CNR, Sezione di Firenze, via Madonna del Piano 10, 50019 Sesto Fiorentino, Florence (Italy)]. E-mail: paolo.moretti@isc.cnr.it

    2006-12-04

    The propagator for the double delta potential is calculated starting from the integral form of the Schroedinger equation. A compact expression of its Laplace transform is found, that can be explicitly inverted in some limiting cases.

  8. The Atchafalaya River Delta. Report 4. Generic Analysis of Delta Development.

    Science.gov (United States)

    1984-01-01

    contemporaneously with delta growth (Donaldson, Martin , and Kanes 1970). The average rate of contour advancement has been ap- proximately 12 m/yr. Assuming the...Donaldson, Martin , ’, and Kanes 1970) shows that the delta has transgressed over 60 m. Average rates of deterioration are reported to be 2.75 m/yr...after 1965 ( Keown , Dardeau, and Causey 1980). Coarse sediment not reaching the delta is precisely the material needed for subaerial land. Third, the

  9. Optimized $\\delta$ expansion for relativistic nuclear models

    CERN Document Server

    Krein, G I; Peres-Menezes, D; Nielsen, M; Pinto, M B

    1998-01-01

    The optimized $\\delta$-expansion is a nonperturbative approach for field theoretic models which combines the techniques of perturbation theory and the variational principle. This technique is discussed in the $\\lambda \\phi^4$ model and then implemented in the Walecka model for the equation of state of nuclear matter. The results obtained with the $\\delta$ expansion are compared with those obtained with the traditional mean field, relativistic Hartree and Hartree-Fock approximations.

  10. Migration in Vulnerable Deltas: A Research Strategy

    Science.gov (United States)

    Hutton, C.; Nicholls, R. J.; Allan, A.

    2015-12-01

    C. Hutton1, & R. J. Nicholls1, , 1 University of Southampton, University Road, Southampton, Hampshire, United Kingdom, SO17 1BJ. cwh@geodata. soton.ac.ukAbstractGlobally, deltas contain 500 million people and with rising sea levels often linked to large number of forced migrants are expected in the coming century. However, migration is already a major process in deltas, such as the growth of major cities such as Dhaka and Kolkata. Climate and environmental change interacts with a range of catchment and delta level drivers, which encompass a nexus of sea-level rise, storms, freshwater and sediment supply from the catchment, land degradation, subsidence, agricultural loss and socio-economic stresses. DECCMA (Deltas, Vulnerability and Climate Change: Migration and Adaptation/CARRIA) is investigating migration in the Ganges-Brahmaputra-Meghna (GBM), Mahanadi and Volta Deltas, including the influence of climate change. The research will explore migration from a range of perspectives including governance and stakeholder analysis, demographic analysis, household surveys of sending and receiving areas, macro-economic analysis, and hazards and hotspot analysis both historically and into the future. Migration under climate change will depend on other adaptation in the deltas and this will be examined. Collectively, integrated analysis will be developed to examine migration, other adaptation and development pathways with a particular focus on the implications for the poorest. This will require the development of input scenarios, including expert-derived exogenous scenarios (e.g., climate change) and endogenous scenarios of the delta developed in a participatory manner. This applied research will facilitate decision support methods for the development of deltas under climate change, with a focus on migration and other adaptation strategies.

  11. Stellar delta matter with delta-meson coupling constants constrained by QCD sum rule

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Antonio Ferreira da [Secretaria de Educacao, Cultura e Desportos do Estado de Roraima (SECD/RR), Boa Vista, RR (Brazil); Oliveira, Jose Carlos Teixeira de [Universidade Federal de Roraima (UFRR), Boa Vista, RR (Brazil); Rodrigues, Hilario [Centro Federal de Educacao Tecnologica (CEFET-RJ), Rio de Janeiro, RJ (Brazil); Duarte, Sergio Barbosa [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil); Chiapparini, Marcelo [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil)

    2010-07-01

    The considerable presence of delta-resonances (30% of baryonic population) in the dense phase of relativistic heavy ion collisions leads to a great interest in the study of the delta matter formation in the deep interior of compact stars. In the present work we determine the equation of state and the population of baryons and leptons and discuss the effects of the baryon-meson coupling constants to the formation of delta matter in the stellar medium. We use the non-linear Walecka model consisting of the octet of baryons of spin 1=2 (n, p, {Lambda}{sup 0}, {Sigma}{sup -}, {Sigma}{sup 0}, {Sigma}{sup +}, {Xi}{sup -}, {Xi}{sup 0}) and baryonic resonances of spin 3=2, represented by the delta resonances ({Delta}{sup -}, ({Delta}{sup 0}, ({Delta}{sup +}, ({Delta}{sup ++}) and {Omega}{sup -}, in the baryonic sector. In the leptonic sector we consider the electrons and muons. The coupling constants between the hyperons {Lambda}, {Sigma}, and {Xi} and the mesons {omega} and {rho} are fixed by using SU(6) symmetry, while the hyperons-{sigma} coupling constants are constrained by the consistence of the hypernuclear potential in the nuclear matter with hypernuclear data. In addition, we use the finite density QCD sum rule to determine the possible values of delta-meson coupling constants. (author)

  12. delta(13)C and delta(2)H isotope ratios in amphetamine synthesized from benzaldehyde and nitroethane.

    Science.gov (United States)

    Collins, Michael; Salouros, Helen; Cawley, Adam T; Robertson, James; Heagney, Aaron C; Arenas-Queralt, Andrea

    2010-06-15

    Previous work in these laboratories and by Butzenlechner et al. and Culp et al. has demonstrated that the delta(2)H isotope value of industrial benzaldehyde produced by the catalytic oxidation of toluene is profoundly positive, usually in the range +300 per thousand to +500 per thousand. Synthetic routes leading to amphetamine, methylamphetamine or their precursors and commencing with such benzaldehyde may be expected to exhibit unusually positive delta(2)H values. Results are presented for delta(13)C and delta(2)H isotope values of 1-phenyl-2-nitropropene synthesized from an industrial source of benzaldehyde, having a positive delta(2)H isotope value, by a Knoevenagel condensation with nitroethane. Results are also presented for delta(13)C and delta(2)H isotope values for amphetamine prepared from the resulting 1-phenyl-2-nitropropene. The values obtained were compared with delta(13)C and delta(2)H isotope values obtained for an amphetamine sample prepared using a synthetic route that did not involve benzaldehyde. Finally, results are presented for samples of benzaldehyde, 1-phenyl-2-nitropropene and amphetamine that had been seized at a clandestine amphetamine laboratory.

  13. Solution structure of 3-oxo-delta5-steroid isomerase.

    Science.gov (United States)

    Wu, Z R; Ebrahimian, S; Zawrotny, M E; Thornburg, L D; Perez-Alvarado, G C; Brothers, P; Pollack, R M; Summers, M F

    1997-04-18

    The three-dimensional structure of the enzyme 3-oxo-delta5-steroid isomerase (E.C. 5.3.3.1), a 28-kilodalton symmetrical dimer, was solved by multidimensional heteronuclear magnetic resonance spectroscopy. The two independently folded monomers pack together by means of extensive hydrophobic and electrostatic interactions. Each monomer comprises three alpha helices and a six-strand mixed beta-pleated sheet arranged to form a deep hydrophobic cavity. Catalytically important residues Tyr14 (general acid) and Asp38 (general base) are located near the bottom of the cavity and positioned as expected from mechanistic hypotheses. An unexpected acid group (Asp99) is also located in the active site adjacent to Tyr14, and kinetic and binding studies of the Asp99 to Ala mutant demonstrate that Asp99 contributes to catalysis by stabilizing the intermediate.

  14. Correlations and agreement between delta-9-tetrahydrocannabinol (THC) in blood plasma and Timeline Follow-Back (TLFB)-assisted self-reported use of cannabis of patients with cannabis use disorder and psychotic illness attending the CapOpus randomized clinical trial

    DEFF Research Database (Denmark)

    Hjorthøj, Carsten Rygaard; Fohlmann, Allan; Larsen, Anne-Mette

    2012-01-01

    disorder and psychosis, providing 239 self-reports of cannabis use and 88 valid blood samples. Measurements Delta-9-tetrahydrocannabinol (THC), 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) detected in plasma using high...

  15. The Okavango: Whose Delta is it?

    Science.gov (United States)

    Magole, Lapologang; Magole, Lefatshe Innocent

    The Okavango Delta is amongst the largest Ramsar sites ( http://www.ramsar.org/sitelist.pdf) in the world and an important wetland for community livelihoods, conservation and tourism in Botswana. Over the years, the utilization of the delta has shifted from communal use to state control, with an increased use for conservation and tourism. This increased use for conservation and tourism has manifested in the physical expansion of the conservation area - Moremi Game Reserve and the formation of Wildlife Management Areas (WMAs) around the reserve, whose primary land use is wildlife utilization. The expansion of the conservation area has translated into several practical matters, including expansion of the area for non-hunting activities or photographic areas. The livelihoods of local communities of the Okavango delta who depended on fishing, hunter-gathering, livestock rearing, rain-fed agriculture and flood recession farming have been negatively affected by the expansion of conservation and tourism in the delta. The livelihoods alternatives in the form of Community Based Natural Resource Management (CBNRM) and tourism have not provided substitutes for the people as the communities are still reliant on the same old livelihood sources as in the past, albeit within smaller and restricted areas. This paper explores the ownership of the natural resources within the Okavango Delta. It asks and attempts to answer the following questions: Who owns and controls the use of the land? Who has access to other resources there in? Who makes the decisions on how the delta resources should be managed and used? Who benefits from the delta resources? We argue firstly that ownership of the delta as defined by legal parameters and demonstrated in natural resource management practice is vested on government. Secondly, government, after assuming ownership of the delta continues to sell its stake to the international community, at the expense of local ownership and access to resources. We

  16. Combination photodynamic therapy using 5-fluorouracil and aminolevulinate enhances tumor-selective production of protoporphyrin IX and improves treatment efficacy of squamous skin cancers and precancers

    Science.gov (United States)

    Maytin, Edward V.; Anand, Sanjay

    2016-03-01

    In combination photodynamic therapy (cPDT), a small-molecule drug is used to modulate the physiological state of tumor cells prior to giving aminolevulinate (ALA; a precursor for protoporphyrin IX, PpIX). In our laboratory we have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can enhance therapeutic effectiveness of ALAbased photodynamic therapy for cutaneous squamous cell carcinoma (SCC). However, only one (5-fluorouracil; 5-FU) is FDA-approved for skin cancer management. Here, we describe animal and human studies on 5-FU mechanisms of action, in terms of how 5-FU pretreatment leads to enhanced PpIX accumulation and improves selectivity of ALA-PDT treatment. In A431 subcutaneous tumors in mice, 5-FU changed expression of heme enzyme (upregulating coproporphyrinogen oxidase, and down-regulating ferrochelatase), inhibited tumor cell proliferation (Ki-67), enhanced differentiation (E-cadherin), and led to strong, tumor-selective increases in apoptosis. Interestingly, enhancement of apoptosis by 5-FU correlated strongly with an increased accumulation of p53 in tumor cells that persisted for 24 h post- PDT. In a clinical trial using a split-body, bilaterally controlled study design, human subjects with actinic keratoses (AK; preneoplastic precursors of SCC) were pretreated on one side of the face, scalp, or forearms with 5-FU cream for 6 days, while the control side received no 5-FU. On the seventh day, the levels of PpIX in 4 test lesions were measured by noninvasive fluorescence dosimetry, and then all lesions were treated with PDT using methyl-aminolevulinate (MAL) and red light (635 nm). Relative amounts of PpIX were found to be increased ~2-fold in 5-FU pretreated lesions relative to controls. At 3 months after PDT, the overall clinical response to PDT (reduction in lesion counts) was 2- to 3-fold better for the 5-FU pretreated lesions, a clinically important result. In summary, 5-FU is a useful adjuvant to aminolevulinate-based PDT

  17. Impact of sea-level rise in a Mediteranean delta: The Ebro delta cast

    NARCIS (Netherlands)

    Sánchez-Arcilla, A.; Stive, M.D.F.; Jiménez, J.A.; García, M.A.

    1993-01-01

    In anticipation of a comprehensive, multidisciplinary study on the impact of climatic change on the Ebro Delta preliminary results are here presented of the response of the outer delta coast to present and future relative sea-level rise. Due to the absence of observations and predictions of regional

  18. Final State Interactions and Delta S=-1, Delta C=\\pm 1 B--decays

    CERN Document Server

    Fayyazuddin, A

    2002-01-01

    The final state interactions (FSI) in Delta S=-1, Delta C=\\pm 1, decays of B-meson are discussed. The rescattering corrections are found to be of order of 15-20%. The strong interaction phase shifts are estimated and their effects on CP-asymmetry are discussed.

  19. A model for the Delta(1600) resonance and gamma N -> Delta(1600) transition

    CERN Document Server

    Ramalho, G

    2010-01-01

    A covariant spectator constituent quark model is applied to study the gamma N -> Delta(1600) transition. Two processes are important in the transition: a photon couples to the individual quarks of the Delta(1600) core (quark core), and a photon couples to the intermediate pion-baryon states (pion cloud). While the quark core contributions are estimated assuming Delta(1600) as the first radial excitation of Delta(1232), the pion cloud contributions are estimated based on an analogy with the gamma N -> Delta(1232) transition. To estimate the pion cloud contributions in the gamma N -> Delta(1600) transition, we include the relevant intermediate states, pi-N, pi-Delta, pi-N(1440) and pi-Delta(1600). Dependence on the four-momentum transfer squared, Q2, is predicted for the magnetic dipole transition form factor, GM*(Q2), as well as the helicity amplitudes, A_1/2(Q2) and A_3/2(Q2). The results at Q2=0 are compared with the existing data.

  20. A model for the Delta(1600) resonance and gamma N -> Delta(1600) transition

    Energy Technology Data Exchange (ETDEWEB)

    G. Ramalho, K. Tsushima

    2010-10-01

    A covariant spectator constituent quark model is applied to study the gamma N -> Delta(1600) transition. Two processes are important in the transition: a photon couples to the individual quarks of the Delta(1600) core (quark core), and a photon couples to the intermediate pion-baryon states (pion cloud). While the quark core contributions are estimated assuming Delta(1600) as the first radial excitation of Delta(1232), the pion cloud contributions are estimated based on an analogy with the gamma N -> Delta(1232) transition. To estimate the pion cloud contributions in the gamma N -> Delta(1600) transition, we include the relevant intermediate states, pi-N, pi-Delta, pi-N(1440) and pi-Delta(1600). Dependence on the four-momentum transfer squared, Q2, is predicted for the magnetic dipole transition form factor, GM*(Q2), as well as the helicity amplitudes, A_1/2(Q2) and A_3/2(Q2). The results at Q2=0 are compared with the existing data.

  1. Impact of sea-level rise in a Mediteranean delta: The Ebro delta cast

    NARCIS (Netherlands)

    Sánchez-Arcilla, A.; Stive, M.D.F.; Jiménez, J.A.; García, M.A.

    1993-01-01

    In anticipation of a comprehensive, multidisciplinary study on the impact of climatic change on the Ebro Delta preliminary results are here presented of the response of the outer delta coast to present and future relative sea-level rise. Due to the absence of observations and predictions of regional

  2. The Enabling Delta Life Initiative - Global Programme of Action on Deltas - Programme description

    NARCIS (Netherlands)

    Driel, van W.F.; Skyllerstedt, S.; Wosten, J.H.M.

    2014-01-01

    Being ‘hotspots’ of human activity with generally high population densities, deltas are vulnerable to changes induced by a range of driving forces, both natural and anthropogenic. In addition to already existing challenges, uncertainty of the possible impacts of climate change, low lying deltas arou

  3. Houtman Abrolhos Isotope (delta 18O, delta 13C) Data for 1795 to 1994

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — DESCRIPTION: VARIABLES AND UNITS: Column #1: core depth in mm Column #2: delta C-13 vs V-PDB Column #3: delta O-18 vs V-PDB Column #4: assigned date in years A.D....

  4. \\Delta Y/ \\Delta Z from the analysis of local K dwarfs

    CERN Document Server

    Gennaro, Mario; Degl'Innocenti, Scilla

    2010-01-01

    The stellar helium-to-metal enrichment ratio, \\Delta Y/\\Delta Z, is a widely studied astrophysical quantity. However, its value is still not precisely constrained. This paper is focused on the study of the main sources of uncertainty which affect the \\Delta Y/\\Delta Z derived from the analysis of the low-main sequence (MS) stars in the solar neighborhood. The possibility to infer the value of \\Delta Y/\\Delta Z from the study of low-MS stars relies on the dependence of the stellar luminosity and effective temperature on the initial Y and Z. The \\Delta Y/\\Delta Z ratio is obtained by comparing the magnitude difference between the observed stars and a reference theoretical zero age main sequence (ZAMS) with the related theoretical magnitude differences computed from a new set of stellar models with up-to-date input physics and a fine grid of chemical compositions. A Monte Carlo approach has been used to evaluate the impact on the result of different sources of uncertainty, i.e. observational errors, evolutionary...

  5. Holocene delta plain development in the Song Hong (Red River) delta, Vietnam

    Science.gov (United States)

    Funabiki, Ayako; Haruyama, Shigeko; Quy, Nguyen Van; Hai, Pham Van; Thai, Dinh Hung

    2007-05-01

    Holocene delta plain development was investigated based on three sediment cores analyzed in detail from the Song Hong (Red River) delta plain in Vietnam. Two cores (DA and PD) from the western delta plain showed both the landward limit of the transgressive estuarine system in the valley incised during the last glacial maximum and floodplain evolution since the middle Holocene. On the other hand, a core (TL) from the eastern delta plain revealed a Pleistocene terrace buried under the deltaic sediments and a slow accumulation rate compared with that in the west. At 8 cal ky BP, the shoreline migrated very close to the present Hanoi city area, and the sedimentary environment changed to tidal flat or salt marsh. Hanoi city marks the northern limit of shoreline transgression. The mangrove swamp expanded from 8 to 5 cal ky BP to the landward limit of the delta plain. Subsequently, the shoreline migrated seaward as a result of delta progradation and sea-level lowering. From 5 cal ky BP, the emerged area evolved into a floodplain and natural levees formed along the abandoned river channels on the western delta plain, but at 2 cal ky, archeological sites indicate that the Holocene terrace in the eastern delta plain was still inundated.

  6. EEG with extreme delta brush in young female with methotrexate neurotoxicity supports NMDA receptor involvement.

    Science.gov (United States)

    Schmidt, Lisbeth Samsø; Kjær, Troels W; Schmiegelow, Kjeld; Born, Alfred Peter

    2017-09-01

    Sub-acute neurotoxicity is a well-known complication to high-dose and intrathecal methotrexate (MTX) treatment of children with leukemia. Symptoms can be treated safely by dextromethorphan, a non-competitive antagonist to N-methyl-D-aspartic acid receptor (NMDAR). In a female with subacute MTX neurotoxicity, we observed an electroencephalographic (EEG) with extreme delta brush. Extreme delta brush is an EEG pattern previously described in patients with NMDAR autoimmune encephalitis. The observations suggest that the mechanism of this neurotoxicity may be mediated by the NMDAR. Furthermore, extreme EEG delta brush should suggest a diagnosis of MTX associated subacute neurotoxicity. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. Treatment of Tourette's syndrome with Delta 9-tetrahydrocannabinol (THC): a randomized crossover trial.

    Science.gov (United States)

    Müller-Vahl, K R; Schneider, U; Koblenz, A; Jöbges, M; Kolbe, H; Daldrup, T; Emrich, H M

    2002-03-01

    Anecdotal reports in Tourette's syndrome (TS) have suggested that marijuana (cannabis sativa) and delta-9-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive ingredient of marijuana, reduce tics and associated behavioral disorders. We performed a randomized double-blind placebo-controlled crossover single-dose trial of Delta(9)-THC (5.0, 7.5 or 10.0 mg) in 12 adult TS patients. Tic severity was assessed using a self-rating scale (Tourette's syndrome Symptom List, TSSL) and examiner ratings (Shapiro Tourette's syndrome Severity Scale, Yale Global Tic Severity Scale, Tourette's syndrome Global Scale). Using the TSSL, patients also rated the severity of associated behavioral disorders. Clinical changes were correlated to maximum plasma levels of THC and its metabolites 11-hydroxy-Delta(9)-tetrahydrocannabinol (11-OH-THC) and 11-nor-Delta(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Using the TSSL, there was a significant improvement of tics (p=0.015) and obsessive-compulsive behavior (OCB) (p = 0.041) after treatment with Delta(9)-THC compared to placebo. Examiner ratings demonstrated a significant difference for the subscore "complex motor tics" (p = 0.015) and a trend towards a significant improvement for the subscores "motor tics" (p = 0.065), "simple motor tics" (p = 0.093), and "vocal tics" (p = 0.093). No serious adverse reactions occurred. Five patients experienced mild, transient side effects. There was a significant correlation between tic improvement and maximum 11-OH-THC plasma concentration. Results obtained from this pilot study suggest that a single-dose treatment with Delta(9)-THC is effective and safe in treating tics and OCB in TS. It can be speculated that clinical effects may be caused by 11-OH-THC. A more long-term study is required to confirm these results.

  8. Potent Dmt-Tic pharmacophoric delta- and mu-opioid receptor antagonists.

    Science.gov (United States)

    Li, Tingyou; Fujita, Yoshio; Shiotani, Kimitaka; Miyazaki, Anna; Tsuda, Yuko; Ambo, Akihiro; Sasaki, Yusuke; Jinsmaa, Yunden; Marczak, Ewa; Bryant, Sharon D; Salvadori, Severo; Lazarus, Lawrence H; Okada, Yoshio

    2005-12-15

    A series of dimeric Dmt-Tic (2',6'-dimethyl-L-tyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) analogues (8-14, 18-22) were covalently linked through diaminoalkane and symmetric or asymmetric 3,6-diaminoalkyl-2(1H)-pyrazinone moieties. All the compounds exhibited high affinity for both delta-opioid receptors [Ki(delta) = 0.06-1.53 nM] and mu-opioid receptors [Ki(mu) = 1.37-5.72 nM], resulting in moderate delta-receptor selectivity [Ki(mu)/Ki(delta) = 3-46]. Regardless of the type of linker between the Dmt-Tic pharmacophores, delta-opioid-mediated antagonism was extraordinarily high in all analogues (pA2 = 10.42-11.28), while in vitro agonism (MVD and GPI bioassays) was essentially absent (ca. 3 to >10 microM). While an unmodified N-terminus (9, 13, 18) revealed weak mu-opioid antagonism (pA2 = 6.78-6.99), N,N'-dimethylation (21, 22), which negatively impacts on mu-opioid-associated agonism (Balboni et al., Bioorg. Med. Chem. 2003, 11, 5435-5441), markedly enhanced mu-opioid antagonism (pA2 = 8.34 and 7.71 for 21 and 22, respectively) without affecting delta-opioid activity. These data are the first evidence that a single dimeric opioid ligand containing the Dmt-Tic pharmacophore exhibits highly potent delta- and mu-opioid antagonist activities.

  9. MODIFICATION OF DELTA FOR CHOOSER OPTIONS

    Directory of Open Access Journals (Sweden)

    Marek Ďurica

    2015-09-01

    Full Text Available Correctly used financial derivatives can help investors increase their expected returns and minimize their exposure to risk. To ensure the specific needs of investors, a large number of different types of non-standard exotic options is used. Chooser option is one of them. It is an option that gives its holder the right to choose at some predetermined future time whether the option will be a standard call or put with predetermined strike price and maturity time. Although the chooser options are more expensive than standard European-style options, in many cases they are a more suitable instrument for investors in hedging their portfolio value. For an effective use of the chooser option as a hedging instrument, it is necessary to check the values of the Greek parameters delta and gamma for the options. Especially, if the value of the parameter gamma is too large, hedging of the portfolio value using only parameter delta is insufficient and brings high transaction costs because the portfolio has to be reviewed relatively often. Therefore, in this article, a modification of delta-hedging as well as using the value of parameter gamma is suggested. Error of the delta modification is analyzed and compared with the error of widely used parameter delta. Typical patterns for the modified hedging parameter variation with various time to choose time for chooser options are also presented in this article.

  10. Notched delta, phenotype, and Angelman syndrome.

    Science.gov (United States)

    Korff, Christian M; Kelley, Kent R; Nordli, Douglas R

    2005-08-01

    The notched delta pattern is one of the characteristic EEG features found in Angelman syndrome patients. The purpose of this study was to evaluate the possibility of using the notched delta pattern as a detection tool for Angelman syndrome patients by analyzing its frequency in a tertiary care pediatric center, its specificity for Angelman syndrome, and the age at which it was observed. The authors performed a retrospective review of the video-EEG recordings of all the patients who had either the notched delta pattern or a phenotype consistent with Angelman syndrome. The notched delta was observed in 1.1% of all the EEGs performed. Its specificity for Angelman syndrome was evaluated at 38%. The youngest age at which it was noted was 14 months. The results indicate that the notched delta pattern is relatively rare, but more frequent than expected, and is easily recognizable. The pattern was observed not only in Angelman syndrome patients, but also in children with a spectrum of conditions wider than reported. It is a powerful detection tool for Angelman syndrome when correlated to a suggestive phenotype, and the association of these features should raise suspicion for Angelman syndrome in both infants and adults.

  11. Tracking Nile Delta vulnerability to Holocene change.

    Directory of Open Access Journals (Sweden)

    Nick Marriner

    Full Text Available Understanding deltaic resilience in the face of Holocene climate change and human impacts is an important challenge for the earth sciences in characterizing the full range of present and future wetland responses to global warming. Here, we report an 8000-year mass balance record from the Nile Delta to reconstruct when and how this sedimentary basin has responded to past hydrological shifts. In a global Holocene context, the long-term decrease in Nile Delta accretion rates is consistent with insolation-driven changes in the 'monsoon pacemaker', attested throughout the mid-latitude tropics. Following the early to mid-Holocene growth of the Nile's deltaic plain, sediment losses and pronounced erosion are first recorded after ~4000 years ago, the corollaries of falling sediment supply and an intensification of anthropogenic impacts from the Pharaonic period onwards. Against the backcloth of the Saharan 'depeopling', reduced river flow underpinned by a weakening of monsoonal precipitation appears to have been particularly conducive to the expansion of human activities on the delta by exposing productive floodplain lands for occupation and irrigation agriculture. The reconstruction suggests that the Nile Delta has a particularly long history of vulnerability to extreme events (e.g. floods and storms and sea-level rise, although the present sediment-starved system does not have a direct Holocene analogue. This study highlights the importance of the world's deltas as sensitive archives to investigate Holocene geosystem responses to climate change, risks and hazards, and societal interaction.

  12. QCD in the {delta}-regime

    Energy Technology Data Exchange (ETDEWEB)

    Bietenholz, W. [Universidad Nacional Autonoma de Mexico, Mexico City (Mexico). Inst. de Ciencias Nucleares; Cundy, N. [Seoul National Univ. (Korea, Republic of). Lattice Gauge Theory Research Center; Goeckeler, M. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Horsley, R.; Zanotti, J.M. [Edinburgh Univ. (United Kingdom). School of Physics; Nakamura, Y. [Tsukuba Univ., Ibaraki (Japan). Center for Computational Sciences; Pleiter, D. [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany); Rakow, P.E.L. [Liverpool Univ. (United Kingdom). Theoretical Physics Div.; Schierholz, G. [Regensburg Univ. (Germany). Inst. fuer Theoretische Physik; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2011-03-15

    The {delta}-regime of QCD is characterised by light quarks in a small spatial box, but a large extent in (Euclidean) time. In this setting a specific variant of chiral perturbation theory - the {delta}-expansion - applies, based on a quantum mechanical treatment of the quasi onedimensional system. In particular, for vanishing quark masses one obtains a residual pion mass M{sup R}{sub {pi}}, which has been computed to the third order in the {delta}-expansion. A comparison with numerical measurements of this residual mass allows for a new determination of some Low Energy Constants, which appear in the chiral Lagrangian. We first review the attempts to simulate 2-flavour QCD directly in the {delta}-regime. This is very tedious, but results compatible with the predictions for M{sup R}{sub {pi}} have been obtained. Then we show that an extrapolation of pion masses measured in a larger volume towards the {delta}-regime leads to good agreement with the theoretical predictions. From those results, we also extract a value for the (controversial) sub-leading Low Energy Constant anti l{sub 3}. (orig.)

  13. Interactions among mu- and delta-opioid receptors, especially putative delta1- and delta2-opioid receptors, promote dopamine release in the nucleus accumbens.

    NARCIS (Netherlands)

    Hirose, N.; Murakawa, K.; Takada, K.; Oi, Y.; Suzuki, T.; Nagase, H.; Cools, A.R.; Koshikawa, N.

    2005-01-01

    The effect of interactions among mu- and delta-opioid receptors, especially the putative delta(1)- and delta(2)-opioid receptors, in the nucleus accumbens on accumbal dopamine release was investigated in awake rats by in vivo brain microdialysis. In agreement with previous studies, perfusion of the

  14. Hydraulic engineering in the social-ecological delta: understanding the interplay between social, ecological, and technological systems in the Dutch delta by means of “delta trajectories”

    NARCIS (Netherlands)

    Staveren, van M.F.; Tatenhove, van J.P.M.

    2016-01-01

    Several of the world's largest deltas have recently been conceptualized as social-ecological delta systems. Although such conceptualizations are valuable in emphasizing complex interaction between social actors and ecological processes in deltas, they do not go into specific dynamics that surround t

  15. Interactions among mu- and delta-opioid receptors, especially putative delta1- and delta2-opioid receptors, promote dopamine release in the nucleus accumbens.

    NARCIS (Netherlands)

    Hirose, N.; Murakawa, K.; Takada, K.; Oi, Y.; Suzuki, T.; Nagase, H.; Cools, A.R.; Koshikawa, N.

    2005-01-01

    The effect of interactions among mu- and delta-opioid receptors, especially the putative delta(1)- and delta(2)-opioid receptors, in the nucleus accumbens on accumbal dopamine release was investigated in awake rats by in vivo brain microdialysis. In agreement with previous studies, perfusion of the

  16. El plan del delta - Holanda

    Directory of Open Access Journals (Sweden)

    Editorial, Equipo

    1963-09-01

    Full Text Available Holland is very poor in land resources. Hence its development has been directed towards intensive industrialization and maximum agricultural exploitation. The western part of the country is below sea level and is occupied by 65 percent of the population. Originally the coast consisted of a number of islands, estuaries and slight elevations. Man has transformed this coastline, first making a number of artificial lakes, or polders, and then converting these into fertile districts. These projects protect the soil by means of dykes, which require careful conservation, but even so violent floods are not infrequent. One of the difficult problems involved in this vast enterprise is the complex system of water supply, lines of communication and flow of the rivers into the sea along the estuary zone. This zone is on the south west, and to protect it a National Commission has been set up. After careful study, it was decided that the best defense against the violence of the sea would consist in closing off the inroads of the sea into the continental coastline. The set of hydraulic projects which constitutes this plan for the improvement of the sea defences will take 25 years to fulfil. The general project is highly ambitious and includes both maritime, road and structural works, in which there is a variety of stonework constructions. This paper describes, in brief outline, the main contents of the 11 headings into which the general construction project has been subdivided. In addition, this is supplemented with information on the projects which are already initiated and on the constructional procedure that is being adopted. Of these latter projects, the Nabla bridge is of particular interest. It is situated on the delta. It is made in prestressed concrete, and consists of 17 spans, of 60 length each. This enormous structure, in addition to its great length, and supporting a 22.8 ms wide roadway, is subjected to the tremendous forces 11» of the sea on one

  17. Correlation between treatment time, photobleaching, inflammation and pain after photodynamic therapy with methyl aminolevulinate on tape-stripped skin in healthy volunteers

    DEFF Research Database (Denmark)

    Lerche, Catharina M; Fabricius, Susanne; Philipsen, Peter A;

    2015-01-01

    Photodynamic therapy (PDT) is an attractive treatment option for skin diseases such as actinic keratosis, since large skin areas can be treated with high response rates and good cosmetic outcomes. Nevertheless inflammation and pain are still major side effects. The aim of this study...... was to investigate the extent to which less time-consuming PDT treatment regimens using methyl aminolevulinate (MAL) decrease protoporphyrin IX (PpIX) photobleaching, inflammation and pain. Twenty-four healthy volunteers were treated with 4 different interventions on each forearm. All 8 fields were tape-stripped 10...... MAL removal. PpIX fluorescence, photobleaching, objective and subjective erythema (as a measure for inflammation), pigmentation and pain were measured. The results showed a significant correlation between incubation time, time until illumination and photobleaching. Furthermore, there was a significant...

  18. NATO-3C/Delta launch

    Science.gov (United States)

    1978-01-01

    NATO-3C, the third in a series of NATO defense-related communication satellites, is scheduled to be launched on a delta vehicle from the Eastern Test Range no earlier than November 15, 1978. NATO-3A and -3B were successfully launched by Delta vehicles in April 1976 and January 1977, respectively. The NATO-3C spacecraft will be capable of transmitting voice, data, facsimile, and telex messages among military ground stations. The launch vehicle for the NATO-3C mission will be the Delta 2914 configuration. The launch vehicle is to place the spacecraft in a synchronous transfer orbit. The spacecraft Apogee Kick motor is to be fired at fifth transfer orbit apogee to circularize its orbit at geosynchronous altitude of 35,900 km(22,260 miles) above the equator over the Atlantic Ocean somewhere between 45 and 50 degrees W longitude.

  19. Liquefaction potential of Nile delta, Egypt

    Science.gov (United States)

    Fergany, Elsayed; Omar, Khaled

    2017-06-01

    Understanding how sedimentary basins respond to seismic-wave energy generated by earthquake events is a significant concern for seismic-hazard estimation and risk analysis. The main goal of this study is assessing the vulnerability index, Kg, as an indicator for liquefaction potential sites in the Nile delta basin based on the microtremor measurements. Horizontal to Vertical spectral ratio analyses (HVSR) of ambient noise data, which was conducted in 2006 at 120 sites covering the Nile delta from south to north were reprocessed using Geopsy software. HVSR factors of amplification, A, and fundamental frequency, F, were calculated and Kg was estimated for each measurement. The Kg value varies widely from south toward north delta and the potential liquefaction places were estimated. The higher vulnerability indices are associated with sites located in southern part of the Nile delta and close to the branches of Nile River. The HVSR factors were correlated with geologic setting of the Nile delta and show good correlations with the sediment thickness and subsurface stratigraphic boundaries. However, we note that sites located in areas that have greatest percentage of sand also yielded relatively high Kg values with respect to sites in areas where clay is abundant. We concluded that any earthquake with ground acceleration more than 50 gal at hard rock can cause a perceived deformation of sandy sediments and liquefaction can take place in the weak zones of Kg ≥ 20. The worst potential liquefaction zones (Kg > 30) are frequently joined to the Damietta and Rosetta Nile River branches and south Delta where relatively coarser sand exists. The HVSR technique is a very sensitive tool for lithological stratigraphy variations in two dimensions and varying liquefaction susceptibility.

  20. All optical binary delta-sigma modulator

    Science.gov (United States)

    Sayeh, Mohammad R.; Siahmakoun, Azad

    2005-09-01

    This paper describes a novel A/D converter called "Binary Delta-Sigma Modulator" (BDSM) which operates only with nonnegative signal with positive feedback and binary threshold. This important modification to the conventional delta-sigma modulator makes the high-speed (>100GHz) all-optical implementation possible. It has also the capability to modify its own sampling frequency as well as its input dynamic range. This adaptive feature helps designers to optimize the system performance under highly noisy environment and also manage the power consumption of the A/D converters.

  1. Measurement of the Muon Decay Parameter delta

    CERN Document Server

    Gaponenko, A N; Davydov, Yu I; Depommier, P; Doornbos, J; Faszer, W; Fujiwara, M C; Gagliardi, C A; Gill, D R; Green, P; Gumplinger, P; Hasinoff, M D; Henderson, R S; Hu, J; Jamieson, B; Kitching, P; Koetke, D D; Krushinsky, A A; Lachin, Yu Yu; MacDonald, J A; MacDonald, R P; Marshall, G M; Mathie, E L; Miasoedov, L V; Mischke, R E; Musser, J R; Nord, P M; Nozar, M; Olchanski, K; Olin, A; Openshaw, R; Porcelli, T A; Poutissou, J M; Poutissou, R; Quraan, M A; Rodning, N L; Selivanov, V; Sheffer, G; Shin, B; Sobratee, F; Stanislaus, T D S; Tacik, R; Torokhov, V D; Tribble, R E; Vasilev, M A; Wright, D H

    2004-01-01

    The muon decay parameter delta has been measured by the TWIST collaboration. We find delta = 0.74964 +- 0.00066(stat.) +- 0.00112(syst.), consistent with the Standard Model value of 3/4. This result implies that the product Pmuxi of the muon polarization in pion decay, Pmu, and the muon decay parameter xi falls within the 90% confidence interval 0.9960 < Pmuxi < xi < 1.0040. It also has implications for left-right-symmetric and other extensions of the Standard Model.

  2. Flood Inundation Modelling in Data Sparse Deltas

    Science.gov (United States)

    Hawker, Laurence; Bates, Paul; Neal, Jeffrey

    2017-04-01

    An estimated 7% of global population currently live in deltas, and this number is increasing over time. This has resulted in numerous human induced impacts on deltas ranging from subsidence, upstream sediment trapping and coastal erosion amongst others. These threats have already impacted on flood dynamics in deltas and could intensify in line with human activities. However, the myriad of threats creates a large number of potential scenarios that need to be evaluated. Therefore, to assess the impacts of these scenarios, a pre-requisite is a flood inundation model that is both computationally efficient and flexible in its setup so it can be applied in data-sparse settings. An intermediate scale, which compromises between the computational speed of a global model and the detail of a case specific bespoke model, was chosen to achieve this. To this end, we have developed an intermediate scale flood inundation model at a resolution of 540m of the Mekong Delta, built with freely available data, using the LISFLOOD-FP hydrodynamic model. The purpose of this is to answer the following questions: 1) How much detail is required to accurately simulate flooding in the Mekong Delta? , 2) What characteristics of deltas are most important to include in flood inundation models? Models were run using a vegetation removed SRTM DEM and a hind-casting of tidal heights as a downstream boundary. Results indicate the importance of vegetation removal in the DEM for inundation extent and the sensitivity of water level to roughness coefficients. The propagation of the tidal signal was found to be sensitive to bathymetry, both within the river channel and offshore, yet data availability for this is poor, meaning the modeller has to be careful in his or her choice of bathymetry interpolation Supplementing global river channel data with more localised data demonstrated minor improvements in results suggesting detailed channel information is not always needed to produce good results. It is

  3. Heat Kernel Estimate for $\\Delta+\\Delta^{\\alpha/2}$ in $C^{1,1}$ open sets

    CERN Document Server

    Chen, Zhen-Qing; Song, Renming

    2010-01-01

    We consider a family of pseudo differential operators $\\{\\Delta+ a^\\alpha \\Delta^{\\alpha/2}; a\\in (0, 1]\\}$ on $\\bR^d$ for every $d\\geq 1$ that evolves continuously from $\\Delta$ to $\\Delta + \\Delta^{\\alpha/2}$, where $\\alpha \\in (0, 2)$. It gives rise to a family of L\\'evy processes $\\{X^a, a\\in (0, 1]\\}$ in $\\bR^d$, where $X^a$ is the sum of a Brownian motion and an independent symmetric $\\alpha$-stable process with weight $a$. We establish sharp two-sided estimates for the heat kernel of $\\Delta + a^{\\alpha} \\Delta^{\\alpha/2}$ with zero exterior condition in a family of open subsets, including bounded $C^{1, 1}$ (possibly disconnected) open sets. This heat kernel is also the transition density of the sum of a Brownian motion and an independent symmetric $\\alpha$-stable process with weight $a$ in such open sets. Our result is the first sharp two-sided estimates for the transition density of a Markov process with both diffusion and jump components in open sets. Moreover, our result is uniform in $a$ in the s...

  4. Abraham Reef Stable Isotope Data (delta 13C, delta 18O, delta 14C) for 1635-1957

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Site: Abraham Reef, 22ó 06'S, 153ó 00'E, Porites australiensus, Radiocarbon (delta 14C) and Stable Isotope (del 18O and del 13C) results from bi-annual samples from...

  5. The microscopic structure of $\\pi NN$, $\\pi N\\Delta$ and $\\pi\\Delta\\Delta$ vertices in a hybrid constituent quark model

    CERN Document Server

    Jung, Ju-Hyun

    2016-01-01

    We present a microscopic description of the strong $\\pi NN$, $\\pi N\\Delta$ and $\\pi\\Delta\\Delta$ vertices. Our starting point is a constituent-quark model supplemented by an additional $3q\\pi$ non-valence component. In the spirit of chiral constituent-quark models, quarks are allowed to emit and reabsorb a pion. This multichannel system is treated in a relativistically invariant way within the framework of point-form quantum mechanics. Starting with a common $SU(6)$ spin-flavor-symmetric wave function for $N$ and $\\Delta$, we calculate the strength of the $\\pi NN$, $\\pi N\\Delta$ and $\\pi\\Delta\\Delta$ couplings and the corresponding vertex form factors. Our results are in accordance with phenomenological fits of these quantities that have been obtained within purely hadronic multichannel models for baryon resonances.

  6. Regulation of /sup 3/H-dopamine release by presynaptic GABA and glutamate heteroreceptors in rat brain nucleus accumbens synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Kovalev, G.I.; Hetey, L.

    1987-06-01

    The aim of this investigation was a neurochemical study of the effect of agonists of different types of GABA receptors - muscimol (type A receptor), baclofen (type B receptor), delta-aminolevulinic acid (DALA; GABA autoreceptor), and also of GABA itself - on tritium-labelled dopamine release, stimulated by potassium cations, from synaptosomes of the nuclei accumbenes of the rat brain.

  7. Homozygous acute intermittent porphyria in a 7-year-old boy with massive excretions of porphyrins and porphyrin precursors.

    NARCIS (Netherlands)

    Hessels, J.; Voortman, G.; Wagen, A. van der; Elzen, C. van der; Scheffer, H.; Zuijderhoudt, F.M.

    2004-01-01

    A 7-year-old boy demonstrating hepatosplenomegaly, mild anaemia, mild mental retardation, yellow-brown teeth and dark red urine had excessively elevated levels of urinary delta-aminolevulinic acid, porphobilinogen and uroporphyrin. Furthermore hepta-, hexa-, penta- and copro(I)porphyrins were highly

  8. Reduced complexity MASH delta-sigma modulator

    OpenAIRE

    Ye, Zhipeng; Kennedy, Michael Peter

    2007-01-01

    A reduced complexity digital multi-stage noise shaping (MASH) delta-sigma modulator for fractional-N frequency synthesizer applications is proposed. A long word is used for the first modulator in a MASH structure; the sequence length is maximized by setting the least significant bit of the input to 1; shorter words are used in subsequent stages. Experimental results confirm simulations

  9. Strong decays of nucleon and $\\Delta$ resonances

    CERN Document Server

    Bijker, R

    1996-01-01

    We study the strong couplings of the nucleon and delta resonances in a collective model. In the ensuing algebraic treatment we derive closed expressions for decay widths which are used to analyze the experimental data for strong decays into the pion and eta channels.

  10. How stable is the Mississippi Delta?

    NARCIS (Netherlands)

    Törnqvist, T.E.; Bick, S.J.; van der Borg, K.; de Jong, A.F.M.

    2006-01-01

    Large deltas are commonly believed to exhibit rapid rates of tectonic subsidence, largely due to sediment loading of the lithosphere. As a result, deltaic plains are prone to accelerated relative sea-level rise, coastal erosion, and wetland loss. Hurricane Katrina's devastation testifies to the seve

  11. Design of Low Power Sigma Delta ADC

    Directory of Open Access Journals (Sweden)

    Mohammed Arifuddin Sohel

    2012-08-01

    Full Text Available A Low power discrete time sigma delta ADC consisting of a second order sigma delta modulator and third order Cascaded Integrated Comb (CIC filter is proposed. The second order modulator is designed to work at a signal band of 20 K Hz at an oversampling ratio of 64 with a sampling frequency of 2.56 MHz. It achieves a signal to noise ratio of 85.2dB and a resolution of 14 bits. The CIC digital filter is designed to implement a decimation factor of 64, operating at a maximum sampling frequency of 2.56 MHz. A second order sigma delta modulator is implemented in 0.18 micron CMOS technology using full custom design and the third order digital CIC decimation filter is implemented in verilog HDL. The complete Sigma Delta ADC, consisting of analog block of second order modulator and digital block of decimator consumes a total power 1.96mW.

  12. Design of Low Power Sigma Delta ADC

    Directory of Open Access Journals (Sweden)

    Mohammed Arifuddin Sohel

    2012-09-01

    Full Text Available A Low power discrete time sigma delta ADC consisting of a second order sigma delta modulator and third order Cascaded Integrated Comb (CIC filter is proposed. The second order modulator is designed to work at a signal band of 20K Hz at an oversampling ratio of 64 with a sampling frequency of 2.56 MHz. It achieves a signal to noise ratio of 85.2dB and a resolution of 14 bits. The CIC digital filter is designed to implement a decimation factor of 64, operating at a maximum sampling frequency of 2.56 MHz. A second order sigma delta modulator is implemented in 0.18micron CMOS technology using full custom design and the third order digital CIC decimation filter is implemented in verilog HDL. The complete Sigma Delta ADC, consisting of analog block of second order modulator and digital block of decimator consumes a total power 1.96mW.

  13. Spectroscopic analyses of soil samples outside Nile Delta of Egypt

    Science.gov (United States)

    Fakhry, Ahmed; Osman, Osama; Ezzat, Hend; Ibrahim, Medhat

    2016-11-01

    Soil in Egypt, especially around Delta is exposed to various pollutants which are affecting adversely soil fertility and stability. Humic Acids (HA) as a main part of soil organic matter (SOM) represent the heart of the interaction process of inorganic pollutants with soil. Consequently, Fourier transform infrared spectroscopy (FTIR) and Nuclear magnetic resonances (NMR) were used to characterize soil, sediment and extracted HA. Resulting data confirmed that the HA was responsible for transporting inorganic pollutants from surface to subsurface reaching the ground water, which may represent a high risk on public health. The transport process is coming as carboxyl in surface soil changed into metal carboxylate then transferred into the carboxyl in bottom soil.

  14. The Niger Delta Avengers, Autonomous Ethnic Clans and Common ...

    African Journals Online (AJOL)

    Nneka Umera-Okeke

    The situation in Niger Delta region has remained an unanswered research question. When oil was discovered .... From the foregone analysis, the greed factor is sufficient to explain the crisis in Niger. Delta given the ..... homeless. The sizeable ...

  15. Habitat Management Plan for Delta and Breton National Wildlife Refuges

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Delta and Breton NWRs Habitat Management Plan provides a long-term vision and specific guidance on managing habitats for the resources of concern at Delta and...

  16. $\\delta-\\delta^\\prime$ generalized Robin boundary conditions and quantum vacuum fluctuations

    CERN Document Server

    Munoz-Castaneda, J M

    2014-01-01

    The effects induced by the quantum vacuum fluctuations of one massless real scalar field on a configuration of two partially transparent plates are investigated. The physical properties of the infinitely thin plates are simulated by means of Dirac-$\\delta-\\delta^\\prime$ point interactions. It is shown that the distortion caused on the fluctuations by this external background gives rise to a generalization of Robin boundary conditions. The $T$-operator for potentials concentrated on points with non defined parity is computed with total generality. The quantum vacuum interaction energy between the two plates is computed using the $TGTG$ formula to find positive, negative, and zero Casimir energies. The parity properties of the $\\delta-\\delta^\\prime$ potential allow repulsive quantum vacuum force between identical plates.

  17. Delta-Bar-Delta and directed random search algorithms to study capacitor banks switching overvoltages

    Directory of Open Access Journals (Sweden)

    Sadeghkhani Iman

    2012-01-01

    Full Text Available This paper introduces an approach to analyse transient overvoltages during capacitor banks switching based on artificial neural networks (ANN. Three learning algorithms, delta-bar-delta (DBD, extended delta-bar-delta (EDBD and directed random search (DRS were used to train the ANNs. The ANN training is based on equivalent parameters of the network and therefore, a trained ANN is applicable to every studied system. The developed ANN is trained with extensive simulated results and tested for typical cases. The new algorithms are presented and demonstrated for a partial 39-bus New England test system. The simulated results show the proposed technique can accurately estimate the peak values of switching overvoltages.

  18. Delta Delta Excitation in Proton-Proton Induced pi0pi0 Production

    CERN Document Server

    Skorodko, T; Bogoslawsky, D; Calen, H; Clement, H; Doroshkevich, E; Demiroers, L; Ekstroem, C; Fransson, K; Gustafsson, L; Hoistad, B; Ivanov, G; Jacewicz, M; Jiganov, E; Johansson, T; Khakimova, O; Keleta, S; Koch, I; Kren, F; Kullander, S; Kupsc, A; Marciniewski, P; Meier, R; Morosov, B; Pauly, C; Petren, H; Petukhov, Y; Povtorejko, A; Ruber, R J M Y; Schoenning, K; Scobel, W; Shwartz, B; Stepaniak, J; Thoerngren-Engblom, P; Tikhomirov, V; Wagner, G J; Wolke, M; Yamamoto, A; Zabierowski, J; Zlomanczuk, J

    2010-01-01

    Exclusive measurements of the $pp \\to pp\\pi^0\\pi^0$ reaction have been performed at CELSIUS/WASA at energies from threshold up to $T_p$ = 1.3 GeV. Total and differential cross sections have been obtained. Here we concentrate on energies $T_p \\ge$ 1 GeV, where the $\\Delta\\Delta$ excitation becomes the leading process. No evidence is found for a significant ABC effect beyond that given by the conventional $t$-channel $\\Delta\\Delta$ excitation. This holds also for the double-pionic fusion to the quasibound $^2$He. The data are compared to model predictions, which are based on both pion and $\\rho$ exchange. Total and differential cross sections are at variance with these predictions and call for a profound modification of the $\\rho$-exchange. A phenomenological modification allowing only a small $\\rho$ exchange contribution leads to a quantitative description of the data.

  19. {Delta}{Delta} excitation in proton-proton induced {pi}{sup 0{pi}0} production

    Energy Technology Data Exchange (ETDEWEB)

    Skorodko, T.; Bashkanov, M. [Physikalisches Institut der Universitaet Tuebingen, D-72076 Tuebingen (Germany); Bogoslawsky, D. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Calen, H. [The Svedberg Laboratory, Uppsala (Sweden); Clement, H., E-mail: Clement@pit.physik.uni-tuebingen.d [Physikalisches Institut der Universitaet Tuebingen, D-72076 Tuebingen (Germany); Doroshkevich, E. [Physikalisches Institut der Universitaet Tuebingen, D-72076 Tuebingen (Germany); Demiroers, L. [Hamburg University, Hamburg (Germany); Ekstroem, C.; Fransson, K. [The Svedberg Laboratory, Uppsala (Sweden); Gustafsson, L.; Hoeistad, B. [Uppsala University, Uppsala (Sweden); Ivanov, G. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Jacewicz, M. [Uppsala University, Uppsala (Sweden); Jiganov, E. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Johansson, T. [Uppsala University, Uppsala (Sweden); Khakimova, O. [Physikalisches Institut der Universitaet Tuebingen, D-72076 Tuebingen (Germany); Keleta, S.; Koch, I. [Uppsala University, Uppsala (Sweden); Kren, F. [Physikalisches Institut der Universitaet Tuebingen, D-72076 Tuebingen (Germany); Kullander, S. [Uppsala University, Uppsala (Sweden)

    2011-01-10

    Exclusive measurements of the pp{yields}pp{pi}{sup 0{pi}0} reaction have been performed at CELSIUS/WASA at energies from threshold up to T{sub p}=1.3 GeV. Total and differential cross sections have been obtained. Here we concentrate on energies T{sub p{>=}}1 GeV, where the {Delta}{Delta} excitation becomes the leading process. No evidence is found for a significant ABC effect beyond that given by the conventional t-channel {Delta}{Delta} excitation. This holds also for the double-pionic fusion to the quasibound {sup 2}He. The data are compared to model predictions, which are based on both {pi}- and {rho}-exchange. Total and differential cross sections are at variance with these predictions and call for a profound modification of the {rho}-exchange. A phenomenological modification allowing only a small {rho}-exchange contribution leads to a quantitative description of the data.

  20. Cost Effectiveness of Imiquimod 5% Cream Compared with Methyl Aminolevulinate-Based Photodynamic Therapy in the Treatment of Non-Hyperkeratotic, Non-Hypertrophic Actinic (Solar) Keratoses: A Decision Tree Model

    OpenAIRE

    Wilson, Edward C F

    2010-01-01

    Background: Actinic keratosis (AK) is caused by chronic exposure to UV radiation (sunlight). First-line treatments are cryosurgery, topical 5-fluorouracil (5-FU) and topical diclofenac. Where these are contraindicated or less appropriate, alternatives are imiquimod and photodynamic therapy (PDT). Objective: To compare the cost effectiveness of imiquimod and methyl aminolevulinate-based PDT (MAL-PDT) from the perspective of the UK NHS. Methods: A decision tree model was populated with data fro...

  1. Genetic polymorphisms in peroxisome proliferator-activated receptor delta associated with obesity.

    Science.gov (United States)

    Shin, Hyoung Doo; Park, Byung Lae; Kim, Lyoung Hyo; Jung, Hye Seung; Cho, Young Min; Moon, Min Kyong; Park, Young Joo; Lee, Hong Kyu; Park, Kyong Soo

    2004-03-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism. Three different PPARs, PPAR-alpha, -gamma, and -delta, have been characterized, and they are distinguished from each other by tissue distribution and cell activation. All PPARs are, to different extents, activated by fatty acids and derivatives. Recently, it has been shown that PPAR-delta serves as a widespread regulator of fat burning, suggesting that it might be a potential target in the treatment of obesity and type 2 diabetes. In an effort to identify polymorphic markers in potential candidate genes for type 2 diabetes, we have sequenced PPAR-delta, including -1,500 bp of the 5' flanking region. Nine polymorphisms were identified in PPAR-delta: four in the intron, one in the 5' untranslated region (UTR), and four in the 3' UTR. Among identified polymorphisms, five common sites, including c.-13454G>T, c.-87T>C, c.2022+12G>A, c.2629T>C, and c.2806C>G, were genotyped in subjects with type 2 diabetes and normal control subjects (n = 702). The genetic associations with the risk of type 2 diabetes and metabolic phenotype were analyzed. No significant associations with the risk of type 2 diabetes were detected. However, several positive associations of PPAR-delta polymorphisms with fasting plasma glucose and BMI were detected in nondiabetic control subjects. The genetic information about PPAR-delta from this study would be useful for further genetic study of obesity, diabetes, and other metabolic diseases.

  2. A delta-catenin signaling pathway leading to dendritic protrusions.

    Science.gov (United States)

    Abu-Elneel, Kawther; Ochiishi, Tomoyo; Medina, Miguel; Remedi, Monica; Gastaldi, Laura; Caceres, Alfredo; Kosik, Kenneth S

    2008-11-21

    Delta-catenin is a synaptic adherens junction protein pivotally positioned to serve as a signaling sensor and integrator. Expression of delta-catenin induces filopodia-like protrusions in neurons. Here we show that the small GTPases of the Rho family act coordinately as downstream effectors of delta-catenin. A dominant negative Rac prevented delta-catenin-induced protrusions, and Cdc42 activity was dramatically increased by delta-catenin expression. A kinase dead LIMK (LIM kinase) and a mutant Cofilin also prevented delta-catenin-induced protrusions. To link the effects of delta-catenin to a physiological pathway, we noted that (S)-3,5-dihydroxyphenylglycine (DHPG) activation of metabotropic glutamate receptors induced dendritic protrusions that are very similar to those induced by delta-catenin. Furthermore, delta-catenin RNA-mediated interference can block the induction of dendritic protrusions by DHPG. Interestingly, DHPG dissociated PSD-95 and N-cadherin from the delta-catenin complex, increased the association of delta-catenin with Cortactin, and induced the phosphorylation of delta-catenin within the sites that bind to these protein partners.

  3. Morphodynamics of a cyclic prograding delta: the Red River, Vietnam

    NARCIS (Netherlands)

    Maren, D.S. van

    2004-01-01

    River deltas are inhabited by over 60% of the world population, and are, consequently, of paramount agricultural and economical importance. They constitute unique wetland envi ronments which gives river deltas ecological importance as well. Additionally, many deltas contain large accumulations of oi

  4. 78 FR 45592 - DeltaPoint Capital IV, LP;

    Science.gov (United States)

    2013-07-29

    ... ADMINISTRATION DeltaPoint Capital IV, LP; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that DeltaPoint Capital IV, L.P., 45 East Avenue... Business Administration (``SBA'') Rules and Regulations (13 CFR 107.730). DeltaPoint Capital IV,...

  5. Comparative assessment of the vulnerability and resilience of 10 deltas : work document

    NARCIS (Netherlands)

    Bucx, T.; Marchand, M.; Makaske, B.; Guchte, van de C.

    2010-01-01

    Background information about: Nile delta (Egypt), Incomati delta (Mozambique), Ganges-Brahmaputra-Meghna (Bangladesh), Yangtze (China), Ciliwung (Indonesia), Mekong (Vietnam), Rhine-Meuse (The Netherlands), Danube (Romania), California Bay-Delta, Mississippi River Delta (USA)

  6. gamma-linolenic acid does not augment long-chain polyunsaturated fatty acid omega-3 status

    NARCIS (Netherlands)

    Brouwer, DAJ; Hettema, Y; van Doormaal, JJ; Muskiet, FAJ

    1998-01-01

    Augmentation of long chain polyunsaturated omega 3 fatty acid (LCPUFA omega 3) status can be reached by consumption of fish oil or by improvement of the conversion of a-linolenic acid (ALA) to LCPUFA omega 3. Since gamma-linolenic acid (GLA) might activate the rate-limiting Delta-6 desaturation, we

  7. gamma-linolenic acid does not augment long-chain polyunsaturated fatty acid omega-3 status

    NARCIS (Netherlands)

    Brouwer, DAJ; Hettema, Y; van Doormaal, JJ; Muskiet, FAJ

    1998-01-01

    Augmentation of long chain polyunsaturated omega 3 fatty acid (LCPUFA omega 3) status can be reached by consumption of fish oil or by improvement of the conversion of a-linolenic acid (ALA) to LCPUFA omega 3. Since gamma-linolenic acid (GLA) might activate the rate-limiting Delta-6 desaturation, we

  8. Evidence for a parity doublet Delta(1920)P33 and Delta(1940)D33 from gammap-->ppi;{0}eta.

    Science.gov (United States)

    Horn, I; Anisovich, A V; Anton, G; Bantes, R; Bartholomy, O; Beck, R; Beloglazov, Yu; Bogendörfer, R; Castelijns, R; Crede, V; Ehmanns, A; Ernst, J; Fabry, I; Flemming, H; Fösel, A; Fuchs, M; Funke, Chr; Gothe, R; Gridnev, A; Gutz, E; Höffgen, St; Hössl, J; Junkersfeld, J; Kalinowsky, H; Klein, F; Klempt, E; Koch, H; Konrad, M; Kopf, B; Krusche, B; Langheinrich, J; Löhner, H; Lopatin, I; Lotz, J; Matthäy, H; Menze, D; Messchendorp, J; Metag, V; Nikonov, V A; Novinski, D; Ostrick, M; van Pee, H; Sarantsev, A V; Schmidt, C; Schmieden, H; Schoch, B; Suft, G; Sumachev, V; Szczepanek, T; Thoma, U; Walther, D; Weinheimer, Chr

    2008-11-14

    Evidence is reported for the existence of a parity doublet of Delta resonances with total angular momentum J=3/2 from photoproduction of the ppi;{0}eta final state. The two parity partners Delta(1920)P33 and Delta(1940)D33 make significant contributions to the reaction. Cascades of resonances into Delta(1232)eta, N(1535)pi, and Na0(980) are clearly observed.

  9. 78 FR 22911 - Delta Air Lines, Inc., Reservation Sales and Customer Care Call Center, Seatac, WA; Delta Air...

    Science.gov (United States)

    2013-04-17

    ... Employment and Training Administration Delta Air Lines, Inc., Reservation Sales and Customer Care Call Center, Seatac, WA; Delta Air Lines, Inc., Reservation Sales and Customer Care Call Center, Sioux City, IA... workers and former workers of Delta Air Lines, Inc., Reservation Sales and Customer Care Call...

  10. Historical Reconstruction of Organic Carbon Inputs to Sediments in the Colville River Delta, Alaska: The Application of Biomarker Proxies

    Science.gov (United States)

    Zhang, X.; Bianchi, T. S.; Allison, M. A.

    2014-12-01

    Arctic permafrost represents about 50% of the total belowground global carbon pool, and thus the fate of this pool, as it thaws in the wake of global warming, warrants close attention. Large-river delta-front estuaries (LDEs) have been shown to be important recorders of natural and human-induced changes in watersheds, as they are critical zones for the exchange of organic carbon between the continents and the ocean. The Colville River is the largest North American Arctic River with a continuous permafrost watershed. Simpson's Lagoon, an eastward distal component of the Colville River Delta is an excellent location for historical reconstruction work since it is an area well protected from intense ice grounding and has minimal bioturbation. Sediment cores were collected from the mouth of the river and the lagoon in August of 2010, and analyzed for bulk organic carbon and nitrogen proxies, biomarkers (including lignin phenols, fatty acids), and compound-specific 13C isotope analysis (CSIA) of fatty acids. Downcore sediment data from CSIA of short-chain fatty acids (C14-C18) to the delta over the past ca. 50 years were found to be more depleted and had a wider isotopic range (-17.0~-33.2‰) than long-chain fatty acids (C22-C30, -30.3~-36.8‰). This possibly reflects alterations of inputs of freshwater flow to the delta which could have resulted in isotopic changes that caused corresponding changes in marine versus freshwater phytoplankton inputs. Downcore short-chain saturated and monounsaturated fatty acid profiles reflected differences in the abundance of bacteria and post-depositional decay of algal inputs across different regions of the delta. Ongoing analyses will also focus on compound-specific radiocarbon analyses (CSRA) of fatty acids and lignin phenols to better understand the changes of organic inputs from terrestrially-derived organic-rich horizons in surface soils vs. old deep permafrost-derived organic horizons.

  11. Beta-methyl substitution of cyclohexylalanine in Dmt-Tic-Cha-Phe peptides results in highly potent delta opioid antagonists.

    Science.gov (United States)

    Tóth, Géza; Ioja, Eniko; Tömböly, Csaba; Ballet, Steven; Tourwé, Dirk; Péter, Antal; Martinek, Tamás; Chung, Nga N; Schiller, Peter W; Benyhe, Sándor; Borsodi, Anna

    2007-01-25

    The opioid peptide TIPP (H-Tyr-Tic-Phe-Phe-OH, Tic:1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) was substituted with Dmt (2',6'-dimethyltyrosine) and a new unnatural amino acid, beta-MeCha (beta-methyl-cyclohexylalanine). This double substitution led to a new series of opioid peptides displaying subnanomolar delta antagonist activity and mu agonist or antagonist properties depending on the configuration of the beta-MeCha residue. The most promising analog, H-Dmt-Tic-(2S,3S)-beta-MeCha-Phe-OH was a very selective delta antagonist both in the mouse vas deferens (MVD) assay (Ke = 0.241 +/- 0.05 nM) and in radioligand binding assay (K i delta = 0.48 +/- 0.05 nM, K i mu/K i delta = 2800). The epimeric peptide H-Dmt-Tic-(2S,3R)-beta-MeCha-Phe-OH and the corresponding peptide amide turned out to be mixed partial mu agonist/delta antagonists in the guinea pig ileum and MVD assays. Our results constitute further examples of the influence of Dmt and beta-methyl substitution as well as C-terminal amidation on the potency, selectivity, and signal transduction properties of TIPP related peptides. Some of these compounds represent valuable pharmacological tools for opioid research.

  12. Spectral factorization using the delta operator

    DEFF Research Database (Denmark)

    Rostgaard, Morten; Poulsen, Niels Kjølstad; Ravn, Ole

    1994-01-01

    In recent years many papers have been published abouth the gamma-operator, mostly caused by the better numerical properties and the rapprochement between continuous and discrete time. A major problem within the LQG-design of a delta-based input-output relation has been how to spectral-factorize i......In recent years many papers have been published abouth the gamma-operator, mostly caused by the better numerical properties and the rapprochement between continuous and discrete time. A major problem within the LQG-design of a delta-based input-output relation has been how to spectral......-factorize in an efficient way. The discrete-time method of Kuccera will not be applied since numerical word-length characteristics will be poor for fast sampling rates. In this paper a new approach is considered. A new gamma-operator (Tustin operator) is introduced, in order to make an iterative and numerical stable...

  13. Nucleon and Delta structure in continuum QCD

    Science.gov (United States)

    Cloet, Ian

    2014-03-01

    Quantum Chromodynamics (QCD) is the only known example in nature of a fundamental quantum field theory that is innately non-perturbative. Solving QCD will have profound implications for our understanding of the natural world, for example, it will explain how light quarks and massless gluons bind together to form the observed mesons and baryons; hence explaining the origin of more than 98% of the mass in the visible universe. Given the challenges posed by QCD, it is insufficient to study hadron ground-states alone if one seeks a solution; in this regard the delta plays a special role as the lightest baryon resonance. I will discuss recent progress using continuum QCD approaches to the study of nucleon and delta properties, with a focus on insights gained by the calculation (and measurement) of their electromagnetic form factors.

  14. Pluviometric anomaly in the Llobregat Delta

    Directory of Open Access Journals (Sweden)

    J. Mazón

    2009-01-01

    Full Text Available The data from surface automatic weather stations show that in the area of the Llobregat delta (northeast of the Iberian Peninsula we can observe greater precipitation than in nearby inland areas (Ordal, Collserola, Garraf, than on the other side of a massif located on the coast (Garraf and than on the northern coast. This distribution of the precipitation could be explained by the formation of a nocturnal surface cold front in the Llobregat delta. In order to analyze in-depth the physical mechanisms that can influence the formation of this front (topography, sea and drainage winds, two rain episodes in the area were simulated with the MM5 mesoscale model, reproducing satisfactorily the physical mechanisms that favor the appearance of the front.

  15. On regularizations of the Dirac delta distribution

    Science.gov (United States)

    Hosseini, Bamdad; Nigam, Nilima; Stockie, John M.

    2016-01-01

    In this article we consider regularizations of the Dirac delta distribution with applications to prototypical elliptic and hyperbolic partial differential equations (PDEs). We study the convergence of a sequence of distributions SH to a singular term S as a parameter H (associated with the support size of SH) shrinks to zero. We characterize this convergence in both the weak-* topology of distributions and a weighted Sobolev norm. These notions motivate a framework for constructing regularizations of the delta distribution that includes a large class of existing methods in the literature. This framework allows different regularizations to be compared. The convergence of solutions of PDEs with these regularized source terms is then studied in various topologies such as pointwise convergence on a deleted neighborhood and weighted Sobolev norms. We also examine the lack of symmetry in tensor product regularizations and effects of dissipative error in hyperbolic problems.

  16. Matrix multiplication on the Intel Touchstone Delta

    Energy Technology Data Exchange (ETDEWEB)

    Huss-Lederman, S.; Jacobson, E.M.; Tsao, A. [Supercomputing Research Center, Bowie, MD (United States); Zhang, G. [CONVEX Computer Corp., Richardson, TX (United States)

    1993-12-31

    Matrix multiplication is a key primitive in block matrix algorithms such as those found in LAPACK. We present results from our study of matrix multiplication algorithms on the Intel Touchstone Delta, a distributed memory message-passing architecture with a two-dimensional mesh topology. We obtain an implementation that uses communication primitives highly suited to the Delta and exploits the single node assembly-coded matrix multiplication. Our algorithm is completely general, able to deal with arbitrary mesh aspect ratios and matrix dimensions, and has achieved parallel efficiency of 86% with overall peak performance in excess of 8 Gflops on 256 nodes for an 8800 {times} 8800 matrix. We describe our algorithm design and implementation, and present performance results that demonstrate scalability and robust behavior over varying mesh topologies.

  17. Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis.

    Directory of Open Access Journals (Sweden)

    Soshi Seike

    Full Text Available Clostridium perfringens delta-toxin is a β-pore-forming toxin and a putative pathogenic agent of C. perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2. All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl β-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis.

  18. Elastic and transition form factors of the \\Delta(1232)

    CERN Document Server

    Segovia, Jorge; Cloët, Ian C; Roberts, Craig D; Schmidt, Sebastian M; Wan, Shaolong

    2013-01-01

    Predictions obtained with a confining, symmetry-preserving treatment of a vector-vector contact interaction at leading-order in a widely used truncation of QCD's Dyson-Schwinger equations are presented for \\Delta and \\Omega baryon elastic form factors and the \\gamma N -> \\Delta transition form factors. This simple framework produces results that are practically indistinguishable from the best otherwise available, an outcome which highlights that the key to describing many features of baryons and unifying them with the properties of mesons is a veracious expression of dynamical chiral symmetry breaking in the hadron bound-state problem. The following specific results are of particular interest. The \\Delta elastic form factors are very sensitive to m_\\Delta. Hence, given that the parameters which define extant simulations of lattice-regularised QCD produce \\Delta-resonance masses that are very large, the form factors obtained therewith are a poor guide to properties of the \\Delta(1232). Considering the \\Delta-b...

  19. [Quantitative relationship between molecular structure of polychlorinated biphenyls (PCBs) and enthalpy change (deltaH), entropy change (deltaS') in chromatographic process].

    Science.gov (United States)

    Zhang, Qing; Dai, Chaozheng

    2005-09-01

    The relationship between the rule of chromatographic retention value and molecular structure is an important part in the research of chromatographic thermodynamics. The topological index structural parameter JG and the topological index adjoining parameter LJ are put forward. Parameter J(G) describes the correlation of quantity and position of chlorine atoms in polychlorinated biphenyl (PCB) molecules. Parameter L(J) describes the ortho-position correlation of chlorine atoms in PCB molecules. The relational expression between the PCB molecular structures and their enthalpy change (deltaH), entropy change (deltaS') in chromatographic process was discovered. The values of enthalpy change and entropy change for about 140 kinds of polychlorinated biphenyls in chromatographic process on three stationary phases, DB-1, DB-5 and DB-1701, were determined. In comparison with deltaH and deltaS' of the experimental data those calculated from the relational expression had the average relative deviations for deltaH and deltaS' are 0.56% -0.97% and 0.55% - 1.06%, respectively.

  20. Performance evaluation of photonic Sigma Delta ADCS

    OpenAIRE

    Tan, Yean Wee

    2010-01-01

    Approved for public release; distribution is unlimited The integration of photonic and electronic components to realize a photonic sigma delta ADC is considered in this thesis. The integration process was broken up into steps. First, the performance of a pair of dual-port Mach-Zehnder interferometers (MZI) modulating a train of narrow high-speed laser pulses from a mode-locked laser was investigated. Various parameters like the half-wave voltage (V) and insertion loss were verified. Nex...