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Sample records for aulacomya atra atra

  1. Accelerator-driven transmutation reactor analysis code system (ATRAS)

    Energy Technology Data Exchange (ETDEWEB)

    Sasa, Toshinobu; Tsujimoto, Kazufumi; Takizuka, Takakazu; Takano, Hideki [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1999-03-01

    JAERI is proceeding a design study of the hybrid type minor actinide transmutation system which mainly consist of an intense proton accelerator and a fast subcritical core. Neutronics and burnup characteristics of the accelerator-driven system is important from a view point of the maintenance of subcriticality and energy balance during the system operation. To determine those characteristics accurately, it is necessary to involve reactions at high-energy region, which are not treated on ordinary reactor analysis codes. The authors developed a code system named ATRAS to analyze the neutronics and burnup characteristics of accelerator-driven subcritical reactor systems. ATRAS has a function of burnup analysis taking account of the effect of spallation neutron source. ATRAS consists of a spallation analysis code, a neutron transport codes and a burnup analysis code. Utility programs for fuel exchange, pre-processing and post-processing are also incorporated. (author)

  2. Accelerator-driven transmutation reactor analysis code system (ATRAS)

    International Nuclear Information System (INIS)

    JAERI is proceeding a design study of the hybrid type minor actinide transmutation system which mainly consist of an intense proton accelerator and a fast subcritical core. Neutronics and burnup characteristics of the accelerator-driven system is important from a view point of the maintenance of subcriticality and energy balance during the system operation. To determine those characteristics accurately, it is necessary to involve reactions at high-energy region, which are not treated on ordinary reactor analysis codes. The authors developed a code system named ATRAS to analyze the neutronics and burnup characteristics of accelerator-driven subcritical reactor systems. ATRAS has a function of burnup analysis taking account of the effect of spallation neutron source. ATRAS consists of a spallation analysis code, a neutron transport codes and a burnup analysis code. Utility programs for fuel exchange, pre-processing and post-processing are also incorporated. (author)

  3. Effects of varied interferons in combination with all-trans retinoic acid (ATRA) on proliferation and differentiation of ATRA-resistent APL cell

    Institute of Scientific and Technical Information of China (English)

    HE Peng-cheng; ZHANG Mei; LI Jing; CAI Rui-bo; LIU Ya-lin; CAO Yun-xin

    2006-01-01

    Objective:To investigate the effects and mechanisms of interferon in combination with alltrans retinoic acid (ATRA) on proliferation and differentiation of ATRA-resistent APL cell. Methods :After MR2 cells (ATRA-resistance cell line) were treated with IFN-α, IFN-γ and ATRA alone or IFN-α and IFN-γ in combination with ATRA respectively. The cell roliferation was tested by MTT test and the cell differentiation was tested through light microscope by NBT test and flow cytometry (FCM). The expression of promyelocytic leukemia (PML) protein was observed by indirect immune fluorescent method. Results: Both IFN-α and IFN-γ could inhibit the proliferation and induce the differentiation of MR2 cells to some extent. The effects were more obvious after both interferons in combination with ATRA respectively (P<0. 05). Moreover, the maturation of MR2 cells induced by IFN-γ+ATRA group was more higher than that by IFN-α+ATRA group (P<0.05). Both interferons could induce the expressions of PML protein. Conclusion :Both interferons can inhibit MR2 cells proliferation, which may be related to the expression of PML protein induced by both interferons. The inducing differentiation effects of IFN-γ+ATRA group on MR2 cells are more powerful than those of IFN-α+ATRA group, which may be related to the different signal transduction pathway of both interferons.

  4. Radiologic features of all-trans-retinoic acid syndrome (ATRAS) - case report

    International Nuclear Information System (INIS)

    ATRA Syndrome appears as a side effect of acute promyelocytic leukemia treatment with ATRA, vitamin A derivative. The etiopathogenesis of the syndrome remains unclear. Fever, generalized edema, pleural or pericardial effusion, respiratory distress, coagulation disorders and sometimes renal failure are the most common clinical symptoms of ATRAS. Radiological features of the syndrome are very diverse. Early diagnosis followed by introduction of appropriate treatment (corticosteroids) prevents worsening of the patients' condition and significantly reduces the risk of death. Although clinical symptomatology of ATRAS has been widely described, there are still few descriptions of its radiological manifestation. A 53-year-old female was referred to the Hematology Department for further detailed diagnostics and appropriate therapy from the district hospital, where she had been primarily admitted due to weakness, easy fatigue, loss of appetite and blood extravasations on the skin of the extremities. The patient's general condition on admission was assessed as quite good. Acute promyelocytic leukemia (AML M3 according to FAB classification) was diagnosed. The introduced treatment included ATRA. On the second day of treatment, the patient developed fever, dyspnea, generalized edema, and coagulation disorders increased. Chest X-ray findings reminded ARDS. The diagnosis of ATRAS was established, which resulted in ATRA withdrawal. After administration of corticosteroids, the patient's condition improved gradually within a few days. ATRA was reintroduced then, since the signs of leukemia had intensified. The patient remains in charge of the Hematology Department. Changes of chest X-ray pictures in AML patients treated with ATRA should be interpreted in clinical context due to lack of radiological features specific for ATRAS. (author)

  5. Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso

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    Gelcimar Moresco

    2011-06-01

    Full Text Available O presente relato apresenta o caso clínico de uma paciente com leucemia promie-locítica aguda tratada com ácido todo-transretinoico (ATRA, que apresentou suspeita de síndrome do ácido transreti-noico (síndrome de ATRA. Com a ocor-rência de leucopenia febril inespecífica, foram associados ao tratamento antimi-crobianos e antifúngicos. A diminuição da função renal, observada inicialmente, contribuiu para a suspeita de síndrome de ATRA, que foi agravada pelos antifúngi-cos. Assim, o uso de ATRA foi suspenso, mas somente 8 dias depois foi caracteriza-da pneumonia e descartada a hipótese de síndrome de ATRA. Nesse contexto, foi discutida a nefrotoxicidade do ATRA e a potencialização desse efeito adverso pelo uso de antifúngicos nefrotóxicos, em par-ticular da anfotericina B, assim como a im-portância do diagnóstico diferencial entre síndrome de ATRA e doença infecciosa.

  6. Inhibition of Zymosan-Induced Inflammatory Factors Expression by ATRA Nanostructured Lipid Carriers

    Science.gov (United States)

    Zhou, Hongyan; Zhang, Wensong; Gao, Xunyi; Zhang, Hongguang; Kong, Ning

    2016-01-01

    Purpose. The study aimed to evaluate the effect of all-trans retinoic acid-loaded nanostructured lipid carriers (ATRA-NLCs) on the zymosan-induced expression of the cytokines IL-4, IL-10, and IFN-γ and the matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) and TLR2 in rabbit corneal fibroblasts (RCFs). Methods. ATRA-NLCs were prepared by emulsification. RCFs were isolated and harvested after four to seven passages in monolayer culture. Cytokine release (IL-4, IL-10, and IFN-γ) induced by zymosan was analyzed by cytokine release assay, reverse transcription, and real-time polymerase chain reaction (RT-PCR) analysis detection. MMP-1, MMP-3, and MMP-13, TIMP-1 and TIMP-2, and TLR2 expression were analyzed by immunoblotting. Results. ATRA-NLCs were resistant to light and physically stable, and the average size of the ATRA-NLCs was 200 nm. ATRA-NLCs increased the zymosan-induced release of IL-4 and IL-10 and decreased the release of IFN-γ by RCFs. ATRA-NLCs decreased the levels of TLR2 and MMPs/TIMPs above. Conclusions. ATRA may be a potent anti-inflammatory agent for the therapy of fungal keratitis (FK). PMID:27340562

  7. Protaeolidiella atra Baba, 1955 versus Pleurolidia juliae Burn, 1966: One or two species?

    Science.gov (United States)

    Carmona, Leila; Pola, Marta; Gosliner, Terrence M.; Cervera, Juan Lucas

    2015-06-01

    Protaeolidiella atra Baba, 1955 and Pleurolidia juliae Burn, 1966 are two species traditionally regarded as the members of Aeolidiidae but recently attributed to Facelinidae. Because of their apparent similarities, Rudman (J Molluscan Stud 56:505-514, 1990) rendered P. juliae as a junior synonym of P. atra. In this paper, we conducted a review of both species and completed their descriptions with new data regarding the anatomy of the reproductive system . P. atra and P. juliae have differences in their colouration, number of cerata and characteristics of their reproductive system. Based on these differences, we conclude that these species are not conspecific and should be regarded as distinct taxa.

  8. ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation.

    Science.gov (United States)

    Clarke, Christopher J; Shamseddine, Achraf A; Jacob, Joseph J; Khalife, Gabrielle; Burns, Tara A; Hannun, Yusuf A

    2016-05-01

    Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-trans retinoic acid (ATRA) in MCF7 cells and implicated nSMase2 in ATRA-induced growth arrest. Here, we further investigated how ATRA regulates nSMase2. We find that ATRA regulates nSMase2 transcriptionally through the retinoic acid receptor-α, but this is independent of previously identified transcriptional regulators of nSMase2 (Sp1, Sp3, Runx2) and is not through increased promoter activity. Epigenetically, the nSMase2 gene is not repressively methylated in MCF7 cells. However, inhibition of histone deacetylases (HDACs) with trichostatin A (TSA) induced nSMase2 comparably to ATRA; furthermore, combined ATRA and TSA treatment was not additive, suggesting ATRA regulates nSMase2 through direct modulation of histone acetylation. Confirming this, the histone acetyltransferases CREB-binding protein and p300 were required for ATRA induction of nSMase2. Finally, use of class-specific HDAC inhibitors suggested that HDAC4 and/or HDAC5 are negative regulators of nSMase2 expression. Collectively, these results identify a novel pathway of nSMase2 regulation and suggest that physiological or pharmacological modulation of histone acetylation can directly affect nSMase2 levels. PMID:27013100

  9. Territory and territorial behavior of migrating Common Coot (Fulica atra)

    Institute of Scientific and Technical Information of China (English)

    ZHANG Wei-wei; LIU Wei; MA Jian-zhang

    2011-01-01

    Territory and territorial behavior of the Common Coot (Fulica atra) were studied in two breeding sites, Anbanghe Nature Reserve and Daqing Longfeng wetland, in Heilongjiang Province, China from April to October in 2008 and 2009.In the breeding season, the breeding pairs occupied an area and protected it throughout the reproduction, and both interspecific and intraspecific conflicts were observed.Territory activities became severe since early May, the peak of territory behaviors appeared at late May, and then declined gradually.The territorial activities level was higher than that in the nest building period than in the laying and incubation periods.The most adopted behavioral model was expelling,which was the least energy cost.The degree of territorial behavior tended to be descended since the development of breeding phase.The territory size differed from 1 333 m2 to above 5 000 m2.Wintering population was observed in Poyang Lake of Jiangxi Province.The coots gathered in the open water; however, there was no territory behavior both in the interspecies and intraspecies in wintering sites.The hypotheses why there was territory behaviors for coots both in the interspecies and intraspecies were also discussed.

  10. Effects of ATRA combined with citrus and ginger-derived compounds in human SCC xenografts

    International Nuclear Information System (INIS)

    NF-κB is a survival signaling transcription factor complex involved in the malignant phenotype of many cancers, including squamous cell carcinomas (SCC). The citrus coumarin, auraptene (AUR), and the ethno-medicinal ginger (Alpinia galanga) phenylpropanoid, 1'-acetoxychavicol acetate (ACA), were previously shown to suppress 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse skin tumor promotion. The goal of the present study was to determine whether AUR and ACA are effective either alone or in combination with all-trans retinoic acid (ATRA) for suppressing SCC tumor growth. We first determined the effects of orally administered ACA (100 mg/kg bw) and AUR (200 mg/kg bw) on lipopolysaccharide (LPS)-induced NF-κB activation in NF-κB-RE-luc (Oslo) luciferase reporter mice. Dietary administration of AUR and ACA ± ATRA was next evaluated in a xenograft mouse model. Female SCID/bg mice were fed diets containing the experimental compounds, injected with 1 × 106 SRB12-p9 cells s.c., palpated and weighed twice a week for 28 days following injection. Both ACA and AUR suppressed LPS-induced NF-κB activation in the report mice. In the xenograft model, AUR (1000 ppm) and ACA (500 ppm) modestly suppressed tumor volume. However, in combination with ATRA at 5, 10, and 30 ppm, ACA 500 ppm significantly inhibited tumor volume by 56%, 62%, and 98%, respectively. The effect of ATRA alone was 37%, 33%, and 93% inhibition, respectively. AUR 1000 ppm and ATRA 10 ppm were not very effective when administered alone, but when combined, strongly suppressed tumor volume by 84%. Citrus AUR may synergize the tumor suppressive effects of ATRA, while ACA may prolong the inhibitory effects of ATRA. Further studies will be necessary to determine whether these combinations may be useful in the control of human SCC

  11. Activation of RARα induces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity.

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    Brigger, D; Schläfli, A M; Garattini, E; Tschan, M P

    2015-01-01

    All-trans retinoic acid (ATRA), a pan-retinoic acid receptor (RAR) agonist, is, along with other retinoids, a promising therapeutic agent for the treatment of a variety of solid tumors. On the one hand, preclinical studies have shown promising anticancer effects of ATRA in breast cancer; on the other hand, resistances occurred. Autophagy is a cellular recycling process that allows the degradation of bulk cellular contents. Tumor cells may take advantage of autophagy to cope with stress caused by anticancer drugs. We therefore wondered if autophagy is activated by ATRA in mammary tumor cells and if modulation of autophagy might be a potential novel treatment strategy. Indeed, ATRA induces autophagic flux in ATRA-sensitive but not in ATRA-resistant human breast cancer cells. Moreover, using different RAR agonists as well as RARα-knockdown breast cancer cells, we demonstrate that autophagy is dependent on RARα activation. Interestingly, inhibition of autophagy in breast cancer cells by either genetic or pharmacological approaches resulted in significantly increased apoptosis under ATRA treatment and attenuated epithelial differentiation. In summary, our findings demonstrate that ATRA-induced autophagy is mediated by RARα in breast cancer cells. Furthermore, inhibition of autophagy results in enhanced apoptosis. This points to a potential novel treatment strategy for a selected group of breast cancer patients where ATRA and autophagy inhibitors are applied simultaneously. PMID:26313912

  12. [The prognostic indicators of development of ATRA-syndrome under treatment of acute promyelocyte leucosis].

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    Skol'skaia, O Iu; Tarasova, L N; Vladimirova, S G; Cherepanova, V V

    2012-10-01

    The application of all-trans-retinoic acid (ATRA) in the protocols of treatment of acute promyelocyte leucosis provided the achievement of 95% of full remissions and fast correction of coagulopathy. Besides, ATRA along with positive impact can exert the side effects, among which the most dangerous is the differentiation syndrome. On the basis of analysis of clinical signs, biochemical, hemostasiologic and morphologic blood indicators it is established that among prognostic criteria of differentiation syndrome development are presence of febrile temperature, decrease of content of thrombocytes lesser than 20-109/l (deep degree of thrombocytopenia), prolongation of index of activated partial thromboplastin time relative to norm before treatment start. Apart from this, the following factors also are among such kind of criteria: decrease of hemoglobin after ATRA prescription before differentiation syndrome development, on-going hypofibrinogenemia and deep degree of thrombocytopenia under concurrent increase of content of urea and creatinine as compared with initial values in treatment dynamics. PMID:23265056

  13. Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Akter, Jesmin [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Takatori, Atsushi, E-mail: atakatori@chiba-cc.jp [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Islam, Md. Sazzadul [Laboratory of Innovative Cancer Therapeutics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakazawa, Atsuko [Department of Pathology, National Center for Child Health and Development, Tokyo (Japan); Ozaki, Toshinori, E-mail: tozaki@chiba-cc.jp [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nagase, Hiroki [Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan); Nakagawara, Akira [Saga Medical Centre, 840-8571 (Japan)

    2014-10-10

    Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.

  14. Atrações e prazeres visuais em um pornô feminino

    OpenAIRE

    Mariana Baltar

    2015-01-01

    Este artigo correlaciona os conceitos de excesso e atrações como estratégicos para refletir sobre processos de engajamento e afetação no campo da pornografia que desestabilizam morais tradicionais em direção a uma política de gêneros. Nesse sentido, mobiliza-se uma lógica de excesso de atrações que estabelece um jogo ambivalente de recusa e adesão aos códigos genéricos mais básicos da pornografia. Os argumentos são empreendidos a partir da análise de Dirty Diaries, um projeto declaradamente a...

  15. Neutron dosimetry and damage calculations for the ATR-A1 irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Greenwood, L.R.; Ratner, R.T. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-09-01

    Neutron fluence measurements and radiation damage calculations are reported for the collaborative US/Japan ATR-A1 irradiation in the Advanced Test Reactor (ATR) at Idaho National Engineering Laboratory (INEL). The maximum total neutron fluence at midplane was 9.4 {times} 10{sup 21} n/cm{sup 2} (5.5 {times} 10{sup 21} n/cm{sup 2} above 0.1 MeV), resulting in about 4.6 dpa in vanadium.

  16. Gateways to Hawai‘i: Genetic Population Structure of the Tropical Sea Cucumber Holothuria atra

    Directory of Open Access Journals (Sweden)

    Derek J. Skillings

    2011-01-01

    Full Text Available Holothuria atra is one of the most common and widest ranging tropical, coral reef sea cucumbers in the world, and here we examine population genetic structure based on mitochondrial COI to aid in determining the appropriate scale for coral reef management. Based on SAMOVA, AMOVA and BARRIER analyses, we show that despite its large range, H. atra has hierarchical, fine-scale population structure driven primarily by between-archipelago barriers, but with significant differences between sites within an archipelago as well. Migrate analyses along with haplotype networks and patterns of haplotype diversity suggest that Hawai‘i and Kingman reef are important centers of the genetic diversity in the region rather than an evolutionary dead-end for migrants from the Indo-Pacific. Finally we show that for H. atra Kingman Reef is the most likely stepping stone between Hawai‘i and the rest of the Pacific, not Japan or Johnston Atoll as previously presumed. Based on our data, Johnston Atoll can instead be seen as an outpost of the Northwestern Hawaiian Islands rather than a gateway to the Hawaiian Archipelago.

  17. Inhibition of p38 MAPK Phosphorylation Is Critical for Bestatin to Enhance ATRA-Induced Cell Differentiation in Acute Promyelocytic Leukemia NB4 Cells.

    Science.gov (United States)

    Qian, Xijun; He, Jingsong; Zhao, Yi; Lin, Maofang

    2016-01-01

    Bestatin has been known as an immunomodulating agent in anti-leukemia treatment. The mechanism by which Bestatin enhances all-trans retinoic acid (ATRA)-induced cell differentiation of acute promyelocytic leukemia (APL) cells is generally attributed to inhibition of cell surface CD13/aminopeptidase N activity. Bestatin also exerts its biological activities besides its ability to inhibit aminopeptidase N enzymatic activity. This article provides data to support an alternative mechanism regarding an important role of inhibition of p38 mitogen-activated protein kinase (MAPK) signal pathway in Bestatin's anti-leukemia effect. Bestatin enhanced ATRA-induced differentiation and inhibited ATRA-driven phosphorylation of p38 MAPK in ATRA-sensitive APL NB4 cells. In contrast, Bestatin could not reverse the differentiation block in ATRA-resistant APL MR2 cells, in which ATRA was unable to induce phosphorylation of p38 MAPK. Moreover, CD13 ligation with anti-CD13 antibody WM-15 resulted in phosphorylation of p38 MAPK, reduced the inhibition of Bestatin on the phosphorylation of p38 MAPK, and completely abolished the enhancement of Bestatin on ATRA-inducing differentiation in NB4 cells. This study shows that inhibition of p38 MAPK phosphorylation is critical for Bestatin to enhance ATRA-induced cell differentiation in ATRA-sensitive APL NB4 cells. Results suggested that pharmacological inhibition of the p38 MAPK pathway might enhance ATRA-dependent differentiation. PMID:24141198

  18. Tratamiento adaptado al riesgo de la leucemia promielocítica aguda con ATRA y quimioterapia

    OpenAIRE

    Montesinos Fernández, Pau

    2016-01-01

    El tratamiento actual de la leucemia promielocítica aguda (LPA) con la combinación de ácido trans-retinóico (ATRA) y quimioterapia proporciona una tasa muy elevada de curaciones. No obstante, aunque estrecho, hay un margen de mejora mediante la reducción de cada una de las diferentes causas de fracaso terapéutico. Dada la heterogeneidad de estas causas de fracaso, planteamos la hipótesis de que un análisis de dichas causas y la identificación de las variables ligadas al paciente, a su enferm...

  19. ÚLCERAS ESCROTALES SECUNDARIAS A TRATAMIENTO CON ÁCIDO TRANSRETINOICO (ATRA

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    Cuevas-Ruiz MV

    2011-01-01

    Full Text Available El ácido trans retinoico es el fármaco de elección en el tratamiento de la Leucemia Promielocítica Aguda. El efecto secundario más grave del fármaco es el síndrome de diferenciación, pero puede ocasionar lesiones en piel y úlceras escrotales. Presentamos el caso de un varón con leucemia promielocítica aguda que recibió ATRA y presentó úlceras escrotales

  20. ÚLCERAS ESCROTALES SECUNDARIAS A TRATAMIENTO CON ÁCIDO TRANSRETINOICO (ATRA)

    OpenAIRE

    Cuevas-Ruiz MV; Jiménez-Alfaro C; Cuevas-Ruiz B

    2011-01-01

    El ácido trans retinoico es el fármaco de elección en el tratamiento de la Leucemia Promielocítica Aguda. El efecto secundario más grave del fármaco es el síndrome de diferenciación, pero puede ocasionar lesiones en piel y úlceras escrotales. Presentamos el caso de un varón con leucemia promielocítica aguda que recibió ATRA y presentó úlceras escrotales

  1. Antitumor and antifungal activities of organic extracts of seacucumber Holothuria atra from the southeast coast of India

    Science.gov (United States)

    Dhinakaran, Devaraj Isaac; Lipton, Aaron Premnath

    2015-02-01

    In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cucumber Holothuria atra is commonly known as the lollyfish. The antifungal activity was detected using agar well diffusion method against the various fungal strains such as Trichoderma viride, Aspergillus niger, Aspergillus flavis, Candida albicans and Penicillium chrysogenum. Relatively high antifungal activity was seen against Candida albicans at 100 μL-1 concentration of extracts. Zone of inhibition was measured at 18 mm of diameter. The anti-tumor activities were detected against the Vero and Hep2 cell lines using MTT assay. The cells were treated with H. atra extract at concentrations 0.078-10mg mL-1. The extract showed high proliferative activity against the Hep2 cells. The body wall extracts of sea cucumber ( H. atra) showed effective antifungal and antitumor activities. All these findings suggest that the extracts could be used for the development of drugs.

  2. Antifungal effect of Sticophus hermanii and Holothuria atra extract and its cytotoxicity on gingiva-derived mesenchymal stem cell

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    Kristanti Parisihni

    2013-12-01

    Full Text Available Background: Sea cucumber had been acknowledged to have some medical properties Sticophus hermanii and Holothuria atra are species of sea cucumber which has been known to have antifungal properties thus potentially explored as therapeutic agent in oral candidiasis. Purpose: The aim of this study was to examine the antifungal property Sticophus hermanii and Holothuria atra extract against Candida albicans and its cytotoxicity to human gingiva-derived mesenchymal stem cell. Methods: The study was an experimental laboratories research with post test only control group design. Methanolic extract of Sticophus hermanii and Holothuria atra in concentrations of 1%, 0.5%; 0.25%; 0.13%, 0.07%; 0.03%, 0.02% and 0.01%; were tested its cytotoxicity on gingiva-derived mesenchymal stem cell. Cell viability were measured by MTT assay. The antifungal property against Candida albicans was tested by disk diffusion method. Data were analyzed by ANOVA followed by LSD. Results: Extract of Sticophus hermanii showed no cytotoxicity in all concentrations (p>0.05, while Holothuria atra showed toxicity in the concentration of 1% and not cytotoxic in the concentrations below (p<0.05. Both sea cucumber extract could inhibit the growth Candida albicans, in vitro, proved by the clear zone around the disc in all concentrations (p<0.05. Conclusion: Stichopus hermanii and Holothuria atra extract had the antifungal effect against Candida albicans. Sea cucumber extract were not cytotoxic togingiva-derived mesenchymal stem cell in the concentration of Sticophus hermanii ≤ 1% and Holothuria atra ≤ 0.5%.Latar belakang: Teripang telah diketahui mempunyai berbagai khasiat medis. Sticophus hermanii dan Holothuria atra adalah spesies teripang yang telah diketahui mempunyai sifat anti jamur sehingga santat potensial untuk diekplorasi sebagai agen terapeutik pada infeksi di rongga mulut. Tujuan: Tujuan dari penelitian ini adalah untuk meneliti sifat anti jamur ekstrak Sticophus hermanii

  3. Isolation and Characterization of Microsatellite Loci in the Chinese Cobra Naja atra (Elapidae

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    Xiang Ji

    2011-07-01

    Full Text Available We characterize thirteen polymorphic microsatellite loci isolated from Naja atra genomic libraries, which were enriched for AC-motif microsatellites. The thirteen loci were screened on a group of 48 individuals from two populations, one in Yong’an and the other in Ganzhou. These markers revealed a relatively high degree of genetic diversity (4–12 alleles per locus and heterozygosity (Ho ranged from 0.213–0.854 and He ranged from 0.301–0.838. Tests for departure from Hardy-Weinberg equilibrium and for linkage disequilibrium were conducted for each of the two populations separately. After sequential Bonferroni correction, none of the 13 loci showed significant departures from Hardy-Weinberg equilibrium. Hierarchical analysis of molecular variance indicated that a small but significant (P < 0.001 proportion (16.0% of the total variation in the microsatellite DNA data were attributable to differences among populations, indicating geographical structuring and restricted gene flow. It could be attributable to the Wuyi mountains in the area having a sufficiently isolating effect to significantly reduce gene flow. Our microsatellite data also showed a low Nm (1.31 value in the two populations from mainland China. Thus, the Yong’an and Ganzhou populations could be treated as distinct evolutionarily significant units (ESUs. The high level of polymorphism revealed by these microsatellite markers will be useful for the study of gene flow, population structure and evolutionary history of N. atra.

  4. Hemolitic action of Naja naja atra cardiotoxin on erythrocytes from different animals

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    J. C. Troiano

    2006-01-01

    Full Text Available A comparative study on the sensitivity of erythrocytes from different vertebrate species (avian, mammalian and reptilian to the hemolytic action caused by cardiotoxin isolated from Naja naja atra venom was carried out. Cardiotoxin was able to induce direct hemolysis in washed erythrocytes from several animals, except for llama. The EC50 values from hemolysis of the most sensitive (cat and the most resistant (snake animal varied approximately tenfold. According to the cell behavior, it was possible to characterize four types of behavior: The first was observed in cat, horse and human cells; the second in rat, rabbit and dog erythrocytes; and the third only in llama erythrocytes, which were resistant to cardiotoxin concentrations up to 300 µg/ml. Finally, avian and reptilian erythrocytes were more resistant to cardiotoxin III-induced hemolysis than those of the mammalian species.

  5. Purification, characterization and primary structure of a chymotrypsin inhibitor from Naja atra venom.

    Science.gov (United States)

    Zhou, Xing-Ding; Jin, Yang; Lu, Qiu-Min; Li, Dong-Sheng; Zhu, Shao-Wen; Wang, Wan-Yu; Xiong, Yu-Liang

    2004-02-01

    A chymotrypsin inhibitor, designated NA-CI, was isolated from the venom of the Chinese cobra Naja atra by three-step chromatography. It inhibited bovine alpha-chymotrypsin with a Ki of 25 nM. The molecular mass of NA-CI was determined to be 6403.8 Da by matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) analysis. The complete amino acid sequence was determined after digestion of S-carboxymethylated inhibitor with Staphylococcus aureus V8 protease and porcine trypsin. NA-CI was a single polypeptide chain composed of 57 amino acid residues. The main contact site with the protease (P1) has a Phe, showing the specificity of the inhibitor. NA-CI shared great similarity with the chymotrypsin inhibitor from Naja naja venom (identities=89.5%) and other snake venom protease inhibitors. PMID:14990218

  6. Status of ATR-A1 irradiation experiment on vanadium alloys and low-activation steels

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Strain, R.V.; Gomes, I.; Smith, D.L. [Argonne National Lab., IL (United States); Matsui, H. [Tohoku Univ. (Japan)

    1996-10-01

    The ATR-A1 irradiation experiment was a collaborative U.S./Japan effort to study at low temperature the effects of neutron damage on vanadium alloys. The experiment also contained a limited quantity of low-activation ferritic steel specimens from Japan as part of the collaboration agreement. The irradiation started in the Advanced Test Reactor (ATR) on November 30, 1995, and ended as planned on May 5, 1996. Total exposure was 132.9 effective full power days (EFPDs) and estimated neutron damage in the vanadium was 4.7 dpa. The vehicle has been discharged from the ATR core and is scheduled to be disassembled in the next reporting period.

  7. Laboratory experiments on membrane filter sampling of airborne mycotoxins produced by Stachybotrys atra corda

    Science.gov (United States)

    Pasanen, A.-L.; Nikulin, M.; Tuomainen, M.; Berg, S.; Parikka, P.; Hintikka, E.-L.

    A membrane filter method for sampling of airborne stachybotrystoxins was studied in the laboratory. Toxigenic strains of Stachybotrys atra on wallpaper, grain, hay and straw were used as toxin sources in the experiments. Air samples were collected on cellulose nitrate and polycarbonate membrane filters at air flow rates of 10-20 ℓ min -1. After the filter sampling, the air was passed through methanol. The results showed that stachybotrystoxins (trichothecenes) were concentrated in airborne fungal propagules, and thus can be collected on filters. Polycarbonate filters with a pore size of 0.2 μm collected the highest percentage of toxic samples. The laboratory experiments indicated that polycarbonate filter sampling for the collection of airborne mycotoxins is a promising method for extension to field measurements.

  8. Antioxidant, antimicrobial and anticancer activity of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis

    Directory of Open Access Journals (Sweden)

    Stanojković Tatjana P

    2011-10-01

    Full Text Available Abstract Background The aim of this study is to investigate in vitro antioxidant, antimicrobial and anticancer activity of the acetone extracts of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis. Methods Antioxidant activity was evaluated by five separate methods: free radical scavenging, superoxide anion radical scavenging, reducing power, determination of total phenolic compounds and determination of total flavonoid content. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method against six species of bacteria and ten species of fungi. Anticancer activity was tested against FemX (human melanoma and LS174 (human colon carcinoma cell lines using MTT method. Results Of the lichens tested, Lecanora atra had largest free radical scavenging activity (94.7% inhibition, which was greater than the standard antioxidants. Moreover, the tested extracts had effective reducing power and superoxide anion radical scavenging. The strong relationships between total phenolic and flavonoid contents and the antioxidant effect of tested extracts were observed. Extract of Cladonia furcata was the most active antimicrobial agent with minimum inhibitory concentration values ranging from 0.78 to 25 mg/mL. All extracts were found to be strong anticancer activity toward both cell lines with IC50 values ranging from 8.51 to 40.22 μg/mL. Conclusions The present study shows that tested lichen extracts demonstrated a strong antioxidant, antimicrobial and anticancer effects. That suggest that lichens may be used as as possible natural antioxidant, antimicrobial and anticancer agents to control various human, animal and plant diseases.

  9. Discovery, structural characterization and functional analysis of alpha-2-macroglobulin, a novel immune-related molecule from Holothuria atra.

    Science.gov (United States)

    Qian, Jing; Ren, Chunhua; Xia, Jianjun; Chen, Ting; Yu, Zonghe; Hu, Chaoqun

    2016-07-10

    The non-specific protease inhibitor alpha-2-macroglobulin (A2M) is a key macromolecular glycoprotein that involved in host immune defense against pathogens in vertebrates and invertebrates. However, no research regarding A2M has been developed in echinoderms to date. In this study, the full-length cDNA of A2M was cloned from the sea cucumber (Holothuria atra), which is a tropical species widely distributed along the coasts of the South China Sea and designated HaA2M. HaA2M possesses all three conserved functional domains of known A2M proteins, including the bait region domain, thioester domain and receptor-binding domain. Compared to fish and shrimp A2Ms, the histidine residue from the catalytical regions is well conserved in HaA2M. HaA2M mRNA was predominantly expressed in coelomocytes and, to a lesser extent, in the body wall, intestine and respiratory tree. A2M activity was detected in the coelomic fluids of H. atra. The mRNA expression and activity levels were investigated in the major immune tissues and coelomic fluids of H. atra after challenge with inactivated Vibrio alginolyticus or polyriboinosinic polyribocytidylic acid [Poly (I: C)]. RNA interference (RNAi)-mediated knockdown of HaA2M resulted in a significant reduction of HaA2M gene transcript level (86%). RNAi-mediated silencing of HaA2M gene significantly decreased the A2M activity (38%) and increased the number of viable bacteria (2.8-fold) in the coelomic fluids of H. atra infected by V. alginolyticus. Our study, as a whole, supplied the evidences for HaA2M as an immune-relevant molecule and it might have multiple functions in the innate immune system of H. atra. PMID:27033585

  10. CLONING PROMOTER OF HUMAN SATB1 GENE AND EFFECT OF ATRA AND CoCl2 ON ITS ACTIVITY

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To explore the structure and activity of SATB1 promoter in different cells, ATRA and CoCl2 effect on its activity. Methods Using luciferase system to assay the promoter activity of human SATB1 gene, three luciferase reporter vectors were constructed which driven by different regions of 5' untranslated sequence from human SATB1 gene, called pGL3-SP2946-luc, pGL3-SP1718-luc and pGL3-SP751-luc, and transfected into Jurkat T, K562, U937 and Hela cells transiently using lipofectinamine, the expression activity was detected at different dosage of ATRA and CoCl2 treatment for different time course. Results The reporter gene expression from SATB1 promoter were high activity in U937 cell, moderate in Jurkat T cell, low activity in K562 cell and showed no obvious activity in Hela cell, the reporter gene expression from pGL3-SP751-luc kept on the higher lever in Jurkat T, K562 and U937 cells than the other two vectors. We also found that the repressive effect of CoCl2 on SATB1 's mRNA expression and the relative luciferase expression from pGL3-SP751-luc in U937 cell was down-regulated obviously by ATRA and CoCl2 in the concentration- and time-dependent manners. Conclusion SATB1 promoter drives gene expression with cell-specificity and its core promoter region maybe exist in the - 751 ~ - 9bp of 5' untranslated region of human SATB1 gene. Combined with the experiment result we found before that SATB1 was down-regulated by ATRA in U937, the results imply that STAB1 maybe is down-regulated by ATRA and CoCl2 through its promoter in the differentiation of myeloid cell line-U937.

  11. Effect of All-Trans Retinoic Acid (ATRA on Viability, Proliferation, Activation and Lineage-Specific Transcription Factors of CD4+ T Cells

    Directory of Open Access Journals (Sweden)

    Katayoon Bidad

    2011-12-01

    Full Text Available All-trans retinoic acid (ATRA, as an active metabolite of vitamin A, has been shown to affect immune cells. This study was performed to evaluate the effect of ATRA on viability, proliferation, activation and lineage-specific transcription factors of CD4+ T cells. CD4+ T cells were  separated  from  heparinized  blood  of  healthy  donors  and  were  cultured  in conditions, some with, some without ATRA.Viability was assessed by PI  flowcytometry and proliferation was measured by MTT assay. CD69 expression was determined by flowcytometry as a measure of cell activation. Lineage-specific transcription  factors  (FOXP3,  RORγt  and  T-bet  were  examined  by intracellular staining and flowcytometry. High doses of ATRA (0.1-1 mM caused extensive cell death in both PBMCs and CD4+ T cells. Doses of ATRA equal to or lower than 10 µM did not  adversely affect cell viability and proliferation in comparison to  culture medium without ATRA.Doses of ATRA between 10 µM and 1nM significantly increased cell activation when compared  to  culture medium without  ATRA. ATRA could increase FOXP3+  and also FOXP3+RORγt+ T cells while it decreased RORγt+ and T-bet+ T cells. This study showed that doses of ATRA up to 10 µM are safe when using with CD4+  T cells in terms of cell viability, proliferation and activation.We  could  also  show  that  ATRA  diverts  the  human  immune  response  in  neutral conditions (without adding polarizing cytokines by increasing FOXP3+  cells and decreasing RORγt+  cells. ATRA could be regarded as a potential therapy in inflammatory conditions and autoimmunities.

  12. Protective and Curative Effects of the Sea Cucumber Holothuria atra Extract against DMBA-Induced Hepatorenal Diseases in Rats

    OpenAIRE

    Dakrory, Ahmed I.; Fahmy, Sohair R; Soliman, Amel M.; Ayman S. Mohamed; Amer, Sayed A.M.

    2015-01-01

    Oxidative stress is a common mechanism contributing to the initiation and progression of hepatic damage. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present study is to evaluate the efficacy of Holothuria atra extract (HaE) as an antioxidant against 7,12-dimethylbenz[a]anthracene- (DMBA-) induced hepatorenal dysfunction. Experimental animals were divided into two main groups: protective and curative. Each group was then divided in...

  13. Development and characterization of polymer-oil nanostructured carrier (PONC) for controlled delivery of all-trans retinoic acid (ATRA)

    Science.gov (United States)

    Narvekar, Mayuri M.

    The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (pretinoic acid to treat highly resistant ovarian cancer.

  14. Antitumor and Antifungal Activities of Organic Extracts of SeacucumberHolothuria atra from the Southeast Coast of India

    Institute of Scientific and Technical Information of China (English)

    Devaraj Isaac DHINAKARAN; Aaron Premnath LIPTON

    2015-01-01

    In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cu-cumberHolothuria atra is commonly known as the lollyfish. The antifungal activity was detected using agar well diffusion method against the various fungal strains such asTrichoderma viride, Aspergillus niger,Aspergillus flavis,Candida albicansandPenicillium chrysogenum. Relatively high antifungal activity was seen againstCandida albicans at 100µL−1 concentration of extracts. Zone of inhibition was measured at 18mm of diameter. The anti-tumor activities were detected against the Vero and Hep2 cell lines using MTT assay. The cells were treated withH. atra extract at concentrations 0.078−10mgmL−1. The extract showed high proliferative activity against the Hep2 cells. The body wall extracts of sea cucumber (H. atra)showed effective antifungal and antitumor activities. All these findings suggest that the extracts could be used for the development of drugs.

  15. STUDY ON EFFECTS OF RED ORPIMENT AND ATRA ON PML GENE AND PROTEIN IN LEUKEMIA CELL LINES

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate PML gene and protein expression and localization in leukemia cell lines. Methods Cell morphology was assayed by Wright's stain and fluorescence stain, and PML mRNA ex- pression by RT-PCR, PML protein localization by immuno-fluorescence. Results NB4 and HL-60 cells dif- ferentiated morphologically after treatment with anti-retinoic acid ( ATRA ) while K562 cells did not differenti- ate. Typical apoptosis was found in each cell line after treatment with red orpiment. Immuno-fluorescence analysis showed, after treatment with ATRA, the fusion protein disappeared in NB4 cells and the PML protein relocated, while HL-60 and K562 cells had no difference from control cells. After treatment with red orpiment , the fusion protein disappeared in NB4 cells, then degraded, which was also seen in HL-60 cells and K562 cells. The expression of PML mRNA was not changed in all three cell lines after treatment with ATRA or red orpi- ment. Conclusion PML plays the role of differentiation and apoptosis inducer in leukemia cells at the trans- lational level. PML in POD plays the role of apoptosis inducer and the growth control of leukemia cells.

  16. Age-related Variation in Snake Venom:Evidence from Two Snakes (Naja atra and Deinagkistrodon acutus) in Southeastern China

    Institute of Scientific and Technical Information of China (English)

    Ying HE; Jianfang GAO; Longhui LIN; Xiaomei MA; Xiang JI

    2014-01-01

    In this study we explored electrophoretic proifles, enzymatic activities and immunoreactivity of neonate and adult venoms from two snakes (Naja atra and Deinagkistrodon acutus) coexisting in southeastern China. Age-related variation in electrophoretic proifles was found in both species and proteolytic and ifbrinogenolytic activity was higher in neonate than adult venoms. Neonate D. acutus venom had higher 5' nucleotidase, PLA2, hyaluronidase and gelatinolytic activity, but lower esterolytic activity, than adult venom. Neonate and adult D. acutus venoms showed identical phosphomonoesterase, LAO and ifbrinolytic activities. Neonate N. atra venom had higher phosphomonoesterase and LAO activity, but lower 5' nucleotidase, PLA2, hyaluronidase and AchE activities than adult venom. Neonate and adult N. atra venoms showed similar gelatinolytic activity. Further, age-dependent immunoreactivity was found in both species, and cross-reactions between homologous venoms and antiserums were closely related to venom composition. We speculate that age-related variation in venom characteristics is possibly driven by evolutionary forces associated with ontogenetic shifts in dietary habits, competition and predation pressure.

  17. Naja naja atra Venom Protects against Manifestations of Systemic Lupus Erythematosus in MRL/lpr Mice

    Directory of Open Access Journals (Sweden)

    Jiali Zhu

    2014-01-01

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease and effective therapy for this pathology is currently unavailable. We previously reported that oral administration of Naja naja atra venom (NNAV had anti-inflammatory and immune regulatory actions. We speculated that NNAV may have therapeutic effects in MRL/lpr SLE mice. Twelve-week-old MRL/lpr mice received oral administration of NNAV (20, 40, and 80 μg/kg or Tripterygium wilfordii polyglycosidium (10 mg/kg daily for 16 weeks. The effects of NNAV on SLE manifestations, including skin erythema, proteinuria, and anxiety-like behaviors, were assessed with visual inspection and Multistix 8 SG strips and open field test, respectively. The pathology of spleen and kidney was examined with H&E staining. The changes in autoimmune antibodies and cytokines were determined with ELISA kits. The results showed that NNAV protected against the manifestation of SLE, including skin erythema and proteinuria. In addition, although no apparent histological change was found in liver and heart in MRL/lpr SLE mice, NNAV reduced the levels of glutamate pyruvate transaminase and creatine kinase. Furthermore, NNAV increased serum C3 and reduced concentrations of circulating globulin, anti-dsDNA antibody, and inflammatory cytokines IL-6 and TNF-α. NNAV also reduced lymphadenopathy and renal injury. These results suggest that NNAV may have therapeutic values in the treatment of SLE by inhibiting autoimmune responses.

  18. Effects of a fraction from Naja naja atra venom on transplanted hepatic carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    XuT; LiuZT

    2002-01-01

    The effects of a fraction from Naja naja atra venom(FNNAV) on inhibiting the growing of hepatic carcinoma and inducing the apoptosis of hepatic carcinoma were studied.It showed that the weight of transplants of hepatic carcinoma was lower both in middle and high concentration FNNAV groups compared with the control group after ten days treatment with FNNAV,and the nude mice of high concentration FNNAV group lived longer than those of the control group.It has been found that the expression of bcl-2 gene in transplants of hepatic carcinoma in FNNAV groups was decreased by using SABC method.By counting the peripheral blood WBC and bone marrow cells it proved that FNNAV did not affect the function of bone marrow in a short period.These results suggest that FNNAV has the anti-tumor effects on transkplanted hepatic carcinoma in nude mice and could prolong the life of mice bearing the tumor.No inhibitory effect of FNNAV on bone marrow was observed.

  19. Influence of all-trans retinoic acid(ATRA) on the expression of NANOG in Glioma cell lines

    Institute of Scientific and Technical Information of China (English)

    Liu Weixian; Yi Fuxin

    2012-01-01

    Objective To investigate the effects of all-trans retinoic acid(ATRA) on the expression of NANOG in glioma cell lines.Methods Each cell line was divided into the experimental group which was treated with ATRA for 5 days,and the control group which was cultured normally without ATRA treatment. Immunocytochemistry and RT-PCR were adopted to detect the expression of NANOG at protein and mRNA level among the three kinds of cell lines. Results Positive rates of NANOG protein in glioma cell lines SHG-44,U87 MG and U251 in control groups were (65.5±3.0)%,(64.8±8.0)% and (64.5±1.2)%, respectively, and the difference was not statistically significant(F=0.190,P=0.829). NANOG mRNA of the three cell lines in the relative content were 0.636 8±0.039 9, 0.642 1±0.063 7, 0.651 6±0.044 4,and the difference was not statistically significant(F=0.427,P=0.662).However,5 days after application of ATRA-induced NANOG protein in the three cell lines,the positive rates of NANOG protein of experimental groups were (36.5±7.3)%,(35.5±7.9)%,(35.2±6.1)%,respectively,compared with the control groups,the differences were statistically significant (FSHG-44=259.1,FU87=129.5,FU251= 431.8,PSHG-44=0.0,PU87=0.0,PU251=0.0),and the relative level of NANOG mRNA in these groups were 0.458 3±0.079 1,0.255 1±0.079 3 and 0.333 1±0.054 0,respectively,compared with the control groups,the difference was significant(FSHG-44=77.8,FU87=277.9,FU251=398.1,PSHG-44=0.0,PU87=0.0,PU251=0.0).Conclusion NANOG which highly expressed in glioma cell line SHG-44,U87 MG and U251 can be reduced by ATRA.

  20. Disease Progression, Response to ACEI/ATRA Therapy and Influence of ACE Gene in IgA Nephritis

    Institute of Scientific and Technical Information of China (English)

    Keng-Thye Woo; Yeow-Kok Lau; Yi Zhao; Fang-E Liu; Hwee-Boon Tan; Eng-Keng Tan; Fook-Chong Stephanie; Choong-Meng Chan; Kok-Seng Wong

    2007-01-01

    Various studies have shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (ID) polymorphism may play a role in the progression to end stage renal failure (ESRF) in patients with IgA nephritis (IgAN). In this randomized controlled trial, patients were followed up for 5 years to determine their long-term renal outcome to ACEI/ATRA therapy and to ascertain if their ACE gene profile could play a role in determining their response to therapy. Seventy-five patients with IgAN were enlisted. Thirty-seven were on ACEI/ATRA therapy for 62±5 months and thirty-eight were untreated and served as controls. All patients had their ACE gene ID polymorphism genotyped. Compared to controls, treated patients had lower serum creatinine (p<0.001), lower proteinuria (p<0.002) and fewer numbers progressing to ESRF (p<0.002). Among patients with genotype Ⅱ, there were less ESRF in the treatment group when compared to the untreated control group (p<0.02). The advantage of therapy was not seen in patients with ID or DD genotypes. ACEI/ATRA therapy was found to be effective in retarding disease progression in IgAN with years to ESRF significantly extended in patients at all levels of renal function, including patients whose outcome were ESRF. Genotyping showed better response to therapy only for those with genotype Ⅱ.The common mechanism is probably through lower levels of ACE, glomerular pressure and proteinuria resulting in reduced renal damage and retardation of progression to ESRF.

  1. RAF-1/MEK/ERK pathway regulates ATRA-induced differentiation in acute promyelocytic leukemia cells through C/EBPβ, C/EBPε and PU.1.

    Science.gov (United States)

    Weng, Xiang-Qin; Sheng, Yan; Ge, Dong-Zheng; Wu, Jing; Shi, Lei; Cai, Xun

    2016-06-01

    MEK/ERK signal pathway was required for the differentiation of granulocytes, megakaryocytes and erythrocytes. Recently, MEK/ERK cascade was reported to be involved in all-trans retinoic acid (ATRA) induced differentiation in acute promyelocytic leukemia (APL) cells. However, the upstream and downstream molecules of MEK/ERK signal pathway in this cell model remains to be elucidated. In this work, we showed that RAF-1 was activated and the blockade of RAF-1 activation attenuated MEK/ERK activation as well as ATRA-induced differentiation. ATRA-enhanced protein levels of C/EBPβ, C/EBPε and PU.1, which were required for differentiation in APL cells, were suppressed by the specific inhibitor of MEK. However, MEK inhibition had no effect on the degradation of PML-RARα fusion protein or the restoration of PML nuclear bodies by ATRA treatment. Taken together, our study suggested that RAF-1/MEK/ERK cascade was involved in ATRA-induced differentiation in APL cells through enhancing the protein level of C/EBPβ, C/EBPε and PU.1. PMID:27101150

  2. Microstructural examination of V-(3-6%)Cr-(3-5%)Ti irradiated in the ATR-A1 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Gelles, D.S. [Pacific Northwest National Lab., Richland, WA (United States)

    1998-09-01

    Microstructural examination results are reported for four heats of V-(3-6%)Cr-(3-5%)Ti irradiated in the ATR-A1 experiment to {approximately}4 dpa at {approximately}200 and 300 C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to be affected by preirradiation heat treatment or composition.

  3. Metabolic Characterization of All-Trans-Retinoic Acid (ATRA)–Induced Craniofacial Development of Murine Embryos Using In Vivo Proton Magnetic Resonance Spectroscopy

    OpenAIRE

    Feifei Qin; Zhiwei Shen; Lihong Peng; Renhua Wu; Xiao Hu; Guishan Zhang; Shijie Tang

    2014-01-01

    AIM: To characterize the abnormal metabolic profile of all-trans-retinoic acid (ATRA)-induced craniofacial development in mouse embryos using proton magnetic resonance spectroscopy (1H-MRS). METHODS: Timed-pregnant mice were treated by oral gavage on the morning of embryonic gestation day 11 (E11) with all-trans-retinoic acid (ATRA). Dosing solutions were adjusted by maternal body weight to provide 30, 70, or 100 mg/kg RA. The control group was given an equivalent volume of the carrier alone....

  4. Tensile and impact properties of vanadium-base alloys irradiated at low temperatures in the ATR-A1 experiment

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Nowicki, L.J.; Billone, M.C.; Chung, H.M.; Smith, D.L. [Argonne National Lab., IL (United States)

    1998-03-01

    Subsize tensile and Charpy specimens made from several V-(4-5)Cr-(4-5)Ti alloys were irradiated in the ATR-A1 experiment to study the effects of low-temperature irradiation on mechanical properties. These specimens were contained in lithium-bonded subcapsules and irradiated at temperatures between {approx}200 and 300 C. Peak neutron damage was {approx}4.7 dpa. Postirradiation testing of these specimens has begun. Preliminary results from a limited number of specimens indicate a significant loss of work-hardening capability and dynamic toughness due to the irradiation. These results are consistent with data from previous low-temperature neutron irradiation experiments on these alloys.

  5. Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

    Directory of Open Access Journals (Sweden)

    Kou-Zhu Zhu

    2013-01-01

    Full Text Available To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg, the native NNAV (untreated with heat; 90 μg/kg, and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-α and IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis.

  6. Morphologic and molecular characteristics of Sarcocystis atraii n. sp. (Apicomplexa: Sarcocystidae) infecting the common coot (Fulica atra) from Egypt.

    Science.gov (United States)

    El-Morsey, Ahmed; El-Seify, Mahmoud; Desouky, Abdel-Razik Y; Abdel-Aziz, Mohamed M; El-Dakhly, Khaled Mohamed; Kasem, Samy; Abdo, Walied; Haridy, Mohie; Sakai, Hiroki; Yanai, Tokuma

    2015-12-01

    A single morphologic type of Sarcocystis cysts found in two out of 43 examined common coots, Fulica atra, is considered to represent a new species for which the name Sarcocystis atraii n. sp. is proposed and its description is provided. Coots were hunted from the vicinity of Brolos Lake located at KafrElsheikh province, Egypt. The structural morphology of the revealed sarcocysts was described using light and transmission electron microscopy. Sarcocysts were found in the leg and thigh muscles. The cysts were microscopic and measured 165-850 μm in length × 50-85 μm in width. Histologically; the sarcocyst wall was wavy and had minute undulations. Ultrastructurally, it measured 1-3 μm in thickness and possessed many mushroom-like villar protrusions sometimes originating from other mushroom-like villar protrusions that measured approximately 0.5-2 μm in length and up to 2 μm in width, with the presence of electron dense ground substance of 300 nm to 1 μm thick. The bradyzoites were elongated, banana-shaped and measured 7.5-14 × 1.5-2.5 μm, with centrally or terminally located nuclei. The ultrastructural features of the cyst wall belonged to type 24. On the basis of sequencing and phylogenic analyses for 18S rRNA , 28S rRNA genes and ITS-1 region; S. atraii n. sp. is considered a genetically distinct species, being most closely related to avian Sarcocystis spp. whose definitive hosts are predatory mammals. PMID:26408592

  7. Antiseptic effect of sea cucumber (Holothuria atra) against multi-organ failure induced by sepsis: Molecular and histopathological study

    Science.gov (United States)

    SAAD, DALIA Y.; BAIOMY, AHMED A.; MANSOUR, AHMED A.

    2016-01-01

    Sepsis is a systemic inflammatory response to infection and severe sepsis patients can develop acute lung and liver injury. The aim of the present study was to evaluate the efficacy of Holothuria atra methanolic body wall extract (HaE), as an antioxidant and anti-inflammatory agent against induced sepsis in a cecal ligation and puncture (CLP) rat model. In total, 30 males albino rats were divided into three groups (n=10 each) as follows: Sham (Sh), which was used as negative control; sepsis (Se), which was used as a positive control and was subjected to CLP surgery; and Ho, which was subjected to CLP and fed with 200 mg/kg (body weight) of HaE, once daily for 7 days. Subsequently, the expression of various genes was detected by polymerase chain reaction, while liver and lung tissues were examined by immunohistochemistry. The expression of Caspase-3 was significantly reduced in liver and lung tissues in the Ho group, while the expression levels of Gsta2, Cat and Sod1 genes were slightly reduced in the Ho group, when compared with the Se group. In addition, expression levels of tumor necrosis factor, interferon-γ, liver interleukin (IL)1b and lung IL1a were reduced in the Ho group compared with the Se group. Furthermore, histopathological changes were observed in liver tissues of the Se group, including congestion of hepatoportal blood vessel and focal hepatic necrosis, while lung tissues showed marked edema, hemorrhage and alveolar septal thickening. The Ho group showed apparent normal hepatic parenchyma and slight interstitial pneumonia. Immunohistochemical staining of caspase-3 in liver and lung tissues showed no expression in the Sh group, strong expression in the Se group and moderate expression in the Ho group. In conclusion, HaE demonstrated beneficial effect against induced sepsis, which may be attributed to its antioxidant and antiapoptotic activities. PMID:27347042

  8. Combination of Nanoparticle-Delivered siRNA for Astrocyte Elevated Gene-1 (AEG-1) and All-trans Retinoic Acid (ATRA): An Effective Therapeutic Strategy for Hepatocellular Carcinoma (HCC).

    Science.gov (United States)

    Rajasekaran, Devaraja; Srivastava, Jyoti; Ebeid, Kareem; Gredler, Rachel; Akiel, Maaged; Jariwala, Nidhi; Robertson, Chadia L; Shen, Xue-Ning; Siddiq, Ayesha; Fisher, Paul B; Salem, Aliasger K; Sarkar, Devanand

    2015-08-19

    Hepatocellular carcinoma (HCC) is a fatal cancer with no effective therapy. Astrocyte elevated gene-1 (AEG-1) plays a pivotal role in hepatocarcinogenesis and inhibits retinoic acid-induced gene expression and cell death. The combination of a lentivirus expressing AEG-1 shRNA and all-trans retinoic acid (ATRA) profoundly and synergistically inhibited subcutaneous human HCC xenografts in nude mice. We have now developed liver-targeted nanoplexes by conjugating poly(amidoamine) (PAMAM) dendrimers with polyethylene glycol (PEG) and lactobionic acid (Gal) (PAMAM-PEG-Gal) which were complexed with AEG-1 siRNA (PAMAM-AEG-1si). The polymer conjugate was characterized by (1)H-NMR, MALDI, and mass spectrometry; and optimal nanoplex formulations were characterized for surface charge, size, and morphology. Orthotopic xenografts of human HCC cell QGY-7703 expressing luciferase (QGY-luc) were established in the livers of athymic nude mice and tumor development was monitored by bioluminescence imaging (BLI). Tumor-bearing mice were treated with PAMAM-siCon, PAMAM-siCon+ATRA, PAMAM-AEG-1si, and PAMAM-AEG-1si+ATRA. In the control group the tumor developed aggressively. ATRA showed little effect due to high AEG-1 levels in QGY-luc cells. PAMAM-AEG-1si showed significant reduction in tumor growth, and the combination of PAMAM-AEG-1si+ATRA showed profound and synergistic inhibition so that the tumors were almost undetectable by BLI. A marked decrease in AEG-1 level was observed in tumor samples treated with PAMAM-AEG-1si. The group treated with PAMAM-AEG-1si+ATRA nanoplexes showed increased necrosis, inhibition of proliferation, and increased apoptosis when compared to other groups. Liver is an ideal organ for RNAi therapy and ATRA is an approved anticancer agent. Our exciting observations suggest that the combinatorial approach might be an effective way to combat HCC. PMID:26079152

  9. Atração e desligamento voluntário de jovens empregados: um estudo de caso no setor jornalístico

    Directory of Open Access Journals (Sweden)

    Lucia Barbosa de Oliveira

    2014-12-01

    Full Text Available Neste estudo de caso de natureza exploratória, desenvolvido em uma grande empresa do setor jornalístico, o objetivo foi analisar fatores de atração e perda de jovens que voluntariamente optaram por deixar a organização. A fundamentação teórica para a pesquisa foi construída a partir dos seguintes pilares: aspirações de trabalho e carreira da chamada geração Y, fatores de atração e retenção e cultura organizacional, tendo em vista a identificação da necessidade de adaptação da cultura da empresa aos novos desafios estratégicos e competitivos que vem enfrentando. O levantamento de dados foi feito por meio de 17 entrevistas em profundidade com jovens da geração Y que pediram demissão após pelo menos um ano de estágio e/ou trabalho na empresa. Como principais fatores de atração, destacaram-se a imagem e a reputação do principal jornal da empresa, que muito contribui para a construção de sua marca empregadora. Por outro lado, alguns traços da cultura organizacional apresentaram contraste com aspectos valorizados pelos participantes, indicando incongruência de valores, que pode estar levando a organização a perder jovens talentos, considerados importantes ante a necessidade de renovar seu quadro funcional e sua cultura. Com relação às motivações pessoais para deixar a empresa, foram identificados três grupos de jovens – idealistas, carreiristas e imediatistas –, orientados por anseios e perspectivas profissionais distintos.

  10. Nalaz crnog daždevnjaka (Salamandra atra Laurenti, 1768; Salamandridae, Caudata) u Parku prirode Žumberak - samoborsko gorje (SZ Hrvatska)

    OpenAIRE

    Jeran, Nina; Đurić, Patra; Žganec, Krešimir

    2011-01-01

    Ovim istraživanjem potvrđena je prisutnost crnog daždevnjaka (Salamandra atra) u Parku prirode Žumberak - Samoborsko gorje, gdje je prethodno zabilježena samo jedna jedinka 1989. godine. Prisutnost i rasprostranjenost vrste istraživani su tijekom vegetacijske sezone 2004. godine na deset različitih lokaliteta u sastojinama planinske bukove šume. U srpnju 2004. g. pronađeno je pet jedinki (četiri mužjaka i jedna ženka) crnog daždevnjaka u bukovoj prašumskoj sastojini Kuta (na oko 900 m n. v.),...

  11. Recombinant expression of a GH12 β-glucanase carrying its own signal peptide from Stachybotrys atra in yeast and filamentous fungi.

    Science.gov (United States)

    Picart, Pere; Orejas, Margarita; Pastor, F I Javier

    2016-08-01

    The β-glucanase Cel12A gene from Stachybotrys atra has been cloned and heterologously expressed in Aspergillus nidulans and Saccharomyces cerevisiae. The recombinant strains constructed, contained the exonic sequence of cel12A including its own signal peptide coding sequence. SDS-PAGE and zymography revealed that recombinant Cel12A has a molecular mass of 24 kDa which agrees with that deduced from its amino acid sequence, indicating that it is expressed in the non-glycosylated active form. Recombinant A. nidulans showed about eightfold greater activity yield than S. cerevisiae recombinant strain, namely 0.71 and 0.09 β-glucanase Units/ml of culture, respectively. In both host strains most of the activity was secreted to the extracellular media, evidencing the functionality of Cel12A signal peptide in yeast and fungi. This novel signal peptide might facilitate the expression and efficient secretion of other recombinant proteins difficult to secrete. PMID:27339304

  12. Metabolic characterization of all-trans-retinoic acid (ATRA-induced craniofacial development of murine embryos using in vivo proton magnetic resonance spectroscopy.

    Directory of Open Access Journals (Sweden)

    Feifei Qin

    Full Text Available AIM: To characterize the abnormal metabolic profile of all-trans-retinoic acid (ATRA-induced craniofacial development in mouse embryos using proton magnetic resonance spectroscopy (1H-MRS. METHODS: Timed-pregnant mice were treated by oral gavage on the morning of embryonic gestation day 11 (E11 with all-trans-retinoic acid (ATRA. Dosing solutions were adjusted by maternal body weight to provide 30, 70, or 100 mg/kg RA. The control group was given an equivalent volume of the carrier alone. Using an Agilent 7.0 T MR system and a combination of surface coil coils, a 3 mm×3 mm×3 mm 1H-MRS voxel was selected along the embryonic craniofacial tissue. 1H-MRS was performed with a single-voxel method using PRESS sequence and analyzed using LCModel software. Hematoxylin and eosin was used to detect and confirm cleft palate. RESULT: 1H-MRS revealed elevated choline levels in embryonic craniofacial tissue in the RA70 and RA100 groups compared to controls (P<0.05. Increased choline levels were also found in the RA70 and RA100 groups compared with the RA30 group (P<0.01. High intra-myocellular lipids at 1.30 ppm (IMCL13 in the RA100 group compared to the RA30 group were found (P<0.01. There were no significant changes in taurine, intra-myocellular lipids at 2.10 ppm (IMCL21, and extra-myocellular lipids at 2.30 ppm (EMCL23. Cleft palate formation was observed in all fetuses carried by mice administered 70 and 100 mg/kg RA. CONCLUSIONS: This novel study suggests that the elevated choline and lipid levels found by 1H-MRS may represent early biomarkers of craniofacial defects. Further studies will determine performance of this test and pathogenetic mechanisms of craniofacial malformation.

  13. Combination of nanoparticle-delivered siRNA for Astrocyte elevated gene-1 (AEG-1) and all-trans retinoic acid (ATRA): an effective therapeutic strategy for hepatocellular carcinoma (HCC)

    OpenAIRE

    Rajasekaran, Devaraja; Srivastava, Jyoti; Ebeid, Kareem; GREDLER, RACHEL; Akiel, Maaged; Jariwala, Nidhi; Robertson, Chadia L.; Shen, Xue-Ning; Siddiq, Ayesha; Fisher, Paul B; Salem, Aliasger K.; Sarkar, Devanand

    2015-01-01

    Hepatocellular carcinoma (HCC) is a fatal cancer with no effective therapy. Astrocyte elevated gene-1 (AEG-1) plays a pivotal role in hepatocarcinogenesis and inhibits retinoic acid-induced gene expression and cell death. Combination of a lentivirus expressing AEG-1 shRNA and all-trans retinoic acid (ATRA) profoundly and synergistically inhibited subcutaneous human HCC xenografts in nude mice. We now have developed liver-targeted nanoplexes by conjugating poly(amidoamine) (PAMAM) dendrimers w...

  14. Improved method for the isolation, characterization and examination of neuromuscular and toxic properties of selected polypeptide fractions from the crude venom of the Taiwan cobra Naja naja atra.

    Science.gov (United States)

    Ständker, L; Harvey, A L; Fürst, S; Mathes, I; Forssmann, W G; Escalona de Motta, G; Béress, L

    2012-09-15

    An improved chromatographic method was developed to isolate and purify polypeptides and proteins from the crude venom of the Taiwan cobra Naja naja atra. The procedure devised is simple, easy to reproduce, and enables large scale isolation of almost all polypeptides and proteins in this cobra venom. Six pure polypeptide fractions of the venom were isolated and characterized using gel filtration on Sephadex G50 (medium), ion exchange chromatography on SP-Sephadex C25, desalting on Sephadex G25 (fine) and preparative HPLC on a RPC 18 column. The neuromuscular activity of these fractions was tested on the chick biventer cervicis nerve-muscle preparation and their toxicity (LD(50)) was determined after i.v. administration in mice. Their antinociceptive activity was tested in the mouse abdominal test by i.v. application. Two of these polypeptide samples had major physiological effects: one acted as a cardiotoxin causing reversible myocardial contractures with no effect on muscle twitches elicited by nerve stimulation (NS); another was a neurotoxin that blocked muscle contractions in response to NS and exogenously added acetylcholine. The cardiotoxic fraction was identified as CTX I, a well-known cardiotoxin present in this venom, and the neurotoxin was identified as neurotoxin-α with an LD50 in mice of 0.075 mg/kg. PMID:22677803

  15. Características y resultado a largo plazo de pacientes mayores con leucemia promielocítica aguda tratados con esquemas terapéuticos basados en ATRA más antraciclinas

    OpenAIRE

    Martínez Cuadrón, David

    2015-01-01

    La leucemia promielocítica aguda (LPA) es un subtipo de leucemia mieloide aguda que se diferencia por una morfología característica y la presencia de la t(15;17) y su correspondiente reordenamiento molecular PML/RARa. Clínicamente, no es infrecuente que se presente con coagulopatía, pudiendo ser la responsable de la muerte del paciente incluso antes del diagnóstico. No obstante, su buena respuesta al tratamiento con ácido holo-trans retinoico (ATRA) se ha traducido en una importante mejoría d...

  16. 广东眼镜蛇毒低分子量多肽的分离纯化与性质鉴定%Purification and Characterization of Low Molecular Weight Polypeptides from the Venom of Guangdong Cobra (Naja Naja Atra)

    Institute of Scientific and Technical Information of China (English)

    郝彩; 韩丽萍; 蒋琳兰; 江伟健

    2011-01-01

    目的 从广东眼镜蛇粗毒中分离纯化出色谱纯的低分子量多肽并对其部分性质进行鉴定.方法 采用化学沉淀法对蛇粗毒进行预处理,经 Sephadex G-50 凝胶过滤和 UND Sphere S 阳离子交换层析得到高纯度低分子量多肽,用SDS-PAGE及HPLC对产物纯度进行鉴定,并用SDS-PAGE和质谱法测定分子量,采用蛙心灌流法考察产物是否具有心脏毒性.结果 结果表明,经分离纯化后得到两种低分子量多肽GI2和GI3,均为单一组分,可达到色谱纯,SDS-PAGE法测得GI2分子量为14 300 Da,质谱法测得GI3分子量为6 725.8 Da,仅GI2具有心脏毒性,收率分别为9.5%和10.1%.结论 通过化学沉淀预处理,并经2次柱色谱可从广东眼镜蛇毒中分离得到两种色谱纯的低分子量多肽,且收率较高.%OBJECTIVE To isolate and characterize some properties of the chromatographically pure low molecular weight polypeptides from the venom of Guangdong cobra (Naja naja atra). METHODS Isolation and purification were carried out by chromatography on Sephadex G-50 and UND Sphere S column after the pretreatment by chemical precipitation. The purity of this product was determined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and HPLC, and its molecular weight was observed by SDS-PAGE and mass spectrography. The cardiotoxicity of the polypeptides was investigated using the frog heart perfusion experiment. RESULTS After the chemical precipitation and Two-step column chromatography, the products, named ‘GI2’ and ‘GI3’, were single components. The molecular weight of GI2 is 14 300 Da observed by SDS-PAGE and GI3 is 6 725.8 Da determined by mass spectrography. The yields of the products were 9.5% and 10. 1%, and only GI2 showed cardiotoxicity. CONCLUSION Two low molecular weight components could be obtained from the venom of Guangdong cobra after chemical precipitation and two-step column chromatographies, with high yield.

  17. Attraction of Neomegalotomus parvus (Westwood(Heteroptera: alydidae to cow urine and ammonia Atração de Neomegalotomus parvus (Westwood (Heteroptera: alydidae por urina de vaca e amônia

    Directory of Open Access Journals (Sweden)

    Jovenil José da Silva

    2010-02-01

    Full Text Available The alydid bug parvus (Westwood is not easily detected in the field and the discovery of attractants may be a suitable way to monitor this species. The attraction of N. parvus to traps (transparent, transparent green and yellow baited with cow urine and ammonia was studied in two field trials. Traps were placed near a terrace with pigeon pea plants (Cajanus cajan L.. Tap water, NaCl 10% aqueous solution (w/v, cow urine, and ammonia (NH4OH 1% aqueous solution were tested as attractants in yellow, transparent and transparent green traps. Green traps baited with cow urine caught more bugs than yellow and transparent traps (3.2 and 7.2 times more, respectively, and more bugs than traps of the same color with just water (no captures or NH4OH solution (14.5 times more. Traps baited with ammonia caught more bugs than traps with water: 14.4, 4.7 and 6.7 times more than transparent green, yellow, and transparent traps, respectively, or NaCl solution: 3.9, 7.6 and 6.2 times, respectively. Both ammonia and cow urine are attractive to N. parvus and may be tested to monitor the bugs in the field.O percevejo alidídeo Neomegalotomus parvus (Westwood não é facilmente detectado no campo e a descoberta de atraentes pode ser uma forma adequada para monitorar a espécie. A atração de N. parvus a armadilhas (transparentes, verde transparente e amarela iscadas com urina de vaca e amônia foi estudada em dois experimentos em campo. Armadilhas foram colocadas próximas a um terraço com plantas de feijão-guandu (Cajanus cajan L.. Água corrente, solução aquosa de NaCl 10% (p/v, urina de vaca e amônia (solução aquosa de NH4OH 1% foram testadas como atraentes em armadilhas amarelas, transparentes e transparentes verdes foram utilizadas. Armadilhas verdes iscadas com urina capturaram mais insetos do que armadilhas amarelas e transparentes (3,2 e 7,2 vezes mais, respectivamente, e mais insetos do que armadilhas da mesma cor com apenas água (zero insetos ou solu

  18. A história da ciência na formação do professor de física: subsídios para um curso sobre o tema atração gravitacional visando às mudanças de postura na ação docente History of Science in teaching education: suggestions for a course plan on gravitational attraction aiming to change teachers' attitudes

    Directory of Open Access Journals (Sweden)

    Sandra Regina Teodoro Gatti

    2004-12-01

    Full Text Available O objetivo desta pesquisa foi estudar como a evolução histórica dos modelos de atração entre corpos, tendo como pano de fundo a evolução dos modelos de mundo, pode auxiliar na formação inicial do docente de Física. Para tanto, sugerimos um planejamento de curso sobre o tema atração gravitacional, destinado principalmente a docentes de Física que atuam no ensino médio. O planejamento do curso foi baseado: em dados sobre a evolução dos modelos de mundo, buscando evidenciar como o conceito de atração gravitacional desenvolveu-se historicamente; nas concepções alternativas mais comuns encontradas na literatura, incluindo um breve esboço de noções diagnosticadas em uma amostra de docentes de Física de ensino médio; e em sugestões de leituras de resultados de pesquisas recentes sobre os processos de ensino e aprendizagem de ciências. Pretende-se fornecer aos docentes elementos de reflexão que lhes proporcionem mudanças de postura, através do questionamento da visão de ciência enquanto processo de construção e sobre sua própria prática de ensino. Partindo de resultados recentes da pesquisa em Ensino de Ciências, a metodologia sugerida privilegia o trabalho coletivo, com a realização de debates e sínteses. As atividades mencionadas são acompanhadas de justificativas sobre a escolha do tema e objetivos.The main purpose of this research was to study how the attraction among bodies, having as background the evolution of models of the world, can help prospective teachers' education. To reach this goal, we suggest a course plan on gravitational attraction, addressed mainly to High School Physics teachers. This course was based: on data about world models' evolution, searching to make clear how the concept of gravitational attraction was historically developed; on the most common alternative conceptions found in the literature, including a brief outline of notions found among in-service High School Physics teachers

  19. 中华眼镜蛇心脏毒素(CardiotoxinⅢ)的克隆及其在大肠杆菌和酵母中的表达%Molecular Cloning and Expression of Cardiotoxin Ⅲ from Naja naja atra in E.coli and Yeast Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    陈兴勇; 吕萍; 刘兢; 徐康森

    2008-01-01

    Chinese cobra (Naja naja atra) cardiotoxins are three-fingered family with 60~62 amino acids bind by four disulfide bonds. CardiotoxinⅢ (CTXⅢ) is one of the major toxic component which can cause hemolysis and cytotoxicity. However, there is no report on the fusion expression of CTXⅢ in soluble form so far. The cloning, expression and purification of recombinant CTX Ⅲ (rCTXⅢ) from Naja naja atra in E. coli and in yeast Pichia pastoris were reported here. CTXⅢ gene, fused with enterokinase in E.coli His-patch Thioredoxin expression system, were expressed in soluble form and released by osmotic-shock treatment. CTX Ⅲ gene was also cloned and expressed in the methylotropic yeast Pichia pastoris pPIC9K expression vector in the first time. The yield of the secretion level was 9.5 mg/L. Using straightforward one-step chromatography procedure, the rCTXⅢ, with three additional amino acids (GYT) at the N-terminal site, was purified to a purity of more than 90% and recovery yield of 65%. The purified rCTX Ⅲ was further characterized by cytotoxic assay with IC50 4.66μg/ml. An effective expression and purification system for recombinant CTXs in P. pastoris was developed, this system will permit us the ready isolation of active cardiotoxins. This protocol can also be easily used for the production of the toxin in a larger scale with low cost.%心脏毒素cardiotoxinⅢ (CTXⅢ)是中华眼镜蛇毒主要组分之一,根据Genbank中已有的CTXs序列设计特异性引物,从中华眼镜蛇毒中克隆出208bp的CTXⅢ片段,并将该基因片段分别克隆至大肠杆菌His-patch ThioredoxinB载体中,重组CTXⅢ经渗透休克分泌至胞外.将CTXⅢ基因插入酵母pPIC9K分泌型表达载体重组表达,N端带有3个氨基酸(GYT)残基的重组CTXⅢ(rCTXⅢ)分泌量达9.5mg/L,经一步凝胶过滤纯化,其纯度达90%以上,纯化率达65%.经细胞毒性实验检测,纯化的rCTXⅢ 12h的IC50为4.66μg/ml,证实重组蛋白具有良好的生物学活性.

  20. Fluxos de capitais internacionais de investidores institucionais para o Brasil: um estudo sobre os fatores de atração e de repulsão Flow of international capital of institutional investors to Brazil: a study of push and pull factors

    Directory of Open Access Journals (Sweden)

    Antônio André Cunha Callado

    2005-06-01

    Full Text Available Os fluxos de capitais internacionais direcionados para o Brasil têm sido bastante significativos. O objetivo desta pesquisa foi identificar os principais fatores de influência sobre os fluxos obtidos através dos Investidores Institucionais estrangeiros. Avaliou-se a influência dos fatores de atração (relacionados ao Brasil e dos fatores de repulsão de capital (relacionados ao ambiente econômico externo sobre esses fluxos. Os dados mensais (de janeiro de 1993 a outubro de 2001 foram coletados no Banco Central do Brasil, FGVDADOS, IBGE e Moody's. Utilizou-se um modelo de correção de erro para avaliar as relações de curto e longo prazos. A variável explicativa que obteve o melhor resultado para o longo prazo foi o spread médio relativo ao risco soberano do Brasil emitido pela agência Moody's. Para o curto prazo, os resultados não se mostraram significativos. O spread relativo ao risco revelou-se importante em sua perspectiva associada à capacidade e intenção que um devedor possui de honrar seus compromissos financeiros de longo prazo, bem como à percepção sobre o risco de inadimplência.There was a sharp increase in the flow of international capital to Brazil in the decade of 1990 after the debt crisis of the previous decade. An analysis of the factors influencing the flow of capital of institutional investors in the decade of l990 was made to evaluate the pull factors, related to the domestic scene, and the push factors, related to the global scene. Data was collected monthly between January 1993 and October 2001 from the Banco Central do Brasil, FGVDADOS, IBGE and Moody's. Over the long term the variable that best explained capital flow was the average spread related to the sovereign risk of Brazil as defined by Moody's. No significant conclusion was found for the short term. The average spread related to risk was crucial considering the perspective associated to the future qualification and willingness of the bond issuer to

  1. Stachybotrys chartarum (atra) contamination of the indoor environment: Health implications

    OpenAIRE

    Bitnun, Ari; Nosal, Robert M

    1999-01-01

    In 1998, widespread contamination of water-damaged school portables with the toxigenic mold Stachybotrys chartarum was detected in the province of Ontario. This mold may cause human disease through direct irritation, type 1 hypersensitivity or the production of toxins. A variety of respiratory, dermatological, eye and constitutional symptoms have been associated with heavy and prolonged exposure to S chartarum. S chartarum has also been potentially implicated as a rare cause of idiopathic pul...

  2. Orchid bee baits attracting bees of the genus Megalopta (Hymenoptera, Halictidae in Bauru region, São Paulo, Brazil: abundance, seasonality, and the importance of odors for dim-light bees Abelhas do gênero Megalopta (Hymenoptera, Halictidae atraídas por iscas químicas usadas para euglossíneos na região de Bauru, SP: abundância, sazonalidade e importância de odores para abelhas crepusculares

    Directory of Open Access Journals (Sweden)

    Fátima R. N. Knoll

    2012-12-01

    Full Text Available Nocturnal bees in the genus Megalopta Smith, 1853 are generally collected using artificial light sources. However, between 1993 and 2000, a total of 946 females (no males were captured were captured using aromatic baits commonly used for orchid bees (Euglossini in five localities in Bauru region, São Paulo, Brazil. Aromatic compounds used in bait traps were: benzyl acetate, eucalyptol, eugenol, skatole, methyl salicylate, and vanillin. The Megalopta species collected were: M. guimaraesi (71.2% of total number of specimens, M. amoena (28.1%, and M. aegis (0.6%. Using the data from these traps, we showed that there was a positive and significant correlation between the abundance of individuals and meteorological factors, rainfall and temperature. Bees were more commonly collected in the spring (September to December and summer (December to March than in the autumn and winter, the latter characterized for being a drier and colder period. Variations in the abundance were also detected among localities and years. The most attractive compounds were eugenol (54%, methyl salicylate (22%, and eucalyptol (16%. The ability to detect smells may have an important role in searching for flowers during dim-light conditions. We suggest the use of aromatic compounds in future studies on the biology of Megalopta in the Neotropical region.Abelhas noturnas do gênero Megalopta (Smith, 1853 são geralmente coletadas usando fontes artificiais de luz. Porém entre os anos de 1993 e 2000, um total de 946 fêmeas de Megalopta foram capturadas (machos não foram capturados usando iscas aromáticas frequentemente usadas para atração de machos de Euglossini, em cinco localidades na região de Bauru, São Paulo, Brasil. Os compostos aromáticos utilizados foram: acetato de benzila, eucaliptol, eugenol, escatol, salicilato de metila e vanilina. As espécies encontradas foram M. guimaraesi (71.2% do total de indivíduos, M. amoena (28.1% and M. aegis (0.6%. De modo geral

  3. Projeto para a Estética: despertando a atração do consumidor

    Directory of Open Access Journals (Sweden)

    Widomar Carpes Jr

    2004-06-01

    Full Text Available Este artigo apresenta um conjunto de recomendações para o projeto estético dos produtos, incluindo os conceitos básicos, as definições semânticas e simbólicas, os mecanismos da percepção estética, os conceitos de complexidade e ordenação, a utilização de cores e outros fatores relevantes. Este trabalho foi estruturado visando apresentar as possibilidades para a utilização dos elementos estéticos em produtos, em termos de extremos como complexidade e ordenação. A partir da identificação destes extremos, os projetistas podem fazer escolhas intermediárias ou extremas para o uso de elementos estéticos nos produtos. A importância do estudo do projeto para a estética está fundamentada no fato da estética ser a primeira característica observada pelo consumidor num produto em exposição, contribuindo decisivamente para a venda.

  4. Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor

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    Zhao Junfeng

    2012-03-01

    Full Text Available Abstract The testicular yolk sac tumor (TYST is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST.

  5. ATR-A1 irradiation experiment on vanadium alloys and low activation steels

    Energy Technology Data Exchange (ETDEWEB)

    Tasi, H.; Strain, R.V.; Gomes, I.; Hins, A.G.; Smith, D.L.

    1996-04-01

    To study the mechanical properties of vanadium alloys under neutron irradiation at low temperatures, an experiment was designed and constructed for irradiation in the Advanced Test Reactor (ATR). The experiment contained Charpy, tensile, compact tension, TEM, and creep specimens of vanadium alloys. It also contained limited low-activation ferritic steel specimens as part of the collaborative agreement with Monbusho of Japan. The design irradiation temperatures for the vanadium alloy specimens in the experiment are {approx}200 and 300{degrees}C, achieved with passive gap-gap sizing and fill gas blending. To mitigate vanadium-to-chromium transmutation from the thermal neutron flux, the test specimens are contained inside gadolinium flux filters. All specimens are lithium-bonded. The irradiation started in Cycle 108A (December 3, 1995) and is expected to have a duration of three ATR cycles and a peak influence of 4.4 dpa.

  6. Nucleosomal organization of chromatin in sperm nuclei of the bivalve mollusc Aulacomya ater.

    Science.gov (United States)

    Olivares, C; Ruiz, S

    1991-03-13

    The sperm nuclei of Aulacomya ater, family Mitylidae, contain three proteins (X, Aa5 and Aa6) which are specific to this cell type coexisting with a set of five somatic-type histones. Information about the chromatin structure resulting from this kind of association is scarce. Therefore, we have probed the structure of this sperm chromatin through digestion with micrococcal nuclease in combination with salt fractionation. The data obtained have allowed us to propose a nucleosomal arrangement for this chromatin. However, two types of nucleosomes would be present in agreement with their protein components. PMID:1861676

  7. Spectroscopic investigations on the binding of persimmon tannin to phospholipase A 2 from Chinese cobra ( Naja naja atra)

    Science.gov (United States)

    Yang, Jie; Zhong, Li; Zou, Bo; Tian, Yan; Xu, Shu-fen; Yao, Ping; Li, Chun-mei

    2012-01-01

    To understand the anti-venom mechanism of persimmon tannin, the interaction between persimmon tannin (PT) and phospholipase A 2 (PLA 2) under physiological conditions was investigated by fluorescence quenching technique in combination with Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra techniques. The results revealed that gradual fluorescence quenching was observed by titration of PLA 2 (2.0 μM) with increasing concentrations of PT (from 0 to 2.025 μM), and the type of quenching was found to be a static quenching process. Stern-Volmer plots were not linear but had an intersection at CPT ≈ 1.0 μM, indicating that PT binded to more than one class of sites on PLA 2. The binding sites calculated on basis of Scatchard plots were about 2, supporting this result. The enthalpy change (Δ H) and entropy change (Δ S) of the binding sites were -17.44 kJ/mol and 59.90 kJ/mol·, separately, suggesting that hydrophobic interaction played a main role in the binding. In addition, synchronous fluorescence, FT-IR and CD spectra showed that dramatic conformational changes in PLA 2 were induced by its interaction with PT.

  8. Isomerization of all-(E)-Retinoic Acid Mediated by Carbodiimide Activation - Synthesis of ATRA Ether Lipid Conjugates

    DEFF Research Database (Denmark)

    Christensen, Mikkel Stochkendahl; Pedersen, Palle Jacob; Andresen, Thomas Lars;

    2010-01-01

    Treatment of the lysolipid 1-O-hexadecyl-sn-phosphatidylcholine with all-(E)-retinoic acid, DCC and DMAP resulted in poor acylation and caused (Z)/(E) isomerization of the alpha-beta double bond. In the presence of a proton source, the carbodiimide-activated all-(E)-retinoic acid undergoes fast...... isomerization to give a final mixture of (13E)/(13Z) isomers in a 3:1 ratio. Similar treatment of (13Z)-retinoic acid leads to the same isomer ratio. The isomerization was circumvented successfully by using a Mitsunobu reaction, which provided an efficient synthesis of all-(E)-retinoic acid sn-2-conjugated to...

  9. Karakterisasi Simplisia dan Uji Aktivitas Antioksidan Ekstrak Etanol Serta Fraksi n-Heksan dan Etilasetat Teripang Holothuria atra Jaeger

    OpenAIRE

    Hutahuruk, Melva Martua

    2016-01-01

    Sea cucumbers are marine invertebrates of the phylum of Echinodermata that much found in Indonesian. Sea cucumber’s contain are high protein and collagen, and mineral, mucopolysacarides, glucasaninoglycans, amino acid and chondroitin. Sea cucumber also contain saponin glycosides and Super oxide dismutase activity thus has great potential to developed in the field of medicine. The purpose of this observed is to establish simplex characterization and antioxidant activity assay of ethanol extrac...

  10. Determination of Mercury Concentration in Different Tissues of Coot (Fulica Atra, Mallard (Anas Platyrhynchos and Great Cormorant (Phalacrocorax Carbon

    Directory of Open Access Journals (Sweden)

    N Bahramifar

    2012-03-01

    Full Text Available Background and Objectives: The heavy metals pollution in aquatic ecosystems especially mercury, always makes concern about health of aquatic organisms. So, the purposes of this study were determination of total mercury in different tissues of the three species of the most important water birds at north of Iran and comparison with world health standards.Materials and Methods: Generally, 51 birds were captured randomly. Then, samples of feather, liver, kidney and muscle were taken and the mercury concentrations were determined by Advanced Mercury Analyzer (Model; Leco, AMA 254.Results: The most amount of accumulated mercury was in great cormorants liver (piscivorous species. Means of mercury concentration in liver of great cormorant, mallard, and coot were 14.80, 2.05, 0.18; in kidney 12.00, 1.90, 0.17; in feather 6.57, 1.09, 0.23 and in muscle 8.67, 0.26, 0.09 mg/kg dry weight respectively. Means Comparison showed significant difference among all tissues (P < 0.05, But there were not significant difference between sexes (P > 0.05Conclusion: The levels of accumulated mercury in all tissues of great cormorant were more than the established limits by WHO, FAO and EPA. The other species had less use limitation, but mercury concentration in mallards was considerable. These results can be a serious warning for consumers these birds, especially vulnerable people.

  11. Determination of Mercury Concentration in Different Tissues of Coot (Fulica Atra), Mallard (Anas Platyrhynchos) and Great Cormorant (Phalacrocorax Carbon)

    OpenAIRE

    N Bahramifar; A Esmaili-Sari; J Azami

    2012-01-01

    Background and Objectives: The heavy metals pollution in aquatic ecosystems especially mercury, always makes concern about health of aquatic organisms. So, the purposes of this study were determination of total mercury in different tissues of the three species of the most important water birds at north of Iran and comparison with world health standards.Materials and Methods: Generally, 51 birds were captured randomly. Then, samples of feather, liver, kidney and muscle were taken and the mercu...

  12. Characterization of the mechanical properties of tough biopolymer fibres from the mussel byssus of Aulacomya ater.

    Science.gov (United States)

    Troncoso, O P; Torres, F G; Grande, C J

    2008-07-01

    Byssus fibres are tough biopolymer fibres produced by mussels to attach themselves to rocks. In this communication, we present the mechanical properties of the byssus from the South American mussel Aulacomya ater which have not been previously reported in the literature. The mechanical properties of the whole threads were assessed by uniaxial tensile tests of dry and hydrated specimens. Elastoplastic and elastomeric stress-strain curves were found for byssal threads from A. ater in the dry and hydrated state, respectively. The results obtained from mechanical tests were modelled using linear, power-law-type and Mooney-Rivlin relationships. These methods for dealing with tensile measurements of mussel byssus have the potential to be used with other stretchy biomaterials. PMID:18321800

  13. Comparative analysis of hemocyte properties from Mytilus edulis desolationis and Aulacomya ater in the Kerguelen Islands.

    Science.gov (United States)

    Caza, France; Betoulle, Stéphane; Auffret, Michel; Brousseau, Pauline; Fournier, Michel; St-Pierre, Yves

    2015-09-01

    The capability of bivalve molluscs to respond to environmental stresses largely depends upon their cellular immunity. Accordingly, shift in habitat conditions following thermal stress or exposure to pollutants may harm sensitive species differently, thereby modulating the biodiversity of a given ecosystem by favoring stress-tolerant species. Here, we have compared the sensitivity of hemocytes from Mytilus edulis desolationis (M. edulis desolationis) and Aulacomya ater (A. ater) to acute thermal stress and exposure to cadmium. The two subantarctic species are commonly found in the same habitat in the isolated Kerguelen archipelago. Our results showed that the phagocytic activity and viability of hemocytes from both species were equally sensitive to increasing concentrations of cadmium. However, although in vitro exposure to cadmium induced apoptosis in hemocytes of M. edulis desolationis and A. ater, flow cytometric analyses showed that the apoptotic profile of both species differed greatly when using Annexin V and YO-PRO-1 as apoptotic markers. We also found that the total hemocyte counts decreased strongly in A. ater but not in M. edulis desolationis following an acute thermal stress. Taken together, these results showed that stress responses differed significantly in hemocytes from both species. This suggests that the co-existence of both species may be at risk following exposure to pollutants and/or changes in temperature. PMID:26382607

  14. Elimination of vibrio cholerae, el tor, in mussels (aulacomya ater) by gamma radiation

    International Nuclear Information System (INIS)

    The D10 value of vibrio cholerae in mussels (aulacomya ater) was determined and this experiment was carried out in vivo. The D10 was 0,138 kGy, being necessary the application of 8D in mussels which is equivalent to a dose obtained from 1,102 kGy in order to remove a recount of 108 vibrios/g, quantity that causes the disease. The optimal dose for the shelf life extension of samples kept under cooling conditions (0-1oC) and examined periodically under the different analytical method criteria was 1 kGy. The shelf life time in raw mussels for the appearance feature reaches 14 days for the witness samples and 31 days for the irradiated samples at 1 kGy. The odor of the witness samples was just accepted until 12 days while the irradiated samples at 1 kGy exceeded this level reaching up to 22 days. For the cooked mussels, the odor feature was just acceptable up to 15 days in contrast to the irradiated samples at 1 kGy that reached 35 days. The shelf life for the flavor in witness samples only reached 14 days while the irradiated samples at 1 kGy were extended until 30 days. It was also studied the use of pH and nitrogenous volatile bases as quality indexes

  15. Histopathology of liver and kidneys of wild living Mallards Anas platyrhynchos and Coots Fulica atra with considerable concentrations of lead and cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Binkowski, Łukasz J., E-mail: ljbinkowski@gmail.com [Institute of Biology, Pedagogical University of Cracow, Podbrzezie 3, 31-054 Cracow (Poland); Sawicka-Kapusta, Katarzyna, E-mail: katarzyna.sawicka-kapusta@uj.edu.pl [Institute of Environmental Sciences, Jagiellonian University, Gronostajowa 7, 30-387 Cracow (Poland); Szarek, Józef, E-mail: szarek@uwm.edu.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland); Strzyżewska, Emilia, E-mail: emijel@wp.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland); Felsmann, Mariusz, E-mail: felsmann.mariusz@wp.pl [Department of Pathophysiology, Forensic Veterinary Medicine and Administration, University of Warmia and Mazury, Oczapowskiego 13, 10-719 Olsztyn (Poland)

    2013-04-15

    Concentrations of cadmium and lead were measured in liver and kidneys of Mallard (n = 60) and Coot (n = 50). Free living birds were collected by hunters in years 2006–2008 in the area of fishponds near Zator in southern Poland. Age group was determined according to the appearance of the plumage (Mallards) and iris color (Coot). Concentrations of metals were measured with ET-AA spectrometer. Among all birds specimens with negligible (n = 5) and high concentrations (Mallards n = 18 and Coots n = 17) of cadmium and lead were chosen for further analysis. Histopathological alterations were observed, ranging from circulatory disturbances, retrogressive changes, inflammations to leukocytic infiltration in liver and kidney. They dominated among birds with the highest concentrations of metals. The control group of birds was characterized by a very small number of mentioned lesions. Probably the higher cadmium and lead concentrations in tissues are co-factors in the development of lesions. - Highlights: ► High levels of Cd and Pb were found in liver and kidneys of Mallard and Coot. ► Lower concentrations were found in young birds. ► Amount of metals exceeded the safety threshold established for edible poultry. ► Histopathological alterations were found in studied tissues. ► Lesions in birds with the highest concentrations of metals were numerous.

  16. (+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo.

    Science.gov (United States)

    dos Santos, G A S; Abreu e Lima, R S; Pestana, C R; Lima, A S G; Scheucher, P S; Thomé, C H; Gimenes-Teixeira, H L; Santana-Lemos, B A A; Lucena-Araujo, A R; Rodrigues, F P; Nasr, R; Uyemura, S A; Falcão, R P; de Thé, H; Pandolfi, P P; Curti, C; Rego, E M

    2012-03-01

    The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy. PMID:21869839

  17. Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acute myeloid leukemia.

    Science.gov (United States)

    Skavland, J; Jørgensen, K M; Hadziavdic, K; Hovland, R; Jonassen, I; Bruserud, O; Gjertsen, B T

    2011-02-01

    Acute myeloid leukemia (AML) frequently comprises mutations in genes that cause perturbation in intracellular signaling pathways, thereby altering normal responses to growth factors and cytokines. Such oncogenic cellular signal transduction may be therapeutic if targeted directly or through epigenetic regulation. We treated 24 selected elderly AML patients with all-trans retinoic acid for 2 days before adding theophylline and the histone deacetylase inhibitor valproic acid (ClinicalTrials.gov NCT00175812; EudraCT no. 2004-001663-22), and sampled 11 patients for peripheral blood at day 0, 2 and 7 for single-cell analysis of basal level and signal-transduction responses to relevant myeloid growth factors (granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor, interleukin-3, Flt3L, stem cell factor, erythropoietin, CXCL-12) on 10 signaling molecules (CREB, STAT1/3/5, p38, Erk1/2, Akt, c-Cbl, ZAP70/Syk and rpS6). Pretreatment analysis by unsupervised clustering and principal component analysis divided the patients into three distinguishable signaling clusters (non-potentiated, potentiated basal and potentiated signaling). Signal-transduction pathways were modulated during therapy and patients moved between the clusters. Patients with multiple leukemic clones demonstrated distinct stimulation responses and therapy-induced modulation. Individual signaling profiles together with clinical and hematological information may be used to early identify AML patients in whom epigenetic and signal-transduction targeted therapy is beneficial. PMID:22829110

  18. Histopathology of liver and kidneys of wild living Mallards Anas platyrhynchos and Coots Fulica atra with considerable concentrations of lead and cadmium

    International Nuclear Information System (INIS)

    Concentrations of cadmium and lead were measured in liver and kidneys of Mallard (n = 60) and Coot (n = 50). Free living birds were collected by hunters in years 2006–2008 in the area of fishponds near Zator in southern Poland. Age group was determined according to the appearance of the plumage (Mallards) and iris color (Coot). Concentrations of metals were measured with ET-AA spectrometer. Among all birds specimens with negligible (n = 5) and high concentrations (Mallards n = 18 and Coots n = 17) of cadmium and lead were chosen for further analysis. Histopathological alterations were observed, ranging from circulatory disturbances, retrogressive changes, inflammations to leukocytic infiltration in liver and kidney. They dominated among birds with the highest concentrations of metals. The control group of birds was characterized by a very small number of mentioned lesions. Probably the higher cadmium and lead concentrations in tissues are co-factors in the development of lesions. - Highlights: ► High levels of Cd and Pb were found in liver and kidneys of Mallard and Coot. ► Lower concentrations were found in young birds. ► Amount of metals exceeded the safety threshold established for edible poultry. ► Histopathological alterations were found in studied tissues. ► Lesions in birds with the highest concentrations of metals were numerous

  19. Turismo e Idosos: o patrimônio imaterial como fator de atração para o turismo cultural no espaço rural

    Directory of Open Access Journals (Sweden)

    Lívia Morais Garcia Lima

    2011-01-01

    Full Text Available A pesquisa tem por objetivo investigar e analisar as formas pelas quais propriedades rurais históricas paulistas se preocupam em proporcionar atividades voltadas para idosos, trabalhando o turismo cultural com uma preocupação voltada à educação patrimonial não-formal e sob um enfoque qualitativo. O método biográfico ou da História Oral é utilizado tanto para a coleta de informações sobre o patrimônio imaterial, como para levantar as demandas do público idoso. Ela é sempre acompanhada da realização de um diário de campo em associação com registros fotográficos das atividades educacionais e turísticas observadas em duas fazendas selecionadas. Para melhor avaliar programas para o público idoso é necessário uma efetiva conexão entre os elementos encontrados em cada fazenda participante, visando à articulação de ações efetivas para o turismo cultural no espaço rural e às diretrizes da Gerontologia.

  20. Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acute myeloid leukemia

    International Nuclear Information System (INIS)

    Acute myeloid leukemia (AML) frequently comprises mutations in genes that cause perturbation in intracellular signaling pathways, thereby altering normal responses to growth factors and cytokines. Such oncogenic cellular signal transduction may be therapeutic if targeted directly or through epigenetic regulation. We treated 24 selected elderly AML patients with all-trans retinoic acid for 2 days before adding theophylline and the histone deacetylase inhibitor valproic acid (ClinicalTrials.gov NCT00175812; EudraCT no. 2004-001663-22), and sampled 11 patients for peripheral blood at day 0, 2 and 7 for single-cell analysis of basal level and signal-transduction responses to relevant myeloid growth factors (granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor, interleukin-3, Flt3L, stem cell factor, erythropoietin, CXCL-12) on 10 signaling molecules (CREB, STAT1/3/5, p38, Erk1/2, Akt, c-Cbl, ZAP70/Syk and rpS6). Pretreatment analysis by unsupervised clustering and principal component analysis divided the patients into three distinguishable signaling clusters (non-potentiated, potentiated basal and potentiated signaling). Signal-transduction pathways were modulated during therapy and patients moved between the clusters. Patients with multiple leukemic clones demonstrated distinct stimulation responses and therapy-induced modulation. Individual signaling profiles together with clinical and hematological information may be used to early identify AML patients in whom epigenetic and signal-transduction targeted therapy is beneficial

  1. Atração e desenvolvimento de Leptoglossus gonagra (Fabr. (Hemiptera: Coreidae em cultivares de abóbora e moranga

    Directory of Open Access Journals (Sweden)

    Baldin Edson Luiz Lopes

    2002-01-01

    Full Text Available As plantas da família Cucurbitaceae são seriamente prejudicadas pelo ataque de insetos, sendo que os danos ocorrem desde a germinação até a colheita e podem ser observados em todas as partes da planta. Dentre os insetos sugadores que atacam a abóbora (Cucurbita moschata e a moranga (C. maxima, as formas jovens e adultas do percevejo Leptoglossus gonagra (Fabr. (Hemiptera: Coreidae merecem destaque por sugarem a seiva das folhas, ramos e frutos novos, nos quais causam necroses, reduzindo a produção. Visando comparar a atratividade de plântulas de cultivares de abóbora e moranga a adultos deste percevejo e os efeitos desses materiais sobre a biologia de ninfas dessa espécie, realizaram-se ensaios sob condições de laboratório. Em teste de atratividade, o cultivar de abóbora BRA015113 destacou-se como o menos atrativo em relação ao cultivar de moranga Exposição, enquanto que o cultivar de abóbora BRA003531 foi o mais atrativo. Todos os cultivares provocaram 100% de mortalidade das ninfas, indicando a presença de componentes antibióticos, adversos ao desenvolvimento de L. gonagra.

  2. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 1.- anallsis cuantitativo.

    OpenAIRE

    Juana María Coha; Elsa Sevillano C.

    2014-01-01

    Se ha determinado, cuantitativamente, presencia de organismos Coliformes y Enterococos en el molusco Aulacomya ater "choro", como índice de contaminación entérica humana, en cada etapa de su preparación hasta "cebiche". Se han pracesado 1,152 especímenes de mercados de Lima y Callao. Los resultados reportan mayores promedios de contaminación para ambos grupos m'crobianos, en choros crudos (etapa a), de mercados ubicados en zonas de menor higiene y mayor población. La temperatura ambien...

  3. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 2.- análisis cualitativo.

    OpenAIRE

    Juana Coha; Elsa Sevillano C.

    2014-01-01

    En 64 muestras (1,152 especímenes) del molusco Aulacomya ater "choro" de los mercados de Lima y Callao, se aislaron especies más representativas de tres principales grupos bacterianos: Entéricos, Enterococos y además, Micrococos. El porcentaje elevado de Escherichia coli en choros crudos (etapa a) y "cebiche" (etapa c) reafirman, como en el Estudio Cuantitativo, contaminación fecal humana; en menor cuantía, especies de Enterocococos, únicamente en choros crudos. Es notable la desi...

  4. Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition) on Aulacomya ater (Molina, 1782) (Bivalvia: Mytilidae) as a Criteria for Effects of Organophosphate Pesticide Exposition

    OpenAIRE

    Eduardo Führer; Anny Rudolph; Claudio Espinoza; Rodrigo Díaz; Marisol Gajardo; Nuria Camaño

    2012-01-01

    The effect of residual concentrations of organophosphate pesticide chlorpyrifos (Lorsban 4E) on the activity of the acetylcholinesterase enzyme and oxygen : nitrogen ratio in the mussel Aulacomya ater was analyzed. Toxicity tests show a sensitivity to the pesticide in the bivalve estimated at 16 μg L-1 (LC50-96 hours). Concentrations between 0.2 and 1.61 μg L-1 were able to inhibit significantly the AChE activity, and concentrations between 0.8 and 1.61 μg L-1 stimulate ammonia excretion and ...

  5. Paleoambientes litorales durante el inicio de la trasgresión marina holocena en bahía Lapataia, canal Beagle, parque nacional Tierra del Fuego Littoral paleoenvironments during the beginning of the Holocene marine transgression in Lapataia Bay, Beagle Channel, National Park of Tierra del Fuego

    Directory of Open Access Journals (Sweden)

    Jorge Rabassa

    2009-12-01

    Full Text Available Los sitios Aserradero Lapataia 1 y 2 presentan depósitos limo-arcillosos portadores de valvas de moluscos: Mulinia edulis, Mytilus chilensis, Aulacomya atra y Yoldia sp. Además predominan los quistes de dinoflagelados, revestimientos de foraminíferos bentónicos y huevos de copépodos. Valvas de Mulinia edulis fueron datadas radiocarbónicamente en 8.094 ± 43 (AA74047 y 8.167 ± 43 (AA74048 a A.P. En Arroyo Baliza depósitos limo-arcillosos son portadores de Venus antiqua, Aulacomya atra, Mytilus chilensis, entre otros. La microflora está dominada por dinoquistes protoperidinioideos, acritarcos y restos de copépodos. Se sugiere ambientes marino-marginales, con baja a moderada salinidad, y altas concentraciones de nutrientes en las aguas superficiales. La datación radiocarbónica sobre Venus antiqua en Arroyo Baliza indica 2.844 ± 34 a A.P. (AA74046. Aserradero Lapataia confirma las edades más antiguas conocidas para la fase estuárica de la transgresión holocena en el canal Beagle. Arroyo Baliza aporta nueva evidencia de la fase regresiva en este canal durante el Holoceno tardío.The Aserradero Lapataia 1 and 2 sites present clayey silty sediments including mollusk shell; Mulinia edulis, Mytilus chilensis, Aulacomya atra and Yoldia sp. Besides, dinoflagelate cysts, covers of benthonic foraminifera and copepod eggs are dominant. The microflora is represented by sporomorphs and fresh to salty water microplancton. Radiocarbon dates on Mulinia edulis shells yielded ages of 8094 ± 43 (AA74047 and 8167 ± 43 (AA74048 yr B.P. At Arroyo Baliza, clayey silts were found including Venus antiqua, Aulacomya atra, Mytilus chilensis, among others, accompanied by acritarchs and remnants of copepods. This association suggests marginal marine environments, with low to moderate salinity, and high nutrient concentration in the surface waters. Radiocarbon dating on Venus antiqua shells yielded 2844 ± 34 yr B.P. (AA74046. Marine deposits of the Aserradero

  6. Localized Th1-, Th2-,and inflamation-associated hepatic and pulmonary immune responses in Ascaris-infected swine are increased by retinoic acid.

    Science.gov (United States)

    Pigs infected with Ascaris suum were treated with all-trans retinoic acid (ATRA) on d–1, d+1, d+3 of infection. Control or infected pigs were given 100 (LD-ATRA) or 1,000 (HD-ATRA) µg/kg ATRA in corn oil, or corn oil alone, and sacrificed at 7 and 14 days after inoculation (DAI) with infective eggs...

  7. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 1.- anallsis cuantitativo.

    Directory of Open Access Journals (Sweden)

    Juana María Coha

    2014-06-01

    Full Text Available Se ha determinado, cuantitativamente, presencia de organismos Coliformes y Enterococos en el molusco Aulacomya ater "choro", como índice de contaminación entérica humana, en cada etapa de su preparación hasta "cebiche". Se han pracesado 1,152 especímenes de mercados de Lima y Callao. Los resultados reportan mayores promedios de contaminación para ambos grupos m'crobianos, en choros crudos (etapa a, de mercados ubicados en zonas de menor higiene y mayor población. La temperatura ambiental en meses de verano, demuestra gran incremento de esta microflora. La temperatura de cocción de la fracción previa al "cebiche" (etapa b, efímina totalmente los contaminantes, reapareciendo Coliformes en éste (etapa el, por los aditivos. El jugo de limón no actuó como bactericida eficaz.

  8. Dinámica de la microflora contaminante en el molusco Aulacomya ater choro crudo y procesado en cebiche: 2.- análisis cualitativo.

    Directory of Open Access Journals (Sweden)

    Juana Coha

    2014-06-01

    Full Text Available En 64 muestras (1,152 especímenes del molusco Aulacomya ater "choro" de los mercados de Lima y Callao, se aislaron especies más representativas de tres principales grupos bacterianos: Entéricos, Enterococos y además, Micrococos. El porcentaje elevado de Escherichia coli en choros crudos (etapa a y "cebiche" (etapa c reafirman, como en el Estudio Cuantitativo, contaminación fecal humana; en menor cuantía, especies de Enterocococos, únicamente en choros crudos. Es notable la desigualdad de frecuencia de E. coli, Streptococcus del grupo D de Lancenfield y Staphylococcus aureus entre las etapas a y e; en el que este último microorganismo se manifiesta con mayor densidad en la etapa de "cebiche", como consecuencia de la manipulación de los aditivos.

  9. Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition) on Aulacomya ater (Molina, 1782) (Bivalvia: Mytilidae) as a Criteria for Effects of Organophosphate Pesticide Exposition.

    Science.gov (United States)

    Führer, Eduardo; Rudolph, Anny; Espinoza, Claudio; Díaz, Rodrigo; Gajardo, Marisol; Camaño, Nuria

    2012-01-01

    The effect of residual concentrations of organophosphate pesticide chlorpyrifos (Lorsban 4E) on the activity of the acetylcholinesterase enzyme and oxygen : nitrogen ratio in the mussel Aulacomya ater was analyzed. Toxicity tests show a sensitivity to the pesticide in the bivalve estimated at 16 μg L(-1) (LC(50-96 hours)). Concentrations between 0.2 and 1.61 μg L(-1) were able to inhibit significantly the AChE activity, and concentrations between 0.8 and 1.61 μg L(-1) stimulate ammonia excretion and decrease oxygen : ammonia-N (O : N) ratio, with respect to the control group. A. ater proved to be a species sensitive to pesticide exposure and easy to handle in lab conditions. Thus, it is recommended as a bioindicator for use in programs of environmental alertness in the Eastern South Pacific coastal zone. PMID:22619673

  10. Integrated Use of Biomarkers (O : N Ratio and Acetylcholinesterase Inhibition on Aulacomya ater (Molina, 1782 (Bivalvia: Mytilidae as a Criteria for Effects of Organophosphate Pesticide Exposition

    Directory of Open Access Journals (Sweden)

    Eduardo Führer

    2012-01-01

    Full Text Available The effect of residual concentrations of organophosphate pesticide chlorpyrifos (Lorsban 4E on the activity of the acetylcholinesterase enzyme and oxygen : nitrogen ratio in the mussel Aulacomya ater was analyzed. Toxicity tests show a sensitivity to the pesticide in the bivalve estimated at 16 μg L-1 (LC50-96 hours. Concentrations between 0.2 and 1.61 μg L-1 were able to inhibit significantly the AChE activity, and concentrations between 0.8 and 1.61 μg L-1 stimulate ammonia excretion and decrease oxygen : ammonia-N (O : N ratio, with respect to the control group. A. ater proved to be a species sensitive to pesticide exposure and easy to handle in lab conditions. Thus, it is recommended as a bioindicator for use in programs of environmental alertness in the Eastern South Pacific coastal zone.

  11. Paleoambientes litorales durante el inicio de la trasgresión marina holocena en bahía Lapataia, canal Beagle, parque nacional Tierra del Fuego

    Directory of Open Access Journals (Sweden)

    Jorge Rabassa

    2009-12-01

    Full Text Available Los sitios Aserradero Lapataia 1 y 2 presentan depósitos limo-arcillosos portadores de valvas de moluscos: Mulinia edulis, Mytilus chilensis, Aulacomya atra y Yoldia sp. Además predominan los quistes de dinoflagelados, revestimientos de foraminíferos bentónicos y huevos de copépodos. Valvas de Mulinia edulis fueron datadas radiocarbónicamente en 8.094 ± 43 (AA74047 y 8.167 ± 43 (AA74048 a A.P. En Arroyo Baliza depósitos limo-arcillosos son portadores de Venus antiqua, Aulacomya atra, Mytilus chilensis, entre otros. La microflora está dominada por dinoquistes protoperidinioideos, acritarcos y restos de copépodos. Se sugiere ambientes marino-marginales, con baja a moderada salinidad, y altas concentraciones de nutrientes en las aguas superficiales. La datación radiocarbónica sobre Venus antiqua en Arroyo Baliza indica 2.844 ± 34 a A.P. (AA74046. Aserradero Lapataia confirma las edades más antiguas conocidas para la fase estuárica de la transgresión holocena en el canal Beagle. Arroyo Baliza aporta nueva evidencia de la fase regresiva en este canal durante el Holoceno tardío.

  12. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity

    OpenAIRE

    Kane, Maureen A.; Folias, Alexandra E.; Wang, Chao; Napoli, Joseph L.

    2010-01-01

    All-trans-retinoic acid (atRA) supports embryonic development, central nervous system function, and the immune response. atRA initiates neurogenesis and dendritic growth in the hippocampus and is required for spatial memory; superphysiological atRA inhibits neurogenesis, causes teratology and/or embryo toxicity, and alters cognitive function and behavior. Because abnormal atRA shares pathological conditions with alcoholism, inhibition of retinol (vitamin A) activation into atRA has been credi...

  13. The adhesive protein of Choromytilus chorus (Molina, 1782) and Aulacomya ater (Molina, 1782): a proline-rich and a glycine-rich polyphenolic protein.

    Science.gov (United States)

    Burzio, L A; Saéz, C; Pardo, J; Waite, J H; Burzio, L O

    2000-06-15

    The adhesive polyphenolic proteins from Aulacomya ater and Choromytilus chorus with apparent molecular masses of 135000 and 105000, respectively, were digested with trypsin and the peptides produced resolved by reversed phase liquid chromatography. About 5 and 12 major peptides were obtained from the protein of A. ater and C. chorus, respectively. The major peptides were purified by reverse-phase chromatography and the amino acid sequence indicates that both polyphenolic proteins consisted of repeated sequence motifs in their primary structure. The major peptides of A. ater contain seven amino acids corresponding to the consensus sequence AGYGGXK, whereas the tyrosine was always found as 3, 4-dihydroxyphenylalanine (Dopa), the X residue in position 6 was either valine, leucine or isoleucine, and the carboxy terminal was either lysine or hydroxylysine. On the other hand, the major peptides of C. chorus ranged in size from 6 to 21 amino acids and the majority correspond to the consensus sequence AKPSKYPTGYKPPVK. Both proteins differ markedly in the sequence of their tryptic peptides, but they share the common characteristics of other adhesive proteins in having a tandem sequence repeat in their primary structure. PMID:11004549

  14. Evidence for absorption of kelp detritus by the ribbed mussel Aulacomya ater using a new /sup 51/Cr-labelled microsphere technique

    Energy Technology Data Exchange (ETDEWEB)

    Stuart, V.; Field, J.G.; Newell, R.C.

    1983-09-15

    A modification of the /sup 51/Cr:/sup 14/C twin-labelling technique is described in which the food source is labelled with /sup 14/C but the /sup 51/Cr is enclosed in a polymeric resin membrane and presented as microspheres of a similar diameter to the food particles. This eliminates the major uptake of /sup 51/Cr which is transferred to the ctenidia and palps of the suspension-feeding mussel Aulacomya ater (Molina) from detritus labelled with /sup 51/Cr. The results suggest that although bacterial cultures based on isolates of kelp bacteria can be absorbed with an efficiency of 67 to 70%, the debris itself is also absorbed with an efficiency of approximately 50%. The kelp debris, which forms an important component of the particulate matter potentially available for consumers, may thus represent an important source of carbon for the filter feeding community adjacent to kelp beds. In contrast to the results obtained in other studies with artificial food sources, the data for kelp debris suggest that A. ater is able to maintain a positive scope for grwoth at the concentrations of suspended organic matter which occur under natural conditions in the kelp bed environment.

  15. Evidence for absorption of kelp detritus by the ribbed mussel Aulacomya ater using a new 51Cr-labelled microsphere technique

    International Nuclear Information System (INIS)

    A modification of the 51Cr:14C twin-labelling technique is described in which the food source is labelled with 14C but the 51Cr is enclosed in a polymeric resin membrane and presented as microspheres of a similar diameter to the food particles. This eliminates the major uptake of 51Cr which is transferred to the ctenidia and palps of the suspension-feeding mussel Aulacomya ater (Molina) from detritus labelled with 51Cr. The results suggest that althoug bacterial cultures based on isolates of kelp bacteria can be absorbed with an efficiency of 67 to 70%, the debris itself is also absorbed with an efficiency of approximately 50%. The kelp debris, which forms an important component of the particulate matter potentially available for consumers, may thus represent an important source of carbon for the filter feeding community adjacent to kelp beds. In contrast to the results obtained in other studies with artificial food sources, the data for kelp debris suggest that A. ater is able to maintain a positive scope for grwoth at the concentrations of suspended organic matter which occur under natural conditions in the kelp bed environment. (orig.)

  16. El regreso a la escuela, Sigamos adelante: Lo que significa para las familias americanas "No dejar atras a ningun nino" (Back to School, Moving Forward: What "No Child Left Behind" Means for America's Families).

    Science.gov (United States)

    Department of Education, Washington, DC. Office of the Secretary.

    This pamphlet for parents Spanish presents the components of the "No Child Left Behind" policy of the George W. Bush administration. Prefaced with remarks by President Bush and Secretary of Education Rod Paige, the pamphlet discusses the importance of high academic standards and provides guidance for parents in interpreting test scores. The…

  17. Attraction of Neomegalotomus parvus (Westwood)(Heteroptera: alydidae) to cow urine and ammonia Atração de Neomegalotomus parvus (Westwood) (Heteroptera: alydidae) por urina de vaca e amônia

    OpenAIRE

    Jovenil José da Silva; Iara Cintra de Arruda-Gatti; Adriana Yatie Mikami; Aline Pissinati; Antônio Ricardo Panizzi; Mauricio Ursi Ventura

    2010-01-01

    The alydid bug parvus (Westwood) is not easily detected in the field and the discovery of attractants may be a suitable way to monitor this species. The attraction of N. parvus to traps (transparent, transparent green and yellow) baited with cow urine and ammonia was studied in two field trials. Traps were placed near a terrace with pigeon pea plants (Cajanus cajan L.). Tap water, NaCl 10% aqueous solution (w/v), cow urine, and ammonia (NH4OH 1% aqueous solution) were tested as attractants in...

  18. Attraction of Astylus variegatus (Germ. (Coleoptera: Melyridae by volatile floral attractants Atração de Astylus variegatus (Germ. (Coleoptera: Melyridae por atraentes florais voláteis

    Directory of Open Access Journals (Sweden)

    Maurício Ursi Ventura

    2007-06-01

    Full Text Available The beetle Astylus variegatus (Germ. (Coleoptera: Melyridae is frequently found in flowers feeding on pollen. Responses of A. variegatus to volatile floral attractants were studied in common beans (Phaseolus vulgaris L. fields. Traps originally designed to capture Diabrotica speciosa (Germ. (Coleoptera: Chrysomelidae, consisted of plastic bottles (2 L with 150 holes (5-mm diameter yellow gold painted and containing inside a plastic strip (3.5 ´ 25 cm with Lagenaria vulgaris (L. powder (0.28% B cucurbitacin - feeding stimulant and arrestant for diabroticites sprayed with carbaril insecticide. Treatments consisted of 1,4-dimethoxybenzene (one or two dispensers per trap, 1,4-dimethoxybenze + indole, 1,4-dimethoxybenzene + cinnameldehyde and control. Volatile average release rates (over ten days was approximately 32 mg day-1 per dispenser under laboratory conditions. 1,4-dimethoxybenzene-lured traps caught significantly more beetles than the control, three and seven days after trap setting. Ten days after the onset of the experiment, there were no differences in number of beetles caught by treatments. Captures were higher in the 1,4-dimethoxybenzene + cinnamaldehyde treatment than in 1,4-dimethoxybenzene only in the first assessment. Adding indole to 1,4-dimethoxybenzene did not improve beetle captures.O besouro Astylus variegatus (Germ. (Coleoptera: Melyridae é freqüentemente encontrado em flores onde se alimenta de pólen. Respostas de A. variegatus a atraentes voláteis florais foram estudadas em campos de feijão, Phaseolus vulgaris L. Armadilhas, originalmente desenvolvidas para capturar Diabrotica speciosa (Germ. (Coleoptera: Chrysomelidae, consistiram de garrafas plástica (2 L com 150 perfurações (5 mm de diâmetro pintadas com tinta amarelo ouro contendo no seu interior uma fita plástica (3,5 ´ 25,0 cm com pó seco de frutos de Lagenaria vulgaris (L. (0,28% de cucurbitacina B estimulante alimentar e arrestante para diabroticíneos pulverizados com inseticida carbaril. Os tratamentos foram: 1,4-dimetoxibenzeno (um ou dois liberadores por armadilha; 1,4-dimetoxibenzeno + indol; 1,4-dimetoxibenzeno + cinamaldeído e testemunha (sem volátil. As taxas de liberação dos semioquímicos (por 10 dias foram de aproximadamente 32 mg dia-1 por liberador em condições de laboratório. Armadilhas iscadas com 1,4-dimetoxibenzeno capturaram mais insetos que a testemunha, três e sete dias após instalação das armadilhas. Dez dias após o início dos experimentos, não foram verificadas diferenças entre os tratamentos, no número de besouros capturados. Capturas foram maiores no tratamento com 1,4-dimetoxibenzeno + cinamaldeído do que no 1,4-dimetoxibenzeno sozinho na primeira avaliação. Adição do indole ao 1,4-dimetoxibenzeno não aumentou as capturas.

  19. Sweet’s syndrome during the treatment of acute promyelocytic leukemia with all-trans retinoic acid

    OpenAIRE

    Park, Chi Jun; Bae, Young Deok; Choi, Ji Yong; Heo, Pil Seog; Lee, Keun Seok; Park, Young Suk; Lee, Jung-Ae

    2001-01-01

    All-trans retinoic acid (ATRA) is the standard induction treatment for acute promyelocytic leukemia (APL). Quite many ATRA-related side effects, including retinoic acid syndrome, were reported. So far, it has rarely been reported that Sweet’s syndrome, characterized by fever, neutrophilia, painful erythematous cutaneous plaques, dense dermal infiltrates of mature neutrophils and rapid response to steroid therapy, is associated with ATRA. In the case that Sweet’s syndrome associated with ATRA ...

  20. Ethanol Effects On Physiological Retinoic Acid Levels

    OpenAIRE

    Napoli, Joseph L.

    2011-01-01

    All-trans-retinoic acid (atRA) serves essential functions during embryogenesis and throughout post-natal vertebrate life. Insufficient or excess atRA causes teratogenic and/or toxic effects in the developing embryo: interference with atRA biosynthesis or signaling likely underlies some forms of cancer. Many symptoms of vitamin A (atRA precursor) deficiency and/or toxicity overlap with those of another pleiotropic agent—ethanol. These overlapping symptoms have prompted research to understand w...

  1. RDH10 is the Primary Enzyme Responsible for the First Step of Embryonic Vitamin A Metabolism and Retinoic Acid Synthesis

    OpenAIRE

    Farjo, Krysten M.; Moiseyev, Gennadiy; Nikolaeva, Olga; Sandell, Lisa L.; Trainor, Paul A; Ma, Jian-xing

    2011-01-01

    Retinoic acid (atRA) signaling is essential for regulating embryonic development, and atRA levels must be tightly controlled in order to prevent congenital abnormalities and fetal death which can result from both excessive and insufficient atRA signaling. Cellular enzymes synthesize atRA from Vitamin A, which is obtained from dietary sources. Embryos express multiple enzymes that are biochemically capable of catalyzing the initial step of Vitamin A oxidation, but the precise contribution of t...

  2. Chmp 1A is a mediator of the anti-proliferative effects of All-trans Retinoic Acid in human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Nguyen Hanh

    2009-02-01

    Full Text Available Abstract Background We recently have shown that Charged multivesicular protein/Chromatin modifying protein1A (Chmp1A functions as a tumor suppressor in human pancreatic tumor cells. Pancreatic cancer has the worst prognosis of all cancers with a dismal 5-year survival rate. Preclinical studies using ATRA for treating human pancreatic cancer suggest this compound might be useful for treatment of pancreatic cancer patients. However, the molecular mechanism by which ATRA inhibits growth of pancreatic cancer cells is not clear. The objective of our study was to investigate whether Chmp1A is involved in ATRA-mediated growth inhibition of human pancreatic tumor cells. Results We performed microarray studies using HEK 293T cells and discovered that Chmp1A positively regulated Cellular retinol-binding protein 1 (CRBP-1. CRBP-1 is a key regulator of All-trans retinoic acid (ATRA through ATRA metabolism and nuclear localization. Since our microarray data indicates a potential involvement of Chmp1A in ATRA signaling, we tested this hypothesis by treating pancreatic tumor cells with ATRA in vitro. In the ATRA-responsive cell lines, ATRA significantly increased the protein expression of Chmp1A, CRBP-1, P53 and phospho-P53 at serine 15 and 37 position. We found that knockdown of Chmp1A via shRNA abolished the ATRA-mediated growth inhibition of PanC-1 cells. Also, Chmp1A silencing diminished the increase of Chmp1A, P53 and phospho-P53 protein expression induced by ATRA. In the ATRA non-responsive cells, ATRA did not have any effect on the protein level of Chmp1A and P53. Chmp1A over-expression, however, induced growth inhibition of ATRA non-responsive cells, which was accompanied by an increase of Chmp1A, P53 and phospho-P53. Interestingly, in ATRA responsive cells Chmp1A is localized to the nucleus, which became robust upon ATRA treatment. In the ATRA-non-responsive cells, Chmp1A was mainly translocated to the plasma membrane upon ATRA treatment. Conclusion

  3. Apoptosis of Human Pancreatic Carcinoma Cells Induced By All-Trans Retinoic Acid and Interferon

    Institute of Scientific and Technical Information of China (English)

    Xiao-hua Wang; Yuan-qin Yin; Ping Ma; Cheng-guang Sui; Fan-dong Meng; Jiang You-hong

    2009-01-01

    Objective: To investigate the apoptosis of human pancreatic carcinoma PC3 cells induced by the combination of all-trans retinoic acid (ATRA) with interferon alpha (IFN-α). Methods: PC3 cells were treated with ATRA and IFN-α. The inhibitory rate of PC3 cell proliferation was detected using MTT method. Cellular apoptosis was determined with flow cytometry. The percentage of PC3 cell apoptosis was assayed using TUNEL methods. Results: ATRA and IFN-α could inhibit cellular proliferation and induces cellular apoptosis of PC3 cells. The inhibitory effect was stronger when the ATRA and IFN-α were combined as a therapy. Conclusion: ATRA inhibits the proliferation of PC3 cells and induce the apoptosis of PC3 cells. The combination of IFN-α with ATRA may enhance these effects on PC3 cells.

  4. Pharmacogenomic analysis of retinoic-acid induced dyslipidemia in congenic rat model

    OpenAIRE

    Krupková, Michaela; Liška, František; Šedová, Lucie; Křenová, Drahomíra; Křen, Vladimír; Šeda, Ondřej

    2014-01-01

    Background All-trans retinoic acid (ATRA, tretinoin) is a vitamin A derivative commonly used in the treatment of diverse conditions ranging from cancer to acne. In a fraction of predisposed individuals, the administration of ATRA is accompanied by variety of adverse metabolic effects, particularly by the induction of hyperlipidemia. We have previously derived a minimal congenic SHR.PD-(D8Rat42-D8Arb23)/Cub (SHR-Lx) strain sensitive to ATRA-induced increase of triacylglycerols and cholesterol ...

  5. PEG-PLA diblock copolymer micelle-like nanoparticles as all-trans-retinoic acid carrier: in vitro and in vivo characterizations

    Science.gov (United States)

    Li, Yuan; Qi, Xian Rong; Maitani, Yoshie; Nagai, Tsuneji

    2009-02-01

    The purpose of this study was to characterize the properties in vitro, i.e. release, degradation, hemolytic potential and anticancer activity, and in vivo disposition of all-trans-retinoic acid (ATRA) in rats after administration of ATRA-loaded micelle-like nanoparticles. The amphiphilic block copolymers consisted of a micellar shell-forming mPEG block and a core-forming PLA block. The mPEG-PLA nanoparticles prepared by an acetone volatilization dialysis procedure were identified as having core-shell structure by 1H NMR spectroscopy. Critical association concentration, drug contents, loading efficiency, particle size and ξ potential were evaluated. The release of ATRA from the nanoparticles and the degradation of PLA were found to be mostly associated with the compositions of the nanoparticles. ATRA release was faster at smaller molecular weight of copolymer and lower drug contents. In vitro, the incorporation of ATRA in mPEG-PLA nanoparticles reduced the hemolytic potential of ATRA. Furthermore, anticancer activity of ATRA against HepG2 cell was increased by encapsulation, which showed an enhancement of tumor treatment of ATRA. In vivo, after intravenous injection to rats, the levels of ATRA in the blood stream and the bioavailability were higher for ATRA-loaded mPEG-PLA nanoparticles than those for ATRA solution. In conclusion, the structure of the mPEG-PLA diblock copolymer could be modulated to fit the demand of in vitro and in vivo characterizations of nanoparticles. The mPEG-PLA nanoparticles' loading ATRA have a promising future for injection administration.

  6. Effect of Retinoic Acid in a Mouse Model of Allergic Rhinitis

    OpenAIRE

    Son, Hye-Lim; Park, Hyang-Rim; Park, Yong-Jin; Kim, Soo-Whan

    2015-01-01

    Purpose All-trans retinoic acid (ATRA) modulates immune responses by affecting T cells. Several studies have revealed that allergic inflammation of the lower airways is negatively associated with the vitamin A concentration. However, the role of ATRA in allergic inflammation of the upper airways is unclear. We investigated the effects of ATRA in an allergic rhinitis mouse model. Methods BALB/c mice except control groups (CON group) were sensitized with and challenged intra-nasally with Dermat...

  7. Promotive Effect of Minoxidil Combined with All-trans Retinoic Acid (tretinoin) on Human Hair Growth in Vitro

    OpenAIRE

    Kwon, Oh Sang; Pyo, Hyun Keol; Oh, Youn Jin; Han, Ji Hyun; Lee, Se Rah; Chung, Jin Ho; Eun, Hee Chul; Kim, Kyu Han

    2007-01-01

    Minoxidil induces hair growth in male pattern baldness and prolongs the anagen phase. All-trans retinoic acid (ATRA) has been reported to act synergistically with minoxidil in vivo: they can enhance more dense hair regrowth than either compound alone. We evaluated the effect of minoxidil combined with ATRA on hair growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth was studied in hair follicle organ culture. In cultured human dermal papilla cells (DPCs) and normal...

  8. Retinoic acid metabolism blocking agents (RAMBAs) for treatment of cancer and dermatological diseases.

    Science.gov (United States)

    Njar, Vincent C O; Gediya, Lalji; Purushottamachar, Puranik; Chopra, Pankaj; Vasaitis, Tadas Sean; Khandelwal, Aakanksha; Mehta, Jhalak; Huynh, Carlic; Belosay, Aashvini; Patel, Jyoti

    2006-07-01

    The naturally occurring retinoids and their synthetic analogs play a key role in differentiation, proliferation, and apoptosis, and their use/potential in oncology, dermatology and a variety of diseases are well documented. This review focuses on the role of all-trans-retinoic acid (ATRA), the principal endogenous metabolite of vitamin A (retinol) and its metabolism in oncology and dermatology. ATRA has been used successfully in differentiated therapy of acute promyelocytic leukemia, skin cancer, Kaposi's sarcoma, and cutaneous T-cell lymphoma, and also in the treatment of acne and psoriasis. However, its usefulness is limited by the rapid emergence of acquired ATRA resistance involving multifactoral mechanisms. A key mechanism of resistance involves ATRA-induced catabolism of ATRA. Thus, a novel strategy to overcome the limitation associated with exogenous ATRA therapy has been to modulate and/or increase the levels of endogenous ATRA by inhibiting the cytochrome P450-dependent ATRA-4-hydroxylase enzymes (particularly CYP26s) responsible for ATRA metabolism. These inhibitors are also referred to as retinoic acid metabolism blocking agents (RAMBAs). This review highlights development in the design, synthesis, and evaluation of RAMBAs. Major emphasis is given to liarozole, the most studied and only RAMBA in clinical use and also the new RAMBAs in development and with clinical potential. PMID:16530416

  9. Population structure, growth and production of a recent brachiopod from the Chilean fjord region

    KAUST Repository

    Baumgarten, Sebastian

    2013-12-04

    Magellania venosa, the largest recent brachiopod, occurs in clusters and banks in population densities of up to 416 ind m-2 in Comau Fjord, Northern Chilean fjord region. Below 15 m, it co-occurs with the mytilid Aulacomya atra and it dominates the benthic community below 20 m. To determine the question of why M. venosa is a successful competitor, the in situ growth rate of the brachiopod was studied and its overall growth performance compared with that of other brachiopods and mussels. The growth in length was measured between February 2011 and March 2012 after mechanical tagging and calcein staining. Settlement and juvenile growth were determined from recruitment tiles installed in 2009 and from subsequent photocensus. Growth of M. venosa is best described by the general von Bertalanffy growth function, with a maximum shell length (L∞) of 71.53 mm and a Brody growth constant (K) of 0.336 year-1. The overall growth performance (OGP index = 5.1) is the highest recorded for a rynchonelliform brachiopod and in the range of that for Mytilus chilensis (4.8-5.27), but lower than that of A. atra (5.74). The maximal individual production (PInd) is 0.29 g AFDM ind-1 year-1 at 42 mm shell length and annual production ranges from 1.28 to 89.25 g AFDM year-1 m-2 (1-57% of that of A. atra in the respective fjords). The high shell growth rate of M. venosa, together with its high overall growth performance may explain the locally high population density of this brachiopod in Comau Fjord. However, the production per biomass of the population (P/B--ratio) is low (0.535) and M. venosa may play only a minor role in the food chain. Settling dynamics indicates that M. venosa is a pioneer species with low juvenile mortality. The coexistence of the brachiopod and bivalve suggests that brachiopod survival is affected by neither the presence of potential brachiopod predators nor that of space competitors (i.e. mytilids).

  10. The Effects of Quercetin and Retinoic acid on Skeletal System of Rat Embryos in Prenatal Period

    Directory of Open Access Journals (Sweden)

    Nahid Gohari-Behbahani

    2014-12-01

    Full Text Available Background: Prenatal rat embryo exposure to retinoid induces some malformations in various organs, the most active and teratogenic metablolite is all-trans-retinoic acid (atRA. The teratogenic effects of some drugs can be prevented by the application of antioxidant drugs and stimulation of the maternal immune system. Also, quercetin, a naturally occurring flavonoid has excellent antioxidant properties. Therefore, in this study, the prophylactic effect of quercetin on teratogenic effects of atRA was evaluated. Materials and Methods: In this experimental study, 40 pregnant rats were divided into 7 groups. Control group received normal saline and test groups received dimethylsulfoxide (DMSO, quercetin (75 mg/kg, quercetin (200 mg/kg, atRA (25 mg/kg, atRA (25 mg/kg plus quercetin (75 mg/kg and atRA (25 mg/kg plus quercetin (200 mg/kg, intraperitoneally at 8-10th days of gestation. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Results: Cleft palate, exencephaly and spina bifida incidence were 30.76%, 61.53% and 30.76% range in group which received only atRA. Cleft palate, exencephaly and spina bifida incidence were 11.11%, 16.66% and 5.55% in group which received atRA plus quercetin (75 mg/kg. However, cleft palate, exencephaly and spina bifida incidence were 10.52%, 10.52% and 0% in group which received atRA plus quercetin (200 mg/kg. The means of weight and length of fetuses from rat that received atRA plus quercetin (75 mg/kg were significantly greater than those received only atRA. Conclusion: It is concluded that quercetin decreased teratogenicity induced by atRA, but this subject needs more detailed evaluation.

  11. Effect of differents baits as attractant for blowflies (diptera at Valonguinho, Universidade Federal Fluminense, Niterói, RJ, Brazil Efeito de diferentes iscas na atração de califorídeos (diptera no campus do Valonguinho, Universidade Federal Fluminense, Niterói, RJ, Brasil

    Directory of Open Access Journals (Sweden)

    José M. D'almeida

    2007-12-01

    Full Text Available It was carried out a survey of blowflies in a área of the Campus (Valonguinho of the Universidade Federal Fluminense, Niterói, Rio de Janeiro. The collections were performed with traps, using baits of fish (sardine, bovine liver, shrimps and banana. Were collected 6015 flies, Chrysomya megacephala and Lucilia eximia were the most frequent (50.55% and 21.52%, respectively. The flies were more abundant in February and March and the most attractive bait was fish (38.32%.Foi realizado um estudo sobre califorideos no Campus do Valonguinho, Universidade Federal Fluminense. A pesquisa foi efetuada de dezembro de 2003 a novembro de 2004, com coletas feitas com armadilhas utilizando iscas à base de peixe (sardinha, fígado bovino, camarão e banana. Foram coletados 6015 califorideos, Chrysomya megacephala e Lucilia eximia foram as mais freqüentes (50,55% e 21, 52%, respectivamente. A isca mais atrativa foi peixe (38,32% com picos populacionais em fevereiro e março.

  12. Protein phosphatase 2A associates with Rb2/p130 and mediates retinoic acid-induced growth suppression of ovarian carcinoma cells

    DEFF Research Database (Denmark)

    Vuocolo, Scott; Purev, Enkhtsetseg; Zhang, Dongmei;

    2003-01-01

    Levels of Rb2/p130 protein are increased 5-10-fold following all-trans-retinoic acid (ATRA) treatment of the retinoid-sensitive ovarian adenocarcinoma cell line CAOV3, but not the retinoid-resistant adenocarcinoma cell line SKOV3. We found that this increase in Rb2/p130 protein levels in ATRA...

  13. The histone demethylase PHF8 governs retinoic acid response in acute promyelocytic leukemia

    DEFF Research Database (Denmark)

    Arteaga, Maria Francisca; Mikesch, Jan-Henrik; Qiu, Jihui;

    2013-01-01

    While all-trans retinoic acid (ATRA) treatment in acute promyelocytic leukemia (APL) has been the paradigm of targeted therapy for oncogenic transcription factors, the underlying mechanisms remain largely unknown, and a significant number of patients still relapse and become ATRA resistant. We...

  14. Catalase Induced by All-Trans Retinoic Acid Is Involved in Antiproliferation of 36B10 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Woo Yoon [Chungbuk National University College of Medicine, Cheongju (Korea, Republic of); Yu, Jae Ran [Konkuk University College of Medicine, Chungju (Korea, Republic of)

    2010-11-15

    All-trans retinoic acid (ATRA) has antiproliferative effects against brain tumor cells. Recently, ATRA has been reported to induce catalase. We investigated whether catalase induction by ATRA is associated with its antiproliferative effects. 36B10 cells were exposed to 0-50{mu}M ATRA for 24 or 48 hours and mRNA, protein, and activity of catalase were measured. Reactive oxygen species (ROS) were measured using 2',7'-dichlorofluorescin diacetate. A clonogenic assay was used to confirm the cytotoxic effect. The mRNA, protein, and activity of catalase were found to increase in a concentration- and incubation- time-dependent manner. The increase in catalase activity induced by ATRA was decreased by the addition of 3-amino-1,2,4-triazole (ATZ). ROS was also increased with ATRA and decreased by the addition of ATZ. The decrease in cell survival induced by ATRA was partly rescued by ATZ. Catalase induction by ATRA is involved in ROS overproduction and thus inhibits the proliferation of 36B10 cells.

  15. Acute effects of all-trans-retinoic acid in ischemic injury

    Science.gov (United States)

    All-trans-retinoic acid (ATRA) is a vitamin A derivative that is important in neuronal patterning, survival, and neurite outgrowth. We investigated the relatively acute effects of ATRA (100 nM and 1 µM) on cell swelling in ischemic injury and on key features hypothesized to contribute to cell swelli...

  16. In vitro induction and differentiation of umbilical cord mesenchymal stem cells into neuron-like cells by alltrans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Wei; Jin; Yao-Peng; Xu; An-Huai; Yang; Yi-Qiao; Xing

    2015-01-01

    AIM: To determine the optimal concentration for inducing the differentiation of human umbilical cord-derived mesenchymal stem cells(h UC-MSCs) into neuron-like cells, although it is understood that all-trans retinoic acid(ATRA) regulates cell proliferation in the nervous system by modulating the balance between mitosis and apoptosis.METHODS: The abilities of ATRA to promote apoptosis as well as neural differentiation were assessed in cultured h UC-MSCs by morphological observation, MTT assay, annexin V-FITC/PI flow cytometry and immunocytochemistry.RESULTS: The data showed that low concentrations of ATRA(0.5 μmol, 0.25 μmol) had no effect on the number of cells. However, treatment with 1.0 μmol or 2.0 μmol ATRA induced a 24.16% and 52.67% reduction in cell number, respectively, compared with vehicle-treated cultures. Further, 4.0 μmol ATRA had a potent effect on cell number, with almost no adherent cells recovered after 24 h. We further showed that 0.5 μmol ATRA caused these cells to express characteristic markers of neuronal progenitor cells.CONCLUSION: Taken together, we conclude that ATRA has a dose-dependent influence on the neural differentiation and apoptosis of h UC-MSCs. These findings have implications on the use of ATRA-differentiated h UC-MSCs for the study of neural degeneration diseases.

  17. Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Jin Man Kim; Sang Wook Kang; Su-Mi Shin; Duck Su Kim; Kyong-Kyu Choi; Eun-Cheol Kim; Sun-Young Kim

    2014-01-01

    All-trans retinoic acid (ATRA) inhibits matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fibroblasts, skin fibroblasts, bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells (HDPCs). The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and-9 in HDPCs. The productions and messenger RNA (mRNA) expressions of MMP-2 and-9 were accessed by gelatin zymography and real-time polymerase chain reaction (PCR), respectively. ATRA was found to decrease MMP-2 level in a dose-dependent manner. Significant reduction in MMP-2 mRNA expression was also observed in HDPCs treated with 25 mmol?L21 ATRA. However, HDPCs treated with ATRA had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions. Taken together, ATRA had an inhibitory effect on MMP-2 expression in HDPCs, which suggests that ATRA could be a candidate as a medicament which could control the inflammation of pulp tissue in vital pulp therapy and regenerative endodontics.

  18. The Achilles tendon resting angle as an indirect measure of Achilles tendon length following rupture, repair, and rehabilitation

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    Michael R. Carmont

    2015-04-01

    Conclusion: The ATRA increases following injury, is reduced by surgery, and then increases again during initial rehabilitation. The angle also correlates with patient-reported symptoms early in the rehabilitation phase and with heel-rise height after 1 year. The ATRA might be considered a simple and effective means to evaluate Achilles tendon function 1 year after the rupture.

  19. EXPERIMENTAL STUDY OF THE DIFFERENTIATION HPV16 SUBGENES-IMMORTALIZED HUMAN ENDOCERVICAL CELLS INDUCED BY ALL-TRANS-RETINOIC ACID

    Institute of Scientific and Technical Information of China (English)

    LI Yi-ming; ZHAO Yong; LIN Xiao

    2005-01-01

    Objective: To investigate the differentiation-inducing effects of all-trans-retinoic (ATRA) to HPV16 subgenesimmortalized human endocervical cells (H8 cell) in vitro. Methods: HPV16 subgenes-immortalized human endocervical cells(H8 cells) were cultured in vitro. After treated with ATRA, the proliferation of immortalized human endocervical cells was measured by MTT assay; morphological changes were observed using M and TEM; cell cycle was analyzed by FCM;expression of Ki67 was tested using immunocytochemistry and the activity of telomerase was tested using PCR-ELISA.Results: ATRA could inhibit proliferation of H8 cells significantly and induce their morphodifferentiation. According to FCM, H8 cells accumulated in G1 phase and expression of Ki67 and activity of telomerase reduced significantly after treatment with ATRA. Conclusion: ATRA could induce the differentiation of H8 cell line obviously, which might be achieved by inhibiting proliferation, blocking cell cycle, and reducing activity of telomerase.

  20. Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management

    Science.gov (United States)

    Govind Babu, K.; Lokesh, K. N.; Suresh Babu, M. C.; Bhat, Gita R.

    2016-01-01

    Background. Acute promyelocytic leukemia is characterized by t(15;17). This leads to the formation of PML/RARα which blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA), a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA. Case Report. We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease. Conclusions. We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed. PMID:26981297

  1. Acute Coronary Syndrome Manifesting as an Adverse Effect of All-trans-Retinoic Acid in Acute Promyelocytic Leukemia: A Case Report with Review of the Literature and a Spotlight on Management

    Directory of Open Access Journals (Sweden)

    K. Govind Babu

    2016-01-01

    Full Text Available Background. Acute promyelocytic leukemia is characterized by t(15;17. This leads to the formation of PML/RARα which blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA, a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA. Case Report. We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease. Conclusions. We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed.

  2. Eosinophils from Murine Lamina Propria Induce Differentiation of Naive T Cells into Regulatory T Cells via TGF-β1 and Retinoic Acid.

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    Hong-Hu Chen

    Full Text Available Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP that displayed high aldehyde dehydrogenase (ALDH activity, a rate-limiting step during all-trans retinoic acid (ATRA synthesis, and expressed TGF-β1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-β1 or ATRA. Peripheral blood (PB eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-β1 and ATRA.

  3. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.

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    Yafang Ma

    Full Text Available Recently, the all-trans retinoic acid (ATRA plus arsenic trioxide (ATO protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL, but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL.We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity.Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009, overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009, complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03. There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07.Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.

  4. All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta

    Science.gov (United States)

    Huo, Lijun; Cui, Dongmei; Yang, Xiao; Gao, Zhenya; Trier, Klaus

    2013-01-01

    Purpose All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed activation of the MAPK pathway could be involved in the response of HSFs exposed to ATRA. Methods HSFs were cultured in Dulbecco Modified Eagle's Medium/F12 (DMEM/F12) and exposed to 1 μmol/l ATRA for 10 min, 30 min, 1 h, 8 h, or 24 h. The activation of extracellular signal-regulated kinase (ERK 1/2), p38, and c-Jun N-terminal kinase (JNK) in HSFs was assessed with western blot analysis and immunocytofluorescence. Results After exposure to ATRA for 24 h, the HSFs appeared shrunken and thinner than the control cells. The intercellular spaces were wider, and the HSFs appeared less numerous than in the control culture. Western blot showed decreased activation of ERK 1/2 in the HSFs from 30 min (p=0.01) to 24 h (p<0.01) after the start of exposure to ATRA, and increased activation of the JNK protein from 10 to 30 min (p<0.01) after the start of exposure to ATRA. Indirect immunofluorescence confirmed changes in activation of ERK 1/2 and JNK in HSFs exposed to ATRA. No change in activation of p38 in HSFs was observed after exposure to ATRA. Pretreatment of the HSFs with LE135, an antagonist of retinoic acid receptor beta (RARβ), abolished the ATRA-induced changes inactivation of ERK 1/2 and JNK. Conclusions ATRA inhibits HSF proliferation by a mechanism associated with modulation of ERK 1/2 and JNK activation and depends on stimulation of retinoic acid receptor beta. PMID:23946634

  5. The effect pathway of retinoic acid through regulation of retinoic acid receptor in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Su Liu; Qiao Wu; Zheng-Ming Chen; Wen-Jin Su

    2001-01-01

    AIM To evaluate the role of RARa gene in mediating the growth inhibitory effect of ail-trans retinoic acid (ATRA)on gastric cancer cells.``METHODS The expression levels of retinoic acid receptors (RARs) in gastric cancer cells were detected by Northern blot. Transient transfection and chlorophenicol acetyl transferase (CAT) assay were used to show the transcriptional activity of β retinoic acid response element (βRARE) and AP-l activity. Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay, respectively. Stable transfection was performed by the method of Lipofectamine, and the cells were screened by G418.``RESULTS ATRA could induce expression level of RARα in MGC80-3, BGCC8823 and SGC-7901 cells obviously,resulting in growth inhibition of these cell lines. After sense RARa gene was transfected into MKN-45 cells that expressed rather Iow level of RARα and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RARα gene was transfected into BGC-825 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823cells. In transient transfection assay, ATRA effectively induced transcriptional activity of βRARE in MGC80-3,BGC.823, SGC-7902 and MKN/RARa cell lines, but not in MKN-45 and BGC/aRARa cell lines. Similar results were observed in measuring anti-AP-l activity by ATRA in these cancer cell lines.``CONCLUSION ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARa; RARa is the major mediator of ATRA action in gastric cancer cells; and adequate level of RAPa is required for ATRA effect on gastric cancer cells.``

  6. Tamoxifen enhances the differentiation-inducing and growth-inhibitory effects of all-trans retinoic acid in acute promyelocytic leukemia cells.

    Science.gov (United States)

    Adachi, Koji; Honma, Yoshio; Miyake, Takaaki; Kawakami, Koshi; Takahashi, Tsutomu; Suzumiya, Junji

    2016-03-01

    All-trans retinoic acid (ATRA) is valuable in differentiation therapy for acute promyelocytic leukemia (APL). However, ATRA has had limited success as a single agent, due to the development of resistance. We found that tamoxifen effectively enhanced the differentiation-inducing effect of ATRA. Tamoxifen alone inhibited the proliferation of myeloid leukemia cell lines while only slightly increasing morphologic differentiation. Tamoxifen effectively enhanced the growth-inhibiting actions of various differentiation-inducing agents. ATRA in the presence of tamoxifen increased NBT reduction and the expression of CD11b in HL-60 cells more effectively than ATRA alone. Tamoxifen also enhanced the differentiation induced by the other inducers tested. ATRA induced the differentiation of APL cell lines NB4 and HT93 and APL cells in primary culture, and this differentiation was also enhanced by tamoxifen. Tamoxifen is one of the most widely used drugs for the treatment of cancer and has few side effects. The combination of ATRA and tamoxifen might be considered for the treatment of APL patients in whom it can be difficult to apply arsenic trioxide or anthracyclines. PMID:26797574

  7. Retinoic Acid Receptors Control Spermatogonia Cell-Fate and Induce Expression of the SALL4A Transcription Factor.

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    Aurore Gely-Pernot

    2015-10-01

    Full Text Available All-trans retinoic acid (ATRA is instrumental to male germ cell differentiation, but its mechanism of action remains elusive. To address this question, we have analyzed the phenotypes of mice lacking, in spermatogonia, all rexinoid receptors (RXRA, RXRB and RXRG or all ATRA receptors (RARA, RARB and RARG. We demonstrate that the combined ablation of RXRA and RXRB in spermatogonia recapitulates the set of defects observed both upon ablation of RAR in spermatogonia. We also show that ATRA activates RAR and RXR bound to a conserved regulatory region to increase expression of the SALL4A transcription factor in spermatogonia. Our results reveal that this major pluripotency gene is a target of ATRA signaling and that RAR/RXR heterodimers are the functional units driving its expression in spermatogonia. They add to the mechanisms through which ATRA promote expression of the KIT tyrosine kinase receptor to trigger a critical step in spermatogonia differentiation. Importantly, they indicate also that meiosis eventually occurs in the absence of a RAR/RXR pathway within germ cells and suggest that instructing this process is either ATRA-independent or requires an ATRA signal originating from Sertoli cells.

  8. Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans

    Science.gov (United States)

    Campione, Elena; Gaziano, Roberta; Marino, Daniele; Orlandi, Augusto

    2016-01-01

    Purpose Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA) is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity. Moreover, ATRA offers the opportunity for systemic therapy. Methods and results We investigated the efficacy of ATRA at different concentrations for its antifungal activity against opportunistic A. fumigatus and C. albicans obtained from clinical samples according to standard protocols. A fungistatic activity of ATRA on A. fumigatus and C. albicans at 0.5–1 mM concentration was documented up to 7 days. Conclusion This is the first evidence of a direct and strong fungistatic activity of ATRA against A. fumigatus and C. albicans. The potential adjuvant therapeutic application of ATRA might be useful in the treatment and/or prevention of systemic mycoses in immunocompromised patients. The discovery of a direct fungistatic activity, in association with its reported immunomodulatory properties, makes ATRA an excellent candidate for new combined antifungal strategies for systemic mycoses in immunocompromised and cancer patients. PMID:27199548

  9. Clinical Study on Prospective Efficacy of All-Trans Acid, Realgar-Indigo Naturalis Formula Combined with Chemotherapy as Maintenance Treatment of Acute Promyelocytic Leukemia

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    Li Xiang-Xin

    2014-01-01

    Full Text Available Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA, Realgar-Indigo naturalis formula (RIF and chemotherapy (CT were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL. Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen, while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX plus 6-mercaptopurine (6-MP alternately (ATRA/CTlow regimen. The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

  10. Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yun; Shen, Shao-Ming; Zhang, Fei-Fei; Wu, Zhao-Xia; Han, Bin [Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China); Wang, Li-Shun, E-mail: jywangls@shsmu.edu.cn [Shanghai Universities E-Institute for Chemical Biology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025 (China)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer ANP32B was down-regulated during ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Knockdown of ANP32B enhanced ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Ectopic expression of ANP32B inhibited ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer ANP32B inhibited ATRA activated transcriptional activity of RAR{alpha}. -- Abstract: The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is a member of a conserved superfamily of nuclear proteins whose functions are largely unknown. In our previous work, ANP32B was identified as a novel direct substrate for caspase-3 and acted as a negative regulator for leukemic cell apoptosis. In this work, we provided the first demonstration that ANP32B expression was down-regulated during differentiation induction of leukemic cells by all-trans retinoic acid (ATRA). Knockdown of ANP32B expression by specific shRNA enhanced ATRA-induced leukemic cell differentiation, while ectopic expression of ANP32B attenuated it, indicating an inhibitory role of ANP32B against leukemic cell differentiation. Furthermore, luciferase reporter assay revealed that ANP32B might exert this role through inhibiting the ATRA dependent transcriptional activity of retinoic acid receptor (RAR{alpha}). These data will shed new insights into understanding the biological functions of ANP32B protein.

  11. Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells

    International Nuclear Information System (INIS)

    Highlights: ► ANP32B was down-regulated during ATRA-induced leukemic cell differentiation. ► Knockdown of ANP32B enhanced ATRA-induced leukemic cell differentiation. ► Ectopic expression of ANP32B inhibited ATRA-induced leukemic cell differentiation. ► ANP32B inhibited ATRA activated transcriptional activity of RARα. -- Abstract: The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is a member of a conserved superfamily of nuclear proteins whose functions are largely unknown. In our previous work, ANP32B was identified as a novel direct substrate for caspase-3 and acted as a negative regulator for leukemic cell apoptosis. In this work, we provided the first demonstration that ANP32B expression was down-regulated during differentiation induction of leukemic cells by all-trans retinoic acid (ATRA). Knockdown of ANP32B expression by specific shRNA enhanced ATRA-induced leukemic cell differentiation, while ectopic expression of ANP32B attenuated it, indicating an inhibitory role of ANP32B against leukemic cell differentiation. Furthermore, luciferase reporter assay revealed that ANP32B might exert this role through inhibiting the ATRA dependent transcriptional activity of retinoic acid receptor (RARα). These data will shed new insights into understanding the biological functions of ANP32B protein.

  12. Cholinergic activation enhances retinoic acid-induced differentiation in the human NB-4 acute promyelocytic leukemia cell line.

    Science.gov (United States)

    Chotirat, Sadudee; Suriyo, Tawit; Hokland, Marianne; Hokland, Peter; Satayavivad, Jutamaad; Auewarakul, Chirayu U

    2016-07-01

    The non-neuronal cholinergic system (NNCS) has been shown to play a role in regulating hematopoietic differentiation. We determined the expression of cholinergic components in leukemic cell lines by Western blotting and in normal leukocyte subsets by flow cytometry and found a heterogeneous expression of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), choline transporter (CHT), M3 muscarinic acetylcholine receptor (M3-mAChR) and α7 nicotinic acetylcholine receptor (α7-nAChR). We then evaluated NNCS role in differentiation of human NB-4 acute promyelocytic leukemia cell line and discovered a dramatic induction of M3-mAChR after all-trans retinoic acid (ATRA) treatment (p<0.0001). Adding carbachol which is a cholinergic agonist to the ATRA treatment resulted in an increase of a granulocytic differentiation marker (CD11b) as compared with ATRA treatment alone (p<0.05), indicating that cholinergic activation enhanced ATRA in inducing NB-4 maturation. The combination of carbachol and ATRA treatment for 72h also resulted in decreased viability and increased cleaved caspase-3 expression when compared with ATRA treatment alone (p<0.05). However, this combination did not cause poly (ADP-ribose) polymerase (PARP) cleavage. Overall, we have shown that NB-4 cells expressed M3-mAChR in a differentiation-dependent manner and cholinergic stimulation induced maturation and death of ATRA-induced differentiated NB-4 cells. PMID:27282572

  13. Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma

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    Chen Wantao

    2008-06-01

    Full Text Available Abstract Background Antisense oligonucleotides against hTR (As-ODN-hTR have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo. Methods In situ human oral squamous cell carcinoma (OSCC models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined. Results Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues. Conclusion The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma.

  14. The effects of PAHs and N-PAHs on retinoid signaling and Oct-4 expression in vitro.

    Science.gov (United States)

    Beníšek, Martin; Kubincová, Petra; Bláha, Luděk; Hilscherová, Klára

    2011-02-01

    Polycyclic aromatic hydrocarbons (PAHs) and their N-heterocyclic analogs (N-PAHs) are important environmental contaminants with negative effects in living organisms, including teratogenicity and embryotoxicity. Though most studies linked their embryotoxicity with aryl hydrocarbon receptor (AhR) and cytochrome P450 activation, the exact mechanism is not known. Other mechanisms such as disruption of retinoid signaling were recently suggested to be of importance. This study investigated PAHs and N-PAHs interference with retinoid signaling in vitro by modulating all-trans retinoic acid (ATRA) mediated response in a reporter gene assay using P19/A15 cell line. Further, effects on pluripotency and differentiation processes were evaluated by measuring octamer-4 (Oct-4), an important pluripotency marker and master differentiation factor. Two of the studied compounds, benz[a]anthracene and benz[c]acridine significantly up-regulated ATRA-mediated response in the co-exposure with a range of ATRA concentrations. Another structural N-PAH variant, 1,7-phenanthroline, downregulated ATRA-mediated response at most of tested ATRA concentrations and exposure times. Interesting concentration-dependent biphasic effects (i.e. downregulation with subsequent up-regulation to control levels) were observed at co-exposures of ATRA and parent PAH phenanthrene. Non significant Oct-4 modulation in co-exposure with ATRA was observed at compounds, which potentiated ATRA-mediated effects in the reporter gene assay. On the other hand, 1,7-phenanthroline and phenanthrene significantly suppressed Oct-4 levels in higher tested concentrations. Our results further extend the knowledge of PAH and N-PAH in vitro effects and indicate that these environmental toxicants may have influence on differentiation process and embryonic development by interfering with ATRA signaling and by modulating levels of Oct-4. PMID:21111795

  15. Antisense oligonucleotides and all-trans retinoic acid have a synergistic anti-tumor effect on oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Antisense oligonucleotides against hTR (As-ODN-hTR) have shown promising results as treatment strategies for various human malignancies. All-trans retinoic acid (ATRA) is a signalling molecule with important roles in differentiation and apoptosis. Biological responses to ATRA are currently used therapeutically in various human cancers. The aim of this study was to evaluate the anti-tumor effects of As-ODN-hTR combined with ATRA in vivo. In situ human oral squamous cell carcinoma (OSCC) models were established by subcutaneous injection of Tca8113 cells. Mice were treated with sense oligonucleotides against hTR(S-ODN-hTR) alone, As-ODN-hTR alone, ATRA alone, As-ODN-hTR plus ATRA, or S-ODN-hTR plus ATRA. Tumor size and weight were assessed in the mice. Telomerase activity was detected by a TRAP assay, apoptotic cells were evaluated with a Tunel assay, the expression of apoptosis-related proteins (Bcl-2 and Bax) was evaluated by immunohistochemistry and ultrastructural morphological changes in the tumor specimen were examined. Both As-ODN-hTR and ATRA can significantly inhibit tumor growth in this OSCC xenograft solid-tumor model, and the combination of the two agents had a synergistic anti-tumorogenic effect. We also demonstrated that this anti-tumor effect correlated with inhibition of telomerase activity. Furthermore, significant increases in the number of apoptotic cells, typical apoptotic morphology and a downregulation of the anti-apoptotic protein, bcl-2 were observed in the treated tissues. The combination of As-ODN-hTR and ATRA has a synergistic anti-tumor effect. This anti-tumor effect can be mainly attributed to apoptosis induced by a decrease in telomerase activity. Bcl-2 plays an important role in this process. Therefore, combining As-ODN-hTR and ATRA may be an approach for the treatment of human oral squamous cell carcinoma

  16. Study of the synergistic effects of all-transretinoic acid and C-phycocyanin on the growth and apoptosis of A549 cells.

    Science.gov (United States)

    Li, Bing; Gao, Mei-Hua; Lv, Cong-Yi; Yang, Peng; Yin, Qi-Feng

    2016-03-01

    In the present study, we investigated the effects of the combination of all-transretinoic acid (ATRA) and natural nontoxic C-phycocyanin (C-PC) on the growth of A549 lung cancer cells in vitro and in vivo. Furthermore, the anticancer mechanism of the drug combination was revealed. Results showed both C-PC and ATRA could inhibit the growth of A549 cells in vivo. The combination of ATRA+C-PC could yield a higher inhibition rate. C-PC exerted a major effect on the proliferation of human embryo lung cells, but ATRA at a high concentration exerted an inhibitory effect. In addition, ATRA+C-PC could decrease the CDK4 mRNA level, but upregulated caspase-3 protein expression and induced cell apoptosis. A mouse model with tumor was constructed by a subcutaneous injection to the left axilla of nu nude (NU/NU) mice. Compared with the control group, the tumor weight was decreased in the single-drug treatment group and was the lowest in the combination group. C-PC+ATRA could upregulate tumor necrosis factor levels and downregulate Bcl-2 expression and the cyclin D1 gene in the tumor. C-PC could promote T cells' activities and spleen weight, but a single use of ATRA exerted an opposite effect. The dosage of ATRA could be reduced when combined with C-PC to reduce the toxic side-effects. In summary, the antitumor effects of the C-PC+ATRA combination were more significant than a single drug in vivo and in vitro. PMID:25812039

  17. All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein

    Directory of Open Access Journals (Sweden)

    Taguchi Takahiro

    2010-12-01

    Full Text Available Abstract Background Imatinib, a selective tyrosine kinase inhibitor, has been used as a standard first-line therapy for irresectable and metastasized gastrointestinal stromal tumor (GIST patients. Unfortunately, most patients responding to imatinib will eventually exhibit imatinib-resistance, the cause of which is not fully understood. The serious clinical problem of imatinib-resistance demands alternative therapeutic strategy. This study was conducted to investigate the effect of all-trans retinoic acid (ATRA on GIST cell lines. Methods Cell proliferation was determined by trypan blue dye exclusion test. Western blot analysis was performed to test the expression of activated KIT, its downstream proteins, and apoptosis associated proteins. The cytotoxic interactions of imatinib with ATRA were evaluated using the isobologram of Steel and Peckham. Results and conclusion In this work, for the first time we have demonstrated that ATRA affected on cell proliferation of GIST-T1 and GIST-882 cell line through inhibition of cell growth in a dose dependent manner and induced apoptosis. High dose of ATRA induced morphologic change in GIST-T1 cells, rounded-up cells, and activated the caspase-3 protein. In further examination, we found that the ATRA-induced apoptosis in GIST-T1 cells was accompanied by the down-regulated expression of survivin and up-regulated expression of Bax protein. Moreover, ATRA suppressed the activity of KIT protein in GIST-T1 cells and its downstream signal, AKT activity, but not MAPK activity. We also have demonstrated that combination of ATRA with imatinib showed additive effect by isobologram, suggesting that the combination of ATRA and imatinib may be a novel potential therapeutic option for GIST treatment. Furthermore, the scracht assay result suggested that ATRA was a potential reagent to prevent the invasion or metastasis of GIST cells.

  18. Defects in embryonic hindbrain development and fetal resorption resulting from vitamin A deficiency in the rat are prevented by feeding pharmacological levels of all-trans-retinoic acid

    OpenAIRE

    White, Jeffrey C.; Shankar, V. Narayanaswamy; Highland, Margaret; Epstein, Miles L; DeLuca, Hector F.; Clagett-Dame, Margaret

    1998-01-01

    Vitamin A is required for reproduction and normal embryonic development. We have determined that all-trans-retinoic acid (atRA) can support development of the mammalian embryo to parturition in vitamin A-deficient (VAD) rats. At embryonic day (E) 0.5, VAD dams were fed purified diets containing either 12 μg of atRA per g of diet (230 μg per rat per day) or 250 μg of atRA per g of diet (4.5 mg per rat per day) or were fed the purified diet supplemented with a source of retinol (100 units of re...

  19. Inhibition of matrix metalloproteinases expression in human dental pulp cells by all-trans retinoic acid

    OpenAIRE

    Kim, Jin Man; Kang, Sang Wook; Shin, Su-Mi; Su Kim, Duck; Choi, Kyong-Kyu; Kim, Eun-Cheol; Kim, Sun-Young

    2013-01-01

    All-trans retinoic acid (ATRA) inhibits matrix metalloproteinase (MMP)-2 and MMP-9 in synovial fibroblasts, skin fibroblasts, bronchoalveolar lavage cells and cancer cells, but activates MMP-9 in neuroblast and leukemia cells. Very little is known regarding whether ATRA can activate or inhibit MMPs in human dental pulp cells (HDPCs). The purpose of this study was to determine the effects of ATRA on the production and secretion of MMP-2 and -9 in HDPCs. The productions and messenger RNA (mRNA)...

  20. FAQ about Recreational Therapy/Therapeutic Recreation

    Science.gov (United States)

    ... is the relationship between recreational therapy and therapeutic recreation? Therapeutic Recreation is the field ​​Recreational ... for individuals with disabilities." About the American Therapeutic Recreation Association: The American Therapeutic Recreation Association (ATRA) is ...

  1. Vitamin A induces inhibitory histone methylation modifications and down-regulates trained immunity in human monocytes

    DEFF Research Database (Denmark)

    Arts, Rob J W; Blok, Bastiaan A; van Crevel, Reinout;

    2015-01-01

    assessed. ATRA inhibited cytokine responses upon restimulation of monocytes, and this effect was exerted through increased expression of SUV39H2, a histone methyltransferase that induces the inhibitory mark H3K9me3. H3K9me3 at promoter sites of several cytokines was up-regulated by ATRA, and inhibition of...... SUV39H2 restored cytokine production. In addition to H3K9me3, the stimulatory histone mark H3K4me3 was down-regulated by ATRA at several promoter locations of cytokine genes. Therefore, we can conclude that ATRA inhibits cytokine production in models of direct stimulation or BCG-induced trained...

  2. Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Lei Yu; Yang-De Zhang; Jun Zhou; De-Ming Yao; Xiang Li

    2013-01-01

    Objective: To indentify target genes of transcription factor CCAAT enhancer-binding proteinβ (CEBPB) in acute promyelocytic leukemia cells induced by all-trans retinoic acid. Methods:A new strategy for high-throughput identification of direct target genes was established by combining chromatin immunoprecipitation (ChIP) with in vitro selection. Then, 106 potential CEBPB binding fragments from the genome of the all-trans retinoic acid (ATRA)-treated NB4 cells were identified. Results: Of them, 82 were mapped in proximity to known or previously predicted genes; 7 were randomly picked up for further confirmation by ChIP-PCR and 3 genes (GALM, ITPR2 and ORM2) were found to be specifically up-regulated in the ATRA-treated NB4 cells, indicating that they might be the down-stream target genes of ATRA. Conclusions: Our results provided new insight into the mechanisms of ATRA-induced granulocytic differentiation.

  3. Anti-inflammatory and anti-hyperalgesic effect of all-trans retinoic acid in carrageenan-induced paw edema in Wistar rats: Involvement of peroxisome proliferator-activated receptor-β/δ receptors

    Directory of Open Access Journals (Sweden)

    Navneet Gill

    2013-01-01

    Conclusion: From above findings, it can be concluded that ATRA exerts anti-inflammatory and anti-hyperalgesic effect, possibly through activation of PPAR-β/δ and subsequent reduction of oxido-nitrosative stress.

  4. Plaat

    Index Scriptorium Estoniae

    2008-01-01

    Laseringi kauplustes müügilolevatest heliplaatidest: Bizarre "Cafe De Flor", Hocico "Memorias Atras", Portishead "Third", Alanis Morissette "Flavors Of Entanglement", Radiohead "The Best Of", Kelder "Vikerkaar ja latimeeria"

  5. MDI 301 suppresses myeloid leukemia cell growth in vitro and in vivo without the toxicity associated with all-trans retinoic acid therapy.

    Science.gov (United States)

    Aslam, Muhammad N; McClintock, Shannon; Khan, Shazli P; Perone, Patricia; Allen, Ronald; Ouillette, Peter D; Dame, Michael K; Cheng, Jason X; Kunkel, Steven L; Varani, James

    2015-08-01

    MDI 301 is a novel 9-cis retinoic acid derivative in which the terminal carboxylic acid group has been replaced by a picolinate ester. MDI 301, a retinoic acid receptor-α - agonist, suppressed the growth of several human myeloid leukemia cell lines (HL60, NB4, OCI-M2, and K562) in vitro and induced cell-substrate adhesion in conjunction with upregulation of CD11b. Tumor growth in HL60-injected athymic nude mice was reduced. In vitro, MDI 301 was comparable to all-trans retinoic acid (ATRA) whereas in vivo, MDI 301 was slightly more efficacious than ATRA. Most importantly, unlike what was found with ATRA treatment, MDI 301 did not induce a cytokine response in the treated animals and the severe inflammatory changes and systemic toxicity seen with ATRA did not occur. A retinoid with these characteristics might be valuable in the treatment of promyelocytic leukemia, or, perhaps, other forms of myeloid leukemia. PMID:26010252

  6. Reversible effect of all-trans-retinoic acid on AML12 hepatocyte proliferation and cell cycle progression

    Science.gov (United States)

    The role of all-trans-retinoic acid (atRA) in the regulation of cellular proliferation and differentiation is well documented. Numerous studies have established the cancer preventive propertiesofatRAwhichfunctionstoregulate levels ofcellcycleproteinsessentialfortheGliS transition...

  7. Genetic and pathologic aspects of retinoic acid-induced limb malformations in the mouse

    OpenAIRE

    Lee, Grace S.; Liao, Xiaoyan; Shimizu, Hirohito; Collins, Michael D.

    2010-01-01

    Because all-trans retinoic acid (atRA) is teratogenic in all species tested and many of the specific defects induced are common across the phylogenetic spectrum, it would be logical to predict that murine strain differences in teratology to this agent are minimal. However, for specific defects, strain susceptibilities are vastly different. Studies with atRA have shown stark differences between C57BL/6 and SWV mouse strains in susceptibility to postaxial forelimb ectrodactyly and ectopic hindl...

  8. DNA Aptamers against Taiwan Banded Krait α-Bungarotoxin Recognize Taiwan Cobra Cardiotoxins

    OpenAIRE

    Ying-Jung Chen; Chia-Yu Tsai; Wan-Ping Hu; Long-Sen Chang

    2016-01-01

    Bungarus multicinctus α-bungarotoxin (α-Bgt) and Naja atra cardiotoxins (CTXs) share a common structural scaffold, and their tertiary structures adopt three-fingered loop motifs. Four DNA aptamers against α-Bgt have been reported previously. Given that the binding of aptamers with targeted proteins depends on structural complementarity, in this study, we investigated whether DNA aptamers against α-Bgt could also recognize CTXs. It was found that N. atra cardiotoxin 3 (CTX3) reduced the electr...

  9. Critical role of all-trans retinoic acid in stabilizing human natural regulatory T cells under inflammatory conditions.

    Science.gov (United States)

    Lu, Ling; Lan, Qin; Li, Zhiyuan; Zhou, Xiaohui; Gu, Jian; Li, Qiang; Wang, Julie; Chen, Maogen; Liu, Ya; Shen, Yi; Brand, David D; Ryffel, Bernhard; Horwitz, David A; Quismorio, Francisco P; Liu, Zhongmin; Li, Bin; Olsen, Nancy J; Zheng, Song Guo

    2014-08-19

    Recent studies have demonstrated that thymus-derived naturally occurring CD4(+)Foxp3(+) regulatory T cells (Tregs) in human and mouse may be unstable and dysfunctional in the presence of proinflammatory cytokines. All-trans RA (atRA), the active derivative of vitamin A, has been shown to regulate Treg and T effector cell differentiation. We hypothesize atRA stabilizes human natural Tregs (nTregs) under inflammatory conditions. atRA prevents human nTregs from converting to Th1 and/or Th17 cells and sustains their Foxp3 expression and suppressive function in vitro or in vivo following encounters with IL-1 and IL-6. Interestingly, adoptive transfer of human nTregs pretreated with atRA significantly enhanced their suppressive effects on xenograft-vs.-host diseases (xGVHDs), and atRA- but not rapamycin-pretreated nTregs sustained the functional activity against xGVHD after stimulation with IL-1/IL-6. atRA suppresses IL-1 receptor (IL-1R) up-regulation, accelerates IL-6R down-regulation, and diminishes their signaling events as well as prevents the up-regulation of STIP1 homology and U-Box containing protein 1 on Foxp3(+) cells following IL-1/IL-6 stimulation. atRA also increases histone acetylation on Foxp3 gene promoter and CpG demethylation in the region of Foxp3 locus (i.e., Treg-specific demethylated region). These results strongly implicate that nTregs primed with atRA may represent a novel treatment strategy to control established chronic immune-mediated autoimmune and inflammatory diseases. PMID:25099355

  10. All-Trans Retinoic Acid Modulates DNA Damage Response and the Expression of the VEGF-A and MKI67 Genes in ARPE-19 Cells Subjected to Oxidative Stress.

    Science.gov (United States)

    Tokarz, Paulina; Piastowska-Ciesielska, Agnieszka Wanda; Kaarniranta, Kai; Blasiak, Janusz

    2016-01-01

    Age-related macular degeneration (AMD) is characterized by the progressive degradation of photoreceptors and retinal pigment epithelium (RPE) cells. ARPE-19 is an RPE cell line established as an in vitro model for the study of AMD pathogenesis. Oxidative stress is an AMD pathogenesis factor that induces DNA damage. Thus, the oxidative stress-mediated DNA damage response (DDR) of ARPE-19 cells can be important in AMD pathogenesis. The metabolism of retinoids-which regulates cell proliferation, differentiation, and the visual cycle in the retina-was reported to be disturbed in AMD patients. In the present work, we studied the effect of all-trans retinoic acid (ATRA, a retinoid) on DDR in ARPE-19 cells subjected to oxidative stress. We observed that ATRA increased the level of reactive oxygen species (ROS), alkali-labile sites in DNA, DNA single-strand breaks, and cell death evoked by oxidative stress. ATRA did not modulate DNA repair or the distribution of cells in cell cycle in the response of ARPE-19 cells to oxidative stress. ATRA induced autophagy in the absence of oxidative stress, but had no effect on this process in the stress. ATRA induced over-expression of proliferation marker MKI67 and neovascularization marker VEGF-A. In conclusion, ATRA increased oxidative stress in ARPE-19 cells, resulting in more lesions to their DNA and cell death. Moreover, ATRA can modulate some properties of these cells, including neovascularization, which is associated with the exudative form of AMD. Therefore, ATRA can be important in the prevention, diagnosis, and therapy of AMD. PMID:27314326

  11. Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells

    OpenAIRE

    MANIWA, YASUHISA; Kasukabe, Takashi; Kumakura, Shunichi

    2015-01-01

    Although all-trans retinoic acid (ATRA) is a standard and effective drug used for differentiation therapy in acute promyelocytic leukemia, ATRA-resistant leukemia cells ultimately emerge during this treatment. Therefore, the development of new drugs or effective combination therapy is urgently needed. We demonstrate that the combined treatment of vitamin K2 and cotylenin A synergistically induced monocytic differentiation in HL-60 cells. This combined treatment also synergistically induced NB...

  12. All-trans retinoic acid impairs the vasculogenic mimicry formation ability of U87 stem-like cells through promoting differentiation

    OpenAIRE

    LING, GENG-QIANG; LIU, YI-JING; Ke, Yi-Quan; Chen, Lei; JIANG, XIAO-DAN; JIANG, CHUAN-LU; Ye, Wei

    2015-01-01

    The poor therapeutic effect of traditional antiangiogenic therapy on glioblastoma multiforme (GBM) may be attributed to vasculogenic mimicry (VM), which was previously reported to be promoted by cancer stem-like cells (SLCs). All-trans retinoic acid (ATRA), a potent reagent which drives differentiation, was reported to be able to eradicate cancer SLCs in certain malignancies. The aim of the present study was to investigate the effects of ATRA on the VM formation ability of U87 glioblastoma SL...

  13. All-trans retinoic acid modulates mitogen-activated protein kinase pathway activation in human scleral fibroblasts through retinoic acid receptor beta

    OpenAIRE

    Huo, Lijun; Cui, Dongmei; Yang, Xiao; Gao, Zhenya; Trier, Klaus; Zeng, Junwen

    2013-01-01

    Purpose All-trans retinoic acid (ATRA) is known to inhibit the proliferation of human scleral fibroblasts (HSFs) and to modulate the scleral intercellular matrix composition, and may therefore serve as a mediator for controlling eye growth. Cell proliferation is regulated by the mitogen-activated protein kinase (MAPK) pathway. The aim of the current study was to investigate whether changed activation of the MAPK pathway could be involved in the response of HSFs exposed to ATRA. Methods HSFs w...

  14. All-trans retinoic acid negatively regulates cytotoxic activities of nature killer cell line 92

    International Nuclear Information System (INIS)

    NK cells are key components of innate immune systems and their activities are regulated by cytokines and hormones. All-trans retinoic acid (ATRA), as a metabolite of vitamin A and an immunomodulatory hormone, plays an important role in regulating immune responses. In the present study, we investigated the effect of ATRA on human NK cell line NK92. We found that ATRA dose-dependently suppressed cytotoxic activities of NK92 cells without affecting their proliferation. To explore the mechanisms underlying the ATRA influence on NK92 cells, we examined the production of cytokines (TNF-α, IFN-γ), gene expression of cytotoxic-associated molecules (perforin, granzyme B, nature killer receptors (NCRs), and NKG2D), and the activation of NF-κB pathways related with immune response. Our results demonstrated that ATRA suppressed NF-κB activity and prevented IκBα degradation in a dose-dependent way, inhibited IFN-γ production and gene expression of granzyme B and NKp46. Our findings suggest that ATRA is a negative regulator of NK92 cell activation and may act as a potential regulator of anti-inflammatory functions in vivo

  15. Enhancement of caffeic acid phenethyl ester on all-trans retinoic acid-induced differentiation in human leukemia HL-60 cells

    International Nuclear Information System (INIS)

    All-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL); however, the response is sometimes very slow. Furthermore, relapse and resistance to treatment often occur despite continued treatment with ATRA. Thereafter, combination treatment strategies have been suggested to circumvent these problems. The present study demonstrates that caffeic acid phenethyl ester (CAPE), a major component of honeybee propolis, enhanced ATRA-induced granulocytic differentiation in HL-60, a human promyelocytic cell line. The differentiation was assessed by Wright-Giemsa stain, nitroblue tetrazolium reduction, and membrane differentiation marker CD11b. In addition, CAPE enhanced ATRA-induced cell cycle arrest at the G1 phase by decreasing the association of cdk2-cyclin E complex. Finally, it was demonstrated that CAPE promoted the ATRA-mediated nuclear transcription activation of RARα assessed by EMSA assay and enhanced the expression of target genes including RARα, C/EBPε, and p21 protein resulting in the differentiation development of leukemia. It is suggested that CAPE possesses the potential to enhance the efficiency of ATRA in the differentiation therapy of APL

  16. The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis.

    Science.gov (United States)

    Shao, Xuejing; Liu, Yujia; Li, Yangling; Xian, Miao; Zhou, Qian; Yang, Bo; Ying, Meidan; He, Qiaojun

    2016-01-01

    The success of all-trans retinoic acid (ATRA) in differentiation therapy for patients with acute promyelocytic leukemia (APL) highly encourages researches to apply this therapy to other types of acute myeloid leukemia (AML). However, AML, with the exception of APL, fails to respond to differentiation therapy. Therefore, research strategies to further sensitize cells to retinoids and to extend the range of AMLs that respond to retinoids beyond APLs are urgently needed. In this study, we showed that TAK165, a HER2 inhibitor, exhibited a strong synergy with ATRA to promote AML cell differentiation. We observed that TAK165 sensitized the AML cells to ATRA-induced cell growth inhibition, G0/G1 phase arrest, CD11b expression, mature morphologic changes, NBT reduction and myeloid regulator expression. Unexpectedly, HER2 pathway might not be essential for TAK165-enhanced differentiation when combined with ATRA, while the enhanced differentiation was dependent on the activation of the RARα/STAT1 axis. Furthermore, the MEK/ERK cascade regulated the activation of STAT1. Taken together, our study is the first to evaluate the synergy of TAK165 and ATRA in AML cell differentiation and to assess new opportunities for the combination of TAK165 and ATRA as a promising approach for future differentiation therapy. PMID:27074819

  17. Activation of Notch1 inhibits medial edge epithelium apoptosis in all-trans retinoic acid-induced cleft palate in mice.

    Science.gov (United States)

    Zhang, Yadong; Dong, Shiyi; Wang, Weicai; Wang, Jianning; Wang, Miao; Chen, Mu; Hou, Jinsong; Huang, Hongzhang

    2016-08-26

    Administration of all-trans retinoic acid (atRA) on E12.0 (embryonic day 12.0) leads to failure of medial edge epithelium (MEE) disappearance and cleft palate. However, the molecular mechanism underlying the relationship between atRA and MEE remains to be identified. In this study, atRA (200 mg/kg) administered by gavage induced a 75% incidence of cleft palate in C57BL/6 mice. Notch1 was up-regulated in MEE cells in the atRA-treated group compared with the controls at E15.0, together with reduced apoptosis and elevated proliferation. Next, we investigated the mechanisms underlying atRA, Notch1 and MEE degradation in palate organ culture. Our results revealed that down-regulation of Notch1 partially rescued the inhibition of atRA-induced palate fusion. Molecular analysis indicated that atRA increased the expression of Notch1 and Rbpj and decreased the expression of P21. In addition, depletion of Notch1 expression decreased the expression of Rbpj and increased the expression of P21. Moreover, inhibition of Rbpj expression partially reversed atRA-induced MEE persistence and increased P21 expression. These findings demonstrate that atRA inhibits MEE degradation, which in turn induces a cleft palate, possibly through the Notch1/RBPjk/P21 signaling pathway. PMID:27343556

  18. Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice

    International Nuclear Information System (INIS)

    Exposure to loud noise can induce temporary or permanent hearing loss, and acoustic trauma is the major cause of hearing impairment in industrial nations. However, the mechanisms underlying the death of hair cells after acoustic trauma remain unclear. In addition to its involvement in cellular stress and apoptosis, the c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is involved in cell survival, transformation, embryonic morphogenesis, and differentiation. JNK is primarily activated by various environmental stresses including noise, and the phenotypic result appears be to cell death. All-trans retinoic acid (ATRA) is an active metabolite of vitamin A that regulates a wide range of biological processes, including cell proliferation, differentiation, and morphogenesis. We evaluated the role of ATRA in preserving hearing in mice exposed to noise that can induce permanent hearing loss. Mice fed with ATRA before and during 3 consecutive days of noise exposure had a more preserved hearing threshold than mice fed sesame oil or saline. Histological and TUNEL staining of the cochlea showed significantly enhanced preservation of the organ of Corti, including outer hair cells and relatively low apoptotic nuclei, in mice-fed ATRA than in mice-fed sesame oil or saline. Phospho-JNK immunohistochemistry showed that ATRA inhibited the activation of JNK. These results suggest that ATRA has an anti-apoptotic effect on cochleae exposed to noise

  19. Reduction of stimulated sodium iodide symporter expression by estrogen receptor ligands in breast cancer cells

    International Nuclear Information System (INIS)

    Purpose: The sodium iodide symporter (NIS) mediates active iodide uptake in lactating breast tissue, and when its levels are enhanced by all-trans retinoic acid (atRA), NIS has been proposed as a target for the imaging and radiotherapy of breast cancer. Importantly, the estrogen receptor α (ERα) is an important regulator of atRA induced NIS gene expression in breast cancer cells. In this study, we investigated the effect of an ER agonist (17β-estradiol, E2) or antagonist [trans-hydroxytamoxifen (TOT) or raloxifene (RAL)] treatment on the regulation of NIS gene expression and iodide uptake in an ERα-positive breast cancer (MCF-7) model. Methods: NIS functional activity was measured in vitro by 125I uptake assay after incubation with E2 (from 10-15 to 10-5 M), TOT (from 5x10-8 to 5x10-6 M), or RAL (from 5x10-8 to 5x10-6 M) in the presence or absence of atRA (10-7 M). Under the same conditions, NIS mRNA expression was examined by reverse transcriptase polymerase chain reaction. Athymic mice with MCF-7 xenograft tumors were treated with atRA alone or atRA together with E2 to evaluate the change of 125I uptake in tumor tissues in vivo. Results: In the iodide uptake study in cells, E2, TOT, or RAL treatment alone did not stimulate 125I uptake. However, when iodide uptake was stimulated by atRA, cotreatment with E2, TOT or RAL decreased 125I uptake in a concentration-dependent manner. The hormone effects on NIS mRNA expression levels in MCF-7 cells were similar. The results of the in vivo biodistribution study showed that 125I uptake was reduced 50% in tumor tissues of mice treated with atRA/E2 as compared to tumors treated only with atRA. Conclusion: Our results suggest that combination treatment of atRA and ER ligands could limit the functional activity of the NIS gene induced by atRA, thereby compromising its use as a target for diagnosis or radiotherapy in breast cancer.

  20. Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans

    Directory of Open Access Journals (Sweden)

    Campione E

    2016-04-01

    Full Text Available Elena Campione,1 Roberta Gaziano,2 Daniele Marino,2 Augusto Orlandi3 1Department of Dermatology, 2Department of Microbiology, 3Department of Anatomic Pathology, University of Rome Tor Vergata, Rome, Italy Purpose: Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity. Moreover, ATRA offers the opportunity for systemic therapy. Methods and results: We investigated the efficacy of ATRA at different concentrations for its antifungal activity against opportunistic A. fumigatus and C. albicans obtained from clinical samples according to standard protocols. A fungistatic activity of ATRA on A. fumigatus and C. albicans at 0.5–1 mM concentration was documented up to 7 days. Conclusion: This is the first evidence of a direct and strong fungistatic activity of ATRA against A. fumigatus and C. albicans. The potential adjuvant therapeutic application of ATRA might be useful in the treatment and/or prevention of systemic mycoses in immunocompromised patients. The discovery of a direct fungistatic activity, in association with its reported immunomodulatory properties, makes ATRA an excellent candidate for new combined antifungal strategies for systemic mycoses in immunocompromised and cancer patients. Keywords: all-trans retinoic acid, fungistatic activity, fungal infections

  1. All-TRANS RETINOIC ACID INTERFERES DEVELOPMENT OF PULMONARY HYPERTENSION INDUCED BY MONOCROTALINE IN RATS

    Institute of Scientific and Technical Information of China (English)

    秦玉明; 周爱卿; 贲晓明; 沈捷; 梁瑛; 李奋

    2001-01-01

    Objective To determine whether all-trans retinoic acid (atRA) affects the metabolism of collagen in main pulmonary artery and exerts an inhibitory effect in rats with pulmonary hypertension induced by monocrotaline . Methods All rats (n=72) were divided into 3 groups as control, model, and atRA . In model and atRA groups, rats (n=48) were assigned at random to be given a single subcutaneous injection of monocrotaline (60mgg/kg) and administrated with either atRA (30rng·kg-1·d-1) for atRA group or saline through oral-gastro intubation for model group. In control group, rats (n=24) received a single subcutaneous injection of an equal volume of 0. 9% saline. On day 7, 14,21 and 28 after monocrotaline or saline injection, cardiovascular catheters were inserted into the pulmonary artery of rats in each group to examine their mean pulmonary artery pressure, in addition with their hydroxyproline content determined by chromometry. Results In comparison with the control rats, the mean pulmonary artery pressure of rats in model group increased significantly on day 21 and up to the peak on day 28 (P<0.01), while their hydroxyproline contents decreased significantly on day 14 ( P < 0.05) and increased significantly on day 21 and 28. The atRA group when compared with the model group show reduction in the content of hydroxyproline and the mean pulmonary artery pressure ( P < 0.01 ). Conclusion The atRA inhibits the accumulation of collagen in main pulmonary artery and interferes the development of pulmonary hypertension which might elicit favorable geometric remodeling of rat pulmonary hypertension induced by monocrotaline.

  2. Combination chemotherapy of doxorubicin, all-trans retinoic acid and low molecular weight heparin based on self-assembled multi-functional polymeric nanoparticles

    Science.gov (United States)

    Zhang, Ting; Xiong, Hui; Zohra Dahmani, Fatima; Sun, Li; Li, Yuanke; Yao, Li; Zhou, Jianping; Yao, Jing

    2015-04-01

    Based on the complementary effects of doxorubicin (DOX), all-trans retinoic acid (ATRA) and low molecular weight heparin (LMWH), the combination therapy of DOX, ATRA and LMWH was expected to exert the enhanced anti-tumor effects and reduce the side effects. In this study, amphiphilic LMWH-ATRA conjugate was synthesized for encapsulating the DOX. In this way, DOX, ATRA and LMWH were assembled into a single nano-system by both chemical and physical modes to obtain a novel anti-tumor targeting drug delivery system that can realize the simultaneous delivery of multiple drugs with different properties to the tumor. LMWH-ATRA nanoparticles exhibited good loading capacities for DOX with excellent physico-chemical properties, good biocompatibility, and good differentiation-inducing activity and antiangiogenic activity. The drug-loading capacity was up to 18.7% with an entrapment efficiency of 78.8%. It was also found that DOX-loaded LMWH-ATRA nanoparticles (DHR nanoparticles) could be efficiently taken up by tumor cells via endocytic pathway, and mainly distributed in cytoplasm at first, then transferred into cell nucleus. Cell viability assays suggested that DHR nanoparticles maintained the cytotoxicity effect of DOX on MCF-7 cells. Moreover, the in vivo imaging analysis indicated that DiR-loaded LMWH-ATRA nanoparticles could target the tumor more effectively as compared to free DiR. Furthermore, DHR nanoparticles possessed much higher anticancer activity and reduced side effects compared to free drugs solution. These results suggested that DHR nanoparticles could be considered as a promising targeted delivery system for combination cancer chemotherapy with lower adverse effects.

  3. Induction of apoptosis and change of bcl—2 expression in macrophage Ana—1 cells by all—trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    YINDELING; XIUHAIREN; 等

    1996-01-01

    Macrophage cells play an important role in the initiation and regulation of the immune response.All-trans retinoic acid (ATRA) and its natural and synthetic analogs (retinoids)affect a large number of biological processes.Recently,retinoids have been shown promise in the therapy and prevention of various cancers.However,many interesting questions related to the activities of retinoids remain to be answered:(I) Molecular mechanisms by which retinoids exert their effects;(Ⅱ)why the clinical uses of retinoids give undesirable side effects of varying severity with a higher frequency of blood system symptoms;(Ⅲ)little is known for its impacts on macrophage cells etc.We set up this experiment,therefore,to examine the apoptosis of ATRA on macrophage Ana-1 cell line.Apoptosis of the cells was quantitated,after staining cells with propidium iodide(PI),by both accounting nuclear condensation and flow cytometry.When the cells were treated with ATRA at or higher than 1μM for more than 24h,significant amount of the apoptotic cells was observed.Induction of apoptosis of Ana-1 cells by ATRA was in time-and dose-dependent manners,exhibiting the similar pattern as the apoptosis induced by actinomycin D (ACTD).ATRA treatment of Ana-1 cells also caused the changes of the mRNA levels of apoptosis-associated gene bcl-2,as detected by Northern blot analysis.The temporal changes of bcl-2 expression by ATRA was also parallel to that by ACTD.In conclusion,ATRA can induce apoptosis in macrophage cells,which may be helpful in understanding of immunological functions retinoids.

  4. A PU.1 suppressive target gene, metallothionein 1G, inhibits retinoic acid-induced NB4 cell differentiation.

    Directory of Open Access Journals (Sweden)

    Naomi Hirako

    Full Text Available We recently revealed that myeloid master regulator SPI1/PU.1 directly represses metallothionein (MT 1G through its epigenetic activity of PU.1, but the functions of MT1G in myeloid differentiation remain unknown. To clarify this, we established MT1G-overexpressing acute promyelocytic leukemia NB4 (NB4MTOE cells, and investigated whether MT1G functionally contributes to all-trans retinoic acid (ATRA-induced NB4 cell differentiation. Real-time PCR analyses demonstrated that the inductions of CD11b and CD11c and reductions in myeloperoxidase and c-myc by ATRA were significantly attenuated in NB4MTOE cells. Morphological examination revealed that the percentages of differentiated cells induced by ATRA were reduced in NB4MTOE cells. Since G1 arrest is a hallmark of ATRA-induced NB4 cell differentiation, we observed a decrease in G1 accumulation, as well as decreases in p21WAF1/CIP1 and cyclin D1 inductions, by ATRA in NB4MTOE cells. Nitroblue tetrazolium (NBT reduction assays revealed that the proportions of NBT-positive cells were decreased in NB4MTOE cells in the presence of ATRA. Microarray analyses showed that the changes in expression of several myeloid differentiation-related genes (GATA2, azurocidin 1, pyrroline-5-carboxylate reductase 1, matrix metallopeptidase -8, S100 calcium-binding protein A12, neutrophil cytosolic factor 2 and oncostatin M induced by ATRA were disturbed in NB4MTOE cells. Collectively, overexpression of MT1G inhibits the proper differentiation of myeloid cells.

  5. Combination chemotherapy of doxorubicin, all-trans retinoic acid and low molecular weight heparin based on self-assembled multi-functional polymeric nanoparticles

    International Nuclear Information System (INIS)

    Based on the complementary effects of doxorubicin (DOX), all-trans retinoic acid (ATRA) and low molecular weight heparin (LMWH), the combination therapy of DOX, ATRA and LMWH was expected to exert the enhanced anti-tumor effects and reduce the side effects. In this study, amphiphilic LMWH–ATRA conjugate was synthesized for encapsulating the DOX. In this way, DOX, ATRA and LMWH were assembled into a single nano-system by both chemical and physical modes to obtain a novel anti-tumor targeting drug delivery system that can realize the simultaneous delivery of multiple drugs with different properties to the tumor. LMWH–ATRA nanoparticles exhibited good loading capacities for DOX with excellent physico-chemical properties, good biocompatibility, and good differentiation-inducing activity and antiangiogenic activity. The drug-loading capacity was up to 18.7% with an entrapment efficiency of 78.8%. It was also found that DOX-loaded LMWH–ATRA nanoparticles (DHR nanoparticles) could be efficiently taken up by tumor cells via endocytic pathway, and mainly distributed in cytoplasm at first, then transferred into cell nucleus. Cell viability assays suggested that DHR nanoparticles maintained the cytotoxicity effect of DOX on MCF-7 cells. Moreover, the in vivo imaging analysis indicated that DiR-loaded LMWH–ATRA nanoparticles could target the tumor more effectively as compared to free DiR. Furthermore, DHR nanoparticles possessed much higher anticancer activity and reduced side effects compared to free drugs solution. These results suggested that DHR nanoparticles could be considered as a promising targeted delivery system for combination cancer chemotherapy with lower adverse effects. (paper)

  6. Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region

    International Nuclear Information System (INIS)

    All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML–RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPε and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML

  7. Identification and characterization of an antennae-specific aldehyde oxidase from the navel orangeworm.

    Directory of Open Access Journals (Sweden)

    Young-Moo Choo

    Full Text Available Antennae-specific odorant-degrading enzymes (ODEs are postulated to inactivate odorant molecules after they convey their signal. Different classes of insect ODEs are specific to esters, alcohols, and aldehydes--the major functional groups of female-produced, hydrophobic sex pheromones from moth species. Esterases that rapidly inactive acetate and other esters have been well-studied, but less is known about aldehyde oxidases (AOXs. Here we report cloning of an aldehyde oxidase, AtraAOX2, from the antennae of the navel orangeworm (NOW, Amyelois transitella, and the first activity characterization of a recombinant insect AOX. AtraAOX2 gene spans 3,813 bp and encodes a protein with 1,270 amino acid residues. AtraAOX2 cDNA was expressed in baculovirus-infected insect Sf21 cells as a ≈280 kDa homodimer with 140 kDa subunits. Recombinant AtraAOX2 degraded Z11Z13-16Ald and plant volatile aldehydes as substrates. However, as expected for aldehyde oxidases, recombinant AtraAOX2 did not show specificity for Z11Z13-16Ald, the main constituent of the sex pheromone, but showed high activity for plant volatile aldehydes. Our data suggest AtraAOX2 might be involved in degradation of a diversity of aldehydes including sex pheromones, plant-derived semiochemicals, and chemical cues for oviposition sites. Additionally, AtraAOX2 could protect the insect's olfactory system from xenobiotics, including pesticides that might reach the sensillar lymph surrounding the olfactory receptor neurons.

  8. Reduction of stimulated sodium iodide symporter expression by estrogen receptor ligands in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Su-Jin; Jang, DooRye; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Katzenellenbogen, John A., E-mail: jkatzene@illinois.ed [Department of Chemistry, University of Illinois, Urbana, IL 61801 (United States); Kim, Dong Wook, E-mail: kimdw@chonbuk.ac.k [Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

    2011-02-15

    Purpose: The sodium iodide symporter (NIS) mediates active iodide uptake in lactating breast tissue, and when its levels are enhanced by all-trans retinoic acid (atRA), NIS has been proposed as a target for the imaging and radiotherapy of breast cancer. Importantly, the estrogen receptor {alpha} (ER{alpha}) is an important regulator of atRA induced NIS gene expression in breast cancer cells. In this study, we investigated the effect of an ER agonist (17{beta}-estradiol, E{sub 2}) or antagonist [trans-hydroxytamoxifen (TOT) or raloxifene (RAL)] treatment on the regulation of NIS gene expression and iodide uptake in an ER{alpha}-positive breast cancer (MCF-7) model. Methods: NIS functional activity was measured in vitro by {sup 125}I uptake assay after incubation with E{sub 2} (from 10{sup -15} to 10{sup -5} M), TOT (from 5x10{sup -8} to 5x10{sup -6} M), or RAL (from 5x10{sup -8} to 5x10{sup -6} M) in the presence or absence of atRA (10{sup -7} M). Under the same conditions, NIS mRNA expression was examined by reverse transcriptase polymerase chain reaction. Athymic mice with MCF-7 xenograft tumors were treated with atRA alone or atRA together with E{sub 2} to evaluate the change of {sup 125}I uptake in tumor tissues in vivo. Results: In the iodide uptake study in cells, E{sub 2}, TOT, or RAL treatment alone did not stimulate {sup 125}I uptake. However, when iodide uptake was stimulated by atRA, cotreatment with E{sub 2}, TOT or RAL decreased {sup 125}I uptake in a concentration-dependent manner. The hormone effects on NIS mRNA expression levels in MCF-7 cells were similar. The results of the in vivo biodistribution study showed that {sup 125}I uptake was reduced 50% in tumor tissues of mice treated with atRA/E{sub 2} as compared to tumors treated only with atRA. Conclusion: Our results suggest that combination treatment of atRA and ER ligands could limit the functional activity of the NIS gene induced by atRA, thereby compromising its use as a target for diagnosis

  9. All-Trans Retinoic Acid Induces Proliferation, Survival, and Migration in A549 Lung Cancer Cells by Activating the ERK Signaling Pathway through a Transcription-Independent Mechanism

    Science.gov (United States)

    Quintero Barceinas, Reyna Sara; García-Regalado, Alejandro; Aréchaga-Ocampo, Elena; Villegas-Sepúlveda, Nicolás; González-De la Rosa, Claudia Haydée

    2015-01-01

    All-trans retinoic acid (ATRA) has been used as an antineoplastic because of its ability to promote proliferation, inhibition, and differentiation, primarily in leukemia; however, in other types of cancer, such as lung cancer, treatment with ATRA is restricted because not all the patients experience the same results. The ERK signaling pathway is dysregulated in cancer cells, including lung cancer, and this dysregulation promotes proliferation and cell invasion. In this study, we demonstrate that treatment with ATRA can activate the ERK signaling pathway by a transcription-independent mechanism through a signaling cascade that involves RARα and PI3K, promoting growth, survival, and migration in lung cancer cells. Until now, this mechanism was unknown in lung cancer cells. The inhibition of the ERK signaling pathway restores the beneficial effects of ATRA, reduces proliferation, increases apoptosis, and blocks the cell migration process in lung cancer cells. In conclusion, our results suggest that the combination of ATRA with ERK inhibitor in clinical trials for lung cancer is warranted. PMID:26557664

  10. Lysyl oxidase-like 4 involvement in retinoic acid epithelial wound healing.

    Science.gov (United States)

    Comptour, Aurélie; Rouzaire, Marion; Belville, Corinne; Bonnin, Nicolas; Daniel, Estelle; Chiambaretta, Frédéric; Blanchon, Loïc; Sapin, Vincent

    2016-01-01

    Vitamin A and its active forms (retinoic acids/RAs) are known to have pro-healing properties, but their mechanisms of action are still poorly understood. This work aimed to identify the cellular and molecular processes by which atRA (all-trans RA) improves wound healing, using an in vivo model of mouse corneal alkali burns and an in vitro cellular human corneal epithelial injury model. Regulation by atRA has been studied on most of the cellular events that occur in wound healing. We investigated the direct influence of atRA on a specific target gene known to be involved in the extracellular matrix (ECM) dynamics, one of the pathways contributing to epithelial repair. Our results demonstrate that atRA promotes corneal epithelial wound healing by acting preferentially on migration. The induction of lysyl oxidase-like 4 (LOXL4) expression by atRA in the corneal epithelium environment was established as essential in the mechanism of atRA-dependent wound healing. Our study describes for the first time a direct link between a retinoic-induced gene and protein, LOXL4, and its general clinical pro-healing properties in ECM dynamics. PMID:27597564

  11. Study of Bcl-2 siRNA Enhancement of Sensitivity of HL-60 Cells to All Trans Retinoic Acid

    Institute of Scientific and Technical Information of China (English)

    Haiyan Hu; Yuan Zhang; Dongmei He

    2008-01-01

    OBJECTIVE To study whether siRNA targeting against the Bcl-2gene can enhance sensitivity of HL-60 cells to all trans retinoic acid (ATRA).METHODS siRNA, which is a leading sequence selected by previous experiments, was transferred into HL-60 cells. At 6 h after transfection, the cells were cultured with ATRA. The cell growth of the HL-60 cells was measured by the MTT assay at 24,48, 72 h. The level of the Bcl-2 protein and ROS (reactive oxygen species) as well as membrane potential of the mitochondria were determined by flowcytometry.RESULTS siRNA significantly increased the inhibitory effect of ATRA on growth of the HL-60 cells. The combination of siRNA with ATRA resulted in a decrease in the Bcl-2 protein level and an increase in the ROS level as well as significantly lowering the mitochondrial membrane potential of the HL-60 cells (P < 0.05).CONCLUSION Effective siRNA targeting of Bcl-2 increases the sensitivity of HL-60 leukemic cells to ATRA by inhibiting the expression of the Bcl-2 protein.

  12. Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin

    Institute of Scientific and Technical Information of China (English)

    Xia LIU; Lei L(U); Bei-bei TAO; Ai-ling ZHOU; Yi-chun ZHU

    2011-01-01

    Aim:To examine the effects of all-trans retinoic acid (atRA) on renal morphology and function as well as on renal plasminogen activator inhibitor-1 (PAI-1) expression and plasmin activity in rats with 5/6 nephrectomy.Methods:Adult male Sprague Dawley rats were given 5/6 nephrectomy or sham operation. Renal function was measured 2 weeks later. The nephrectomized rats were assigned to groups matched for proteinuria and treated with vehicle or atRA (5 or 10 mg/kg by gastric gavage once daily) for the next 12 weeks. Rats with sham operation were treated with vehicle. At the end of the treatments,kidneys were collected for histological examination, Western blot analysis, and enzymatic activity measurements.Results:The 5/6 nephrectomy promoted hypertension, renal dysfunction, and glomerulosclerosis. These changes were significantly reduced in the atRA-treated group. The expressions of PAI-1 and α-smooth muscle actin (α-SMA) were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAI-1 and α-SMA. However, piasmin activity remained unchanged following atRA treatment.Conclusion:Treatment with atRA ameliorates glomerulosclerosis and improves renal function in rats with 5/6 nephrectomy. This is associated with a decrease in PAI-1 and α-SMA, but not with a change in plasmin activity.

  13. Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663

    Directory of Open Access Journals (Sweden)

    Zhuan Zhou

    2011-04-01

    Full Text Available Abstract Background Differentiation of the acute myeloid leukemia (AML cell line HL-60 can be induced by all trans-retinoic acid (ATRA; however, the mechanism regulating this process has not been fully characterized. Methods Using bioinformatics and in vitro experiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation. Results Six microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV backbone incorporating the spleen focus forming virus (SFFV-F promoter to drive miR-663 expression, as the CMV (Cytomegalovirus promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiation in vitro. Conclusions Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies

  14. Growth Inhibition and Apoptosis Induced by Retinoic Acid Combined with Interferon Alpha-2a on Transitional Cell Carcinoma of Bladder

    Institute of Scientific and Technical Information of China (English)

    QIANLi-xin; LIUXun-liang; ZHOUJian-wei; MonicaLiebert; ZOUChang-chun; ZOUChang-ping

    2004-01-01

    To identify new favorable agents and develop novel approaches for the chemoprevention and treatment of superficial bladder cancer and invesligate the effects of combination of relinoids and interferon α-2a on growth inhibition and apoptosis induction in bladder cancer cell lines. Methods: Four bladder cancer cell lines, grade 1 to 3,and two retinoids, all-trans-retinoic acid(ATRA) ,9.cis retinoic acid(9cRA) ,combined with inteferon α-2a(INF),were used in the study.We compared the competence of these agents to inhibit growth, induce apoptosis, affect the exptession of nuclear retinoid receptors, and modulate STAT1 protein. Resu/ts: Most of the bladder cancer cell lines were resistant to the effect of ATRA and 9cRA on growth inhibition and apoptosis induction, even at higher concentration (10-5M).The effects of ATRA and 9c RA on cell growth and apoptosis were enhanced by INF α-2a.Combination of ATRA and IFNa-2a induced ~ and Slat 1 expression in three bladder cancer cell lines, ~: The results demonstrated that INFw2a synergize with the inhibitory effect of ATRA and 9c RA on the growth intn'bition and apoptosis of bladder cancer cells in vitro, which suggested that it has a potenlJal intexest for the trealment of transitimml cell carcinmna of bladder.

  15. Perlecan Heparan Sulfate Is Required for the Inhibition of Smooth Muscle Cell Proliferation by All-trans-Retinoic Acid.

    Science.gov (United States)

    Tran-Lundmark, Karin; Tannenberg, Philip; Rauch, Bernhard H; Ekstrand, Johan; Tran, Phan-Kiet; Hedin, Ulf; Kinsella, Michael G

    2015-02-01

    Smooth muscle cell (SMC) proliferation is a key process in stabilization of atherosclerotic plaques, and during restenosis after interventions. A clearer understanding of SMC growth regulation is therefore needed to design specific anti-proliferative therapies. Retinoic acid has been shown to inhibit proliferation of SMCs both in vitro and in vivo and to affect the expression of extracellular matrix molecules. To explore the mechanisms behind the growth inhibitory activity of retinoic acid, we hypothesized that retinoids may induce the expression of perlecan, a large heparan sulfate proteoglycan with anti-proliferative properties. Perlecan expression and accumulation was induced in murine SMC cultures by all-trans-retinoic acid (AtRA). Moreover, the growth inhibitory effect of AtRA on wild-type cells was greatly diminished in SMCs from transgenic mice expressing heparan sulfate-deficient perlecan, indicating that the inhibition is perlecan heparan sulfate-dependent. In addition, AtRA influenced activation and phosphorylation of PTEN and Akt differently in wild-type and mutant SMCs, consistent with previous studies of perlecan-dependent SMC growth inhibition. We demonstrate that AtRA regulates perlecan expression in SMCs and that the inhibition of SMC proliferation by AtRA is, at least in part, secondary to an increased expression of perlecan and dependent upon its heparan sulfate-chains. PMID:25078760

  16. The impact on outcome of the addition of all-trans retinoic acid to intensive chemotherapy in younger patients with nonacute promyelocytic acute myeloid leukemia: overall results and results in genotypic subgroups defined by mutations in NPM1, FLT3, and CEBPA.

    Science.gov (United States)

    Burnett, Alan K; Hills, Robert K; Green, Claire; Jenkinson, Sarah; Koo, Kenneth; Patel, Yashma; Guy, Carol; Gilkes, Amanda; Milligan, Donald W; Goldstone, Anthony H; Prentice, Archibald G; Wheatley, Keith; Linch, David C; Gale, Rosemary E

    2010-02-01

    We investigated the benefit of adding all-trans retinoic acid (ATRA) to chemotherapy for younger patients with nonacute promyelocytic acute myeloid leukemia and high-risk myelodysplastic syndrome, and considered interactions between treatment and molecular markers. Overall, 1075 patients less than 60 years of age were randomized to receive or not receive ATRA in addition to daunorubicin/Ara-C/thioguanine chemotherapy with Ara-C at standard or double standard dose. There were data on FLT3 internal tandem duplications and NPM1 mutations (n = 592), CEBPA mutations (n = 423), and MN1 expression (n = 195). The complete remission rate was 68% with complete remission with incomplete count recovery in an additional 16%; 8-year overall survival was 32%. There was no significant treatment effect for any outcome, with no significant interactions between treatment and demographics, or cytarabine randomization. Importantly, there were no interactions by FLT3/internal tandem duplications, NPM1, or CEBPA mutation. There was a suggestion that ATRA reduced relapse in patients with lower MN1 levels, but no significant effect on overall survival. Results were consistent when restricted to patients with normal karyotype. ATRA has no overall effect on treatment outcomes in this group of patients. The study did not identify any subgroup of patients likely to derive a significant survival benefit from the addition of ATRA to chemotherapy. PMID:19965647

  17. Effects of All-trans Retinoic Acid on hTERT Gene Expression and Telomerase Activity of HL-60 Cells

    Institute of Scientific and Technical Information of China (English)

    HEDongmei; ZHANGYuan

    2003-01-01

    Objective: To investigate the effects of all-trans retinoic acid (ATRA) on human telomerase reverse transcriptase (hTERT) protein expression and telomerase activity in HL-60 cells. Methods: The expression of hTERT protein was assayed by immunofluorescence using fluoresce isothiocyanate label and telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay with HL-60 cells untreated or treated with ATRA. Cell cycle was analyzed by flow cytometry. Results: After treatment with 1μmol/L ATRA for 24, 48, 72 h, mean fluorescence intensity of hTERT protein in HL-60 cells was 61.87±4.36, 37.47±2.85, 33.45±2.37,respectively. There was a significant decrease in hTERT protein expression compared to the cells untreated, and the effect had statistically significant difference (P<0.05).Telomerase activity was decreased significantly in HL-60 cells treated with 1μmol/L ATRA for 48, 72h as compared to the cells untreated (P<0.05). Conclusion: ATRA could inhibit telomerase activity and hTERT gene expression in HL-60 cells.

  18. Vav promotes differentiation of human tumoral myeloid precursors

    International Nuclear Information System (INIS)

    Vav is one of the genetic markers that correlate with the differentiation of hematopoietic cells. In T and B cells, it appears crucial for both development and functions, while, in non-lymphoid hematopoietic cells, Vav seems not involved in cell maturation, but rather in the response of mature cells to agonist-dependent proliferation and phagocytosis. We have previously demonstrated that the amount and the tyrosine phosphorylation of Vav are up-regulated in both whole cells and nuclei of tumoral promyelocytes induced to granulocytic maturation by ATRA and that tyrosine-phosphorylated Vav does not display any ATRA-induced GEF activity but contributes to the regulation of PI 3-K activity. In this study, we report that Vav accumulates in nuclei of ATRA-treated APL-derived cells and that the down-modulation of Vav prevents differentiation of tumoral promyelocytes, indicating that it is a key molecule in ATRA-dependent myeloid maturation. On the other hand, the overexpression of Vav induces an increased expression of surface markers of granulocytic differentiation without affecting the maturation-related changes of the nuclear morphology. Consistent with an effect of Vav on the transcriptional machinery, array profiling shows that the inhibition of the Syk-dependent tyrosine phosphorylation of Vav reduces the number of ATRA-induced genes. Our data support the unprecedented notion that Vav plays crucial functions in the maturation process of myeloid cells, and suggest that Vav can be regarded as a potential target for the therapeutic treatment of myeloproliferative disorders

  19. Apoptotic effect and mechanisms of AHPN on human skin malignant melanoma cell A375

    Institute of Scientific and Technical Information of China (English)

    Min Pan; Zhenhui Peng; Shengxiang Xiao; Jianwen Ren; Yan Liu; Xiaoli Li; Zhengxiao Li

    2008-01-01

    Objective: To study apoptotic effects of synthetic retinoic acid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid(AHPN) on human skin malignant melanoma A375 cells in comparison with the natural iigand all-trans-retinoic acid(ATRA) in vitro and the mechanisms related to the actions of AHPN. Methods:MTT assay was used to determine the anti-proliferative effects of AHPN and ATRA on A375 cells. Flow cytometry was performed to investigate the influence of AHPN and ATRA on cell cycle and cell apoptosis. In addition, transfection and luciferase activity assays were employed to explore the mechanisms of how AHPN executes its proapoptotic function. Results:Firstly, AHPN promoted apoptosis and G1 arrest in A375 cells compared with ATRA. Secondly, the activity of NF-kB in A375 cells treated with AHPN increased 2-3 times compared with solvent DMSO treatment. Conelusion:AHPN,in comparison with ATRA, is a more effective alternative for therapy of malignant melanoma. The potentially proapoptotic function of AHPN requires activation of NF-kB.

  20. Arsenic trioxide and all-trans retinoic acid target NPM1 mutant oncoprotein levels and induce apoptosis in NPM1-mutated AML cells.

    Science.gov (United States)

    Martelli, Maria Paola; Gionfriddo, Ilaria; Mezzasoma, Federica; Milano, Francesca; Pierangeli, Sara; Mulas, Floriana; Pacini, Roberta; Tabarrini, Alessia; Pettirossi, Valentina; Rossi, Roberta; Vetro, Calogero; Brunetti, Lorenzo; Sportoletti, Paolo; Tiacci, Enrico; Di Raimondo, Francesco; Falini, Brunangelo

    2015-05-28

    Nucleophosmin (NPM1) mutations represent an attractive therapeutic target in acute myeloid leukemia (AML) because they are common (∼30% AML), stable, and behave as a founder genetic lesion. Oncoprotein targeting can be a successful strategy to treat AML, as proved in acute promyelocytic leukemia by treatment with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO), which degrade the promyelocytic leukemia (PML)-retinoic acid receptor fusion protein. Adjunct of ATRA to chemotherapy was reported to be beneficial for NPM1-mutated AML patients. Leukemic cells with NPM1 mutation also showed sensibility to ATO in vitro. Here, we explore the mechanisms underlying these observations and show that ATO/ATRA induce proteasome-dependent degradation of NPM1 leukemic protein and apoptosis in NPM1-mutated AML cell lines and primary patients' cells. We also show that PML intracellular distribution is altered in NPM1-mutated AML cells and reverted by arsenic through oxidative stress induction. Interestingly, similarly to what was described for PML, oxidative stress also mediates ATO-induced degradation of the NPM1 mutant oncoprotein. Strikingly, NPM1 mutant downregulation by ATO/ATRA was shown to potentiate response to the anthracyclin daunorubicin. These findings provide experimental evidence for further exploring ATO/ATRA in preclinical NPM1-mutated AML in vivo models and a rationale for exploiting these compounds in chemotherapeutic regimens in clinics. PMID:25795919

  1. In silico modelling of a cancer stem cell-targeting agent and its effects on tumour control during radiotherapy

    Science.gov (United States)

    Marcu, Loredana G.; Marcu, David

    2016-01-01

    Head and neck cancers (HNC), like most solid tumours, contain a subpopulation of cancer stem cells (CSC) that are commonly responsible for treatment failure. Conventional therapies are unsuccessful in controlling CSCs, thus novel, targeting therapies are needed. A promising agent is ATRA (All-trans-retinoic acid) that was shown to induce CSC differentiation, cell cycle redistribution and CSCs radiosensitisation. To add to the limited data, this work simulated the effects of ATRA on a virtual HNC and evaluated tumour response to radiotherapy. A Monte Carlo technique was employed to grow a HNC consisting of all lineages of cancer cells. The biologically realistic input parameters led to a pre-treatment CSC population of 5.9%. The Linear Quadratic model was employed to simulate radiotherapy. ATRA-induced differentiation, cell arrest and apoptosis were modelled, based on literature data. While the effect of differentiation was marginal, the strongest influence on CSC subpopulation was displayed by ATRA’s cell arrest effect via an exponential behaviour of the dose-response curve. The apoptotic effect induced by ATRA shows linear correlation between the percentage of apoptotic cells and dose required to eradicate CSCs. In conclusion, ATRA is a potent CSC-targeting agent with viable impact on tumour control when combined with radiotherapy. PMID:27573059

  2. Retinoic acid decreases the severity of Salmonella enterica serovar Typhimurium mediated gastroenteritis in a mouse model.

    Science.gov (United States)

    Sinha, Ritam; Howlader, Debaki Ranjan; Mukherjee, Priyadarshini; Rai, Sulabh; Nag, Dhrubajyoti; Koley, Hemanta

    2016-07-01

    Gastroenteritis is a global burden; it's the major cause of morbidity and mortality both in adults and children of developing countries. Salmonella is one of the leading causes of bacteria-mediated gastroenteritis and due to its increasing multidrug antibiotic resistance; Salmonella-mediated gastroenteritis is difficult to control. Retinoic acid, the biologically active agent of vitamin A has an anti-inflammatory effect on experimental colitis. In this study we have shown All trans retinoic acid (ATRA) treatment down regulates Salmonella-mediated colitis in a murine model. Macroscopic signs of inflammation such as decrease in body weight and cecum weight, shorter length of proximal colon and pathological score of colitis were observed less in ATRA treated mice than in a vehicle control group. ATRA treatment not only reduced pro-inflammatory cytokine responses, such as TNF-α, IL-6, IL-1β, IFN-γ and IL-17 production but also increased IL-10 response in the supernatant of intestinal tissue. Results also suggested that ATRA treatment enhances the number of FoxP3-expressing T regulatory cells in MLN and also decreases bacterial load in systemic organs. We concluded that ATRA treatment indeed reduces Salmonella Typhimurium-mediated gastroenteritis in mice, suggesting it could be an important part of an alternative therapeutic approach to combat the disease. PMID:26858186

  3. A novel PAD4/SOX4/PU.1 signaling pathway is involved in the committed differentiation of acute promyelocytic leukemia cells into granulocytic cells.

    Science.gov (United States)

    Song, Guanhua; Shi, Lulu; Guo, Yuqi; Yu, Linchang; Wang, Lin; Zhang, Xiaoyu; Li, Lianlian; Han, Yang; Ren, Xia; Guo, Qiang; Bi, Kehong; Jiang, Guosheng

    2016-01-19

    All-trans retinoic acid (ATRA) treatment yields cure rates > 80% through proteasomal degradation of the PML-RARα fusion protein that typically promotes acute promyelocytic leukemia (APL). However, recent evidence indicates that ATRA can also promote differentiation of leukemia cells that are PML-RARα negative, such as HL-60 cells. Here, gene expression profiling of HL-60 cells was used to investigate the alternative mechanism of impaired differentiation in APL. The expression of peptidylarginine deiminase 4 (PADI4), encoding PAD4, a protein that post-translationally converts arginine into citrulline, was restored during ATRA-induced differentiation. We further identified that hypermethylation in the PADI4 promoter was associated with its transcriptional repression in HL-60 and NB4 (PML-RARα positive) cells. Functionally, PAD4 translocated into the nucleus upon ATRA exposure and promoted ATRA-mediated differentiation. Mechanistic studies using RNAi knockdown or electroporation-mediated delivery of PADI4, along with chromatin immunoprecipitation, helped identify PU.1 as an indirect target and SOX4 as a direct target of PAD4 regulation. Indeed, PAD4 regulates SOX4-mediated PU.1 expression, and thereby the differentiation process, in a SOX4-dependent manner. Taken together, our results highlight an association between PAD4 and DNA hypermethylation in APL and demonstrate that targeting PAD4 or regulating its downstream effectors may be a promising strategy to control differentiation in the clinic. PMID:26673819

  4. Potential role of nuclear receptor ligand all-trans retinoic acids in the treatment of fungal keratitis

    Directory of Open Access Journals (Sweden)

    Hong-Yan Zhou

    2015-08-01

    Full Text Available Fungal keratitis (FK is a worldwide visual impairment disease. This infectious fungus initiates the primary innate immune response and, later the adaptive immune response. The inflammatory process is related to a variety of immune cells, including macrophages, helper T cells, neutrophils, dendritic cells, and Treg cells, and is associated with proinflammatory, chemotactic and regulatory cytokines. All-trans retinoic acids (ATRA have diverse immunomodulatory actions in a number of inflammatory and autoimmune conditions. These retinoids regulate the transcriptional levels of target genes through the activation of nuclear receptors. Retinoic acid receptor α (RAR α, retinoic acid receptor γ (RAR γ, and retinoid X receptor α (RXR α are expressed in the cornea and immune cells. This paper summarizes new findings regarding ATRA in immune and inflammatory diseases and analyzes the perspective application of ATRA in FK.

  5. Potential role of nuclear receptor ligand all-trans retinoic acids in the treatment of fungal keratitis

    Institute of Scientific and Technical Information of China (English)

    Hong-Yan; Zhou; Wei; Zhong; Hong; Zhang; Miao-Miao; Bi; Shuang; Wang; Wen-Song; Zhang

    2015-01-01

    ·Fungal keratitis(FK) is a worldwide visual impairment disease. This infectious fungus initiates the primary innate immune response and, later the adaptive immune response. The inflammatory process is related to a variety of immune cells, including macrophages, helper T cells, neutrophils, dendritic cells, and Treg cells, and is associated with proinflammatory, chemotactic and regulatory cytokines. All-trans retinoic acids(ATRA)have diverse immunomodulatory actions in a number of inflammatory and autoimmune conditions. These retinoids regulate the transcriptional levels of target genes through the activation of nuclear receptors.Retinoic acid receptor α(RAR α), retinoic acid receptor γ(RAR γ), and retinoid X receptor α(RXR α) are expressed in the cornea and immune cells. This paper summarizes new findings regarding ATRA in immune and inflammatory diseases and analyzes the perspective application of ATRA in FK.

  6. Spatial and temporal characteristics of rainfall across Ganjiang River Basin in China

    Science.gov (United States)

    Xiao, Yang; Zhang, Xiang; Wan, Hui; Wang, Yeqiao; Liu, Cheng; Xia, Jun

    2016-04-01

    The hydrological variations of Ganjiang River Basin have significant influence on the ecological environment of Poyang Lake, which is one of the largest freshwater lake and wetland in the world. This study analyzed the spatial and temporal characteristics of rainfall across Ganjiang River Basin. The analyses include annual total rainfall amount (ATRA), annual total rainy day (ATRD) and annual mean daily rainfall intensity (AMDRI). To detect changes in the hydrological trends, data from 19 rainfall stations from 1953 to 2013 were used in the analyses. First, quality control and homogeneity detection was carried out to examine the annual rainfall series. Second, the spatial correlation analysis was used to identify the spatial relationship among the measurements from different stations. Finally, the statistics of coefficient of variation (CV) and average were used to analyze the interannual variation trend. The modified Mann-Kendall (MMK) trend test method was used to detect the temporal characteristics of rainfall. The results include: (1) Some outliers were detected and corrected. (2) The correlation of ATRA and ATRD series of all the stations had lower spatial variability while the AMDRI series of all the stations had higher spatial variability. On the other hand, the ATRA, ATRD and AMDRI series of single stations show similar spatial variability and the influencing radius of the rainfall events was less than 50 km. (3) the rainfall at the northern and southern parts of the basin had smaller CV. Further, by applying the MMK test method to the ATRA, ATRD, and AMDRI series, the ATRA series has an increasing trend which is opposite to that of the ATRD series. The increasing trend in the ATRA series also led to the increasing trend in the AMDRI series. These stations are mainly in central and northern parts of the basin which are more likely to experience droughts and floods. Thus, for the central and northern parts of the basin, they should receive particular

  7. Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.

    Science.gov (United States)

    Wu, Lizhi; Chaudhary, Sandeep C; Atigadda, Venkatram R; Belyaeva, Olga V; Harville, Steven R; Elmets, Craig A; Muccio, Donald D; Athar, Mohammad; Kedishvili, Natalia Y

    2016-01-01

    UAB30 is an RXR selective agonist that has been shown to have potential cancer chemopreventive properties. Due to high efficacy and low toxicity, it is currently being evaluated in human Phase I clinical trials by the National Cancer Institute. While UAB30 shows promise as a low toxicity chemopreventive drug, the mechanism of its action is not well understood. In this study, we investigated the effects of UAB30 on gene expression in human organotypic skin raft cultures and mouse epidermis. The results of this study indicate that treatment with UAB30 results in upregulation of genes responsible for the uptake and metabolism of all-trans-retinol to all-trans-retinoic acid (ATRA), the natural agonist of RAR nuclear receptors. Consistent with the increased expression of these genes, the steady-state levels of ATRA are elevated in human skin rafts. In ultraviolet B (UVB) irradiated mouse skin, the expression of ATRA target genes is found to be reduced. A reduced expression of ATRA sensitive genes is also observed in epidermis of mouse models of UVB-induced squamous cell carcinoma and basal cell carcinomas. However, treatment of mouse skin with UAB30 prior to UVB irradiation prevents the UVB-induced decrease in expression of some of the ATRA-responsive genes. Considering its positive effects on ATRA signaling in the epidermis and its low toxicity, UAB30 could be used as a chemoprophylactic agent in the treatment of non-melanoma skin cancer, particularly in organ transplant recipients and other high risk populations. PMID:27078158

  8. All-trans retinoic acid as a single agent induces complete remission in a patient with acute leukemia of M2a subtype

    Institute of Scientific and Technical Information of China (English)

    陈子兴; 王阳; 王玮; 贡静霞; 薛永权

    2002-01-01

    Objective To present a special case with the karyotype and molecular marker of acute myeloid leukemia (AML)-M2 who was induced to complete remission by all-trans retinoic acid (ATRA) alone.Methods A recently hospitalized young female patient with acute leukemia was initially diagnosed as M3 subtype based on morphological French-American-British (FAB) classification. Karyotype analysis using standard G and R banding techniques and RT-PCR were applied to further define the diagnosis. After primarily cultured bone marrow cells from the iliac aspiration were tested for in vitro induced differentiation, the patient was treated with oral all-trans retinoic acid alone, 60?mg per day until complete remission was achieved. Peripheral blood and bone marrow changes were monitored over the whole treatment course.Results The characteristic chromosomal aberration for M3, the t(15;17) reciprocal translocation, was not found while a t(8;21) translocation was verified. Furthermore, an amplified product of the AML-1/ETO fusion gene instead of the PML/RARα fusion gene was detected by RT-PCR and the diagnosis was corrected from M3 to M2. Primary cultured bone marrow cells can be fully induced to terminal differentiation after 4 days exposure to ATRA. A hematological complete remission was achieved after 40 days treatment with ATRA as a single therapeutic agent, suggesting an alternative pathway mediating ATRA-induced myeloid differentiation. Conclusion A leukemia patient with a subtype other than M3, such as M2 in this case, may also be induced to complete remission by the mechanism of ATRA-induced terminal differentiation. This implies that there may be a pathway other than PML/RARα fusion gene product which mediates ATRA-induced myeloid maturation in leukemia cells.

  9. Ex vivo immunomodulatory effect of all-trans-retinoic acid during Behçet's disease: a study in Algerian patients.

    Science.gov (United States)

    Djeraba, Zineb; Boumedine, Karim; Arroul-Lammali, Amina; Otmani, Fifi; Belguendouz, Houda; Touil-Boukoffa, Chafia

    2014-02-01

    Uveitis, recurrent oral and genital ulcerations associated with skin lesions are the major symptoms of a chronic multisystemic inflammatory disorder known as Behçet's disease (BD). High prevalence of this dreaded disease has been observed in the Mediterranean basin, including Algeria and along the Silk Road. Although the etiologic agent of this disease remains uncertain, many hypotheses have been advanced in its pathogenesis. Our team has previously reported high levels of nitric oxide (NO) in sera of BD patients, suggesting its deleterious effect during chronic inflammation. In our current study, the aim is to investigate the ex vivo immunomodulatory effect of all-trans-retinoic acid (ATRA) on NO pathway in Algerian BD patients. First, peripheral blood mononuclear cells isolated from active and inactive BD patients and healthy controls were cultured with different concentrations of ATRA. NO production was estimated with the Griess method. To elucidate the underlying mechanisms of ATRA effect on NO production, we analyze inducible nitric oxide synthase expression and nuclear factor-κB (NF-κB) activity by immunofluorescence test. Our results revealed a higher production of NO in active BD compared with the inactive stage and healthy controls. We observed that ATRA inhibits NO production in BD both in active and inactive stages and inhibits NF-κB translocation. In conclusion, we report a relationship between NO production and the disease activity. ATRA down-regulates NO production in BD patients. This immunomodulatory effect seems to be mediated through NF-κB pathway. All these findings suggest that ATRA could be considered as a promising therapy for BD. PMID:24369064

  10. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  11. Loss-of-Function of HtrA1 Abrogates All-Trans Retinoic Acid-Induced Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells Through Deficiencies in p70S6K Activation.

    Science.gov (United States)

    Glanz, Stephan; Mirsaidi, Ali; López-Fagundo, Cristina; Filliat, Gladys; Tiaden, André N; Richards, Peter J

    2016-05-01

    All-trans retinoic acid (ATRA) is a potent inducer of osteogenic differentiation in mouse adipose-derived stromal cells (mASCs), although the underlying mechanisms responsible for its mode of action have yet to be completely elucidated. High temperature requirement protease A1 (HtrA1) is a newly recognized modulator of human multipotent stromal cell (MSC) osteogenesis and as such, may play a role in regulating ATRA-dependent osteogenic differentiation of mASCs. In this study, we assessed the influence of small interfering RNA (siRNA)-induced repression of HtrA1 production on mASC osteogenesis and examined its effects on ATRA-mediated mammalian target of rapamycin (mTOR) signaling. Inhibition of HtrA1 production in osteogenic mASCs resulted in a significant reduction of alkaline phosphatase activity and mineralized matrix formation. Western blot analyses revealed the rapid activation of Akt (Ser473) and p70S6K (Thr389) in ATRA-treated mASCs, and that levels of phosphorylated p70S6K were noticeably reduced in HtrA1-deficient mASCs. Further studies using mTOR inhibitor rapamycin and siRNA specific for the p70S6K gene Rps6kb1 confirmed ATRA-mediated mASC osteogenesis as being dependent on p70S6K activation. Finally, transfection of cells with a constitutively active rapamycin-resistant p70S6K mutant could restore the mineralizing capacity of HtrA1-deficient mASCs. These findings therefore lend further support for HtrA1 as a positive mediator of MSC osteogenesis and provide new insights into the molecular mode of action of ATRA in regulating mASC lineage commitment. PMID:26950191

  12. Comparison of anthracycline-based combination chemotherapy with or without all-trans retinoic acid in acute promyelocytic leukemia

    International Nuclear Information System (INIS)

    To compare survival in Acute Promyelocytic Leukemia (APL) patients treated with or without All-Trans Retinoic Acid (ATRA). Longitudinal, comparative study. All consecutive newly diagnosed patients of acute promyelocytic leukemia, treated at Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, between May 2001 and April 2007, were included and given chemotherapy according to availability of ATRA. Diagnosis was confirmed on morphology/ karyotyping/ molecular analysis. Eligibility criteria included confirmed morphologic diagnosis and/or by demonstration of t(15;17) and/or PML/RAR macro re-arrangement, no prior chemotherapy, normal hepatic and renal function, Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 and no contraindications to ATRA (history of sensitivity to Vit. A or other retinoids). All patients having history of cardiac failure (LVEF 150 macro mol/L and pregnancy were excluded from this study. Survival was calculated from the date of chemotherapy to death or last follow-up according to Kaplan-Meier and Cox (Proportional hazard) regression analysis methods. During the 6 years study period, 31 newly diagnosed patients with acute promyelocytic leukemia received treatment at AFBMTC. Seventeen patients received anthracycline-based remission induction and consolidation chemotherapy, while 14 received ATRA-based remission induction, consolidation and by two years maintenance therapy. Overall Survival (OS), Disease Free Survival (DFS) and mortality were 29.4%, 29.4% and 70.6% respectively in 17 patients who received anthracycline based chemotherapy, whereas in patients who received ATRA-based chemotherapy OS, DFS and mortality was 71.4%, 64.2% and 28.6% respectively. Major causes of mortality were septicemia and chemotherapy related toxicity. Response to ATRA-based chemotherapy in patient cohort was better as compared with anthracycline based chemotherapy (71.4% vs. 29.4%) in terms of survival and mortality. (author)

  13. Retinoid receptor-specific agonists regulate bovine in vitro early embryonic development, differentiation and expression of genes related to cell cycle arrest and apoptosis.

    Science.gov (United States)

    Rodríguez, A; Díez, C; Caamaño, J N; de Frutos, C; Royo, L J; Muñoz, M; Ikeda, S; Facal, N; Alvarez-Viejo, M; Gómez, E

    2007-11-01

    A major goal in reproductive biotechnology is the identification of pathways that regulate early embryonic development and the allocation of cells to the inner cell mass (ICM) and trophectoderm (TE). Retinoids regulate the development and differentiation of the bovine blastocyst in vitro, although the involvement of the retinoid X receptors (RXRs) remains to be clarified. This paper compares the effect of a synthetic RXR agonist (LG100268; LG) with that of the retinoic acid receptor (RAR) agonist all-trans retinoic acid (ATRA) on blastulation. In vitro-produced morulae were treated for 48 h with LG (0.1 microM, 1 microM and 10 microM), ATRA 0.7 microM, or no additives. Treatment with ATRA did not increase the rate of development; however, the LG 0.1 microM treatment increased both the blastocyst development and hatching rate. Cell numbers increased in the ICM with LG 10 microM, while a dose-dependent reduction was observed in the TE in the presence of LG. Gene expression levels of p53 and p66 did not vary with LG but increased with ATRA. Both LG and ATRA activated bax, a pro-apoptotic gene and H2A.Z, a cell cycle-related gene. The above effects suggest the existence of active p53-dependent and -independent apoptotic pathways for ATRA and LG, respectively, in the bovine embryo. The expression of p53 and H2A.Z showed a strong, positive correlation (r=0.93; pdevelopment and differentiation. PMID:17869331

  14. Development and quality of bovine morulae cultured in serum-free medium with specific retinoid receptor agonists.

    Science.gov (United States)

    Gómez, Enrique; Rodríguez, Aida; Muñoz, Marta; Caamaño, José Néstor; Carrocera, Susana; Martín, David; Facal, Nieves; Díez, Carmen

    2008-01-01

    Retinoids regulate development and differentiation of the bovine blastocyst in vitro, although the underlying mechanisms remain to be clarified. A challenge in reproductive biotechnology is the identification of pathways that regulate early embryonic development and their influence on blastocyst differentiation, apoptosis and survival to cryopreservation as traits of embryo quality. The present paper analyses the effects of short-term exposure (24 h) to retinoids on in vitro-produced bovine morulae. Immature cumulus oocyte complexes were in vitro matured and fertilised. Presumptive zygotes were subsequently cultured in modified synthetic oviduct fluid up to Day 6, in which morulae were randomly allocated to the different experimental groups. The treatments consisted of 0.1 microM LG100268 (LG; a retinoid X receptor agonist), 0.7 microM all-trans retinoic acid (ATRA; a retinoic acid receptor agonist) or no additives. Day 8 blastocyst development was increased in the ATRA-treated group compared with the LG and untreated embryos. In Day 7 embryos, the number of total cells and cells allocated to the trophectoderm were higher in the ATRA-treated group compared with untreated embryos. Apoptosis in the inner cell mass increased after LG treatment, whereas ATRA had no effect. After vitrification and warming, survival and hatching rates of Day 7 blastocysts did not change with retinoid treatment. Within the LG-treated and untreated blastocyst groups, survival and hatching rates were higher for Day 7 than Day 8 embryos; however, Day 8 blastocysts treated with ATRA showed improved hatching rates. In conclusion, treatment of morulae with ATRA in serum-free medium improves embryo development and quality without increasing the incidence of apoptosis and necrosis. PMID:19007552

  15. Protective effect of ginsenoside Rb1 against intestinal ischemia-reperfusion induced acute renal injury in mice.

    Directory of Open Access Journals (Sweden)

    Qian Sun

    Full Text Available Ginsenoside Rb1 (RB1, the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA was used as an inhibitor of NF-E2-related factor-2 (Nrf2 signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1 sham group, (2 IIR group, (3 RB1 group, (4 sham + ATRA group, (5 IIR + ATRA group, and (6 RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO. Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN, serum creatinine (Scr and neutrophil gelatinase-associated lipocalin (NGAL, which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1 and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE pathway.

  16. Retinoid X Receptor Agonists Upregulate Genes Responsible for the Biosynthesis of All-Trans-Retinoic Acid in Human Epidermis.

    Directory of Open Access Journals (Sweden)

    Lizhi Wu

    Full Text Available UAB30 is an RXR selective agonist that has been shown to have potential cancer chemopreventive properties. Due to high efficacy and low toxicity, it is currently being evaluated in human Phase I clinical trials by the National Cancer Institute. While UAB30 shows promise as a low toxicity chemopreventive drug, the mechanism of its action is not well understood. In this study, we investigated the effects of UAB30 on gene expression in human organotypic skin raft cultures and mouse epidermis. The results of this study indicate that treatment with UAB30 results in upregulation of genes responsible for the uptake and metabolism of all-trans-retinol to all-trans-retinoic acid (ATRA, the natural agonist of RAR nuclear receptors. Consistent with the increased expression of these genes, the steady-state levels of ATRA are elevated in human skin rafts. In ultraviolet B (UVB irradiated mouse skin, the expression of ATRA target genes is found to be reduced. A reduced expression of ATRA sensitive genes is also observed in epidermis of mouse models of UVB-induced squamous cell carcinoma and basal cell carcinomas. However, treatment of mouse skin with UAB30 prior to UVB irradiation prevents the UVB-induced decrease in expression of some of the ATRA-responsive genes. Considering its positive effects on ATRA signaling in the epidermis and its low toxicity, UAB30 could be used as a chemoprophylactic agent in the treatment of non-melanoma skin cancer, particularly in organ transplant recipients and other high risk populations.

  17. Leukocyte and leukocyte function

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950368 A study on the relationship hetween morphol-ogy and gene hepterogeneity in acute promyelocyticleukemia.XIONG Shumin(熊树民),et al.shanghaiHematol Instit & Ruijin Hosp,Shanghai,200025.ChinJ Intern Med 1995;34(3):165-168.Aucte promyelocytic leukemia (APL) can be treatedby all-trans retinoic acid (ATRA) with high completeremission rate.50 cases of APL diagnosed morphologi-cally were studied on their cytogenetics,molecular bi-ology and response to treatment with ATRA.Fortyfive cases showed chromosomal translocation t(5;17)and PML/RAR α fusion gene (PML+RARα+APL)

  18. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells.

    Directory of Open Access Journals (Sweden)

    Zhenya Gao

    Full Text Available All-trans retinoic acid (ATRA plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2 and matrix metalloproteinase 2 (MMP-2 and to explore the signaling pathway of retinoic acid in cultured acute retinal pigment epithelial 19 (ARPE-19 cells.The effects of ATRA (concentrations from 10-9 to 10-5 mol/l on the expression of retinoic acid receptors (RARs in ARPE-19 cells were examined at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR and western blot assay, respectively. The effects of treating ARPE-19 cells with ATRA concentrations ranging from 10-9 to 10-5 mol/l for 24 h and 48 h or with 10-6mol/l ATRA at different times ranging from 6h to 72h were assessed using real-time quantitative PCR (qPCR and enzyme-linked immunosorbent assay (ELISA. The contribution of RARβ-induced activation of ARPE-19 cells was confirmed using LE135, an antagonist of RARβ.RARβ mRNA levels significantly increased in the ARPE-19 cells treated with ATRA for 24h and 48h. These increases in RARβ mRNA levels were dose dependent (at concentrations of 10-9 to 10-5 mol/l with a maximum effect observed at 10-6 mol/l. There were no significant changes in the mRNA levels of RARα and RARγ. Western blot assay revealed that RARβ protein levels were increased significantly in a time-dependent manner in ARPE-19 cells treated with 10-6 mol/l ATRA from 12 h to 72 h, with a marked increase observed at 24 h and 48 h. The upregulation of RARβ and the ATRA-induced secretion in ARPE-19 cells could be inhibited by the RARβ antagonist LE135.ATRA induced upregulation of RARβ in ARPE-19 cells and stimulated these cells to secrete BMP-2 and MMP-2.

  19. Long-distance retinoid signaling in the zebra finch brain.

    Directory of Open Access Journals (Sweden)

    Tina C Roeske

    Full Text Available All-trans retinoic acid (ATRA, the main active metabolite of vitamin A, is a powerful signaling molecule that regulates large-scale morphogenetic processes during vertebrate embryonic development, but is also involved post-natally in regulating neural plasticity and cognition. In songbirds, it plays an important role in the maturation of learned song. The distribution of the ATRA-synthesizing enzyme, zRalDH, and of ATRA receptors (RARs have been described, but information on the distribution of other components of the retinoid signaling pathway is still lacking. To address this gap, we have determined the expression patterns of two obligatory RAR co-receptors, the retinoid X receptors (RXR α and γ, and of the three ATRA-degrading cytochromes CYP26A1, CYP26B1, and CYP26C1. We have also studied the distribution of zRalDH protein using immunohistochemistry, and generated a refined map of ATRA localization, using a modified reporter cell assay to examine entire brain sections. Our results show that (1 ATRA is more broadly distributed in the brain than previously predicted by the spatially restricted distribution of zRalDH transcripts. This could be due to long-range transport of zRalDH enzyme between different nuclei of the song system: Experimental lesions of putative zRalDH peptide source regions diminish ATRA-induced transcription in target regions. (2 Four telencephalic song nuclei express different and specific subsets of retinoid-related receptors and could be targets of retinoid regulation; in the case of the lateral magnocellular nucleus of the anterior nidopallium (lMAN, receptor expression is dynamically regulated in a circadian and age-dependent manner. (3 High-order auditory areas exhibit a complex distribution of transcripts representing ATRA synthesizing and degrading enzymes and could also be a target of retinoid signaling. Together, our survey across multiple connected song nuclei and auditory brain regions underscores the

  20. O Mercosul e as controvérsias sobre investimentos

    OpenAIRE

    Vivian Daniele Rocha Gabriel; José Augusto Fontoura Costa

    2015-01-01

    O Direito Internacional de Investimentos foi criado a fim de respaldar os investidores estrangeiros contra atos soberanos dos Estados receptores de investimentos, seja através de tratados de investimentos, seja através da arbitragem mista e da criação do ICSID. Os países do MERCOSUL mostraram-se atraídos por esse arcabouço jurídico, contudo, no século XXI, com a ascensão de novos membros no MERCOSUL, a contínua atração de investimentos e a existência de outras alternativas regionais fazem com...

  1. Localized Th1-, Th2-, T Regulatory Cell-, and Inflammation-Associated Hepatic and Pulmonary Immune Responses in Ascaris suum-Infected Swine Are Increased by Retinoic Acid▿ †

    OpenAIRE

    Dawson, Harry; Solano-Aguilar, Gloria; Beal, Madeline; Beshah, Ethiopia; Vangimalla, Vandana; Jones, Eudora; Botero, Sebastian; Joseph F. Urban

    2009-01-01

    Pigs infected with Ascaris suum or controls were given 100 μg (low-dose) or 1,000 μg (high-dose) all-trans retinoic acid (ATRA)/kg body weight in corn oil or corn oil alone per os on days after inoculation (DAI) −1, +1, and +3 with infective eggs. Treatment with ATRA increased interleukin 4 (IL4) and IL12p70 in plasma of infected pigs at 7 DAI and augmented bronchoalveolar lavage (BAL) eosinophilia observed at 7 and 14 DAI. To explore potential molecular mechanisms underlying these observatio...

  2. Color preference of Anastrepha obliqua (Diptera, Tephritidae Preferência de cor por Anastrepha obliqua (Macquart (Diptera, Tephritidae

    Directory of Open Access Journals (Sweden)

    Guillermo López-Guillén

    2009-01-01

    Full Text Available The color preference of A. obliqua was evaluated in two-choice tests. The results showed that both sexes were attracted to wavelengths ranging from 340 nm to 670 nm, although the broad major peak of attraction occurred between 380 and 570 nm.A preferência de cor por A. obliqua foi avaliada em testes de dupla escolha. Os resultados mostraram que ambos os sexos foram atraídos aos comprimentos de onda que variam de 340 nm a de 670 nm, embora o principal pico da atração de A. obliqua tenha ocorrido entre 380 e 570 nm.

  3. Study of irradiation creep of vanadium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Strain, R.V.; Smith, D.L. [Argonne National Lab., IL (United States)] [and others

    1997-08-01

    Thin-wall tubing was produced from the 832665 (500 kg) heat of V-4 wt.% Cr-4 wt.% Ti to study its irradiation creep behavior. The specimens, in the form of pressurized capsules, were irradiated in Advanced Test Reactor and High Flux Isotope Reactor experiments (ATR-A1 and HFIR RB-12J, respectively). The ATR-A1 irradiation has been completed and specimens from it will soon be available for postirradiation examination. The RB-12J irradiation is not yet complete.

  4. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells

    Science.gov (United States)

    Gao, Zhenya; Huo, Lijun; Cui, Dongmei; Yang, Xiao; Zeng, Junwen

    2016-01-01

    Purpose All-trans retinoic acid (ATRA) plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE) cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 2 (MMP-2) and to explore the signaling pathway of retinoic acid in cultured acute retinal pigment epithelial 19 (ARPE-19) cells. Methods The effects of ATRA (concentrations from 10−9 to 10−5 mol/l) on the expression of retinoic acid receptors (RARs) in ARPE-19 cells were examined at the mRNA and protein levels using reverse transcription-polymerase chain reaction (RT-PCR) and western blot assay, respectively. The effects of treating ARPE-19 cells with ATRA concentrations ranging from 10−9 to 10−5 mol/l for 24 h and 48 h or with 10-6mol/l ATRA at different times ranging from 6h to 72h were assessed using real-time quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). The contribution of RARβ-induced activation of ARPE-19 cells was confirmed using LE135, an antagonist of RARβ. Results RARβ mRNA levels significantly increased in the ARPE-19 cells treated with ATRA for 24h and 48h. These increases in RARβ mRNA levels were dose dependent (at concentrations of 10−9 to 10−5 mol/l) with a maximum effect observed at 10−6 mol/l. There were no significant changes in the mRNA levels of RARα and RARγ. Western blot assay revealed that RARβ protein levels were increased significantly in a time-dependent manner in ARPE-19 cells treated with 10−6 mol/l ATRA from 12 h to 72 h, with a marked increase observed at 24 h and 48 h. The upregulation of RARβ and the ATRA-induced secretion in ARPE-19 cells could be inhibited by the RARβ antagonist LE135. Conclusion ATRA induced upregulation of RARβ in ARPE-19 cells and stimulated

  5. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    International Nuclear Information System (INIS)

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  6. Id1 and Id2 are relevant target genes of C/EBP alpha in acute myeloid leukemia

    OpenAIRE

    Erichsen, S.

    2012-01-01

    Die Induktion der Differenzierung ist eine Möglichkeit, die akute myeloische Leukämie zu behandeln. Die Substanz ATRA führt in der akuten Promyelozytenleukämie zur Differenzierung der Leukämiezellen. Die Substanz CDDO induziert granulozytäre Differenzierung durch Induktion des Transkriptionsfaktors C/EBPa. Die Identifikation von C/EBPa-Zielgenen verspricht daher neue Ansätze für Differenzierungstherapien. In der vorliegenden Arbeit wurde gezeigt, dass die Behandlung von HL60-Zellen mit ATRA z...

  7. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    OpenAIRE

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 C...

  8. Hepatic vitamin A preloading reduces colorectal cancer metastatic multiplicity in a mouse xenograft model

    OpenAIRE

    Park, Eun Young; Pinali, Daniel; Lindley, Krista; Lane, Michelle A.

    2012-01-01

    Previous research in our laboratory showed that retinol inhibited all-trans retinoic acid (ATRA)-resistant human colon cancer cell invasion via a retinoic acid receptor (RAR)-independent mechanism in vitro. The objective of the current study was to determine if dietary vitamin A supplementation inhibited metastasis of ATRA-resistant colon cancer cells in a nude mouse xenograft model. Female nude mice (BALB/cAnNCr-nu/nu, n=14 per group) consumed a control diet (2400 IU retinyl palmitate/kg die...

  9. Oncogenic fusion proteins expressed in immature hematopoietic cells fail to recapitulate the transcriptional changes observed in human AML

    DEFF Research Database (Denmark)

    Rapin, N; Porse, B T

    2014-01-01

    Reciprocal chromosomal translocations are observed in one-third of acute myeloid leukemia (AML) cases. Targeting and understanding the effects of the resulting aberrant oncogenic fusion proteins may help developing drugs against specific leukemic subtypes, as demonstrated earlier by the use of ATRA...

  10. Current standard treatment of adult acute promyelocytic leukaemia.

    Science.gov (United States)

    Lo-Coco, Francesco; Cicconi, Laura; Breccia, Massimo

    2016-03-01

    The outcome of patients with acute promyelocytic leukaemia (APL) has dramatically improved over the last two decades, due to the introduction of combined all-trans retinoic acid (ATRA) and chemotherapy regimens and, more recently, to the advent of arsenic trioxide (ATO). ATRA and anthracycline-based chemotherapy remains a widely used strategy, providing cure rates above 80%, but it is associated with risk of severe infections and occurrence of secondary leukaemias. ATO is the most effective single agent in APL and, used alone or in combination with ATRA or ATRA and reduced-intensity chemotherapy, results in greater efficacy with considerably less haematological toxicity. The toxic profile of ATO includes frequent, but manageable, QTc prolongation and increase of liver enzymes. Two large randomized studies have shown that ATRA + ATO is superior to ATRA + chemotherapy for newly diagnosed low-risk APL resulting in 2-4 year event-free survival rates above 90% and very few relapses. According to real world data, the spectacular progress in APL outcomes reported in clinical trials has not been paralleled by a significant improvement in early death rates, this remains the most challenging issue for the final cure of the disease. PMID:26687281

  11. Retinoic Acid Syndrome in Patients following the Treatment of Acute Promyelocytic Leukemia with All-trans Retinoic Acid

    Directory of Open Access Journals (Sweden)

    Yung-Cheng Su

    2009-10-01

    Full Text Available Background: Retinoic acid syndrome (RAS is a potentially lethal complication during alltransretinoic acid (ATRA treatment of acute promyelocytic leukemia(APL. The incidence and risk factors have been shown to vary in differentseries. In this study we want to establish the incidence of RAS in our hospitaland try to elucidate factors that increase its risk.Methods: We retrospectively analyzed 102 patients diagnosed with APL betweenAugust 1993 and December 2007 at Chang Gung Memorial Hospital,Taiwan. All patients received ATRA as an induction regimen with or withoutconventional chemotherapy.Results: Eight of the 102 patients (7.8% experienced RAS which developed after amedian of 9 days (range: 2 to 23 days of ATRA treatment. Respiratory distressand fever were the most common presentations, occurring in 7 of 8patients (87.5%. Age, gender, morphological or molecular subtypes, an initialwhite blood cell (WBC count of more than 10 x 109/L and concurrentchemotherapy did not statistically attribute to the occurrence of RAS. Onepatient developed RAS manifesting with pulmonary hemorrhage but experienceda complete recovery after administration of high-dose dexamethasone.The RAS-related mortality was 12.5% (1 out of 8 patients.Conclusion: The incidence of RAS in this study was similar to those of other series withATRA and concurrent chemotherapy. Age, gender, morphological or molecularsubtypes, an initial leukocyte count of more than 10 x 109/L or the presenceof concurrent chemotherapy is not significantly associated with theoccurrence of the RAS.

  12. UV-A emission from fluorescent energy-saving light bulbs alters local retinoic acid homeostasis.

    Science.gov (United States)

    Hellmann-Regen, Julian; Heuser, Isabella; Regen, Francesca

    2013-12-01

    Worldwide bans on incandescent light bulbs (ILBs) drive the use of compact fluorescent light (CFL) bulbs, which emit ultraviolet (UV) radiation. Potential health issues of these light sources have already been discussed, including speculation about the putative biological effects on light exposed tissues, yet the underlying mechanisms remain unclear. We hypothesized photoisomerization of all-trans retinoic acid (at-RA), a highly light sensitive morphogen, into biologically less active isomers, as a mechanism mediating biological effects of CFLs. Local at-RA is anti-carcinogenic, entrains molecular rhythms and is crucial for skin homeostasis. Therefore, we quantified the impact of CFL irradiation on extra- and intracellular levels of RA isomers using an epidermal cell culture model. Moreover, a biologically relevant impact of CFL irradiation was assessed using highly at-RA-sensitive human neuroblastoma cells. Dose-dependent conversion of extra- and intracellular at-RA into the biologically less active 13-cis-isomer was significantly higher in CFL vs. ILB exposure and completely preventable by employing a UV-filter. Moreover, pre-irradiation of culture media by CFL attenuated at-RA-specific effects on cell viability in human at-RA-sensitive cells in a dose-dependent manner. These findings point towards a biological relevance of CFL-induced at-RA decomposition, providing a mechanism for CFL-mediated effects on environmental health. PMID:24135972

  13. Non-coding RNAs change their expression profile after Retinoid induced differentiation of the promyelocytic cell line NB4

    Directory of Open Access Journals (Sweden)

    Caporaso Maria G

    2010-01-01

    Full Text Available Abstract Background The importance of non-coding RNAs (ncRNAs as fine regulators of eukaryotic gene expression has emerged by several studies focusing on microRNAs (miRNAs. miRNAs represent a newly discovered family of non coding-RNAs. They are thought to be crucial players of human hematopoiesis and related tumorigenesis and to represent a potential tool to detect the early stages of cancer. More recently, the expression regulation of numerous long ncRNAs has been linked to cell growth, differentiation and cancer although the molecular mechanism of their function is still unknown. NB4 cells are promyelocytic cells that can be induced to differentiation upon retinoic acid (ATRA treatment and represent a feasible model to study changes of non coding RNAs expression between cancer cells and their terminally differentiated counterpart. Findings we screened, by microarray analysis, the expression of 243 miRNAs and 492 human genes transcribing for putative long ncRNAs different from miRNAs in NB4 cells before and after ATRA induced differentiation. Our data show that 8 miRNAs, and 58 long ncRNAs were deregulated by ATRA induced NB4 differentiation. Conclusion our data suggest that ATRA-induced differentiation lead to deregulation of a large number of the ncRNAs that can play regulatory roles in both tumorigenesis and differentiation.

  14. AcEST: DK958578 [AcEST

    Lifescience Database Archive (English)

    Full Text Available A0S7R2_ONCHC Class III peroxidase OS=Oncidium Gower Ra... 228 4e-58 tr|A5AGY5|A5A...>tr|A0S7R2|A0S7R2_ONCHC Class III peroxidase OS=Oncidium Gower Ramsey PE=2 SV=1 Length = 332 Score = 228 bit

  15. Management of acute promyelocytic leukemia: Recommendations from an expert panel on behalf of the European LeukemiaNet

    NARCIS (Netherlands)

    M.A. Sanz (Miguel Angel); D. Grimwade (David); M.S. Tallman (Martin); B. Löwenberg (Bob); P. Fenaux (Pierre); E.H. Estey (Elihu); T. Naoe (Tomoki); E. Lengfelder (Eva); T. Büchner (Thomas); H. Döhner (Hartmut); A.K. Burnett (Alan); F. Lo-Coco (Francesco)

    2009-01-01

    textabstractThe introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of this disease. Several treatment strategies using these agents, usually in combination with

  16. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    Science.gov (United States)

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

  17. The Retinoic Acid Receptor-a Mediates Human T-Cell Activation and Th2 Cytokine Production

    Science.gov (United States)

    We have recently demonstrated that all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis RA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-g and TNF-a expression by activated human T cells and reducing the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated ...

  18. Differentiation of stem cells upon deprivation of exogenous FGF2

    DEFF Research Database (Denmark)

    Kjartansdóttir, Kristín Rós; Gabrielsen, Anette; Reda, Ahmed;

    2012-01-01

    fibroblast growth factor 2 (FGF2) is supporting spontaneous differentiation of hESCs cultured on human foreskin fibroblast (hFF) monolayers towards germ cell lineage. Additionally to depriving the hESCs of exogenous FGF2, cells were stimulated with all-trans retinoic acid (ATRA). To get a more comprehensive...

  19. Synthesis and anti-tumor activity of all-trans retinoic acid derivatives

    Institute of Scientific and Technical Information of China (English)

    Juan Shen; Jing Bo Shi; Fei Hu Chen; Yuan Wang; Jing Jing Ruan; Yua Huang

    2009-01-01

    A series of retinoate and retinamide derivatives were designed, synthesized, and their anti-tumor activities were investigated in NB4 by MTT and flow cytometry assays (FCM). All compounds showed cytotoxicity, especially compounds 1a and 1d exhibited a higher cytotoxicity than other derivatives and all-traus retinoic acid (ATRA). Furthermore, compound ld could induce NB4 cell lines differentiation efficiently.

  20. Inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Yun-Feng Piao; Yang Shi; Pu-Jun Gao

    2003-01-01

    AIM: To study the inhibitory effect of all-trans retinoic acid on human hepatocellular carcinoma cell line SMMC-7721and to explore the mechanism of its effect.METHODS: SMMC-7721 cells were divided into two groups, one treated with all-trans retinoic acid (ATRA) for 5 days and the other as a control group. Light microscope and electron microscope were used to observe the morphological changes. Telomerase activity was analyzed with silver-stained telomere repeated assay protocal (TRAP). Expression of Caspase-3 was demonstrated with western blot.RESULTS: ATRA-treated cells showed differentiation features including small and pyknotic nuclei, densely stained chromatin and fewer microvilli. Besides, ATRA could inhibit the activity of telomerase, promote the expression of Caspase-3 and its activation.CONCLUSION: Telomerase activity and Caspase-3expression are changed in human hepatocellular carcinoma cell line SMMC-7721 treated with all-trans retinioc acid.The inhibition of telomerase activity and the activation of Caspase-3 may be the key steps through which ATRA inhibits the proliferation of SMMC-7721 cell line.

  1. Experimental study of the enhancement effect of aminopeptidase N inhibitor ubenimex on the differentiation induction activity of all-trans-retinoic acid in acute promyeiocytic leukemia cells and its mechanism

    Institute of Scientific and Technical Information of China (English)

    钱习军

    2006-01-01

    Objective To investigate the effect of aminopeptidase N inhibitor ubenimex on differentiation induction of alltrans -retinoic acid (ATRA) in acute promyelocytic leukemia (APL) cells and its mechanism. Methods The expression of CD11b was analyzed by flow cytometry and nitroblue-tetrazolium (NBT) reduction assay was per-

  2. All-trans retinoic acid combined with 5-Aza-2 Prime -deoxycitidine induces C/EBP{alpha} expression and growth inhibition in MLL-AF9-positive leukemic cells

    Energy Technology Data Exchange (ETDEWEB)

    Fujiki, Atsushi [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Imamura, Toshihiko, E-mail: imamura@koto.kpu-m.ac.jp [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Sakamoto, Kenichi; Kawashima, Sachiko; Yoshida, Hideki; Hirashima, Yoshifumi; Miyachi, Mitsuru; Yagyu, Shigeki; Nakatani, Takuya [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Sugita, Kanji [Department of Pediatrics, University of Yamanashi, Yamanashi (Japan); Hosoi, Hajime [Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer We tested whether ATRA and 5-Aza affect AML cell differentiation and growth. Black-Right-Pointing-Pointer Cell differentiation and growth arrest were induced in MLL-AF9-expressing cells. Black-Right-Pointing-Pointer Increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1 were also observed. Black-Right-Pointing-Pointer MLL-AF4/AF5q31-expressing cells are less sensitive to ATRA and 5-Aza. Black-Right-Pointing-Pointer Different MLL fusion has distinct epigenetic properties related to RA pathway. -- Abstract: The present study tested whether all-trans retinoic acid (ATRA) and 5-Aza-2 Prime -deoxycitidine (5-Aza) affect AML cell differentiation and growth in vitro by acting on the CCAAT/enhancer binding protein {alpha} (C/EBP{alpha}) and c-Myc axis. After exposure to a combination of these agents, cell differentiation and growth arrest were significantly higher in human and murine MLL-AF9-expressing cells than in MLL-AF4/AF5q31-expressing cells, which were partly associated with increased expression of C/EBP{alpha}, C/EBP{epsilon}, and PU.1, and decreased expression of c-Myc. These findings indicate that MLL-AF9-expressing cells are more sensitive to ATRA and 5-Aza, indicating that different MLL fusion proteins possess different epigenetic properties associated with retinoic acid pathway inactivation.

  3. Function of all-trans retinoic acid observation on similar myopia changes in cultivated rabbit retinal pigment epithelium and relation with myopia relevant factors.

    Science.gov (United States)

    Xing, Bin

    2016-03-01

    To observe the role of all-trans retinoic acid (ATRA) during the similar myopia changes of cultured rabbit retinal pigment epithelium (RPE) cells, as well as the variation changes and relationships with myopic correlation factors such as hepatocyte growth factor (HGF) and matrix metalloprateinase-2 (MMP-2). Rabbit RPE cells of primary generation were selected and cultured to fifth generation by subculture. Then the morphology of RPE cells were observed and cell vitality was analyzed by using the Trypan blue reject test. The expressions of HGF and MMP-2 in RPE cells were tested by using an immunobistochemistry method. The HGF concentration in RPE cell culture fluid was detected by applying enzyme-linked immunosorbnent assay (ELISA). As the ATRA concentration enhanced and action time prolonged, the survival rate of RPE cells was reduced, but the expressions of HGF and MMP-2 increased, so did the secretion of HGF. ATRA concentration with no less than 5nM/ml was able to induce the growth inhibition of RPE cells and the decrease in survival rate, which was similar to the changes in RPE cells in myopia. With the actin of ATRA, the expressions of HGF and MMP-2 increased in RPE cells, with more distinct in HGF increase. PMID:27113312

  4. All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells

    International Nuclear Information System (INIS)

    Highlights: ► AHR and ARNT transcriptionally regulate genes related to metabolisms such as CYP1A1. ► We investigated the effect of retinoic acid (RA) on the function of AHR/ARNT. ► RA inhibited the recruitment of ARNT, not AHR, to the regulatory region of CYP1A1. ► It resulted in a reduction of constitutive expression of CYP1A1 to less than half. -- Abstract: Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) are well-conserved transcription factors among species. However, there are a very limited number of reports on the physiological function of AHR, particularly on the regulation of AHR by endogenous compounds. We hence investigated the effects of all-trans retinoic acid (atRA) on cytochrome P450 (CYP) 1A1 gene transcription as a model of AHR-regulated transcription mechanisms in HepG2 cells, a human hepatoma cell line. Treatment with atRA significantly reduced transactivation and expression of CYP1A1 mRNA to less than half of its control value, and this inhibitory effect was mediated by RARα. The result of chromatin immunoprecipitation assay indicated that treatment with atRA at 1–100 nM drastically inhibited the recruitment of ARNT to DNA regions containing xenobiotic responsive elements. In conclusion, atRA at physiological concentrations could reduce AHR-mediated gene transcription via the inhibition of recruitment of ARNT to relevant DNA regions.

  5. The common coot as sentinel species for the presence of West Nile and Usutu flaviviruses in Central Europe

    Czech Academy of Sciences Publication Activity Database

    Straková, Petra; Šikutová, Silvie; Jedličková, Petra; Sitko, J.; Rudolf, Ivo; Hubálek, Zdeněk

    2015-01-01

    Roč. 102, October (2015), s. 159-161. ISSN 0034-5288 EU Projects: European Commission(XE) 261504 Institutional support: RVO:68081766 Keywords : West Nile virus * Usutu virus * Common coot * Fulica atra * Surveillance * Mosquito-borne viruses * Culex spp. Subject RIV: EG - Zoology Impact factor: 1.409, year: 2014

  6. Connexin32‑mediated antitumor effects of suicide gene therapy against hepatocellular carcinoma: In vitro and in vivo anticancer activity.

    Science.gov (United States)

    Wu, Lun; Zhou, Wen-Bo; Shen, Feng; Liu, Wei; Wu, Hong-Wei; Zhou, Shi-Ji; Li, Sheng-Wei

    2016-04-01

    Normal hepatocytes express connexin32 (Cx32), which forms gap junctions at cell‑cell contact areas. The aim of the present study was to investigate whether Cx32 mediates the cell death‑inducing effects of ultrasound microbubbles carrying the herpes simplex virus thymidine kinase (HSV‑TK) suicide gene against hepatocellular carcinoma cells in vitro and in vivo. HepG2 cells were exposed to different concentrations of trans‑retinoic acid (ATRA) in culture, to evaluate the intrinsic antitumor effect of ATRA. Detailed in‑vitro and in‑vivo investigations on the antitumor effects of ATRA via Cx32 mediation were performed, and the possible underlying mechanisms of action of the compound were then examined. The gene expression of HSV‑TK transfected by ultrasound wave irradiation in the HepG2 cells was quantified using reverse transcription‑quantitative polymerase chain reaction analysis. The effects on cell death were assessed using an MTT assay. The protein expression levels of Cx32 in ATRA‑untreated or ATRA‑treated tissues were quantified by immunohistochemical analysis and Western blot assays. The HSV‑TK gene was successfully transfected into the HepG2 cell using ultrasound wave irradiation, and was stably expressed. Compared with the other groups, the HSV‑TK gene group treated with ATRA exhibited an increased number of apoptotic cells (Psuicide gene therapy system, which may provide a potential strategy for hepatocellular carcinoma treatment. PMID:26935255

  7. Current management of newly diagnosed acute promyelocytic leukemia.

    Science.gov (United States)

    Cicconi, L; Lo-Coco, F

    2016-08-01

    The management of acute promyelocytic leukemia (APL) has considerably evolved during the past two decades. The advent of all-trans retinoic acid (ATRA) and its inclusion in combinatorial regimens with anthracycline chemotherapy has provided cure rates exceeding 80%; however, this widely adopted approach also conveys significant toxicity including severe myelosuppression and rare occurrence of secondary leukemias. More recently, the advent of arsenic trioxide (ATO) and its use in association with ATRA with or without chemotherapy has further improved patient outcome by allowing to minimize the intensity of chemotherapy, thus reducing serious toxicity while maintaining high anti-leukemic efficacy. The advantage of ATRA-ATO over ATRA chemotherapy has been recently demonstrated in two large randomized trials and this option has now become the new standard of care in low-risk (i.e. non-hyperleukocytic) patients. In light of its rarity, abrupt onset and high risk of early death and due to specific treatment requirements, APL remains a challenging condition that needs to be managed in highly experienced centers. We review here the results of large clinical studies conducted in newly diagnosed APL as well as the recommendations for appropriate diagnosis, prevention and management of the main complications associated with modern treatment of the disease. PMID:27084953

  8. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Orfali, Nina [Cork Cancer Research Center, University College Cork, Cork (Ireland); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); McKenna, Sharon L. [Cork Cancer Research Center, University College Cork, Cork (Ireland); Cahill, Mary R. [Department of Hematology, Cork University Hospital, Cork (Ireland); Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu [Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States); Mongan, Nigel P., E-mail: nigel.mongan@nottingham.ac.uk [Faculty of Medicine and Health Science, School of Veterinary Medicine and Science, University of Nottingham, LE12 5RD (United Kingdom); Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA. (United States)

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects.

  9. Differentiation syndrome in patients with acute promyelocytic leukemia treated with all- trans retinoic acid and anthracycline chemotherapy: Characteristics, outcome, and prognostic factors

    NARCIS (Netherlands)

    P. Montesinos (Pau); J.M. Bergua (Juan Miguel); E. Vellenga (Edo); C. Rayón (Chelo); R. Parody (Ricardo); J. de Serna (Javier); A. León (Angel); J. Esteve (Jordi); G. Milone (Gustavo); G. Debén (Guillermo); C. Rivas (Concha); M. González (Marcos); M. Tormo (Mar); D.M. Joaquín; J.D. González (José David); S. Negri (Silvia); E. Amutio (Elena); S. Brunet (Salut); B. Löwenberg (Bob); M.A. Sanz (Miguel Angel)

    2009-01-01

    textabstractDifferentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all- trans retinoic acid (ATRA). Detailed knowl- edge about DS has remained limited. We present an analysis of the incidence, char- a

  10. Studies of antifungal activity of forsskalea tenacissima

    International Nuclear Information System (INIS)

    Antifungal activity of different extracts from Forsskalea tenacissima prepared by solvent-solvent extraction and vacuum liquid chromatography (VLC) was determined. Extracts were found to be active against Candida albicans, Trichophyton mentagrophyte, Allescheria boydii, Microsporum canis, Aspergillus niger, Drechslera rostrata, Nigrospora oryzae, Stachybotrys atra, Curvularia lunata, Trichophyton semii and Trichophyton schoenleinii. (author)

  11. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia

    International Nuclear Information System (INIS)

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies. - Highlights: • Normal and aberrant retinoid signaling in hematopoiesis and leukemia is reviewed. • We suggest a novel role for RARα in the development of X-RARα gene fusions in APL. • ATRA therapy in APL activates transcription and promotes onco-protein degradation. • Autophagy may be involved in both onco-protein degradation and differentiation. • Pharmacologic autophagy induction may potentiate ATRA's therapeutic effects

  12. First report of (homo)anatoxin-a and dog neurotoxicosis after ingestion of benthic cyanobacteria in The Netherlands

    NARCIS (Netherlands)

    Faassen, E.J.; Harkema, H.; Begemann, L.L.J.; Lürling, M.F.L.L.W.

    2012-01-01

    In April and May 2011, three dogs died and one dog became ill after swimming in Lake IJmeer (The Netherlands). At the time, the lake was infested with the benthic cyanobacterial species Phormidium. A Eurasian Coot (Fulica atra) and a Black-headed Gull (Chroicocephalus ridibundus) also died near Lake

  13. First report of (homo)anatoxin-a and dog neurotoxicosis after ingestion of benthic cyanobacteria in The Netherland

    NARCIS (Netherlands)

    Faassen, E.J.; Harkema, L.; Begeman, L.; Lürling, M.

    2012-01-01

    In April and May 2011, three dogs died and one dog became ill after swimming in Lake IJmeer (The Netherlands). At the time, the lake was infested with the benthic cyanobacterial species Phormidium. A Eurasian Coot (Fulica atra) and a Black-headed Gull (Chroicocephalus ridibundus) also died near Lake

  14. Contrasting Roles For All-Trans Retinoic Acid in TGF-ß-mediated Induction of Foxp3 and Il10 Genes in Developing Regulatory T Cells

    Science.gov (United States)

    Extrathymic induction of regulatory T cells (Treg) is essential to the regulation of effector T cell responses in the periphery. TGF-ß has been shown to induce Foxp3-expressing Tregs both in vitro and in vivo. More recently, the vitamin A metabolite, all-trans retinoic acid (at-RA), has been found t...

  15. Regulation of vitamin D receptor expression by retinoic acid receptor alpha in acute myeloid leukemia cells.

    Science.gov (United States)

    Marchwicka, Aleksandra; Cebrat, Małgorzata; Łaszkiewicz, Agnieszka; Śnieżewski, Łukasz; Brown, Geoffrey; Marcinkowska, Ewa

    2016-05-01

    Acute myeloid leukemia (AML) is the predominant acute leukemia among adults, characterized by an accumulation of malignant immature myeloid precursors. A very promising way to treat AML is differentiation therapy using either all-trans-retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D), or the use of both these differentiation-inducing agents. However, the effect of combination treatment varies in different AML cell lines, and this is due to ATRA either down- or up-regulating transcription of vitamin D receptor (VDR) in the cells examined. The mechanism of transcriptional regulation of VDR in response to ATRA has not been fully elucidated. Here, we show that the retinoic acid receptor α (RARα) is responsible for regulating VDR transcription in AML cells. We have shown that a VDR transcriptional variant, originating in exon 1a, is regulated by RARα agonists in AML cells. Moreover, in cells with a high basal level of RARα protein, the VDR gene is transcriptionally repressed as long as RARα agonist is absent. In these cells down-regulation of the level of RARα leads to increased expression of VDR. We consider that our findings provide a mechanistic background to explain the different outcomes from treating AML cell lines with a combination of ATRA and 1,25D. PMID:26969398

  16. Field evidence for the potential of waterbirds as dispensers of aquatic organisms

    NARCIS (Netherlands)

    Charalambidou, I.; Santamaria, L.

    2005-01-01

    Field collections during November of green-winged teal (Anas crecca), mallard (Anas platyrhynchos), and coot (Fulica atra) feces in Denmark, England, and France were used to examine the potential of waterbirds to disperse aquatic plant, algae, and invertebrate species across Europe. A total of 216 f

  17. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  18. Acute and chronic exposure in mussel (aulacomya ater) and clam (semelle solida) with Cs137

    International Nuclear Information System (INIS)

    Two of the most common Peruvian benthonic molluscs, have been shown to be effective concentrators of Cesium-137 and have also proven useful as indicators of that radionuclide in their natural environment, according with results in this paper. However the clam is a better indicator, when determining environmental acute release of Cesium-137 due to reactor accidents, nuclear tests, accidents in nuclear ships, submarines and radioactive material transport, and the mussel for a continuous monitoring of environmental radio contaminant levels. (author). 11 refs

  19. Regulatory CD8{sup +} T cells induced by exposure to all-trans retinoic acid and TGF-{beta} suppress autoimmune diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Minoru [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Yasuda, Hisafumi, E-mail: yasuda@med.kobe-u.ac.jp [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Abe, Yasuhisa; Sasaki, Hirotomo; Shimizu, Mami; Arai, Takashi; Okumachi, Yasuyo; Moriyama, Hiroaki; Hara, Kenta; Yokono, Koichi; Nagata, Masao [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-03-26

    Antigen-specific regulatory CD4{sup +} T cells have been described but there are few reports on regulatory CD8{sup +} T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8{sup +} T cells from 8.3-NOD transgenic mice. CD8{sup +} T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-{beta}, and all-trans retinoic acid (ATRA) for 5 days. CD8{sup +} T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-{beta} and ATRA had low Foxp3{sup +} expression (1.7 {+-} 0.9% and 3.2 {+-} 4.5%, respectively). In contrast, CD8{sup +} T cells induced by exposure to IGRP, SpDCs, TGF-{beta}, and ATRA showed the highest expression of Foxp3{sup +} in IGRP-reactive CD8{sup +} T cells (36.1 {+-} 10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8{sup +} T cells cultured with IGRP, SpDCs, TGF-{beta}, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8{sup +} T cells suppressed the proliferation of diabetogenic CD8{sup +} T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-{beta} induces CD8{sup +}Foxp3{sup +} T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

  20. All Trans-Retinoic Acid Mediates MED28/HMG Box-Containing Protein 1 (HBP1)/β-Catenin Signaling in Human Colorectal Cancer Cells.

    Science.gov (United States)

    Lee, Ming-Fen; Hsieh, Nien-Tsu; Huang, Chun-Yin; Li, Chun-I

    2016-08-01

    Vitamin A is required for normal body function, including vision, epithelial integrity, growth, and differentiation. All trans-retinoic acid (ATRA), a family member of vitamin A, has been explored in treating acute promyelocytic leukemia and other types of cancer. Dysregulated Wnt/β-catenin signaling and disrupted cadherin-catenin complex often contribute to colorectal malignancy. MED28, a mammalian Mediator subunit, is found highly expressed in breast and colorectal cancers. Our laboratory has also reported that MED28 regulates cell growth, migration, and invasion in human breast cancer cells. In the current study we investigated the effect of ATRA on MED28 and Wnt/β-catenin signaling in colorectal cancer. HCT116, HT29, SW480, and SW620, four human colorectal cancer cell lines representing different stages of carcinogenesis and harboring critical genetic changes, were employed. Our data indicated that regardless of genetic variations among these cells, suppression of MED28 reduced the expression of cyclin D1, c-Myc, and nuclear β-catenin, but increased the expression of E-cadherin and HMG box-containing protein 1 (HBP1) where HBP1 has been described as a negative regulator of the Wnt/β-catenin signaling. The reporter activity of an HBP1 promoter increased upon MED28 knockdown, but decreased upon MED28 overexpression. ATRA reduced the expression of MED28 and mimicked the effect of MED28 suppression in down-regulating Wnt/β-catenin signaling. Taken together, ATRA can reverse the suppressive effect of MED28 on HBP1 and E-cadherin and inactivate the Wnt/β-catenin pathway in colorectal cancer, suggesting a protective effect of ATRA against colorectal cancer. J. Cell. Physiol. 231: 1796-1803, 2016. © 2015 Wiley Periodicals, Inc. PMID:26660958

  1. Interference of PAHs and their N-heterocyclic analogs with signaling of retinoids in vitro.

    Science.gov (United States)

    Benísek, Martin; Bláha, Ludek; Hilscherová, Klára

    2008-12-01

    Retinoids are dietary hormones acting through nuclear receptors for retinoic acid, important especially during embryonic development. This study focuses on the disruption of signaling pathways of retinoids by polycyclic aromatic hydrocarbons (PAHs) and their N-heterocyclic analogs (N-PAHs), important environmental contaminants with numerous biological effects. In vitro test with P19/A15 cell line stably transfected with luciferase reporter gene under control of retinoic acid-responsive elements was used to investigate both direct activation of retinoic acid receptors and modulation of response induced by natural ligand all-trans retinoic acid (ATRA) by 26 PAHs and N-PAHs. While none of individual compounds alone activated retinoic acid receptors, many of them modulated ATRA-mediated activity both after 6 h and 24 h exposure. Majority of compounds active after 6h downregulated ATRA-mediated activity (most effective were two analogs of dibenz[a,h]anthracene with LOECs about 185 nM), while most compounds active after 24h upregulated the effects of ATRA (most effective benz[a]acridine and dibenz[a,i]acridine caused 400% induction of ATRA response). Quantitative structure-activity relationship analysis identified molecular volume and dipole moment as the most important descriptors of inhibitory effects after 6h, while length, total molecular energy, gap-HOMO/LUMO and Van der Waals energy are important descriptors for stimulatory effects of PAHs and N-PAHs. This study demonstrates those abundant pollutants such as PAHs and their analogs interfere in vitro with retinoid signaling, which could play role in some in vivo effects of these organic contaminants such as teratogenicity. PMID:18835432

  2. Effect of differentiating agents (all-trans retinoic acid and phorbol 12-myristate 13-acetate on drug sensitivity of HL60 and NB4 cells in vitro.

    Directory of Open Access Journals (Sweden)

    Jadwiga Mirecka

    2008-12-01

    Full Text Available In vitro studies have shown that human myeloid leukemia cell lines: HL60 and NB4 can be stimulated to differentiation by various agents, for example, all-trans retinoic acid (ATRA and phorbol 12-myristate 13-acetate (PMA. The purpose of this study was to investigate whether differentiation of HL60 and NB4 leukemia cell lines induced by ATRA and PMA alters their drug sensitivity. The differentiation along the neutrophil lineage (upon stimulation with ATRA and along the monocyte/macrophage lineage (upon stimulation with PMA was proved by decreased proliferative potential of cells, changes in their morphology, increased ability for NBT reduction and increased expression of CD11b and CD14 cell surface markers. The effect of drugs: cytosine arabinoside, daunorubicin, mitoxantrone and etoposide was examined by Alamar Blue test (proliferation and survival rates, as well as by evaluation of cell smears stained with Hoechst 33342 (apoptotic index. Differentiation resulted in the change of drug sensitivity in both cell lines: the differentiation along the neutrophil pathway (after stimulation with ATRA increased sensitivity to cytosine arabinoside and mitoxantrone but decreased sensitivity to etoposide; the differentiation along the monocyte/macrophage pathway (induced by PMA resulted in the decreased sensitivity of both cell lines to all drugs tested. In conclusion, we have shown that ATRA- and PMA-mediated differentiation of HL60 and NB4 cell lines results in the changes of their drug sensitivity. Our data may provide a contribution to a strategy aimed at a rational combination of differentiating agents and conventional anticancer drugs.

  3. Effect of All-Trans Retinoic Acid on the Pancreas of Streptozotocin-Induced Diabetic Rat.

    Science.gov (United States)

    Eltony, Sohair A; Elmottaleb, Nashwa A; Gomaa, Asmaa M; Anwar, Mamdouh M; El-Metwally, Tarek H

    2016-03-01

    All-trans Retinoic acid (atRA) is instructive for the development of endocrine pancreas and is an integral component of β-cell induction protocols. We showed that atRA induces glucose-responsive endocrine transdifferentiation of pleomorphic pancreatic ductal adenocarcinoma cells in vitro. This study aimed to detect the role of atRA in improving the histological changes of the pancreas in diabetic rats. Forty young male Wistar rats were used and divided into three groups. Group I: normal vehicle control (N = 5). Group II: streptozotocin-induced diabetic rats (N = 20) were followed up at 0.0, 1, 2, and 4 weeks. Group III: streptozotocin-induced diabetic rats (N = 15) treated with atRA (2.5 mg/kg/day), were followed up at 1, 2, and 4 weeks. Specimens from the pancreas were processed for light, electron microscopy and pancreatic insulin mRNA expression. Blood samples were assayed for the levels of glucose, insulin, and total peroxides. In the atRA-treated group, the number of the islets and the islet area significantly increased. Strong insulin-immunoreactive endocrine-like cells were observed nearby the pancreatic acini and the interlobular ducts. Interestingly, insulin-positive cells seemed to arise from pancreatic acinar and ductal epithelium. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. Pancreatic insulin mRNA and blood indices were almost normalized. AtRA improved the histological changes of the pancreas and the blood indices in diabetic rats. Anat Rec, 299:334-351, 2016. © 2015 Wiley Periodicals, Inc. PMID:26704900

  4. Regulatory CD8+ T cells induced by exposure to all-trans retinoic acid and TGF-β suppress autoimmune diabetes

    International Nuclear Information System (INIS)

    Antigen-specific regulatory CD4+ T cells have been described but there are few reports on regulatory CD8+ T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8+ T cells from 8.3-NOD transgenic mice. CD8+ T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-β, and all-trans retinoic acid (ATRA) for 5 days. CD8+ T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-β and ATRA had low Foxp3+ expression (1.7 ± 0.9% and 3.2 ± 4.5%, respectively). In contrast, CD8+ T cells induced by exposure to IGRP, SpDCs, TGF-β, and ATRA showed the highest expression of Foxp3+ in IGRP-reactive CD8+ T cells (36.1 ± 10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8+ T cells cultured with IGRP, SpDCs, TGF-β, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8+ T cells suppressed the proliferation of diabetogenic CD8+ T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-β induces CD8+Foxp3+ T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

  5. Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia.

    Science.gov (United States)

    De Stefano, V; Teofili, L; Sica, S; Mastrangelo, S; Di Mario, A; Rutella, S; Salutari, P; Rumi, C; d'Onofrio, G; Leone, G

    1995-11-01

    The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its reversal by administration of all-trans retinoic acid (ATRA) have been investigated. Bone marrow promyelocytic blasts from nine patients with APL were cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9) were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and then assayed for procoagulant activity (PCA), elastase activity, tissue factor (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase-type plasminogen activator (u-PA) antigen. PCA was determined by a recalcification assay. Elastase was measured by an amidolytic assay (S-2484). TF, t-PA, and u-PA antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant promyelocytes isolated from the patients had increased levels of PCA and TF as compared with the control polymorphonucleates, and low levels of elastase, t-PA, and u-PA; the patient blast PCA level was significantly related to the degree of hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and was significantly correlated to the TF antigen values. In the cultures without ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels remained essentially unchanged. In the presence of ATRA, all parameters (except u-PA) decreased during the culture time. Thus, a major role of the promyelocytic blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA. PMID:7579461

  6. All-trans retinoic acid inhibited angiotensin Ⅱ-induced increase in cell growth and collagen secretion of neonatal cardiac fibroblasts

    Institute of Scientific and Technical Information of China (English)

    Yan HE; Ying HUANG; Li ZHOU; Li-min LU; Yi-chun ZHU; Tai YAO

    2006-01-01

    Aim:To determine whether all-trans retinoic acid (atRA) acts to modulate angiotensin Ⅱ (Ang Ⅱ) -induced cardiac fibroblast cell growth and collagen secretion.Methods:Cultured neonatal rat cardiac fibroblasts (CF) were used in the experiment.A 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect cell growth of the CF;and immunocytochemistry and Western blotting were used to measure the production and secretion of collagen and the expression of transforming growth factor-β1 (TGF-β1) by the CF.Results:atRA (1×10-7 to 1×10-5mol/L) inhibitedtheAngⅡ-induced increase in cell growth of CF (P<0.05).Ang Ⅱ stimulated the secretion of collagen types Ⅰ and Ⅲ by the CF. This eflfect was blocked by AT1 receptor antagonist losartan (1×10-6 mol/L) ,but notbyAT2 receptorantagonistPDl23319 (upto 1×10-6mol/L).Exposure of CF to atRA (1×10-5mol/L) attenuated the Ang Ⅱ-induced increase in the secretion of collagen types I and Ⅲ (P<0.05).atRA (1×10-5mol/L) also blocked the Ang Ⅱ-induced increase in the expression of TGF-β1.Conclusion:atRA inhibits the Ang Ⅱ-induced increase in cell growth and collagen secretion of neonatal rat CF.The effect of atRA is possibly mediated by lowering the TGF-β1 level.These observations support the notion that atRA is a potential candidate for the prevention and therapy of cardiac remodeling.

  7. Perspectives of differentiation therapies of acute myeloid leukemia: the search for the molecular basis of patients’ variable responses to 1,25-dihydroxyvitamin D and vitamin D analogs.

    Directory of Open Access Journals (Sweden)

    MałgorzataCebrat

    2014-05-01

    Full Text Available The concept of differentiation therapy of cancer is approximately 40 years old. Despite many encouraging results obtained in laboratories, both in vitro and in vivo studies, the only really successful clinical application of differentiation therapy was all-trans-retinoic acid (ATRA based therapy of acute promyelocytic leukemia (APL. ATRA, which induces granulocytic differentiation of APL leukemic blasts, has revolutionized the therapy of this disease by converting it from a fatal to a curable one. However, ATRA does not work for other acute myeloid leukemias (AMLs. Since 1,25-dihydroxyvitamin D3 (1,25D is capable of inducing monocytic differentiation of leukemic cells, the idea of treating other AMLs with vitamin D analogs (VDAs was widely accepted. Also some types of solid cancers responded to in vitro applied VDAs, and hence it was postulated that VDAs can be used in many clinical applications. However, early clinical trials in which cancer patients were treated either with 1,25D or with VDAs, did not lead to conclusive results. In order to search for a molecular basis of such unpredictable responses of AML patients towards VDAs, we performed ex vivo experiments using patient’s blast cells. Experiments were also performed using 1,25D-responsive and 1,25D-non responsive cell lines, to study their mechanisms of resistance towards 1,25D-induced differentiation. We found that one of the possible reasons might be due to a very low expression level of vitamin D receptor (VDR mRNA in resistant cells, which can be increased by exposing the cells to ATRA. Our considerations concerning the molecular mechanism behind the low VDR expression and its regulation by ATRA are reported in this paper.

  8. Effect of all-trans retinoic acid combined with trichostatin A on the nude mice bearing human follicular thyroid carcinoma

    International Nuclear Information System (INIS)

    Objective: To study the changes of iodine uptake of the follicular thyroid carcinoma cell line (FTC-133) and nude mice bearing human follicular thyroid carcinoma after the induction with all-trans retinoic acid (ATRA), trichostatin A (TSA) or ATRA combined with TSA. Methods: After the induction with ATRA, TSA, or ATRA combined with TSA in different concentrations for 96 h, the iodine uptake of FTC-133 cells was observed. The concentrations for different groups were as follows: ATRA 1.0 ×10-6 mol/L(Alow group), ATRA 1.0 × 10-4 mol/L (Ahigh group), TSA 1.65 ×10-7 mol/L (T group), Alow + T group, Ahigh + T group and ethanol (control group). Cell quantities and morphology were observed by HE staining. FTC-133 cells were subcutaneously injected into nude mice. Twelve nude mice were randomly divided into 4 groups after tumor formation: ATRA group (2 mg/kg, intragastric administration), TSA group (10 mg/kg, intraperitoneal injection), combined therapy group (ATRA + TSA, the same doses as above) and saline control group (10 ml/kg, intragastric and intraperitoneal administration, respectively). Drugs were administered to the tumor-bearing mice according to the mouse body mass daily. At the 22nd day, the tumor-bearing mice were injected with 37 MBq 131I intraperitoneally. The biodistribution of 131I and gamma imaging were performed at 4, 6, 12 and 24 h after the injection respectively. Histopathological examinations of the tumor samples were taken after imaging completion. The results were analyzed by analysis of variance (ANOVA) with SPSS 13.0. Results: The cellular iodine uptake were (23 885 ± 616.0) and (13 849 ±728.2) counts · min-1 · 10-6 cells in the Alow + T group and Ahigh + T group respectively, and the data were (985 ± 84.2) - (17 600 ± 782.7) counts · min-1 · 10-6 in the other groups (F=600.879, P<0.001). The % ID/g of tumor at 6 h was 6.17 ±0.46 in the combined group and it increased to 9.34 ±0.61 at 12 h and 11.19 ± 0.98 at 24 h. The % ID/g of

  9. Subsidized optimal ART for HIV-positive temporary residents of Australia improves virological outcomes: results from the Australian HIV Observational Database Temporary Residents Access Study

    Directory of Open Access Journals (Sweden)

    Kathy Petoumenos

    2015-02-01

    Full Text Available Introduction: HIV-positive (HIV+ temporary residents living in Australia legally are unable to access government subsidized antiretroviral treatment (ART which is provided via Medicare to Australian citizens and permanent residents. Currently, there is no information systematically being collected on non-Medicare eligible HIV+ patients in Australia. The objectives of this study are to describe the population recruited to the Australian HIV Observational Database (AHOD Temporary Residents Access Study (ATRAS and to determine the short- and long-term outcomes of receiving (subsidized optimal ART and the impact on onwards HIV transmission. Methods: ATRAS was established in 2011. Eligible patients were recruited via the AHOD network. Key HIV-related characteristics were recorded at baseline and prospectively. Additional visa-related information was also recorded at baseline, and updated annually. Descriptive statistics were used to describe the ATRAS cohort in terms of visa status by key demographic characteristics, including sex, region of birth, and HIV disease status. CD4 cell count (mean and SD and the proportion with undetectable (<50 copies/ml HIV viral load are reported at baseline, 6 and 12 months of follow-up. We also estimate the proportion reduction of onward HIV transmission based on the reduction in proportion of people with detectable HIV viral load. Results: A total of 180 patients were recruited to ATRAS by June 2012, and by July 2013 39 patients no longer required ART via ATRAS, 35 of whom became eligible for Medicare-funded medication. At enrolment, 63% of ATRAS patients were receiving ART from alternative sources, 47% had an undetectable HIV viral load (<50 copies/ml and the median CD4 cell count was 343 cells/µl (IQR: 222–479. At 12 months of follow-up, 85% had an undetectable viral load. We estimated a 75% reduction in the risk of onward HIV transmission with the improved rate of undetectable viral load. Conclusions: The

  10. Induction of CYP26A1 by Metabolites of Retinoic Acid: Evidence That CYP26A1 Is an Important Enzyme in the Elimination of Active Retinoids

    Science.gov (United States)

    Topletz, Ariel R.; Tripathy, Sasmita; Foti, Robert S.; Shimshoni, Jakob A.; Nelson, Wendel L.

    2015-01-01

    All-trans-retinoic acid (atRA), the active metabolite of vitamin A, induces gene transcription via binding to nuclear retinoic acid receptors (RARs). The primary hydroxylated metabolites formed from atRA by CYP26A1, and the subsequent metabolite 4-oxo-atRA, bind to RARs and potentially have biologic activity. Hence, CYP26A1, the main atRA hydroxylase, may function either to deplete bioactive retinoids or to form active metabolites. This study aimed to determine the role of CYP26A1 in modulating RAR activation via formation and elimination of active retinoids. After treatment of HepG2 cells with atRA, (4S)-OH-atRA, (4R)-OH-atRA, 4-oxo-atRA, and 18-OH-atRA, mRNAs of CYP26A1 and RARβ were increased 300- to 3000-fold, with 4-oxo-atRA and atRA being the most potent inducers. However, >60% of the 4-OH-atRA enantiomers were converted to 4-oxo-atRA in the first 12 hours of treatment, suggesting that the activity of the 4-OH-atRA was due to 4-oxo-atRA. In human hepatocytes, atRA, 4-OH-atRA, and 4-oxo-atRA induced CYP26A1 and 4-oxo-atRA formation was observed from 4-OH-atRA. In HepG2 cells, 4-oxo-atRA formation was observed even in the absence of CYP26A1 activity and this formation was not inhibited by ketoconazole. In human liver microsomes, 4-oxo-atRA formation was supported by NAD+, suggesting that 4-oxo-atRA formation is mediated by a microsomal alcohol dehydrogenase. Although 4-oxo-atRA was not formed by CYP26A1, it was depleted by CYP26A1 (Km = 63 nM and intrinsic clearance = 90 μl/min per pmol). Similarly, CYP26A1 depleted 18-OH-atRA and the 4-OH-atRA enantiomers. These data support the role of CYP26A1 to clear bioactive retinoids, and suggest that the enzyme forming active 4-oxo-atRA may be important in modulating retinoid action. PMID:25492813

  11. 全反式维A酸对UVB照射的A375细胞酪氨酸酶代谢及铜锌超氧化物歧化酶的影响%Effects of all-trans retinoic ac id on tyrosinase metabolism and Cu/Zn superoxide dismutase mRNA expression in A375 cells irradiated by ultraviolet B

    Institute of Scientific and Technical Information of China (English)

    蒋帅; 魏大鹏; 罗志娟; 陈菊萍

    2012-01-01

    Objective To evaluate the effects of all-trans retinoic acid (ATRA) on melanin content,activity and protein expression of tyrosinase,mRNA expression of Cu/Zn superoxide dismutase (SOD) in A375 cells irradiated with ultraviolet B (UVB).Methods Cultured A375 cells were classified into 6 groups:ATRA+UVB group treated with ATRA after UVB irradiation,hydroquinone+UVB group treated with hydroquinone after UVB irradiation,UVB group and ATRA group treated with UVB irradiation and ATRA respectively,negative control group receiving no treatment.Melanin content and tyrosinase activity were determined by NaOH solubilization assay and dopa-oxidation assay respectively at 24,48 and 72 hours after the addition of ATRA into medium.Western blot was performed to detect the protein expression of tyrosinase,and real-time quantitative PCR to measure the mRNA expressions of tyrosinase and Cu/Zn SOD in A375 cells after 24-hour culture with ATRA.Results The melanin content and tyrosinase activity decreased in UVB-irradiated cells after being treated with ATRA for 24,48 and 72 hours.The protein (gray scale) and mRNA (2-△△Ct value) expression levels of tyrosinase were 0.72 ± 0.070 and 1.400 ± 0.135 respectively at 24 hours after UVB irradiation,decreased to 0.42 ± 0.056 (P <0.01) and 0.810 ± 0.062 (P < 0.01 ) respectively after additional treatment with ATRA.The mRNA expression level of Cu/Zn SOD was 0.323 ± 0.066 in A375 cells at 24 hours after UVB irradiation,and increased to 0.625 ±0.103 (P < 0.01 ) after additional treatment with ATRA.Conclusion ATRA can suppress UVB-induced increase in melanin synthesis and elevate Cu/Zn SOD level in A375 cells,likely through tyrosinase pathway.%目的 探讨全反式维A酸(ATRA)对中波紫外线(UVB)照射的人A375黑素瘤株细胞黑素含量、酪氨酸酶及铜锌超氧化物歧化酶(Cu/ZnSOD)的影响.方法 将培养的A375细胞分为6组:ATRA+UVB组:A375细胞照射UVB后加入全反式维A酸;氢醌+UVB组:照射UVB后

  12. RAI,one candidate gene associated with differentiation of human lung adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    王雪皎; 张睿; 刘芝华; 王秀琴; 丁芳; 郭明洲; 吴旻

    2000-01-01

    From all-trans retinoic acid (ATRA)-treated human lung adenocarcinoma GLC-82 cells and control, subtractive cDNA library has been constructed using subtractive hybridization technique in our laboratory. The screening of the cDNA subtractive library resulted in identification of a clone containing cDNA fragment of one ATRA-induced gene (RAI) in GLC-82 cells. The positive clone with full-length cDNA of RAI was identified by screening fetal brain cDNA library using colony hybridization technique, and then sequenced. RT-PCR results showed that RAI was expressed in many different human fetal tissues. These results suggest that RAI may be involved in cell differentiation and play an important role in vital activities of cells.

  13. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  14. Sorafenib plus all-trans retinoic acid for AML patients with FLT3-ITD and NPM1 mutations.

    Science.gov (United States)

    Guenounou, Sarah; Delabesse, Eric; Récher, Christian

    2014-12-01

    Knowledge of the molecular basis of acute myeloid leukaemia has increased considerably in the past few years, and therapies targeting specific molecular defects of this disease are intensively investigated. Patients with both NPM1 and FLT3-ITD mutations encompass 20% of cytogenetically normal AML. The multikinase and FLT3 inhibitor, sorafenib, has shown some efficacy in patients with relapsed FLT3-ITD(+) AML. In addition, it is suggested that all-trans retinoic acid (ATRA) used in combination with chemotherapy has shown to improve outcome of patients harbouring NPM1 mutations. We report here the clinical course of three patients with refractory or relapsed FLT3-ITD(+) /NPM1(+) AML who achieved significant response upon sorafenib and ATRA combination. PMID:24689895

  15. Resposta de fêmeas de Encarsia formosa Gahan (Hymenoptera: Aphelinidae) aos odores do hospedeiro e da planta-hospedeira em olfatômetro de quatro vias Response of female Encarsia formosa Gahan (Hymenoptera: Aphelinidae) to host and plant-host odors

    OpenAIRE

    Kátia Maria de Medeiros Siqueira; Angela Maria Isidro Farias

    2003-01-01

    A crescente importância da mosca-branca Bemisia tabaci raça B (Hemiptera: Aleyrodidae) como praga agrícola tem incentivado a busca de inimigos naturais que possam ser utilizados em programas de controle biológico. Estudou-se a atração de fêmeas de Encarsia formosa (Hymenoptera: Aphelinidae) aos odores emanados pelo seu hospedeiro - a mosca-branca B. tabaci raça B - em plantas de tomate, em olfatômetro de quatro vias. O parasitóide não apresentou atração aos odores da planta de tomate nem ao c...

  16. Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients.

    Science.gov (United States)

    Testa, Ugo; Lo-Coco, Francesco

    2016-04-01

    All trans retinoic acid (ATRA) has revolutionized the therapy of acute promyelocytic leukemia (APL). Treatment of this leukemia with ATRA in combination with chemotherapy has resulted in complete remission rates >90 % and long-term remission rates above 80 %. Furthermore, the combination of ATRA and arsenic trioxide (ATO) was shown to be safe and effective in frontline treatment and, for patients with low and intermediate risk disease, possibly superior to the standard ATRA and anthracycline-based regimen. However, in spite of this tremendous progress, APL still remains associated with a high incidence of early death due to the frequent occurrence of an abrupt bleeding diathesis. This hemorrhagic syndrome more frequently develops in high-risk APL patients, currently defined as those exhibiting >10 × 10(9)/L WBC at presentation. In addition to high WBC count, other molecular and immunophenotypic features have been associated with high-risk APL. Among them, the expression in APL blasts of the stem/progenitor cell antigen CD34, the neural adhesion molecule (CD56), and the T cell antigen CD2 help to identify a subset of patients at higher risk of relapse and often the expression of these markers is associated with high WBC count. At the molecular level, the short PML/RARA isoform and FLT3-internal tandem duplication (ITD) mutations have been associated with increased relapse risk. These observations indicate that extended immunophenotypic and molecular characterization of APL at diagnosis including evaluation of CD2, CD56, and CD34 antigens and of FLT3 mutations may help to better design risk-adapted treatment in this disease. PMID:26920716

  17. All-trans retinoic acid inhibits the recruitment of ARNT to DNA, resulting in the decrease of CYP1A1 mRNA expression in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Marumi; Ikenaka, Yoshinori [Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818 (Japan); Ishizuka, Mayumi, E-mail: ishizum@vetmed.hokudai.ac.jp [Laboratory of Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, N18 W9, Kita-ku, Sapporo 060-0818 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer AHR and ARNT transcriptionally regulate genes related to metabolisms such as CYP1A1. Black-Right-Pointing-Pointer We investigated the effect of retinoic acid (RA) on the function of AHR/ARNT. Black-Right-Pointing-Pointer RA inhibited the recruitment of ARNT, not AHR, to the regulatory region of CYP1A1. Black-Right-Pointing-Pointer It resulted in a reduction of constitutive expression of CYP1A1 to less than half. -- Abstract: Aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) are well-conserved transcription factors among species. However, there are a very limited number of reports on the physiological function of AHR, particularly on the regulation of AHR by endogenous compounds. We hence investigated the effects of all-trans retinoic acid (atRA) on cytochrome P450 (CYP) 1A1 gene transcription as a model of AHR-regulated transcription mechanisms in HepG2 cells, a human hepatoma cell line. Treatment with atRA significantly reduced transactivation and expression of CYP1A1 mRNA to less than half of its control value, and this inhibitory effect was mediated by RAR{alpha}. The result of chromatin immunoprecipitation assay indicated that treatment with atRA at 1-100 nM drastically inhibited the recruitment of ARNT to DNA regions containing xenobiotic responsive elements. In conclusion, atRA at physiological concentrations could reduce AHR-mediated gene transcription via the inhibition of recruitment of ARNT to relevant DNA regions.

  18. The proteosome inhibitor MG132 attenuates Retinoic Acid Receptor trans-activation and enhances trans-repression of Nuclear Factor κB. Potential relevance to chemo-preventive interventions with retinoids

    Directory of Open Access Journals (Sweden)

    Rosier Randy N

    2004-03-01

    Full Text Available Abstract Background Nuclear factor kappa B (NFκB is a pro-malignant transcription factor with reciprocal effects on pro-metastatic and anti-metastatic gene expression. Interestingly, NFκB blockade results in the reciprocal induction of retinoic acid receptors (RARs. Given the established property of RARs as negative regulators of malignant progression, we postulated that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression. Using Line 1 tumor cells as a model for signal regulation of metastatic gene expression, we investigated the reciprocal interactions between NFκB and RARs in response to the pan-RAR agonist, all-trans retinoic acid (at-RA and the pan-RAR antagonist, AGN193109. Results At-RA [0.1–1 μM] dose-dependently activated RAR and coordinately trans-repressed NFκB, while AGN193109 [1–10 μM] dose-dependently antagonized the effects of at-RA. At-RA and AGN193109 reciprocally regulate pro-metastatic matrix metalloprotease 9 (MMP 9 and its endogenous inhibitor, the tissue inhibitor of metalloprotease 1 (TIMP 1, in a manner consistent with the putative roles of NFκB and RAR in malignant progression. Activation of RAR concurs with its ubiquitination and proteosomal degradation. Accordingly, the proteosome inhibitor, MG132 [5 μM], blocked RAR degradation, quelled RAR trans-activation and enhanced RAR trans-repression of NFκB. Conclusion We conclude that reciprocal interactions between NFκB and RARs constitute a signaling module in metastatic gene expression and malignant progression and propose that the dissociative effect of proteosome inhibitors could be harnessed towards enhancing the anticancer activity of retinoids.

  19. HEMOPOIETIC SYSTEM

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    2006261 Enhancement of all - trans retinoic acid -induced differentiation by bufalin in primary culture of acute promyelocytic leukmia cells. ZHOU Zhitu (周志图),et al. Dept Med Oncol, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Intern Med 2006; 45(4):314-317. Objective:To investigate the effect of bufalin combined with all -trans retinoic acid induced (ATRA) differentiation of acute promyelocytic leukemia ( API) cells

  20. The all-trans retinoic acid (atRA)-regulated gene Calmin (Clmn) regulates cell cycle exit and neurite outgrowth in murine neuroblastoma (Neuro2a) cells

    Energy Technology Data Exchange (ETDEWEB)

    Marzinke, Mark A. [Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544 (United States); Clagett-Dame, Margaret, E-mail: dame@biochem.wisc.edu [Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706-1544 (United States); Pharmaceutical Science Division, University of Wisconsin-Madison, Madison, WI 53705-2222 (United States)

    2012-01-01

    The vitamin A metabolite all-trans retinoic acid (atRA) functions in nervous system development and regulates cell proliferation and differentiation. Neuroblastoma cells (SH-SY5Y and Neuro2a or N2A) exposed to atRA undergo growth inhibition and neuronal differentiation, both of which are preceded by an increase in Clmn mRNA. Treatment of N2A cells with atRA produces a reduction in phosphohistone 3 immunostaining and BrdU incorporation, both indicators of a reduction in cell proliferation. These effects are nearly eliminated in atRA-treated shClmn knockdown cells. Loss of Clmn in the mouse N2A cell line also results in a significant reduction of atRA-mediated neurite outgrowth, a response that can be rescued by reintroduction of the Clmn sequence. In contrast, ectopic overexpression of Clmn produces an increase in the cyclin dependent kinase inhibitor, p21{sup Cip1}, a decrease in cyclin D1 protein and an increase in hypophosphorylated Rb, showing that Clmn participates in G{sub 1}/S arrest. Clmn overexpression alone is sufficient to inhibit N2A cell proliferation, whereas both Clmn and atRA must be present to induce neurite outgrowth. This study shows that the atRA-responsive gene Clmn promotes exit from the cell cycle, a requisite event for neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer Calmin is a retinoic acid-responsive gene. Black-Right-Pointing-Pointer Calmin promotes cell cycle exit in N2A cells. Black-Right-Pointing-Pointer Calmin overexpression increases p21Cip1 and decreases cyclin D1. Black-Right-Pointing-Pointer Calmin is required for RA-induced growth inhibition and neurite outgrowth.

  1. Retinoic Acid Drives Aryl Hydrocarbon Receptor Expression and Is Instrumental to Dioxin-Induced Toxicity during Palate Development

    OpenAIRE

    Jacobs, Hugues; Dennefeld, Christine; Féret, Betty; Viluksela, Matti; Håkansson, Helen; Mark, Manuel; Ghyselinck, Norbert B.

    2011-01-01

    Background: Palate development depends on complex events and is very sensitive to disruption. Accordingly, clefts are the most common congenital malformations worldwide, and a connection is proposed with fetal exposure to toxic factors or environmental contaminants, such as dioxins. There is increasing evidence that dioxin interferes with all-trans-retinoic acid (atRA), a hormone-like signal derived from vitamin A, which plays an essential role during embryonic development. Although similarit...

  2. Aproximaci??n a la s??ntesis de aureol, un meroterpeno bioactivo de origen marino

    OpenAIRE

    Rivas Basc??n, Nazaret

    2013-01-01

    El desarrollo de metodolog??as de s??ntesis sostenibles y eficientes hacia compuestos org??nicos con interesantes propiedades biol??gicas ha atra??do la atenci??n de los grupos de investigaci??n dedicados a la s??ntesis org??nica.1 En este contexto hemos abordado una aproximaci??n sint??tica hacia aureol mediante una metodolog??a de s??ntesis eficiente y compatible con el medio ambiente.

  3. Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Eun Sun Yoo

    2011-03-01

    Full Text Available Since the successful introduction of all-trans-retinoic acid (ATRA and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70&#8210;89%. Moreover, arsenic trioxide (ATO, which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leukemia/ retinoic acid receptor-alpha (PML/RAR?#6752;isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

  4. Retinoic Acid Inhibits Airway Smooth Muscle Cell Migration

    OpenAIRE

    Day, Regina M.; Lee, Young H.; Park, Ah-Mee; Suzuki, Yuichiro J.

    2006-01-01

    Airway remodeling in chronic asthma is characterized by increased smooth muscle mass that is associated with the reduction of the bronchial lumen as well as airway hyperresponsiveness. The development of agents that inhibit smooth muscle growth is therefore of interest for therapy to prevent asthma-associated airway remodeling. All-trans retinoic acid (ATRA) suppresses growth of vascular smooth muscle cells (SMCs) from the systemic and pulmonary circulation. The present study investigated the...

  5. Lutzomyia gasparviannai Martins, Godoy & Silva, 1962, probable vector of Leishmania mexicana ssp. in Viana municipality, Espírito Santo State, Brazil

    Directory of Open Access Journals (Sweden)

    Aloísio Falqueto

    1985-12-01

    Full Text Available Dos flebótomos atraídos pelo Proechimys iheringi numa área onde esse roedor foi achado naturalmente infectado por Leishmania mexicana ssp., 98,1% foram Lutzomyia gasparviannai, o que sugere que essa espécie não antropofílica seja o transmissor entre os roedores mas não habitualmente ao homem.

  6. Microstructural examination of V–(Fe or Cr)–Ti alloys after thermal-creep or irradiation-creep tests

    OpenAIRE

    Fukumoto, K.; Takahashi, S.; KURTZ, R.J.; Smith, D. L.; Matsui, H

    2005-01-01

    Microstructural examinations have been performed on irradiation-creep and thermal-creep pressurized tube specimensof V–3Fe–4Ti–0.1Si in order to understand failure and creep mechanisms. There are no typical microstructuraldifferences between unstressed and pressurized creep tube specimens irradiated in ATR-A1 in the irradiation temperatureregime from 212 to 300 ℃. Failed thermal creep specimens show dislocation structures dependent on the tubespecimen geometry. This can be interpreted in term...

  7. Retinoic Acid Biosynthesis Is Impaired in Human and Murine Endometriosis1

    OpenAIRE

    Pierzchalski, Keely; Taylor, Robert N.; Nezhat, Ceana; Jones, Jace W.; Napoli, Joseph L.; Yang, Guixiang; Kane, Maureen A.; Sidell, Neil

    2014-01-01

    Endometriosis is characterized by the presence of endometrial glands and stroma in extrauterine sites. Our objective was to determine whether endometriotic lesions (ELs) from women with endometriosis have altered retinoid levels compared with their eutopic endometrium, and to test the hypothesis that defects in all-trans retinoic acid (ATRA) biosynthesis in EL is related to reduced expression of cellular retinol-binding protein type 1 (RBP1). Retinoids were evaluated by liquid chromatography-...

  8. Negative Regulation of JAK2 by H3K9 Methyltransferase G9a in Leukemia

    OpenAIRE

    Son, Hye-Ju; Kim, Ji-Young; Hahn, Yoonsoo; Seo, Sang-Beom

    2012-01-01

    Histone methylation at specific lysine residues is a crucial regulatory process in transcriptional regulation. Using chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis, we found that the H3K9-me2 target gene JAK2 was an important factor during differentiation of the HL-60 promyelocytic leukemia cell line by all-trans-retinoic acid (ATRA) treatment. Here, we report that the H3K9 methyltransferase G9a negatively regulated JAK2 transcription in histone methyltransferas...

  9. Una interpretación numérica de la crónica de Huamán Poma de Ayala

    Directory of Open Access Journals (Sweden)

    Marcín Mróz

    1984-12-01

    Full Text Available Retoma de uno de los temas que ha atraído especial atención de distintos estudiosos siguiendo una línea de análisis iniciada por Juan Ossio en su tesis de 1970. El autor del presente artículo realiza una interpretación numérica de las edades de la humanidad según el gran cronista indio.

  10. Validation of a Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Method for Determination of All-Trans Retinoic Acid in Human Plasma and Its Application to a Bioequivalence Study

    Directory of Open Access Journals (Sweden)

    Jing-Bo Peng

    2014-01-01

    Full Text Available A sensitive, reliable and specific LC-MS-MS method was developed and validated for the identification and quantitation of all-trans retinoic acid (ATRA in human plasma. Acitretin was used as the internal standard (IS. After liquid-liquid extraction of 500 μL plasma with methyl tert-butyl ether (MTBE, ATRA and the IS were chromatographed on a HyPURITY C18 column (150 mm × 2.1 mm, 5 μm with the column temperature set at 40 °C. The mobile phase was consisted of 40% phase A (MTBE–methanol–acetic acid, 50:50:0.5, v/v and 60% phase B (water–methanol–acetic acid, 50:50:0.5, v/v with a flow rate of 0.3 mL/min. The API 4000 triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM mode via the positive electrospray ionization interface using the transition m/z 301.4 → 123.1 for ATRA and m/z 326.9 → 177.1 for IS, respectively. The calibration curve was linear over the range of 0.45–217.00 ng/mL (r ≥ 0.999 with a lower limit of quantitation (LLOQ of 0.45 ng/mL. The intra- and inter-day precisions values were below 8% relative standard deviation and the accuracy was from 98.98% to 106.19% in terms of relative error. The validated method was successfully applied in a bioequivalence study of ATRA in Chinese healthy volunteers.

  11. Hermaphroditic, demasculinized frogs after exposure to the herbicide atrazine at low ecologically relevant doses

    OpenAIRE

    Hayes, Tyrone B.; Collins, Atif; Lee, Melissa; Mendoza, Magdelena; Noriega, Nigel; Stuart, A. Ali; Vonk, Aaron

    2002-01-01

    Atrazine is the most commonly used herbicide in the U.S. and probably the world. It can be present at several parts per million in agricultural runoff and can reach 40 parts per billion (ppb) in precipitation. We examined the effects of atrazine on sexual development in African clawed frogs (Xenopus laevis). Larvae were exposed to atrazine (0.01–200 ppb) by immersion throughout larval development, and we examined gonadal histology and laryngeal size at metamorphosis. Atra...

  12. Loss of CRABP-II Characterizes Human Skin Poorly Differentiated Squamous Cell Carcinomas and Favors DMBA/TPA-Induced Carcinogenesis.

    Science.gov (United States)

    Passeri, Daniela; Doldo, Elena; Tarquini, Chiara; Costanza, Gaetana; Mazzaglia, Donatella; Agostinelli, Sara; Campione, Elena; Di Stefani, Alessandro; Giunta, Alessandro; Bianchi, Luca; Orlandi, Augusto

    2016-06-01

    Retinol and its derivatives play an important role in epidermal growth and differentiation and represent chemopreventive agents in nonmelanoma skin cancer. Retinoic acid binding protein II (CRABP-II) is a cytoplasmic receptor that critically regulates all-trans-retinoic acid (ATRA) trafficking. We documented the marked reduced expression of CRABP-II and its promoter methylation in human poorly differentiated squamous cell carcinomas. To investigate the role of CRABP-II in skin carcinogenesis we used skin lesion induction by dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate in CRABP-II-knockout C57BL/6 mice. We observed earlier and more diffuse epidermal dysplasia, greater incidence and severity of tumors, reduced expression of cytokeratin 1/cytokeratin 10 and involucrin, increased proliferation, and impaired ATRA inhibition of tumor promotion compared with wild-type animals. CRABP-II-transfected HaCaT, FaDu, and A431 cells showed expression of differentiation markers, retinoic acid receptor-β/-γ signaling, ATRA sensitivity, and suppression of EGFR/v-akt murine thymoma viral oncogene homolog 1 (AKT) pathways in a fatty acid binding protein 5/peroxisome proliferator-activated receptor-β/-δ-independent manner. The opposite was true in keratinocytes isolated from CRABP-II-knockout mice. Finally, CRABP-II accumulation induced ubiquitination-associated reduction of EGFR. Our results showed reduced CRABP-II expression in human poorly differentiated squamous cell carcinomas, and its gene deletion favored experimental skin carcinogenesis and impaired ATRA antitumor efficacy, likely modulating EGFR/AKT pathways and retinoic acid receptor-β/-γ signaling. Therapeutic interventions aimed at restoring CRABP-II-mediated signaling may amplify therapeutic retinoid efficacy in nonmelanoma skin cancer. PMID:26945879

  13. Atrazine Removal from Aqueous Solutions using Submerged Biological Aerated Filter

    OpenAIRE

    Mohammad Ali Baghapour; Simin Nasseri; Zahra Derakhshan

    2013-01-01

    Atrazine is widely used in the agriculture as an herbicide. Due to its high mobility, Atrazine leaks into the groundwaters, surface waters, and drinking water wells. Many physical and chemical methods have been suggested for removing Atrazine from aquatic environments. However, these methods are very costly, have many performance problems, produce a lot of toxic intermediates which are very harmful and dangerous, and cannot completely mineralize Atrazine. In this study, biodegradation of Atra...

  14. The Expression of Bone Morphogenetic Protein 2 and Matrix Metalloproteinase 2 through Retinoic Acid Receptor Beta Induced by All-Trans Retinoic Acid in Cultured ARPE-19 Cells

    OpenAIRE

    Zhenya Gao; Lijun Huo; Dongmei Cui; Xiao Yang; Junwen Zeng

    2016-01-01

    Purpose All-trans retinoic acid (ATRA) plays an important role in ocular development. Previous studies found that retinoic acid could influence the metabolism of scleral remodeling by promoting retinal pigment epithelium (RPE) cells to secrete secondary signaling factors. The purpose of this study was to investigate whether retinoic acid affected secretion of bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 2 (MMP-2) and to explore the signaling pathway of retinoic acid in cu...

  15. Thermal conditions during juvenile development affect adult dispersal in a spider

    OpenAIRE

    Bonte, Dries; Travis, Justin M. J.; Clercq, Nele De; Zwertvaegher, Ingrid; Lens, Luc

    2008-01-01

    Abstract: Understanding the causes and consequences of dispersal is a prerequisite for the effective management of natural populations. Rather than treating dispersal as a fixed trait, it should be considered a plastic process that responds to both genetic and environmental conditions. Here, we consider how the ambient temperature experienced by juvenile Erigone atra, a spider inhabiting crop habitat, influences adult dispersal. This species exhibits 2 distinct forms of dispersal, ballooning ...

  16. Retinoid- and sodium-butyrate– induced decrease in heat shock protein 70 membrane-positive tumor cells is associated with reduced sensitivity to natural killer cell lysis, growth delay, and altered growth morphology

    OpenAIRE

    Gehrmann, Mathias; Schönberger, Johann; Zilch, Tanja; Rossbacher, Lydia; Thonigs, Gerald; Eilles, Christoph; Multhoff, Gabriele

    2005-01-01

    Human tumors frequently present heat shock protein 70 (Hsp70) on their cell membranes, whereas corresponding normal tissues fail to do so. Therefore, an Hsp70 membrane-positive phenotype provided a tumor-specific marker. Moreover, membrane-bound Hsp70 provides a target structure for the cytolytic attack mediated by natural killer (NK) cells. Vitamin A derivatives 13-cis retinoic acid (13-RA) and all-trans retinoic acid (ATRA) and sodium-butyrate (SBU) are known for their redifferentiating cap...

  17. Inorganic Carbon Turnover caused by Digestion of Carbonate Sands and Metabolic Activity of Holothurians

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, Kenneth; Silverman, Jacob; Kravitz, Benjamin S.; Rivlin, Tanya; Schneider-Mor, Aya; Barbosa, Sergio; Byrne, Maria; Caldeira, Ken

    2013-11-20

    Recent measurements have shown that holothurians (sea cucumbers) play an important role in the cycling of CaCO3 in tropical coral reef systems through ingestion and processing of carbonate sediment. In this study inorganic additional aspects of carbon turnover were determined in laboratory incubations of Holothuria atra, H. leucospilota and Stichopus herrmanni from One Tree Reef, Great Barrier Reef. The pH values of the gut lumen ranged from 6.1 to 6.7 in animals with empty digestive tracts as opposed to 7.0 to 7.6 when digestive tracts were filled with sediment. Empty gut volume estimates for H. atra and S. herrmanni were 36 ± 4 mL and 151 ± 14 mL, respectively. Based on these measurements it is estimated that these species process 19 ± 2kg and 80 ± 7kg CaCO3 sand yr-1 per individual, respectively. The annual dissolution rates of H. atra and S. herrmanni of 6.5±1.9g and 9.6±1.4g, respectively, suggest that 0.05±0.02% and 0.1±0.02% of the CaCO3 processed through their gut annually is dissolved. During the incubations the CaCO3 dissolution was 0.07±0.01%, 0.04±0.01% and 0.21±0.05% of the fecal casts for H. atra, H. leucospilota and S. herrmanni, respectively. The CaCO3 saturation state for both aragonite and calcite minerals during laboratory incubations decreased markedly due to a greater increase in dissolved inorganic carbon (DIC) relative to total alkalinity (AT) as a result of respiration by the animals. Our results support the hypothesis that deposit feeders such as sea cucumbers play an important ecological role in the coral reef CaCO3 cycle.

  18. CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities

    OpenAIRE

    Lee, Young-jin; Jones, Letetia C.; Timchenko, Nikolai A.; Perrotti, Danilo; Tenen, Daniel G; Kogan, Scott C.

    2006-01-01

    CCAAT/enhancer binding proteins (C/EBPs) play critical roles in myelopoiesis. Dysregulation of these proteins likely contributes to the pathogenesis of myeloid disorders characterized by a block in granulopoiesis. In one such disease, acute promyelocytic leukemia (APL), a promyelocytic leukemia–retinoic acid receptor α (PML-RARα) fusion protein is expressed as a result of a t(15;17) chromosomal translocation. Treatment of PML-RARα leukemic cells with all-trans retinoic acid (ATRA) causes them...

  19. Radular marks produced by grazing gastropods of the rocky intertidal

    Directory of Open Access Journals (Sweden)

    Yván Reyes

    2014-06-01

    Full Text Available We had used artificial surfaces to examine the radular marks of four common grazing gastropods from Ancon Bay. In this work we show radular marks on dental wax surface of the trochid Tegula atra (Lesson, 1830, the fissurellid Fissurella peruviana Lamarck, 1822, the lottid Lottia ceciliana (Orbigny, 1841 and the littorinid Nodilittorina peruviana (Lamarck, 1822. In addition, the radular type is described to each species to relate it to the produced mark.

  20. Energy Metabolism Regulates Retinoic Acid Synthesis and Homeostasis in Physiological Contexts

    OpenAIRE

    Obrochta, Kristin Marie

    2014-01-01

    Mounting evidence supports a regulated and reciprocal relationship between retinoid homeostasis and energy metabolism, with a physiologically relevant consequence of disrupted energy balance. This research was motivated by an observation that all-trans-retinoic acid (atRA), and biosynthetic precursors, were responsive to acute shifts in energy status, in wild type animals with normal body weight and glucose tolerance, i.e. not consequent to metabolic syndrome. My dissertation was designed to ...

  1. Qualitative and Quantitative Saponin Contents in Five Sea Cucumbers from the Indian Ocean

    OpenAIRE

    Patrick Flammang; Pascal Gerbaux; Séverine Van Dyck

    2010-01-01

    To avoid predation, holothuroids produce feeding-deterrent molecules in their body wall and viscera, the so-called saponins. Five tropical sea cucumber species of the family Holothuriidae were investigated in order to study their saponin content in two different organs, the body wall and the Cuvierian tubules. Mass spectrometry techniques (MALDI- and ESI-MS) were used to detect and analyze saponins. The smallest number of saponins was observed in Holothuria atra, which contained a total of fo...

  2. MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia.

    Science.gov (United States)

    Garzon, R; Pichiorri, F; Palumbo, T; Visentini, M; Aqeilan, R; Cimmino, A; Wang, H; Sun, H; Volinia, S; Alder, H; Calin, G A; Liu, C-G; Andreeff, M; Croce, C M

    2007-06-14

    MicroRNAs (miRNAs) are small non-coding RNAs of 19-25 nucleotides that are involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. However, little is known about the role of miRNAs in granulopoiesis. Here, we report the expression of miRNAs in acute promyelocytic leukemia patients and cell lines during all-trans-retinoic acid (ATRA) treatment by using a miRNA microarrays platform and quantitative real time-polymerase chain reaction (qRT-PCR). We found upregulation of miR-15a, miR-15b, miR-16-1, let-7a-3, let-7c, let-7d, miR-223, miR-342 and miR-107, whereas miR-181b was downregulated. Among the upregulated miRNAs, miR-107 is predicted to target NFI-A, a gene that has been involved in a regulatory loop involving miR-223 and C/EBPa during granulocytic differentiation. Indeed, we have confirmed that miR-107 targets NF1-A. To get insights about ATRA regulation of miRNAs, we searched for ATRA-modulated transcription factors binding sites in the upstream genomic region of the let-7a-3/let-7b cluster and identified several putative nuclear factor-kappa B (NF-kappaB) consensus elements. The use of reporter gene assays, chromatin immunoprecipitation and site-directed mutagenesis revealed that one proximal NF-kappaB binding site is essential for the transactivation of the let-7a-3/let-7b cluster. Finally, we show that ATRA downregulation of RAS and Bcl2 correlate with the activation of known miRNA regulators of those proteins, let-7a and miR-15a/miR-16-1, respectively. PMID:17260024

  3. Retinoid Differentiation Therapy for Common Types of Acute Myeloid Leukemia

    OpenAIRE

    Philip Hughes; Geoffrey Brown

    2012-01-01

    Many cancers arise in a tissue stem cell, and cell differentiation is impaired resulting in an accumulation of immature cells. The introduction of all-trans retinoic acid (ATRA) in 1987 to treat acute promyelocytic leukemia (APL), a rare subtype of acute myeloid leukemia (AML), pioneered a new approach to obtain remission in malignancies by restoring the terminal maturation of leukemia cells resulting in these cells having a limited lifespan. Differentiation therapy also offers the prospect o...

  4. A Novel mTORC1-Dependent, Akt-Independent Pathway Differentiates the Gut Tropism of Regulatory and Conventional CD4 T Cells.

    Science.gov (United States)

    Chen, Leo C; Nicholson, Yawah T; Rosborough, Brian R; Thomson, Angus W; Raimondi, Giorgio

    2016-08-15

    The vitamin A metabolite all-trans retinoic acid (ATRA) induces a gut-homing phenotype in activated CD4(+) conventional T cells (Tconv) by upregulating the integrin α4β7 and the chemokine receptor CCR9. We report that, in contrast to mouse Tconv, only ∼50% of regulatory T cells (Treg) upregulate CCR9 when stimulated by physiological levels of ATRA, even though Tconv and Treg express similar levels of the retinoic acid receptor (RAR). The resulting bimodal CCR9 expression is not associated with differences in the extent of their proliferation, level of Foxp3 expression, or affiliation with naturally occurring Treg or induced Treg in the circulating Treg pool. Furthermore, we find that exposure of Treg to the mechanistic target of rapamycin (mTOR) inhibitor rapamycin suppresses upregulation of both CCR9 and α4β7, an effect that is not evident with Tconv. This suggests that in Treg, ATRA-induced upregulation of CCR9 and α4β7 is dependent on activation of a mTOR signaling pathway. The involvement of mTOR is independent of Akt activity, because specific inhibition of Akt, pyruvate dehydrogenase kinase-1, or its downstream target glycogen synthase kinase-3 did not prevent CCR9 expression. Additionally, Rictor (mTOR complex [mTORC]2)-deficient Treg showed unaltered ability to express CCR9, whereas Raptor (mTORC1)-deficient Treg were unable to upregulate CCR9, suggesting the selective participation of mTORC1. These findings reveal a novel difference between ATRA signaling and chemokine receptor induction in Treg versus Tconv and provide a framework via which the migratory behavior of Treg versus Tconv might be regulated differentially for therapeutic purposes. PMID:27402696

  5. NIR and visible investigation of some potential SERS-active substrates for studying antitumour agent all- trans retinoic acid

    Science.gov (United States)

    Beljebbar, A.; Sockalingum, G. D.; Morjani, H.; Angiboust, J. F.; Manfait, M.

    1997-01-01

    Red and near-infrared excited Fourier transform surface-enhanced Raman spectra of an anticancer agent, all- trans retinoic acid (ATRA), adsorbed on gold island films are reported. Best results have been obtained with plates 80 Å and 40 Å thick respectively in the red and near-infrared and at concentrations of 10 -5 and 5 × 10 -6 M with a spinning system. The use of near-infrared laser excitation with low photon energy, allows us to overcome the problems of isomerisation when the sample is exposed for a long time to the laser radiation. Comparison between the Raman and SERS spectra in the visible shows that the adsorption on the surface does not perturb the structure of ATRA and confirms the long range enhancement of the island films with this type of molecule. Spectral data show that while gold island films and colloids are appropriate substrates for use with red excitation, silver and gold colloids as well as gold island films exhibit satisfactory enhancement levels in the near-infrared. This study will in the future allow us to choose the appropriate system that will serve to investigate the interaction of ATRA with its target in vitro and the effect of this differentiating agent in human leukaemia cell lines such as K562 and HL60.

  6. All-trans retinoic acid ameliorates glycemic control in diabetic mice via modulating pancreatic islet production of vascular endothelial growth factor-A.

    Science.gov (United States)

    Chien, Chiao-Yun; Yuan, Tze-An; Cho, Candy Hsin-Hua; Chang, Fang-Pei; Mao, Wan-Yu; Wu, Ruei-Ren; Lee, Hsuan-Shu; Shen, Chia-Ning

    2016-09-01

    Patients with type 1 diabetes mellitus are associated with impairment in vitamin A metabolism. This study evaluated whether treatment with retinoic acid, the biologically active metabolite of vitamin A, can ameliorate diabetes. All-trans retinoic acid (atRA) was used to treat streptozotocin (STZ)-induced diabetic mice which revealed atRA administration ameliorated blood glucose levels of diabetic mice. This hyperglycemic amelioration was accompanied by an increase in the amount of β cells co-expressed Pdx1 and insulin and by restoration of the vascular laminin expression. The atRA-induced production of vascular endothelial growth factor-A from the pancreatic islets was possibly the key factor that mediated the restoration of islet vascularity and recovery of β-cell mass. Furthermore, the combination of islet transplantation and atRA administration significantly rescued hyperglycemia in diabetic mice. These findings suggest that vitamin A derivatives can potentially be used as a supplementary treatment to improve diabetes management and glycemic control. PMID:27381866

  7. Disseminated Exfoliative Dermatitis Associated with All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Yonal Ipek

    2012-01-01

    Full Text Available Acute promyelocytic leukemia (APL is a biologically and clinically separate type of acute myeloid leukemia characterized by a translocation involving the retinoic acid receptor-alpha (RARa locus on chromosome 17, the great majority of which is t(15; 17(q24.1; q21.1 (Collins (1998, Melnick and Licht (1999, and Grimwade (1999. Retinoic acid is a critical ligand in the differentiation pathway of multiple tissues, mediated through binding to an RAR. All-trans retinoic acid (ATRA is a subgroup of the retinoid family, which induces complete remission (CR in APL by causing differentiation and apoptosis in immature malignant promyelocytes rather than inducing cell death by cytotoxicity (Warrell et al. (1993, Liu et al. (2000, and Cassinat et al. (2001. ATRA-associated toxicity consisting of headache, fever, weakness, fatigue, dry skin, dermatitis, gastrointestinal disorders, and hypertriglyceridemia has been shown to be mild (Kurzrock et al. (1993. Herein, we describe a patient with APL that developed an erythematous reaction of the whole body followed by desquamation and exfoliation during ATRA therapy.

  8. Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

    Directory of Open Access Journals (Sweden)

    Yoshihiro Akimoto

    2014-06-01

    Full Text Available Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470–488. However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

  9. Acute promyelocytic leukemia: where did we start, where are we now, and the future.

    Science.gov (United States)

    Coombs, C C; Tavakkoli, M; Tallman, M S

    2015-01-01

    Historically, acute promyelocytic leukemia (APL) was considered to be one of the most fatal forms of acute leukemia with poor outcomes before the introduction of the vitamin A derivative all-trans retinoic acid (ATRA). With considerable advances in therapy, including the introduction of ATRA initially as a single agent and then in combination with anthracyclines, and more recently by development of arsenic trioxide (ATO)-containing regimens, APL is now characterized by complete remission rates of 90% and cure rates of ∼80%, even higher among low-risk patients. Furthermore, with ATRA-ATO combinations, chemotherapy may safely be omitted in low-risk patients. The disease is now considered to be the most curable subtype of acute myeloid leukemia (AML) in adults. Nevertheless, APL remains associated with a significant incidence of early death related to the characteristic bleeding diathesis. Early death, rather than resistant disease so common in all other subtypes of AML, has emerged as the major cause of treatment failure. PMID:25885425

  10. Treatment with 5-Azacytidine Accelerates Acute Promyelocytic Leukemia Leukemogenesis in a Transgenic Mouse Model

    Science.gov (United States)

    Scaglioni, Pier Paolo; Cai, Lu Fan; Majid, Samia M.; Yung, Thomas M.; Socci, Nicholas D.; Kogan, Scott C.; Kopelovich, Levy; Pandolfi, Pier Paolo

    2011-01-01

    A key oncogenic force in acute promyelocytic leukemia (APL) is the ability of the promyelocytic leukemia–retinoic acid receptor α (PML-RARA) oncoprotein to recruit transcriptional repressors and DNA methyltransferases at retinoic acid–responsive elements. Pharmacological doses of retinoic acid relieve transcriptional repression inducing terminal differentiation/apoptosis of the leukemic blasts. APL blasts often harbor additional recurrent chromosomal abnormalities, and significantly, APL prevalence is increased in Latino populations. These observations suggest that multiple genetic and environmental/dietary factors are likely implicated in APL. We tested whether dietary or targeted chemopreventive strategies relieving PML-RARA transcriptional repression would be effective in a transgenic mouse model. Surprisingly, we found that 1) treatment with a demethylating agent, 5-azacytidine, results in a striking acceleration of APL; 2) a high fat, low folate/choline–containing diet resulted in a substantial but nonsignificant APL acceleration; and 3) all-trans retinoic acid (ATRA) is ineffective in preventing leukemia and results in ATRA-resistant APL. Our findings have important clinical implications because ATRA is a drug of choice for APL treatment and indicate that global demethylation, whether through dietary manipulations or through the use of a pharmacologic agent such as 5-azacytidine, may have unintended and detrimental consequences in chemopreventive regimens. PMID:21779489

  11. Mechanisms of all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells

    Indian Academy of Sciences (India)

    Ji-Wang Zhang; Jian Gu; Zhen-Yi Wang; Sai-Juan Chen; Zhu Chen

    2000-09-01

    Retinoic acids (RA) play a key role in myeloid differentiation through their agonistic nuclear receptors (RAR/RXR) to modulate the expression of target genes. In acute promyelocytic leukemia (APL) cells with rearrangement of retinoic acid receptor (RAR) (including: PML-RAR, PLZF-RAR, NPM-RAR, NuMA-RAR or STAT5b-RAR) as a result of chromosomal translocations, the RA signal pathway is disrupted and myeloid differentiation is arrested at the promyelocytic stage. Pharmacologic dosage of all-trans retinoic acid (ATRA) directly modulates PML-RAR and its interaction with the nuclear receptor co-repressor complex, which restores the wild-type RAR/RXR regulatory pathway and induces the transcriptional expression of downstream genes. Analysing gene expression profiles in APL cells before and after ATRA treatment represents a useful approach to identify genes whose functions are involved in this new cancer treatment. A chronologically well coordinated modulation of ATRA-regulated genes has thus been revealed which seems to constitute a balanced functional network underlying decreased cellular proliferation, initiation and progression of maturation, and maintenance of cell survival before terminal differentiation.

  12. The Retinoic Acid Receptor-α mediates human T-cell activation and Th2 cytokine and chemokine production

    Directory of Open Access Journals (Sweden)

    Key Michael

    2008-04-01

    Full Text Available Abstract Background We have recently demonstrated that all-trans-retinoic acid (ATRA and 9-cis-retinoic acid (9-cis RA promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-γ and TNF-α expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA, and the retinoic acid receptor-α (RAR-α-selective agonist, AM580 but not with the RAR-β/γ ligand, 4-hydroxyphenylretinamide (4-HPR. Results The increase in type 2 cytokine production by these retinoids correlated with the expression of the T cell activation markers, CD69 and CD38. The RAR-α-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-α-selective antagonist, RO 41–5253, inhibited these effects. Conclusion These results strongly support a role for RAR-α engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.

  13. Extraction of atrazine and its metabolites using supercritical fluids and enhanced-fluidity liquids

    Science.gov (United States)

    Shows; Olesik

    2000-09-01

    Supercritical fluid and enhanced-fluidity liquid extractions are performed on spiked sediment samples containing atrazine (ATRA) and five of its metabolites including desisopropyldesethylatrazine, desethylhydroxyatrazine (DEHA), desisopropylatrazine, desethylatrazine, and hydroxyatrazine (HA). The hydroxylated metabolites are of particular interest because of their increased water solubility and the fact that their high polarity makes them difficult to analyze. Soxhlet extractions using methanol are conducted for the purpose of comparison. Results of the extractions show that the hydroxy-containing metabolites of ATRA are not effectively extracted with supercritical CO2 alone. The solvating or desorbing power of carbon dioxide appears too low to extract HA and DEHA. The extraction recoveries of the hydroxylated metabolites increase when enhanced-fluidity liquid mixtures of methanol/CO2 are used, and these rates increase with the methanol concentration. Enhanced-fluidity ternary liquid mixtures of H2O/methanol/CO2 yield the best recoveries for these compounds. ATRA recoveries are equally effective when using supercritical CO2 or enhanced-fluidity mixtures. The other nonhydroxy-containing metabolites require the increased solvent strength of either large percentages of methanol in CO2 or ternary mixtures of H2O, methanol, and CO2 for high recoveries. Recoveries with enhanced-fluidity liquid ternary mixtures are better than the recoveries from Soxhlet for all the compounds in the study. PMID:11011724

  14. Influence of suppressor gene p16 on retinoic acid inducing cancer cell A549 differentiation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To investigate the role of suppressor gene p16 in the process of differential regulation of retinoic acid (RA) on the A549 lung cancer cells.Methods Tumor suppressor gene p16 was transferred into A549 cells and the cells were treated with all-trans retinoic acid (ATR) at the dosage of 5×10-6 mol/L for 4 d. After that, the proliferation and differentiation of A549 cells were examined by growth curve and cytometry analysis, the change of lung lineage-specific marker MUC1 was tested by immunohistochemical staining. Meanwhile, Western blot was used to observe the change of p16 protein expression in A549 cells treated with ATRA.Results ATRA could obviously inhibit the growth and induce the differentiation of A549 Cells that were transferred with p16 gene. There were more cells arrested in G1/G0 phase and the expression of MUG1 was markedly down-regulated than in control cells. The expression of p16 protein was up-regulated in A549 cells treated with ATRA.Conclusion Suppressor gene p16 could enhance the effects of RA and proliferated suppression and differential induction of A549 cells.

  15. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    Science.gov (United States)

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse; Fenaux, Pierre; Degos, Laurent; Chomienne, Christine; Chevret, Sylvie; Dombret, Hervé

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR and 3 PR (26%), 75% of the responders and 36% of the non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated patients had a longer OS than relapsed/refractory patients. In patients who fulfilled the 6 planned cycles, OS did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be a surrogate for survival with this approach. During therapy, early platelet response and demethylation of the FZD9, ALOX12, HPN, and CALCA genes were associated with clinical response. Finally, there was no evidence for the restoration of an ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons to conventional care in patients with high-risk AML, at least in those presenting previously untreated disease and low blast count. PMID:21293051

  16. Relationship between struc-ture and function of JWA in the modulation of cell differ-entiation

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To elucidate the structure characteristic, regulation of expression and the potential function of JWA——a novel retinoic acid responsible and cytoskeleton associate gene, a rat JWA homologue gene and a 621-bp JWA promoter fragment were cloned and analyzed. Using reverse transcription-polymerase chain reaction (RT-PCR), JWA mRNA expression in NIH3T3, K562 and human primary acute promyelocytic leukaemia (APL) cells have been investigated after treatment with all trans retinoic acid (ATRA), N-4-hydroxyphenyl-retinamide (4HPR), arsenic trioxide (As2O3), Phorbol-12-myristate-13-acetate (TPA) and dimethyl sulfoxide (DMSO). The results showed that there is a complete TPA responsive element (TRE) existed in the promoter of JWA at ?437 to ?443 bp; rat JWA homologue gene showed that there are four nucleotides different from human JWA within coding region. After treatment with TPA, an uneven pattern of JWA transcription existed in different cell lines, suggesting that even TPA induces cell differentiation in different cell lines, and it may be referred to different signal pathways. In ATRA pretreated APL cells, all the above chemicals induce cellular differentiation and down regulate JWA transcription in vitro. This suggests that pretreatment of ATRA on APL cells seems a precondition for turning on JWA involved signal pathway.

  17. Limited selection of sodium channel blocking toxin-producing bacteria from paralytic shellfish toxin-contaminated mussels (Aulacomya ater).

    Science.gov (United States)

    Vásquez, Mónica; Grüttner, Carol; Möeller, Blanca; Moore, Edward R B

    2002-01-01

    Paralytic shellfish toxins (PSTs) are sodium channel blocking (SCB) toxins, produced by cyanobacteria, as well as by marine dinoflagellates and their associated bacteria, and cause serious health and economic concern worldwide. In a previous study, approximately 70% of the bacteria enriched from PST-contaminated shellfish tissue and isolated on marine agar medium were observed to produce SCB toxins. In the study reported here, the high percentage of cultivable toxigenic bacteria is demonstrated to be obtained through a marked selection on marine agar medium. The cultivable as well as the total bacterial diversity associated with PST-contaminated shellfish collected from the Magallanes region in the south of Chile has been analysed. Approximately 80% of bacterial isolates, analysed by restriction analysis of PCR amplified ribosomal DNA (i.e., ARDRA fingerprinting), were limited to only two genotypic OTUs (operational taxonomic unit). Sequence determination and analysis of the 16S rDNA from representative isolates of both OTUs established them to be closely related to species of the Psychrobacter genus of the gamma-subclass of the Proteobacteria. The total bacterial diversity in the shellfish was further analysed, using a cultivation-independent strategy of extraction of total DNA from contaminated tissue, PCR-amplification of bacterial 16S rRNA genes, cloning of the PCR products and analysis of the cloned 16S rDNA sequence types by fingerprinting and sequencing. Only 2% of the cloned sequence types corresponded to species of the Psychrobacter genus. The 16S rDNA sequence types detected clustered with species of the y-Proteobacteria subclass, the Cytophaga-Flexibacter-Bacteroides (CFB), the Fusobacteria and the Firmicutes phyla. The level of diversity observed within the libraries of cloned 16S rDNA was markedly greater than that observed among isolates obtained through marine agar enrichment cultures from the same shellfish tissue. Additionally the predominant cloned 16S rDNA sequence types detected from samples of the surrounding seawater demonstrated no correlation with those observed in the PST-contaminated mussels. PMID:12238500

  18. Activation of RAS/ERK alone is insufficient to inhibit RXRα function and deplete retinoic acid in hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ai-Guo, E-mail: wangaiguotl@hotmail.com; Song, Ya-Nan; Chen, Jun; Li, Hui-Ling; Dong, Jian-Yi; Cui, Hai-Peng; Yao, Liang; Li, Xue-Feng; Gao, Wen-Ting; Qiu, Ze-Wen; Wang, Fu-Jin; Wang, Jing-Yu, E-mail: wangjingyus@163.com

    2014-09-26

    Highlights: • The activation of RAS/ERK is insufficient to inhibit RXRα function and deplete RA. • The retinoid metabolism-related genes are down-regulated by ras oncogene. • The atRA has no effect on preventing hepatic tumorigenesis or curing the developed hepatic nodules. - Abstract: Activation of RAS/ERK signaling pathway, depletion of retinoid, and phosphorylation of retinoid X receptor alpha (RXRα) are frequent events found in liver tumors and thought to play important roles in hepatic tumorigenesis. However, the relationships among them still remained to be elucidated. By exploring the transgenic mouse model of hepatic tumorigenesis induced by liver-specific expression of H-ras12V oncogene, the activation of RAS/ERK, the mRNA expression levels of retinoid metabolism-related genes, the contents of retinoid metabolites, and phosphorylation of RXRα were determined. RAS/ERK signaling pathway was gradually and significantly activated in hepatic tumor adjacent normal liver tissues (P) and hepatic tumor tissues (T) of H-ras12V transgenic mice compared with normal liver tissues (Wt) of wild type mice. On the contrary, the mRNA expression levels of retinoid metabolism-related genes were significantly reduced in P and T compared with Wt. Interestingly, the retinoid metabolites 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (atRA), the well known ligands for nuclear transcription factor RXR and retinoic acid receptor (RAR), were significantly decreased only in T compared with Wt and P, although the oxidized polar metabolite of atRA, 4-keto-all-trans-retinoic-acid (4-keto-RA) was significantly decreased in both P and T compared with Wt. To our surprise, the functions of RXRα were significantly blocked only in T compared with Wt and P. Namely, the total protein levels of RXRα were significantly reduced and the phosphorylation levels of RXRα were significantly increased only in T compared with Wt and P. Treatment of H-ras12V transgenic mice at 5-week

  19. Activation of RAS/ERK alone is insufficient to inhibit RXRα function and deplete retinoic acid in hepatocytes

    International Nuclear Information System (INIS)

    Highlights: • The activation of RAS/ERK is insufficient to inhibit RXRα function and deplete RA. • The retinoid metabolism-related genes are down-regulated by ras oncogene. • The atRA has no effect on preventing hepatic tumorigenesis or curing the developed hepatic nodules. - Abstract: Activation of RAS/ERK signaling pathway, depletion of retinoid, and phosphorylation of retinoid X receptor alpha (RXRα) are frequent events found in liver tumors and thought to play important roles in hepatic tumorigenesis. However, the relationships among them still remained to be elucidated. By exploring the transgenic mouse model of hepatic tumorigenesis induced by liver-specific expression of H-ras12V oncogene, the activation of RAS/ERK, the mRNA expression levels of retinoid metabolism-related genes, the contents of retinoid metabolites, and phosphorylation of RXRα were determined. RAS/ERK signaling pathway was gradually and significantly activated in hepatic tumor adjacent normal liver tissues (P) and hepatic tumor tissues (T) of H-ras12V transgenic mice compared with normal liver tissues (Wt) of wild type mice. On the contrary, the mRNA expression levels of retinoid metabolism-related genes were significantly reduced in P and T compared with Wt. Interestingly, the retinoid metabolites 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (atRA), the well known ligands for nuclear transcription factor RXR and retinoic acid receptor (RAR), were significantly decreased only in T compared with Wt and P, although the oxidized polar metabolite of atRA, 4-keto-all-trans-retinoic-acid (4-keto-RA) was significantly decreased in both P and T compared with Wt. To our surprise, the functions of RXRα were significantly blocked only in T compared with Wt and P. Namely, the total protein levels of RXRα were significantly reduced and the phosphorylation levels of RXRα were significantly increased only in T compared with Wt and P. Treatment of H-ras12V transgenic mice at 5-week

  20. Pulmonary administration of integrin-nanoparticles regenerates collapsed alveoli.

    Science.gov (United States)

    Horiguchi, Michiko; Kojima, Hisako; Sakai, Hitomi; Kubo, Hiroshi; Yamashita, Chikamasa

    2014-08-10

    Chronic obstructive pulmonary disease (COPD) is an intractable pulmonary disease, causes widespread and irreversible alveoli collapse. In search of a treatment target molecule, which is able to regenerate collapsed alveoli, we sought to identify a factor that induces differentiation in human alveolar epithelial stem cells using all-trans retinoic acid (ATRA), whose alveolar repair capacity has been reported in animal experiments. When human alveolar epithelial stem cells were exposed to ATRA at a concentration of 10μM for over seven days, approximately 20% of the cells differentiated into each of the type-I and type-II alveolar epithelial cells that constitute the alveoli. In a microarray analysis, integrin-α1 and integrin-β3 showed the largest variation in the ATRA-treated group compared with the controls. Furthermore, the effect of the induction of differentiation in human alveolar epithelial stem cells using ATRA was suppressed by approximately one-fourth by siRNA treatments with integrin α1 and integrin β3. These results suggested that integrin α1 and β3 are factors responsible for the induction of differentiation in human alveolar epithelial stem cells. We accordingly investigated whether integrin nanoparticles also had a regenerative effect in vivo. Elastase-induced COPD model mouse was produced, and the alveolar repair effect of pulmonary administration using nanoparticles of integrin protein was evaluated by X-ray CT scanning. Improvement in the CT value in comparison with an untreated group indicated that there was an alveolar repair effect. In this study, it was shown that the differentiation-inducing effect on human alveolar epithelial stem cells by ATRA was induced by increased expression of integrin, and that the induced integrin enhanced phosphorylation signaling of AKT, resulting in inducing differentiations. Furthermore, the study demonstrated that lung administration of nanoparticles with increased solubility and stability of integrin

  1. Identification of tumor invasion-related differentially expressed genes in different grades and all-trans retinoic acid-treated astrocytoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Yi Zeng; Zhong Yang; Yangyun Han; Chao You

    2008-01-01

    BACKGROUND: Although several genetic aberrations and gene expressional changes have been shown to exist in tumors and different grades of astrocytomas, as well as in normal tissues, the gene profiling and genetic pathways associated with malignant transformation and progression remain unclear. OBJECTIVE: To identity differentially expressed genes related to tumor invasion from various grades and all-trans retinoic acid (ATRA)-treated astrocytoma cell lines by cDNA microarray. DESIGN, TIME AND SETTING: In vitro gene experiment was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA from January to October 2007. MATERIALS: Two different grades of astrocytoma cell lines CHG-5 (WHO grade Ⅱ) and SHG-44 (WHOgrade Ⅳ) were developed by our laboratory; a cell differentiation-inducing agent ATRA and a human cDNA microarray technology were used to determine differentially expressed genes (City University of Hong Kong). METHODS: Total RNA was extracted using the Trizol test kit. Reverse transcription was performed using Superscript Ⅱ reverse transcriptase. The eDNA product (target DNA) was marked with fluorochromes Cy3 (normal SHG-44) and Cy5 (CHG-5 or ATRA-treated SHG-44), followed by chip hybridization. MAIN OUTCOME MEASURES: Gene expression profiles of CHG-5 vs. SttG-44 and ATRA-treated vs. Normal SHG-44 were performed to identify differentially expressed genes. Several of these genes were randomly selected for Northern Blot analysis. The identification of genes that were similarly regulated (overlapping) was performed by comparing gene expression profiles between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. RESULTS: No significant differences were observed between CHG5 and SHG-44 cell line morphology. Under confocal microscopy. GFAP staining intensity of CHG5 cells was greater than SHG-44 cells (t = 6.078, P = 0.004). Growth curve analysis demonstrated that the speed of SHG-44 cell

  2. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Anna Falanga

    2011-12-01

    Full Text Available Acute promyelocytic leukemia (APL is a distinct subtype of myeloid leukemia characterized by t(15;17 chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha. APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta and tumor necrosis factor (TNF-alpha], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.

  3. Transcriptional upregulation of restin by p53

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Restin, belonging to the melanoma-associated antigen superfamily, was firstly cloned from the differentiated HL-60 cells when induced by all-trans retinoic acid ( ATRA ) in our lab. Our previous results showed that restin might be correlated to cell cycle arrest. Due to the importance of p53 in the regulation of cell growth and the relationship between p53 and ATRA, we tried to test the relationship between p53 and restin. Firstly, transfection results showed that p53 was able to upregulate the expression of restin at the transcriptional level when p53 was transfected into eukaryotic cells. Secondly, the bioinformatics analysis revealed that the upstream sequence (about 2 kb) from the first ATG of the ORF of restin gene contained a p53 binding site. In order to confirm that p53 was involved in the transcriptional regulation of restin, we cloned the upstream sequence of restin and constructed the promoter luciferase reporter system. From the luciferase activity, we demonstrated that the promoter of restin gene could be induced by ATRA. Then, another two luciferase reporter plasmids driven by the reporter of restin with no (RP?p53-luc) or mutant (mRP-luc) p53 binding site were constructed to see the regulation of restin by p53. Results showed that the transcriptional upregulation of restin gene was not due to the putative p53 binding site on the upstream of restin gene. We proposed that p53 upregulated restin transcription through an indirect way rather than direct interaction with the cis-activating element of the restin promoter.

  4. Transcriptional upregulation of restin by p53

    Institute of Scientific and Technical Information of China (English)

    WANG RuiHua; LU Fan; FU HaiYan; WU YouSheng; YANG GuoDong; ZHAO WenMing; Zhao ZhongLiang

    2007-01-01

    Restin, belonging to the melanoma-associated antigen superfamily, was firstly cloned from the differentiated HL-60 cells when induced by all-trans retinoic acid ( ATRA ) in our lab. Our previous results showed that restin might be correlated to cell cycle arrest. Due to the importance of p53 in the regulation of cell growth and the relationship between p53 and ATRA, we tried to test the relationship between p53 and restin. Firstly, transfection results showed that p53 was able to upregulate the expression of restin at the transcriptional level when p53 was transfected into eukaryotic cells. Secondly, the bioinformatics analysis revealed that the upstream sequence (about 2 kb) from the first ATG of the ORF of restin gene contained a p53 binding site. In order to confirm that p53 was involved in the transcriptional regulation of restin, we cloned the upstream sequence of restin and constructed the promoter luciferase reporter system. From the luciferase activity, we demonstrated that the promoter of restin gene could be induced by ATRA. Then, another two luciferase reporter plasmids driven by the reporter of restin with no (RP△p53-luc) or mutant (mRP-luc) p53 binding site were constructed to see the regulation of restin by p53. Results showed that the transcriptional upregulation of restin gene was not due to the putative p53 binding site on the upstream of restin gene. We proposed that p53 upregulated restin transcription through an indirect way rather than direct interaction with the cis-activating element of the restin promoter.

  5. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Huai, Lei; Wang, Cuicui; Zhang, Cuiping; Li, Qihui; Chen, Yirui; Jia, Yujiao; Li, Yan; Xing, Haiyan; Tian, Zheng; Rao, Qing; Wang, Min [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China); Wang, Jianxiang, E-mail: wangjx@ihcams.ac.cn [State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020 (China)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer Metformin induces differentiation in NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces activation of the MEK/ERK signaling pathway in APL cells. Black-Right-Pointing-Pointer Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. Black-Right-Pointing-Pointer Metformin induces the relocalization and degradation of the PML-RAR{alpha} fusion protein. Black-Right-Pointing-Pointer The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RAR{alpha} and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  6. Targeting head and neck cancer stem cells to overcome resistance to photon and carbon ion radiation.

    Science.gov (United States)

    Bertrand, Gérald; Maalouf, Mira; Boivin, Antony; Battiston-Montagne, Priscillia; Beuve, Michael; Levy, Antonin; Jalade, Patrice; Fournier, Claudia; Ardail, Dominique; Magné, Nicolas; Alphonse, Gersende; Rodriguez-Lafrasse, Claire

    2014-02-01

    Although promising new radiation therapy techniques such as hadrontherapy are currently being evaluated in the treatment of head and neck malignancies, local control of head and neck squamous cell carcinoma (HNSCC) remains low. Here, we investigated the involvement of cancer stem-like cells (CSCs) in a radioresistant HNSCC cell line (SQ20B). Stem-like cells SQ20B/SidePopulation(SP)/CD44(+)/ALDH(high) were more resistant to both photon and carbon ion irradiation compared with non-CSCs. This was confirmed by a BrdU labeling experiment, which suggests that CSCs were able to proliferate and to induce tumorigenicity after irradiation. SQ20B/SP/CD44(+)/ALDH(high) were capable of an extended G2/M arrest phase in response to photon or carbon ion irradiation compared with non-CSCs. Moreover, our data strongly suggest that resistance of CSCs may result from an imbalance between exacerbated self-renewal and proliferative capacities and the decrease in apoptotic cell death triggering. In order to modulate these processes, two targeted pharmacological strategies were tested. Firstly, UCN-01, a checkpoint kinase (Chk1) inhibitor, induced the relapse of G2/M arrest and radiosensitization of SQ20B-CSCs. Secondly, all-trans retinoic acid (ATRA) resulted in an inhibition of ALDH activity, and induction of the differentiation and radiosensitization of SQ20B/SP/CD44(+)/ALDH(high) cells. The combination of ATRA and UCN-01 treatments with irradiation drastically decreased the surviving fraction at 2Gy of SQ20B-CSCs from 0.85 to 0.38 after photon irradiation, and from 0.45 to 0.21 in response to carbon ions. Taken together, our results suggest that the combination of UCN-01 and ATRA represent a promising pharmacological-targeted strategy that significantly sensitizes CSCs to photon or carbon ion radiation. PMID:23955575

  7. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

    Directory of Open Access Journals (Sweden)

    Tamer M Fouad

    2011-01-01

    Full Text Available

    The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate

  8. Nuclear and mitochondrial multilocus phylogeny and survey of alkaloid content in true salamanders of the genus Salamandra (Salamandridae).

    Science.gov (United States)

    Vences, Miguel; Sanchez, Eugenia; Hauswaldt, J Susanne; Eikelmann, Daniel; Rodríguez, Ariel; Carranza, Salvador; Donaire, David; Gehara, Marcelo; Helfer, Véronique; Lötters, Stefan; Werner, Philine; Schulz, Stefan; Steinfartz, Sebastian

    2014-04-01

    The genus Salamandra represents a clade of six species of Palearctic salamanders of either contrasted black-yellow, or uniformly black coloration, known to contain steroidal alkaloid toxins in high concentrations in their skin secretions. This study reconstructs the phylogeny of the genus Salamandra based on DNA sequences of segments of 10 mitochondrial and 13 nuclear genes from 31 individual samples representing all Salamandra species and most of the commonly recognized subspecies. The concatenated analysis of the complete dataset produced a fully resolved tree with most nodes strongly supported, suggesting that a clade composed of the Alpine salamander (S. atra) and the Corsican fire salamander (S. corsica) is the sister taxon to a clade containing the remaining species, among which S. algira and S. salamandra are sister species. Separate analyses of mitochondrial and nuclear data partitions disagreed regarding basal nodes and in the position of the root but concordantly recovered the S. atra/S. corsica as well as the S. salamandra/S. algira relationship. A species-tree analysis suggested almost simultaneous temporal splits between these pairs of species, which we hypothesize was caused by vicariance events after the Messinian salinity crisis (from late Miocene to early Pliocene). A survey of toxins with combined gas chromatography/mass spectroscopy confirmed the presence of samandarine and/or samandarone steroidal alkaloids in all species of Salamandra as well as in representatives of their sister group, Lyciasalamandra. Samandarone was also detected in lower concentrations in other salamandrids including Calotriton, Euproctus, Lissotriton, and Triturus, suggesting that the presence and possible biosynthesis of this alkaloid is plesiomorphic within the Salamandridae. PMID:24412216

  9. CLINICAL FEATURES AND CLINICAL OUTCOME OF ACUTE PROMYELOCYTIC LEUKEMIA PATIENTS TREATED AT CAIRO NATIONAL CANCER INSTITUTE IN EGYPT

    Directory of Open Access Journals (Sweden)

    Ola Khorshid

    2011-12-01

    Full Text Available The current study reports the clinical features and treatment outcome of 67 patients with acute promyelocytic leukemia (APL presented to National Cancer Institute (NCI-Cairo, in Egypt from January 2007 to January 2011. The median follow-up time was 36 months. All patients were treated with the simultaneous administration of all-trans retinoic acid (ATRA and anthracyclin. The treatment protocol was modified due to resource limitations at the NCI-Cairo by replacing of idarubicin with doxorubicin in most of the cases and the inclusion of cytarbine during the consolidation phase only in pediatric patients. All patients who achieved molecular complete remission (CRm after consolidation received two-year maintenance treatment with low dose chemotherapy composed of 6 mercaptopurine, methotrexate and intermittent ATRA courses. The median age at presentation was 29 years. There was a slight male predominance (53%.  Bleeding was the most common presenting symptom (79%. Most patients had an intermediate risk Sanz score (49% and 34% had a high risk score.  All patients achieved molecular CR at end of consolidation therapy with a median duration of 100 days. The main therapeutic complications during the induction phase were febrile neutropenia (42%, bleeding (18% and differentiation syndrome (11%. Five patients died at diagnosis due to bleeding, three died during induction chemotherapy due to febrile neutropenia (n=2 and bleeding (n=1 and one patient died during consolidation therapy due to febrile neutropenia.  The 3-year OS was 89% and relapse rate was 3%. Adapting standard AIDA treatment protocols to limited resources by reducing dose-intensity during treatment consolidation, using ATRA in the consolidation phase and alternative anthracyclin (doxorubicin may be a valid treatment option in developing countries. In spite of the increased incidence of high and intermediate risk score APL in our sample, we reported an acceptable CR rate, toxicity and OS.

  10. Acute promyelocytic leukemia, study of predictive factors for Differentiation Syndrome, single center experience

    International Nuclear Information System (INIS)

    Reports about patients with acute promyelocytic leukemia from the Middle East are few; in this study we are reporting our single center experience of treating 29 patients over 6 years. Acute promyelocytic leukemia treatment response is markedly improved after the introduction of ATRA. Treatment related complication is still an important issue particularly Differentiation Syndrome. Prediction to its occurrence has been tried by other groups. We aimed to study all the possible predictive factors of acute promyelocytic leukemia. Our chemotherapy induction protocol is AIDA protocol which includes ATRA 45 mg/m2/d in divided doses every 12h, and Idarubicin 12 mg/ m2/d IV on days 3, 5, 7, and 9. Differentiation Syndrome occurred in 48.3% of patients and was mainly presented by pulmonary symptoms in 55.2%, 6 cases died during induction. None of the predictive factors studied showed a statistically significant difference between patients who developed Differentiation Syndrome and those who did not. Differentiation Syndrome did not affect overall survival. Cox regression showed an inverse yet a non significant association between PET- HEMA and overall survival probability (P = 0.168). In conclusion, Differentiation Syndrome has no clear predictive factor to date. The best approach is to hold ATRA and give dexamethasone which is quite effective as reported in the literature. PETHEMA risk model has a moderately significant prognostic value look for all possible predictive factors of Differentiation syndrome (DS) which were first described in 1992 by frankel et al. (4) and represented the major complication through this disease course: studies had reported conflicting results about this (5,6). In addition we will compare our data to other areas of the world

  11. All-trans retinoic acid inhibits vascular endothelial growth factor expression in a cell model of neutrophil activation.

    Science.gov (United States)

    Tee, Meng Kian; Vigne, Jean-Louis; Taylor, Robert N

    2006-03-01

    Infiltrating neutrophil granulocytes are a particularly rich source of vascular endothelial growth factor (VEGF) in the endometrium and may contribute to the angiogenesis of endometriosis lesions. The objective of this study is to evaluate the expression and regulation of VEGF in endometrial neutrophils and in a model of neutrophil differentiation relevant to endometriosis. Immunohistochemistry was performed on endometriosis patient biopsies and cultured neutrophil-like HL-60 cells were assessed. The study was set in a reproductive biology division within an academic medical center. Endometrial biopsies were performed on women with endometriosis and HL-60 cells were treated with all-trans retinoic acid (atRA) and dimethyl sulfoxide in vitro. Immunofluorescence histochemistry, VEGF mRNA and protein quantification, and transfection studies of VEGF gene promoter-luciferase constructs were all main outcome measures. Immunofluorescence studies verified the presence of neutrophils in eutopic endometrium from women with endometriosis. Examination of the regulation of VEGF using differentiated HL-60 cells as a model, revealed that atRA induced a dose- and time-dependent suppression of VEGF mRNA and protein. Transient transfection, truncation, EMSA, and site-directed mutagenesis of human VEGF promoter-luciferase constructs in HL-60 cells indicated that atRA repressed VEGF gene transcription via a direct repeat 1 element located between -443 and -431 bp relative to the transcription initiation site. Because retinoic acid is synthesized de novo in endometrial cells under the influence of progesterone, our findings suggest that the up-regulated VEGF and angiogenesis in tissue from women with endometriosis may reflect failure of neutrophil differentiation in these cases, and provide a rationale for retinoid therapy in this condition. PMID:16322068

  12. Activation of Tax protein by c-Jun-N-terminal kinase is not dependent on the presence or absence of the early growth response-1 gene product.

    Science.gov (United States)

    Parra, Eduardo; Gutierréz, Luís; Ferreira, Jorge

    2016-02-01

    The Tax protein of human T cell leukemia virus type 1 plays a major role in the pathogenesis of adult T cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. In the present study, we investigated whether the EGR-1 pathway is involved in the regulation of Tax-induced JNK expression in human Jurkat T cells transfected to express the Tax protein in the presence or absence of PMA or ionomycin. Overexpression of EGR-1 in Jurkat cells transfected to express Tax, promoted the activation of several genes, with the most potent being those that contained AP-1 (Jun/c-Fos), whereas knockdown of endogenous EGR-1 by small interfering RNA (siRNA) somewhat reduced Tax-mediated JNK-1 transcription. Additionally, luciferase-based AP-1 and NF-κB reporter gene assays demonstrated that inhibition of EGR-1 expression by an siRNA did not affect the transcriptional activity of a consensus sequence of either AP-1 or NF-κB. On the other hand, the apoptosis assay, using all-trans retinoic acid (ATRA) as an inducer of apoptosis, confirmed that siRNA against EGR-1 failed to suppress ATRA-induced apoptosis in Jurkat and Jurkat-Tax cells, as noted by the low levels of both DEVDase activity and DNA fragmentation, indicating that the induction of apoptosis by ATRA was Egr-1-independent. Finally, our data showed that activation of Tax by JNK-1 was not dependent on the EGR-1 cascade of events, suggesting that EGR-1 is important but not a determinant for the activity for Tax-induced proliferation of Jurkat cells. PMID:26573109

  13. Seed dormancy breaking diterpenoids from the liverwort Plagiochila sciophila and their differentiation inducing activity in human promyelocytic leukemia HL-60 cells.

    Science.gov (United States)

    Kenmoku, Hiromichi; Tada, Hiroyuki; Oogushi, Megumi; Esumi, Tomoyuki; Takahashi, Hironobu; Noji, Masaaki; Sassa, Takeshi; Toyota, Masao; Asakawa, Yoshinori

    2014-07-01

    To obtain the structural diversity of bioactive compounds similar to cotylenins and fusicoccins that modulate 14-3-3 protein-protein interactions in eukaryotes, screening tests were carried out using the lettuce seed dormancy breaking-assay. An acetone extract of the liverwort Plagiochila sciophila exhibited significant activity against the seeds in the presence of the plant hormone abscisic acid. Activity-guided fractionation of the extract afforded the isolation of seven novel fusicoccane-type diterpenoids, named fusicosciophins A-E (1-5), 8-deacetyl (6) and 9-deacetyl fusicosciophin E (7). Their structures were determined by spectroscopic methods and X-ray crystallographic analyses. All the pure isolated compounds (1-7) exhibited moderate lettuce seed dormancy breaking activity. In addition, the differentiation-inducing activity and cytotoxicity of these isolates, together with fusicoccin A (FC-A) and all-trans retinoic acid (ATRA), were evaluated in human promyelocytic leukemia HL-60 cells and human mouth epidermal carcinoma KB cells, respectively. Fusicosciophins (2 and 4) and FC-A exhibited moderate differentiation-inducing activity (EC50 31.2-59.1 microM) compared with ATRA (EC50 0.3 microM), while 2, 4 and ATRA exhibited higher selectivity indices (IC50/EC50 >3.38-667) than FC-A (IC50/EC50 1.05). This is the first report on the isolation of fusicoccane-type diterpenoids from liverworts having seed dormancy breaking activity and differentiation-inducing activity in mammal cells. PMID:25230492

  14. Snake Cathelicidin NA-CATH and Smaller Helical Antimicrobial Peptides Are Effective against Burkholderia thailandensis.

    Directory of Open Access Journals (Sweden)

    Ryan J Blower

    Full Text Available Burkholderia thailandensis is a Gram-negative soil bacterium used as a model organism for B. pseudomallei, the causative agent of melioidosis and an organism classified category B priority pathogen and a Tier 1 select agent for its potential use as a biological weapon. Burkholderia species are reportedly "highly resistant" to antimicrobial agents, including cyclic peptide antibiotics, due to multiple resistance systems, a hypothesis we decided to test using antimicrobial (host defense peptides. In this study, a number of cationic antimicrobial peptides (CAMPs were tested in vitro against B. thailandensis for both antimicrobial activity and inhibition of biofilm formation. Here, we report that the Chinese cobra (Naja atra cathelicidin NA-CATH was significantly antimicrobial against B. thailandensis. Additional cathelicidins, including the human cathelicidin LL-37, a sheep cathelicidin SMAP-29, and some smaller ATRA peptide derivatives of NA-CATH were also effective. The D-enantiomer of one small peptide (ATRA-1A was found to be antimicrobial as well, with EC50 in the range of the L-enantiomer. Our results also demonstrate that human alpha-defensins (HNP-1 & -2 and a short beta-defensin-derived peptide (Peptide 4 of hBD-3 were not bactericidal against B. thailandensis. We also found that the cathelicidin peptides, including LL-37, NA-CATH, and SMAP-29, possessed significant ability to prevent biofilm formation of B. thailandensis. Additionally, we show that LL-37 and its D-enantiomer D-LL-37 can disperse pre-formed biofilms. These results demonstrate that although B. thailandensis is highly resistant to many antibiotics, cyclic peptide antibiotics such as polymyxin B, and defensing peptides, some antimicrobial peptides including the elapid snake cathelicidin NA-CATH exert significant antimicrobial and antibiofilm activity towards B. thailandensis.

  15. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Laura Russo

    2011-01-01

    Full Text Available

    Acute promyelocytic leukemia (APL is a distinct subtype of myeloid leukemia characterized by t(15;17 chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha. APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC.

    Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta and tumor necrosis factor (TNF-alpha], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes.

    ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field.

    In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.

  16. Screening of differentially expressed genes related to differentiation and proliferation by gene expression profiling of different grade astrocytoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Yi Zeng; Zhong Yang; Yangyun Han; Chao You

    2008-01-01

    BACKGROUND: The detection of differential gene expression in brain is possible by cDNA microarray technology, and the screening of differentially expressed genes might provide a biological basis for gene-targeted therapy for tumors. OBJECTIVE: To detect the differential expression of genes among astrocytoma SHG-44 (WHO grade IV), CHG-5 (WHO grade II), and ATRA-treated SHG-44 cell lines by cDNA microarray. DESIGN: Laboratory experiments in vitro.SETTING: Department of Neurobiology, the Third Military Medical University. MATERIALS: The experiment was performed at the Department of Neurobiology in the Third Military Medical University of the Chinese PLA from January to October 2007. The SHG-44 cell line (WHO grade Ⅳ) was established by Prof. Ziwei Du, and the CHG-5 cell line (WHO grade II) was set up by Prof. Xiuwu Bian from the Third Military Medical University of the Chinese PLA. The cDNA microarray containing 9182 known genes was prepared and provided by Dr. Yang Zhong at the City University of Hong Kong. MAIN OUTCOME MEASURES: The identification of genes that were similarly regulated (overlapping) during tumor progression and differentiation, by comparison of gene expression profiles between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. RESULTS: Thirty-one overlapping genes were found to have similar regulatory effects on astrocytomas; among them, twenty genes were up-regulated and eleven were down-regulated in both comparisons between CHG-5 and SHG-44 cells, and between SHG-44 cells with or without treatment with ATRA. The four reported genes, SERPINF1, MAPK11, HIF1A and SOD2, were up-regulated in this study.CONCLUSION: The differentially expressed genes in different grade astrocytoma cell lines were revealed primarily by cDNA microarray; among them, five identified overlapping genes, SERPINF1, MAPK11, DCTN2, HIF1A and SOD2, were related to the malignant progression of astrocytoma cells.

  17. Metformin induces differentiation in acute promyelocytic leukemia by activating the MEK/ERK signaling pathway

    International Nuclear Information System (INIS)

    Highlights: ► Metformin induces differentiation in NB4 and primary APL cells. ► Metformin induces activation of the MEK/ERK signaling pathway in APL cells. ► Metformin synergizes with ATRA to trigger maturation of NB4 and primary APL cells. ► Metformin induces the relocalization and degradation of the PML-RARα fusion protein. ► The study may be applicable for new differentiation therapy in cancer treatment. -- Abstract: Recent studies have shown that metformin, a widely used antidiabetic agent, may reduce the risk of cancer development. In this study, we investigated the antitumoral effect of metformin on both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells. Metformin induced apoptosis with partial differentiation in an APL cell line, NB4, but only displayed a proapoptotic effect on several non-M3 AML cell lines. Further analysis revealed that a strong synergistic effect existed between metformin and all-trans retinoic acid (ATRA) during APL cell maturation and that metformin induced the hyperphosphorylation of extracellular signal-regulated kinase (ERK) in APL cells. U0126, a specific MEK/ERK activation inhibitor, abrogated metformin-induced differentiation. Finally, we found that metformin induced the degradation of the oncoproteins PML-RARα and c-Myc and activated caspase-3. In conclusion, these results suggest that metformin treatment may contribute to the enhancement of ATRA-induced differentiation in APL, which may deepen the understanding of APL maturation and thus provide insight for new therapy strategies.

  18. Lipocalin 2, a Regulator of Retinoid Homeostasis and Retinoid-mediated Thermogenic Activation in Adipose Tissue.

    Science.gov (United States)

    Guo, Hong; Foncea, Rocio; O'Byrne, Sheila M; Jiang, Hongfeng; Zhang, Yuanyuan; Deis, Jessica A; Blaner, William S; Bernlohr, David A; Chen, Xiaoli

    2016-05-20

    We have recently characterized the role of lipocalin 2 (Lcn2) as a new adipose-derived cytokine in the regulation of adaptive thermogenesis via a non-adrenergic pathway. Herein, we explored a potential non-adrenergic mechanism by which Lcn2 regulates thermogenesis and lipid metabolism. We found that Lcn2 is a retinoic acid target gene, and retinoic acid concurrently stimulated UCP1 and Lcn2 expression in adipocytes. Lcn2 KO mice exhibited a blunted effect of all-trans-retinoic acid (ATRA) on body weight and fat mass, lipid metabolism, and retinoic acid signaling pathway activation in adipose tissue under the high fat diet-induced obese condition. We further demonstrated that Lcn2 is required for the full action of ATRA on the induction of UCP1 and PGC-1α expression in brown adipocytes and the restoration of cold intolerance in Lcn2 KO mice. Interestingly, we discovered that Lcn2 KO mice have decreased levels of retinoic acid and retinol in adipose tissue. The protein levels of STRA6 responsible for retinol uptake were significantly decreased in adipose tissue. The retinol transporter RBP4 was increased in adipose tissue but decreased in the circulation, suggesting the impairment of RBP4 secretion in Lcn2 KO adipose tissue. Moreover, Lcn2 deficiency abolished the ATRA effect on RBP4 expression in adipocytes. All the data suggest that the decreased retinoid level and action are associated with impaired retinol transport and storage in adipose tissue in Lcn2 KO mice. We conclude that Lcn2 plays a critical role in regulating metabolic homeostasis of retinoids and retinoid-mediated thermogenesis in adipose tissue. PMID:27008859

  19. Role of JWA in acute promyelocytic leukemia cell differentiation and apoptosis triggered by retinoic acid, 12-tetradecanoylphorbol-13-acetate and arsenic trioxide

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    JWA, a cytoskeleton associated gene, was primarily found to be regulated by all trans-retinoic acid (ATRA), 13 cis-retinoic acid (13 cis-RA) and 12-tetradecano- ylphorbol-13-acetate (TPA). Our previous data showed that JWA might be involved in both cellular differentiation and apoptosis induced by several chemicals. In this study, we addressed the possible mechanism of JWA in the regulation of cell differentiation and apoptosis in NB4, a human acute promyelocytic leukemia cell line. CD11b/CD33 expression and cell cycle were analyzed for detecting of cell differentiation and apoptosis. Both reverse-transcription polymerase chain reaction (RT-PCR) and Western blot assays were used for understanding the expressions of JWA. The results showed that under the indicated concentrations ATRA (10?6 mol/L) and As2O3 (10?6 mol/L) induced cell differentiation and apoptosis separately; while both 4HPR (10?6 mol/L) and TPA (10?7 mol/L) showed dual-directional effects on NB4 cells, they not only trigger cells' differentiation but also induce cells apoptosis at the same time. All chemicals up-regulated JWA expression whatever they trigger cells either differentiation or apoptosis; however, it seems that the chemicals have no effect on PML/RAR? in the treated NB4 cells. Anti-sense JWA oligonucleotide could partially block the ability of TPA in inducing cell differentiation and apoptosis via direct signal pathway. Interestingly, a high molecular weight JWA protein (JWAF) was identified only in de novo primary APL cells and it was also responsible for ATRA treatment. It raises questions of whether the JWAF is a novel APL specific marker and, how it was involved in the known mechanism of APL.

  20. Preferencias y expectativas profesionales de los estudiantes avanzados de comunicación social : Datos de una encuesta piloto para el debate académico

    OpenAIRE

    Jorge, José Eduardo

    2009-01-01

    Una encuesta entre los estudiantes con 11 o más materias aprobadas de la Facultad de Periodismo y Comunicación Social de la Universidad Nacional de La Plata arroja resultados de interés para la discusión académica. La temática política ocupa el primer lugar entre las preferencias de los alumnos que optan por la especialidad periodística. La comunicación institucional atrae a la mayoría de los futuros planificadores, seguida por la comunicación política. También el periodismo institucional rec...

  1. Mejora de la competitividad del sistema portuario español mediante la optimización del servicio de manipulación de mercancías

    OpenAIRE

    Parra Serrano, María del Pilar

    2012-01-01

    El transporte marítimo, responsable de la canalización del 90% de los flujos comerciales internacionales, se organiza en torno a los puertos. Éstos, que resultan plataformas indispensables para el desarrollo de la economía, compiten entre sí para maximizar el tráfico atraído hacia sus instalaciones. El papel estratégico de los puertos tiene un expreso reconocimiento en el contexto de la Unión Europea, tanto desde la óptica del comercio como bajo el prisma del transporte. No en vano, por lo...

  2. Caracterización de las antocianinas de la flor de ceibo como sensibilizadores naturales para su uso en celdas fotovoltaicas

    OpenAIRE

    María Paula Enciso; María Fernanda Cerdá Bresciano

    2014-01-01

    La energía solar es la fuente de energía más promisoria del futuro, ya que la conversión directa de luz solar en energía eléctrica mediante el uso de celdas solares posee muchas ventajas sobre los métodos usados en la actualidad, debido a que no genera desechos o contaminantes.En particular, las celdas solares sensibilizadas con pigmentos (DSSC) o celdas de Graetzel representan una alternativa a las convencionales celdas solares de silicio. En las últimas tres décadas han atraído considerable...

  3. INCENDIARIOS "Es preferible morir por el fuego, en combate, que morir en casa, por el hambre: Fidel Castro" Arson

    OpenAIRE

    Lisieux Elaine de BorbaTelles; Helena Dias de Castro Bins; Alcina Juliana Soares Barros; Franklin Escobar Córdoba

    2012-01-01

    Antecedentes. El concepto de fuego siempre ha atraído la atención del hombre. En la literatura abundan referencias a este término, que tanto puede representar poder y pasión como terror y destrucción. El incendio es un delito de fácil ejecución, pero de difícil investigación. La prevalencia de este delito es de 1,13%. La incidencia de este crimen está creciendo alrededor del mundo, provocando un impacto social importante por las pérdidas financieras, muertes, lesiones físicas y secuelas emoci...

  4. Es preferible morir por el fuego, en combate, que morir en casa, por el hambre: Fidel castro

    OpenAIRE

    Borba Telles, Lisieux Elaine de; Bins, Helena Dias de Castro; Barros, Alcina Juliana Soares; Escobar Córdoba, Franklin

    2012-01-01

    Antecedentes. El concepto de fuego siempre ha atraído la atención del hombre. En la literatura abundan referencias a este término, que tanto puede representar poder y pasión como terror y destrucción. El incendio es un delito de fácil ejecución, pero de difícil investigación. La prevalencia de este delito es de 1,13%. La incidencia de este crimen está creciendo alrededor del mundo, provocando un impacto social importante por las pérdidas financieras, muertes, lesiones físicas y secuelas emoci...

  5. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    OpenAIRE

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated dr...

  6. Armies sand Politics, Moscú, Pashentsev N., Evgeny, y Miniar-Beloruchev V. Constantine (coord.), Moscú, Russian Progressive Review, 2002, 398 pp.

    OpenAIRE

    Burgos, Elizabeth

    2005-01-01

    Las Fuerzas Armadas en América Latina, pese a la singularidad de su presencia en la vida política y a su peso en el seno del Estado, y, al carácter intervencionista de su acción, es un fenómeno que atrae poco a los investigadores. El debate se ha abordado, principalmente, desde el prisma de los Derechos Humanos. Sin embargo, en los últimos tiempos se observa un resuelto interés en los medios académicos por su estudio como elemento ineludible dentro del panorama político del contienente. Prueb...

  7. BCL-xL/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells

    International Nuclear Information System (INIS)

    The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia–retinoic acid receptor, alpha fusion protein (PML–RARα). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates >80% by activating transcription and proteasomal degradation of retinoic acid receptor, alpha (RARα). Whereas combination therapy with As2O3 has increased survival further, patients that experience relapse and are refractory to atRA and/or As2O3 is a clinically significant problem. BCL-2 family proteins regulate apoptosis and over-expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) family proteins has been associated with chemotherapeutic resistance in APL including impairment of the ability of atRA to induce growth arrest and differentiation. Here we investigated the novel BH3 domain mimetic, JY-1-106, which antagonizes the anti-apoptotic BCL-2 family members B-cell lymphoma-extra large (BCL-xL) and myeloid cell leukemia-1 (MCL-1) alone and in combination with retinoids including atRA, AM580 (RARα agonist), and SR11253 (RARγ antagonist). JY-1-106 reduced cell viability in HL-60 cells alone and in combination with retinoids. The combination of JY-1-106 and SR11253 had the greatest impact on cell viability by stimulating apoptosis. These studies indicate that dual BCL-xL/MCL-1 inhibitors and retinoids could work cooperatively in leukemia treatment. - Highlights: • Novel Bcl-xL/Mcl-1 inhibitor JY-1-106 reduces HL60 cell viability. • JY-1-106 is investigated in combination with retinoic acid, AM580, and SR11253. • AM580 is an RARα agonist; SR11253 is an RARγ antagonist. • Combined use of JY-1-106/SR11253 exhibited the greatest cell viability reduction. • JY-1-106 alone or in combination with retinoids induces apoptosis

  8. Ludicidade e desenvolvimento de competências em compreensão na leitura

    OpenAIRE

    Marques, Sara Margarida Costa

    2011-01-01

    O presente estudo visava determinar o papel que a ludicidade poderá desempenhar no desenvolvimento de competências em compreensão na leitura. Com esta finalidade, procedeu-se à concepção e implementação de uma intervenção didáctica, centrada na abordagem de uma obra de leitura integral, de índole narrativa, com uma turma de alunos do 2º Ciclo do Ensino Básico, recorrendo a uma metodologia de investigação-acção. Foram recolhidos dados relativos às suas representações (atra...

  9. Atrayendo Talento: estrategias de Movilidad de los profesionales altamente cualificados en España

    OpenAIRE

    González Ramos, Ana M.

    2011-01-01

    En las últimas décadas, se ha realizado un gran esfuerzo centrado en la formación de los profesionales españoles altamente cualificados. Además, la competitividad económica y la evolución positiva de los indicadores de ciencia y la innovación tecnológica han atraído el talento extranjero. El presente artículo se centra en las estrategias protagonizadas por el personal altamente cualificado en el sistema nacional de I+D+I, así como en la adecuación de los programas de movilidad y la normativa ...

  10. Simbiosis entre la reproducción asistida en España y los servicios de interpretación

    OpenAIRE

    Torroba Hernán, Beatriz

    2016-01-01

    La Reproducción Asistida (de aquí en adelante, RA) ha experimentado un auge importante también gracias a la llegada de pacientes extranjeros no hispanohablantes que vienen a España atraídos por una ley más permisiva. El objetivo central de este estudio es demostrar la simbiosis cada vez más definida entre la RA y los intérpretes. La premisa que planteo es que la sociedad está modificando su percepción y realidad respecto a los nuevos modelos familiares y a las fronteras lingüístico-cultur...

  11. Fenómenos dinámicos de estabilidad de un buque en olas longitudinales: resonancia paramétrica. Influencia en el proyecto y equipo. Guía operacional al capitán

    OpenAIRE

    Juana Gamo, Javier de

    2015-01-01

    El fenómeno de balance paramétrico se ha convertido en un tema de actualidad en los últimos años debido al aumento de accidentes relacionados y las discusiones en OMI debido a su indiscutible importancia en la seguridad del buque, su carga y tripulación. Por esta razón, su estudio ha atraído el interés de universidades, administraciones y sociedades de clasificación. Esta tesis trata el fenómeno de balance paramétrico desde diferentes puntos de vista. Primero, se estudiaran los diferentes es...

  12. Aspectos de la construcción del conocimiento sobre la sociedad Aspects of the construction of knowledge about society

    OpenAIRE

    Juan Delval

    2007-01-01

    El niño tiene que construir modelos o representaciones de la realidad social en la que vive, para tratar de dar un sentido al mundo que le rodea y además esas representaciones sirven de marco para su acción. La mayor parte de esas representaciones mentales no son simples copias de las de los adultos, sino que constituyen una construcción personal y difieren cualitativamente de las de los mayores. El estudio del desarrollo del conocimiento sobre la sociedad en el niño atrae cada vez más atenci...

  13. Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model

    DEFF Research Database (Denmark)

    Agrawal-Singh, Shuchi; Koschmieder, Steffen; Gelsing, Sandra;

    2010-01-01

    role of Pim2 with promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha), we used a well-established PML-RARalpha (PRalpha) mouse model. Pim2 coexpression in PRalpha-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PRalpha cells...... immature myeloid cells, compared with the previously described APL disease induced by PRalpha. However, it also clearly resembled an APL-like phenotype and showed signs of differentiation upon all-trans retinoic acid (ATRA) treatment in vitro. These results support the hypothesis that Pim2, which is also a...

  14. La educación inclusiva frente a las desigualdades sociales: un estado de la cuestion y algunas reflexiones geograficas

    OpenAIRE

    Rambla, Francesc Xavier, 1966-; Tarabini-Castellani, Aina; Ferrer i Julià, Ferran; Verger, Antoni

    2008-01-01

    Este artículo establece un estado de la cuestión e la educación inclusiva en el mundo y sugiere algunas reflexiones al respecto. El primer apartado recuerda las conexiones ineludibles entre las preocupaciones educativas por la educación inclusiva y las preocupaciones más generales por la desigualdad. El segundo consigna los criterios de búsqueda de las publicaciones académicas, y observa dos grandes temas en sus contenidos: sobre todo, el cambio interno de las escuelas atrae las miradas, pero...

  15. Como es arriba es abajo: Simbolismo de los astros en Hermetismo y astrología

    OpenAIRE

    Aznar, Susana

    2016-01-01

    La cultura forma nuestra cosmovisio¿n de la realidad. Actualmente nuestra cultura esta¿ repleta de si¿mbolos e ima¿genes que de forma silenciosa transmiten sus mensajes a nuestro inconsciente. Entre todos compartimos una visio¿n global, ya que todos somos ba¿sicamente lo mismo: Seres humanos. Nuestra psique inconsciente presenta unos arquetipos que son presentes en todo el mundo, formando lo que se conoce como inconsciente colectivo. Mirando atra¿s en la historia nos damos cuenta que mucho...

  16. Determinantes das Intenções de Comprar Viagens Online: Uma abordagem Holística

    OpenAIRE

    Amaro, Suzanne; Duarte, Paulo

    2014-01-01

    A compra de viagens online tem atraído investigadores dado o seu significativo crescimento, originando uma crescente literatura nesta área de investigação. Contudo, estudos sobre o que motiva os consumidores a comprar online têm sido fragmentados. De facto, os estudos existentes em grande parte baseiam-se no Modelo de Aceitação de Tecnologia (Davis, 1985, 1989), na Teoria da Ação Refletida (Fishbein & Ajzen, 1975), na Teoria do Comportamento Planeado (Ajzen, 1991), ou na Teoria de Difusão de ...

  17. Disseminated Exfoliative Dermatitis Associated with All-Transretinoic Acid in the Treatment of Acute Promyelocytic Leukemia

    OpenAIRE

    Yonal Ipek; Dogru Hulya; Aktan Melih

    2012-01-01

    Acute promyelocytic leukemia (APL) is a biologically and clinically separate type of acute myeloid leukemia characterized by a translocation involving the retinoic acid receptor-alpha (RARa) locus on chromosome 17, the great majority of which is t(15; 17)(q24.1; q21.1) (Collins (1998), Melnick and Licht (1999), and Grimwade (1999)). Retinoic acid is a critical ligand in the differentiation pathway of multiple tissues, mediated through binding to an RAR. All-trans retinoic acid (ATRA) is a sub...

  18. Bioecologia e conservação das populações de Salmo trutta (L.) na bacia hidrográfica do rio Tua (NE Portugal)

    OpenAIRE

    Santos, Miguel Horta

    2014-01-01

    A truta-de-rio, Salmo trutta (L.), é uma espécie que habita os rios de montanha do Norte e Centro de Portugal. É frequentemente usada como atração turística e alvo importante e popular da pesca desportiva em Portugal e na Europa. Neste âmbito, o objetivo do presente trabalho consistiu no estudo da bioecologia e conservação da truta-de-rio no Nordeste Transmontano e em particular no Alto Tua, inserido na área protegida do Parque Natural de Montesinho. Durante a primavera de 2014 foi avaliad...

  19. Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism

    OpenAIRE

    Ross, A. Catharine; Zolfaghari, Reza

    2011-01-01

    The active metabolite of vitamin A, retinoic acid (RA), is a powerful regulator of gene transcription. RA is also a therapeutic drug. The oxidative metabolism of RA by certain members of the cytochrome P450 (CYP) superfamily helps to maintain tissue RA concentrations within appropriate bounds. The CYP26 family—CYP26A1, CYP26B1, and CYP26C1—is distinguished by being both regulated by and active toward all-trans-RA (at-RA) while being expressed in different tissue-specific patterns. The CYP26A1...

  20. 4-Oxoretinol, a new natural ligand and transactivator of the retinoic acid receptors.

    OpenAIRE

    Achkar, C C; Derguini, F; Blumberg, B; Langston, A; Levin, A A; Speck, J; Evans, R M; Bolado, J; Nakanishi, K; Buck, J.; Gudas, L J

    1996-01-01

    All-trans-retinoic acid (at-RA) induces cell differentiation in a wide variety of cell types, including F9 embryonic teratocarcinoma cells, and can influence axial pattern formation during embryonic development. We now identify a novel retinoid synthetic pathway in differentiating F9 cells that results in the intracellular production of 4-oxoretinol (4-oxo-ROL) from retinol (vitamin A). Approximately 10-15% of the total retinol in the culture is metabolized to 4-hydroxyretinol and 4-oxo-ROL b...

  1. Novel targeted therapy for acute myeloid leukemia with a dual FLT3 and JAK2 inhibitor

    Institute of Scientific and Technical Information of China (English)

    Yin-jun LOU

    2012-01-01

    Acute myeloid leukemia (AML) is a highly malignant hematopoietic tumor.The use of all-trans retinoic acid (ATRA) and arsenic trioxide,which began from China,has resulted in revolution of the acute promyelocytic leukemia (APL) that appears curable in more than 70% of patients[1].However,the treatment regimen for nonAPL AML particularly in older patients has progressed little in the past two decades.Intensive efforts have been made toward the development of novel target agents,which are based on newfound pathophysiological events crucial for cancers.

  2. Italian municipalities' NPFM reforms: an institutional theory perspective

    OpenAIRE

    Elisabetta Reginato; Isabella Fadda; Aldo Pavan

    2010-01-01

    Entender las razones del fracaso o el éxito de las reformas impulsada por el NPFM es un tema que ha atraído recientemente la atención de la literatura sobre la gestión del sector público. Sobre la base de un estudio de caso realizado en el gobierno local italiano, la investigación analiza el estado de real aplicación de las reformas mencionadas anteriormente, y contribuye al debate teórico sobre las razones que explican las diferencias entre los cambios formales y sustanciales en la administr...

  3. La inserción de las ciudades del Mediterráneo español en el espacio de la globalización a través de la red de empresas multinacionales: el caso de la ciudad de Valencia

    OpenAIRE

    Salom Carrasco, Julia

    2013-01-01

    El objetivo de la comunicación es definir la posición de las ciudades del Mediterráneo español en las redes económicas mundiales a partir del análisis de las relaciones de propiedad y filiación de las empresas multinacionales ubicadas en ellas, así como caracterizar el alcance espacial y la especialización sectorial de los enlaces que las conectan con dichas redes. A nivel internacional, el aumento de la globalización ha atraído la atención sobre los conceptos de “world cities” (Hall, ...

  4. Los mercados públicos en la ciudad contemporánea : el caso de Barcelona

    OpenAIRE

    Guàrdia Bassols, Manuel; Oyón Bañales, José Luis

    2007-01-01

    La historia de los mercados ha sido escasamente estudiada, aunque exista un notable consenso de que han sido la fuerza modeladora de las ciudades europeas desde el medioevo. En la ciudad contemporánea las formas comerciales han atraído fundamentalmente por su novedad. Han interesado así en los distintos momentos históricos los pasajes, los grandes almacenes, los autoservicios, los supermercados o los centros comerciales. Pasada la primera fase de construcción de los nuevos los mercados metáli...

  5. Los mercados públicos en la ciudad contemporánea

    OpenAIRE

    Guàrdia Bassols, Manuel; Oyón Bañales, José Luis

    2007-01-01

    La historia de los mercados ha sido escasamente estudiada, aunque exista un notable consenso de que han sido la fuerza modeladora de las ciudades europeas desde el medioevo. En la ciudad contemporánea las formas comerciales han atraído fundamentalmente por su novedad. Han interessado así en los distintos momentos históricos los pasajes, los grandes almacenes, los autoservicios, los supermercados o los centros comerciales. Pasada la primera fase de construcción de los nuevos los mercados metál...

  6. Determination of element composition of three lichens and their distribution in King George Island, Antarctica

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Cross-section slices of Usnea antarctica Du Rietz, Usnea aurantiaco-atra (Jacq.) Bory. and Cladonia sp. at upper, middle and basal positions were prepared, respectively. The element composition and relative content were determined by SEM and EDS at the surface, intermediate and inner layers in each slice, respectively. The result indicated that the composition of element is mostly same in these lichens. The relative content of Al, Si, K and Ca elements is high, and P is close at each position. The result is of benefit to study the structure and physiological characteristics of lichens, and to analyze geological environment in Antarctica.

  7. Empenhamento organizacional nos trabalhadores temporários

    OpenAIRE

    Oliveira, Eduardo André da Silva

    2009-01-01

    Dissertação de mestrado em Gestão de Recursos Humanos O estudo do empenhamento organizacional tem concitado o interesse de académicos e profissionais da gestão de recursos humanos. Segundo Swailes (2000), torna-se difícil encontrar na literatura organizacional dos últimos trinta anos, um tópico que tenha atraído tanta atenção como o empenhamento. Aos práticos, interessa a sua compreensão para instilar e manter uma cultura de empenhamento na organização. Este interesse recrudesc...

  8. Guerra, psicología social y derechos humanos: procesos de gubernamentalidad y estado de excepción policial en torno al "15m", Catalunya 2011-2012

    OpenAIRE

    Benedicto Salmerón, Rubén A.

    2015-01-01

    Esta tesis analiza la posible correspondencia de la actuación policial-gubernamental sobre las movilizaciones sociales en torno al ‘15M' en Catalunya con marcos generales estratégicos de pensamiento de guerra, en donde no se distingue la paz de la guerra y la acción sobre las variables psicosociales desempeña un papel clave y transversal. En torno al 15 de mayo de 2011, se produjo en el Estado español una ola de movilizaciones sociales en protesta por la situación de profundas crisis que atra...

  9. El vínculo entre sexualidad y violencia en el teatro de Angélica Liddell

    OpenAIRE

    Topolska, Ewelina Maria

    2014-01-01

    Angélica Liddell’s surge to (relative) fame in recent years (a process which began in 2000, peaking around 2008/09) resulted in an increasing number of articles being published about her theatre, not to mention a significant number of interviews she gave for the Spanish and international press. There is also a doctoral thesis by Ana Vidal Egea concerning Atra Bilis’ (the name of Liddell’s group) work. However, no existing study engaged in detailed analysis of the artist’s theatrical productio...

  10. Padronização da técnica imunoenzimática do ELISA de captura, no sistema avidina-biotina para a identificação de sangue ingerido por Lutzomyia (Lutzomyia) longipalpis (Lutz & Neiva, 1912) Enzyme-linked Immunosorbent Assay biotin/avidin method standardization, for identification of Lutzomyia (Lutzomyia) longipalpis bloodmeals (Lutz & Neiva, 1912)

    OpenAIRE

    Ana Maria Marassá; Cleide Aschenbrenner Consales; Eunice Aparecida Bianchi Galati

    2004-01-01

    A identificação de sangue ingerido pelos insetos é um importante parâmetro para elucidar aspectos ligados à transmissão de zoonoses, dentre elas, as leishmanioses. Dos métodos empregados para esclarecer a atração de vetores por animais que possam atuar como reservatórios dessas parasitoses, destacam-se os imunológicos. O estudo teve como objetivo, padronizar a técnica imunoenzimática de captura e titular amostras de sangue ingerido em fêmeas de flebotomíneos ingurgitadas de Lutzomyia longipal...

  11. Maduración y desove del pargo amarillo Lutjanus argentiventris (Peters, 1869) en condiciones controladas de temperatura y fotoperíodo

    OpenAIRE

    Martínez, R.A. (Raquel)

    2003-01-01

    El cultivo de peces marinos ha atraído considerable atención en la última década, experimentando un gran auge en años recientes. Esto se debe principalmente al desarrollo y optimización de la tecnología de cultivo en jaulas, como también al mejoramiento de las técnicas de producción de juveniles, lo que ha incrementado el número de especies para las cuales existen cultivos de orientación comercial. En las circunstancias actuales, para que el cultivo de peces sea rentable es necesario controla...

  12. Primary Survey on Herpetofauna in Campus of Hechi University in Central Guangxi%河池学院校园两栖爬行动物初步调查

    Institute of Scientific and Technical Information of China (English)

    蒋爱伍; 粟通萍; 于家捷; 梁晓凤

    2011-01-01

    A primary survey on herpetofauna was conducted by specimen collecting and interviewing in campus of Hechi University, central Guangxi, during July 2008 to December 2009. Totally 26 species were detected in this survey. Among them, 6 species of 4 families, 1 order belonged to the class Amphibia, and 20 species of 7 families, 2 orders belonged to the class Reptilia. The dominant Amphibia is Polypedates leucomystax, and the dominant Reptilia is Rhabdphis subminiatus,Naja atra and Eumeces chinensis. 6 species of 12 snakes are vipers in the campus, and Naja atra is the most dangerous. The Amphibia depend on running water have already disappeared along with urbanization, and the species breeding or preying on the building,such as Pol y pedates leucom ystax , Naja atra and Hem idact ylus bowrin gii , can adapt the habitat of urban.%2008年7月至2009年12月,利用标本采集和访问的方法对河池学院校园内两栖爬行动物资源进行了初步的调查,共记录到两栖爬行动物26种,其中两栖动物1目4科6种,爬行动物2目7科20种.在校园中最常见的两栖动物是斑腿泛树蛙(Polypedates leucomystax),最常见的爬行动物是红脖颈槽蛇(Rhabdphissubminiatus)、舟山眼镜蛇(Naja atra)和中国石龙子(Eumeces chinensis).在校园分布的12种蛇类中,6种为毒蛇,其中舟山眼镜蛇的危害最为严重.师生在工作和学习要特别注意防止咬伤.与周边地区相比,在城市化过程中,流水型的两栖动物最容易灭绝;能利用建筑物繁殖或捕食的种类,如斑腿泛树蛙、原尾蜥虎和舟山眼镜蛇等,在城市化过程中占有较大的优势.

  13. Mujer Pagana/ Mujer Cristiana en Ad uxorem de Tertuliano

    OpenAIRE

    López Abelaira, Elena

    2016-01-01

    Desde los primeros años del cristianismo la figura de la mujer no ha pasado desapercibida para los distintos autores. Nos parece muy interesante la figura de Tertuliano, autor africano de los siglos II-III d. C. Pagano de formación y atraído por el mensaje y las vivencias de la nueva religión, pero confundido por la radicalidad que surgieron en las sectas del cristianismo. Es el primer escritor cristiano del norte de África que se ocupó ampliamente de la mujer virgen, viuda y casada. Sient...

  14. Sílvia Cezar Miskulin, Os intelectuais cubanos e a política cultural da Revolução 1965-1975, São Paulo, Alameda, 2009, 301 p.

    OpenAIRE

    Burgos, Elizabeth

    2009-01-01

    Particularmente atraída por la historia de los intelectuales y la palabra impresa, inspirándose en la visión de Jean-François Sirinelli, la autora privilegia esta área de estudio puesto que la historia de los intelectuales forma parte de un campo que se sitúa en el cruce entre historia política, historia de las ideas, de las ideas políticas e historia cultural, que para ella constituye un campo de estudio fundamental. En efecto, en lo tocante a la Revolución Cubana, la relación de los intele...

  15. Estudo ecotoxicológico da exposição ao chumbo e à nanopartícula de dióxido de titânio em Hoplias malabaricus

    OpenAIRE

    Rossi, Stéfani Cibele

    2013-01-01

    Resumo: O aumento do uso de nanomateriais em diversos produtos nas diferentes áreas, tais como eletrônicos, cosméticos, alimentos e medicamentos tem atraído a atenção da comunidade científica devido as propriedades desconhecidas desses materiais, tais como a cinética no ambiente e a interação com outras substâncias presentes no mesmo. Apesar de diferentes estudos terem demostrado baixa toxicidade das nanopartículas de dióxido de titânio (TiO2),outros apontam para um possível efeito modulador ...

  16. Holothurian (Holothuroidea Community Structure in Some Coastal Waters of Kai Besar Island, South-East Maluku

    Directory of Open Access Journals (Sweden)

    Eddy Yusron

    2004-04-01

    Full Text Available During October and November 1990 the holothurian community inhabiting littoral areas was assessed at five locations : Borang, Ohoiwait, Nuwahan, Wahadan and Kurit Wur. This involved five ecological indices: density, species richness, diversity, evenness and similarity. It was revealed that the holothurian community consisted of 14 species in which five among them occurred in all locations at higher densities: Holothuria edulis, H. scabra, H. nobilis, H. atra and Stichopus chloronatus. Small variations of the ecological indices at all locations may indicate that the community characteristics at the five locations were relatively similar.

  17. La influencia del anarquismo en la práctica educativa y la producción teatral de Berisso (1900-1930)

    OpenAIRE

    Perez Sbrascini, Ricardo A.

    2014-01-01

    La influencia anarquista en la ciudad de Berisso contiene un carácter filosófico-político de origen en los pensadores y teóricos europeos tales como Bakunin, Kropotkin, Proudhon, Malatesta, arribado a estas tierras por las oleadas inmigratorias atraídas por la gran oferta laboral que posibilitaban los frigoríficos de la ciudad, quienes contenían a la mitad de los trabajadores del rubro cárnico de la Argentina, además de otras industrias de la zona. En lo que respecta a la educación anarqui...

  18. Heurísticas para localização de sensores

    OpenAIRE

    Silva, Diogo Filipe Martins Ferreira da

    2013-01-01

    Tese de mestrado em Investigação Operacional, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2013 Neste trabalho é desenvolvido o algoritmo de atração, uma heurística inspirada em algoritmos evolutivos, tendo como objetivo a resolução de problemas contínuos de localização e cobertura. Numa primeira parte o problema é abordado tendo em conta uma cobertura binária, tornando o problema mais simples e a explicação das ideias chave da heurística mais clara. Depois de co...

  19. Planificación de Diferentes Clases de Aplicaciones en Entornos No Dedicados Considerando Procesadores Multicore

    OpenAIRE

    García Gutiérrez, José Ramón

    2010-01-01

    Descripció del recurs: el 27 de juny de 2011 A día de hoy es prácticamente imposible encontrar una gran institución que no disponga de un parque de ordenadores considerable, debido al alto nivel de informatización de la sociedad actual. El enorme potencial que representan estos miles de ordenadores atrae poderosamente la atención en los ámbitos científicos e industriales, generando opciones viables para su aprovechamiento. Las universidades, instituciones que históricamente se han mantenid...

  20. Traducción y adaptación transcultural de la escala SQLS para medir la calidad de vida en pacientes con esquizofrenia en Colombia

    OpenAIRE

    Peña Solano, Diana Marcela

    2011-01-01

    El estudio de la calidad de vida y de la sensación subjetiva de bienestar de los pacientes es un fenómeno relativamente nuevo, que ha atraído la atención de los profesionales de la salud, apenas en las tres últimas décadas. Durante 1850 y 1950, la medicina estuvo dominada por el tema de la cura de las enfermedades, mientras que el tratamiento de enfermedades crónicas, discapacitantes e incurables recibía menor atención (1). En los últimos años ésta tendencia ha cambiado. La calidad de vida...

  1. BCL-x{sub L}/MCL-1 inhibition and RARγ antagonism work cooperatively in human HL60 leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Perri, Mariarita; Yap, Jeremy L.; Yu, Jianshi [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Cione, Erika [Department of Pharmacy, Health and Nutritional Sciences, Ed. Polifunzionale, University of Calabria, 87036 Rende, CS (Italy); Fletcher, Steven [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States); Kane, Maureen A., E-mail: mkane@rx.umaryland.edu [Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 N Pine Street, Baltimore, MD 21201 (United States)

    2014-10-01

    The acute promyelocytic leukemia (APL) subtype of acute myeloid leukemia (AML) is characterized by chromosomal translocations that result in fusion proteins, including the promyelocytic leukemia–retinoic acid receptor, alpha fusion protein (PML–RARα). All-trans retinoic acid (atRA) treatment is the standard drug treatment for APL yielding cure rates >80% by activating transcription and proteasomal degradation of retinoic acid receptor, alpha (RARα). Whereas combination therapy with As{sub 2}O{sub 3} has increased survival further, patients that experience relapse and are refractory to atRA and/or As{sub 2}O{sub 3} is a clinically significant problem. BCL-2 family proteins regulate apoptosis and over-expression of anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) family proteins has been associated with chemotherapeutic resistance in APL including impairment of the ability of atRA to induce growth arrest and differentiation. Here we investigated the novel BH3 domain mimetic, JY-1-106, which antagonizes the anti-apoptotic BCL-2 family members B-cell lymphoma-extra large (BCL-x{sub L}) and myeloid cell leukemia-1 (MCL-1) alone and in combination with retinoids including atRA, AM580 (RARα agonist), and SR11253 (RARγ antagonist). JY-1-106 reduced cell viability in HL-60 cells alone and in combination with retinoids. The combination of JY-1-106 and SR11253 had the greatest impact on cell viability by stimulating apoptosis. These studies indicate that dual BCL-x{sub L}/MCL-1 inhibitors and retinoids could work cooperatively in leukemia treatment. - Highlights: • Novel Bcl-x{sub L}/Mcl-1 inhibitor JY-1-106 reduces HL60 cell viability. • JY-1-106 is investigated in combination with retinoic acid, AM580, and SR11253. • AM580 is an RARα agonist; SR11253 is an RARγ antagonist. • Combined use of JY-1-106/SR11253 exhibited the greatest cell viability reduction. • JY-1-106 alone or in combination with retinoids induces apoptosis.

  2. SÍNTESE DA PENEIRA MOLECULAR MCM-41 DERIVADA DA CINZA DA CASCA DO ARROZ

    OpenAIRE

    Renata Martins Braga; Najara Maira Teodoro; Dulce Maria de Araujo Melo; Flávia de Medeiros Aquino; Joana Maria de Farias Barros; Julio Cezar de Oliveira Freitas

    2013-01-01

    As peneiras moleculares MCM-41 têm atraído grande interesse devido as suas propriedades de alta área específica, volume e diâmetro de poros controláveis. Estes materiais são aplicados em diversos ramos da indústria química como adsorventes, suportes catalíticos e catalisadores heterogêneos em vários processos. Neste trabalho, o MCM-41 foi sintetizado a partir da cinza da casca do arroz, natural e tratada quimicamente, como fontes alternativas de sílica, denominadas CCA-MCM-41 e CCAL-MCM-41, r...

  3. La internacionalización de la educación superior y el análisis de las motivaciones y su impacto en el turismo local : El caso de la Facultad de Ciencias Económicas de la UNLP

    OpenAIRE

    Roldán, Melisa Yanina

    2015-01-01

    La hipótesis que orienta el presente trabajo de tesis parte del supuesto de un incremento de turistas académicos atraídos por la Universidad Nacional de La Plata a la ciudad y sostiene que el mismo se debe a la influencia que el actual contexto económico, político y social provoca en las motivaciones de este segmento y a las ventajas comparativas que la UNLP posee en términos educativos. El objetivo consiste en comprender las motivaciones que inciden en los turistas académicos encontrados ...

  4. El multilateralismo como intervencionismo. Estados Unidos y la Sociedad de Naciones en América Latina (1930-1946)

    OpenAIRE

    Sánchez Román, José Antonio

    2015-01-01

    Este artículo analiza una dinámica de intervenciones de Estados Unidos en América Latina que no ha atraído suficientemente la atención de los historiadores. En los años treinta y cuarenta, cuando Europa se hundía en una nueva confrontación bélica, ciertos sectores del gobierno y del mundo empresarial norteamericano intentaron articular una nueva relación con los países del continente basada en una propuesta de multilateralismo que se había configurado dentro de la Sociedad de Naciones (SN). E...

  5. Investigation of the Role of All-Trans Retinoid Acid in Inducing Differentiation of Retinoblastoma in Vivo%维甲酸诱导分化视网膜母细胞瘤的机理研究

    Institute of Scientific and Technical Information of China (English)

    王艳; 高解春; 董岿然; 陈莲; 王舒宜

    2011-01-01

    Objective To investigate the role and possible mechanism of all-trans retinoid acid in inducing differentiation of retinoblastoma in nude mice. Methods SO-RB50 suspense cell mixture was injected into bilateral armpits of male nude mice, and model of retinoblastoma nude mice was established. The size and weight of tumors were observed twice every week ,tumors' structure were recorded under microscope and electro-microscope, tumors' DNA index was calculated, relative quantities of gene CyclinDl ,CDK4 and ICAM-1 were measured by trans-transcription polymerase chain reaction and fluorescent quantity. Results At the end of the experiment, average tumor weight of ATRA group( 2. 750± 0. 302 ) g was lower than that of control group ( 7.150 ±1. 228 ) g( P = 0.008 ), and average tumor weight of Vitamin A deficient group( 11. 483 ± 2. 271 ) g( P = 0. 003 ). Under microscope, necrosis without inflammation was found in retinoblastoma cells in ATRA group, cells in control group appeared the same as those in original xenograft, retinoblastom cells in Vitamin A deficient group had a higher nuclear-plasma ratio than that of control group. Under electro-microscope, retinoblastoma cells in ATRA group contained swelled and bubble-like mitochondrion and much less ribosomes than those in control group. Cells in Vitamin A deficient group contained more free ribosomes and less lysosomes in the plasma than those in control group. Trans-transcription PCR and fluorescent quantity showed the relative quantity of CyclinD1 was the lowest in ATRA group( P =0.012) and highest in Vitamin A deficient group( P =0.017 ) ;the relative quantity of CDK4 was lowest in ATRA group(P =0.010) and highest in Vitamin A deficient group( P =0. 029). There was no statistical significance in ICAM-1 between ATRA group and control group(P =0.071 ) or between Vitamin A deficient group and control group ( P= 0.083 ). Conclusion The growth of retinoblastoma xenograft in ATRA group was restrained by ATRA, and Vitamin

  6. Prácticas de innovación abierta en PYMEs : El caso del auto superdeportivo mexicano VUHL

    OpenAIRE

    Ramirez-Portilla, Andres; Cagno, Enrico; Brown, Terrence

    2014-01-01

    Es bien sabido que la innovación impulsa el desarrollo de las organizaciones de diferentes tamaños e industrias. Mientras para las grandes empresas es relativamente fácil innovar debido a sus recursos, en el caso de las pequeñas y medianas empresas (PYMEs) el escenario es más complicado. Sin embargo, existen modelos para gestionar la innovación que han probado ser útiles para apoyar a varios tipos de empresas. La Innovación Abierta (Open Innovation) es uno de estos modelos que ha atraído la a...

  7. Gothic Fiction in an Australian Landscape: An Analysis of Gabrielle Lord's Tooth and Claw, Elizabeth Jolley's The Well and Tim Winston's In the Winter Dark

    OpenAIRE

    Baines Alarcos, María Pilar; Arizti, Bárbara

    2012-01-01

    La literatura gótica ha atraído a un gran número de lectores a lo largo de los siglos. El secreto de su éxito parece estar en su habilidad para aludir temas intrínsecos al ser humano y su flexibilidad para adaptarse a cualquier situación espacial y temporal. Los espectros, monstruos y misterios del gótico esconden significados psicológicos y culturales más profundos que merecen ser estudiados. Desde un punto de vista cultural, la evolución de este género corre paralela al de la historia e ide...

  8. Podcasts na licenciatura em biologia aplicada : diversidade na tipologia e duração

    OpenAIRE

    Aguiar, Cristina; Carvalho, Ana Amélia Amorim; Maciel, Romana

    2009-01-01

    A facilidade em criar podcasts, aliada às enormes potencialidades que este tipo de tecnologia oferece, têm atraído os profissionais ligados ao ensino para a exploração progressiva desta ferramenta em diferentes contextos pedagógicos e com finalidades diversas. Na Universidade do Minho, decorre um projecto que visa auscultar a receptividade à utilização pedagógica de podcasts no ensino universitário, articulando as suas especificidades e imple...

  9. Análisis del turismo residencial en Denia

    OpenAIRE

    Jueguen Graucob, Moira Cristina; RODRIGUEZ SANABRA, GERARDO JAVIER

    2012-01-01

    El presente proyecto se centra en la evolución del turismo residencial en la localidad alicantina de Denia durante los últimos 20 años y el comportamiento de los extranjeros usuarios del mismo. Además de ello también se estudiará el impacto de este tipo de turismo en el sector inmobiliario y la economía local, y el perfil de turista que es atraído por este fenómeno.

  10. Turismo, Autenticidade e Cultura Urbana: percurso teórico, com paragens breves em Évora e Coimbra

    OpenAIRE

    Fortuna, Carlos

    1995-01-01

    o turismom é um fenómeno que tem atraído um notável esforço de análise sociológica nos últimos anos. Este texto comenta grande parte desta sociologia do turismo nomeadamente a que diz mais directamente respeito ao turismo cultural e urbano. Ao mesmo tempo, sugerem-se algumas linhas de interpretação do fenómeno, sob a influência de outras áreas do pensamento sociológico contemporâneo. Assim, sugere-se que o estudo do turismo seja feito, à luz de (1) transfor...

  11. Produção e desenvolvimento da cultura de Physalis L. submetida a diferentes níveis de condutividade elétrica da solução nutritiva Production and development of culture of Physalis L. subjected to different levels of electrical conductivity of nutrient solution

    OpenAIRE

    Alessandra Ianckievicz; Hideaki Wilson Takahashi; Gustavo Adolfo de Freitas Fregonezi; Fernando Kikuchi Rodini

    2013-01-01

    Physalis peruviana L., muito conhecida na Colômbia e originaria dos Andes Sul-americanos, tem atraído alguns produtores aqui no Brasil por produzir uma fruta com alto valor de mercado. Como se trata de uma cultura adaptada a algumas regiões brasileiras, o fornecimento de nutrientes é um dos aspectos importantes que precisa ser desenvolvido para aumentar a produtividade. O trabalho objetivou estabelecer as faixas ideais de concentração de nutrientes, utilizando a condutividade elétrica da solu...

  12. Anti-inflammatory and anti-hyperalgesic effect of all-trans retinoic acid in carrageenan-induced paw edema in Wistar rats: Involvement of peroxisome proliferator-activated receptor-β/δ receptors

    OpenAIRE

    Navneet Gill; Bijjem, Krishna Reddy V.; Sharma, Pyare L

    2013-01-01

    Objective: In this study, we investigated the role of peroxisome proliferator-activated receptors (PPAR)-β/δ receptors in carrageenan-induced inflammation and in the anti-inflammatory effects of all-trans retinoic acid (ATRA). Materials and Methods: The λ-carrageenan (0.1 ml of 1% w/v) was injected into intra-plantar (i.pl.) region of the hind paw to produce acute inflammation. Paw volume was measured by using the mercury plethysmography. Further, mechanical and thermal hyperalgesia (TH) ...

  13. Propiedades nutraceúticas del licopeno Nutraceutical properties of lycopene

    OpenAIRE

    Krzysztof N Waliszewski; Gabriela Blasco

    2010-01-01

    Las recomendaciones dietarias en los últimos años proponen el incremento del consumo de alimentos que contienen fitoquímicos, ya que éstos proveen efectos benéficos para la salud humana y juegan un papel importante en la prevención de enfermedades crónicas. El licopeno, carotenoide responsable del color rojo de los tomates, ha atraído la atención debido a sus propiedades biológicas y fisicoquímicas en la prevención de enfermedades crónicas como cáncer, enfermedades cardiovasculares y neurodeg...

  14. Avances en el tratamiento de los pacientes con Leucemia Promielocítica Aguda en Recaída

    Directory of Open Access Journals (Sweden)

    A. Sanz Miguel

    2006-04-01

    Full Text Available Hasta la demostración de la actividad sobresaliente del trióxido de arsénico (ATO en recaídas de pacientes con leucemia promielocítica (LPA, el tratamiento de rescate en esta enfermedad consistía en la readministración de ácido holo-trans retinóico (ATRA y quimioterapia para inducir la remisión, generalmente conteniendo citarabina a altas dosis, seguido de consolidación y/o trasplante de progenitores hematopoyéticos (TPH.

  15. Avances en el tratamiento de los pacientes con Leucemia Promielocítica Aguda en Recaída

    OpenAIRE

    A. Sanz Miguel

    2006-01-01

    Hasta la demostración de la actividad sobresaliente del trióxido de arsénico (ATO) en recaídas de pacientes con leucemia promielocítica (LPA), el tratamiento de rescate en esta enfermedad consistía en la readministración de ácido holo-trans retinóico (ATRA) y quimioterapia para inducir la remisión, generalmente conteniendo citarabina a altas dosis, seguido de consolidación y/o trasplante de progenitores hematopoyéticos (TPH).

  16. Comida em redes transacionais: construindo a identidade macaense

    OpenAIRE

    Gaspar, Marisa

    2014-01-01

    As festas do Partido dos Comes e Bebes (PCB) constituem-se como uma forma de integração, funcionamento e manutenção da comunidade macaense em Portugal. Este grupo informal organizado com o propósito de juntar os macaenses em reuniões de comensalidade, proporciona aos convivas o nostálgico regresso a um passado em Macau, através dos amigos que se reveem, do ambiente que se vive e, sobretudo, através da saudosa comida macaense que se identifica, cheira e saboreia, de resto, a principal atração ...

  17. Sea Cucumber Resources At Tanjung Pai Waters Padaido Biak Numfor Papua

    Directory of Open Access Journals (Sweden)

    Eddy Yusron

    2004-12-01

    Full Text Available Observation on sea cucumber diversity was carried out at coastal waters of Pai and Imbeyomi Islands in the Padaido Island Biak Numfor. Sampling was done by using a transect quadrant of 1 m x 1 m. This sampling and observation on its microhabitat were conducted by snorkling. Analyses on the sea cucumber community structure were based on its frequency of occurance, diversity, and density. The results showed that at both locations 10 species of sea cucumber were found where Holothuria edulis, H. atra, and H. nobilis were predominant common and more evenly distributed than the other species.

  18. Abelardo Sánchez León (Ed.). Sensibilidad de frontera. Comunicación y voces populares

    OpenAIRE

    Constant, Chloé

    2015-01-01

    Sensibilidad de frontera. Comunicación y voces populares, constituye la publicación del seminario sobre «lo popular» organizado por el departamento de comunicaciones de la PUCP en el año 2012, y que reunió a ponentes de distintos ámbitos: académicos, profesionales de marketing, teatro, televisión, entre otros. Esta obra atrae sin duda por su carátula ante cualquier otro motivo. Íconos peruanos, entre la santidad, la música, la televisión y el deporte, aparecen representados con colores encend...

  19. Anti-inflammatory and anti-hyperalgesic effect of all-trans retinoic acid in carrageenan-induced paw edema in Wistar rats: Involvement of peroxisome proliferator-activated receptor-β/δ receptors

    Science.gov (United States)

    Gill, Navneet; Bijjem, Krishna Reddy V.; Sharma, Pyare L.

    2013-01-01

    Objective: In this study, we investigated the role of peroxisome proliferator-activated receptors (PPAR)-β/δ receptors in carrageenan-induced inflammation and in the anti-inflammatory effects of all-trans retinoic acid (ATRA). Materials and Methods: The λ-carrageenan (0.1 ml of 1% w/v) was injected into intra-plantar (i.pl.) region of the hind paw to produce acute inflammation. Paw volume was measured by using the mercury plethysmography. Further, mechanical and thermal hyperalgesia (TH) were assessed by using the dynamic plantar aesthesiometer and plantar test apparatus, respectively. In addition, markers of oxido-nitrosative stress were assessed spectrophotometrically in the hind paw tissue 5 h post-carrageenan. Results: An i.pl injection of carrageenan has produced a marked mechanical hyperalgesia (MH) and TH in ipsilateral paw, which was associated with significant elevated oxido-nitrosative stress. Treatment with ATRA (5 mg/kg/p.o/4 days) and GW0742, a selective PPAR-β/δ receptor agonist (0.1 mg/kg/i.p/4 days), significantly decreased the paw volume, mechanical and TH as compared to vehicle control. Administration of GSK0660, selective PPAR-β/δ receptor antagonist, at a dose of (0.3 mg/kg/i.p/4 days), did not produce a significant effect on carrageenan-induced paw edema, MH and TH. However, co-administration of GSK0660 (0.3 mg/kg/i.p/4 days) along with both ATRA (5 mg/kg/p.o/4 days) and GW0742 (0.1 mg/kg/i.p/4 days), significantly reverse the decreased paw edema, MH, and TH. These observed ameliorative effects on inflammatory pain symptoms are correlated with the extent of reduction of oxido-nitrosative stress. Conclusion: From above findings, it can be concluded that ATRA exerts anti-inflammatory and anti-hyperalgesic effect, possibly through activation of PPAR-β/δ and subsequent reduction of oxido-nitrosative stress. PMID:23833373

  20. Etchenique, Jorge, Pampa Libre. Anarquistas en la pampa argentina, Santa Rosa (La Pampa) : Universidad Nacional de Quilmes / Ediciones Amerindia, 2000

    OpenAIRE

    Gutiérrez, Talía Violeta

    2000-01-01

    El accionar del anarquismo en la Argentina durante las primeras décadas del siglo XX ha atraído la atención de los historiadores, aunque en la mayoría de los casos como parte de estudios mayores dedicados al movimiento obrero. Por su parte, la conflictividad social en la región pampeana ha sido y es actualmente objeto de investigaciones provenientes de diversas áreas de las ciencias sociales. Sin embargo, es un aspecto de la historia regional que ofrece aún un vasto campo de investigación. En...

  1. Simulación de la tasa de reciclaje de productos electrónicos Un modelo de dinámica de sistemas para la red de logística inversa

    OpenAIRE

    Pilar Arroyo López; Mariana Villanueva Bringas; Juan Gaytán Iniestra; Marco García Vargas

    2014-01-01

    Debido a las tendencias actuales en cuanto al desarrollo e in - novación de las tecnologías de la información, el ciclo de vida de los equipos electrónicos se ha reducido considerablemen - te, lo que ha resultado en la generación de grandes volúmenes de residuos ( e-waste ) que pueden provocar serios problemas ambientales debido a la toxicidad de algunos de sus compo - nentes. Esta problemática ha atraído la atención de gobiernos, empresas y consumidores que buscan diseñar estrategias para el...

  2. example of paclitaxel

    OpenAIRE

    Doktorovova, Slavomira; Lopes, Carla Martins; Souto, Eliana B

    2009-01-01

    Os vectores coloidais de natureza lipídica têm atraído particular atenção para o desenvolvimento de terapias mais seguras e eficazes aplicadas a várias doenças. As vantagens da utilização das nanopartículas lipídicas são exemplificadas utilizando o paclitaxel, um anticancerígeno particularmente interessante para o desenvolvimento de novas formas farmacêuticas mais adequadas para o tratamento do cancro. De facto, este fármaco apresenta problemas de insolubilidade aquosa e sérios...

  3. Métodos para atrair a abelha Apis mellifera L. em cultura de abacate (Persea americana Mill.) Methods to attract honeybee Apis mellifera L. to avocado tree (Persea americana Mill)

    OpenAIRE

    Darclet Terezinha Malerbo Souza; Simone Rodrigues da Silva; Vagner de Alencar Arnaut de Toledo

    2002-01-01

    O presente experimento teve como objetivo avaliar métodos de atração da abelha Apis mellifera L. (Hymenoptera, Apidae) em duas variedades de abacate (Persea americana Mill.). Os atrativos utilizados foram extratos de Cymbopogon citratus, Ocimum basilicum, Lippia alba, folha de Citrus sp, folha de Eucaliptus sp. e o eugenol e o linalol (SIGMA). Os tratamentos utilizados foram: coberto; descoberto pulverizado (DP); descoberto com tubos e descoberto não pulverizado (DNP). Observou-se que a atrat...

  4. impacto na saúde oral

    OpenAIRE

    Silva, Bruna Loureiro Oliveira de Sousa e

    2012-01-01

    Os distúrbios alimentares traduzem-se em comportamentos, quer pela falta, quer pelo excesso da ingestão de alimentos O crescente aumento destes distúrbios, nomeadamente a obsessão pelos corpos magros, relaciona-se com o impacto que os media tem na sociedade, uma vez que a magreza é vista como mecanismo de atração sexual e mecanismo de integração social. Das desordens alimentares fazem parte a anorexia nervosa, a bulimia nervosa e a obesidade. Ao contrário da obesidade, a anorexia ne...

  5. Notas para reflexionar acerca de las identidades (sexuales) de varones que sociabilizan mediante internet

    OpenAIRE

    Peplo, Fernando Franco

    2013-01-01

    La sociabilidad virtual se ha transformado en una práctica habitual por parte de varones que se sienten sexualmente atraídos por otros varones porque ofrece anonimato, fluidez y la disponibilidad constante para iniciar vínculos. Estas características se tornan más relevantes en aquellas localidades pequeñas o medianas del interior del país puesto que “la discreción y la reserva” en relación a las experiencias homosexuales constituyen bienes muy preciados, en especial para aquellos sujetos que...

  6. Morals in business organizations: an approach based on strategic value and strength for business management

    OpenAIRE

    Pablo Ruiz Palomino; Bañón Gomis, Alexis J.; Carmen Ruiz Amaya

    2011-01-01

    [ES] Durante las últimas décadas, la ética empresarial ha atraído un gran interés tanto a nivel académico como profesional. En la actualidad, la ética empresarial está siendo crecientemente implementada como disciplina necesaria en los planes de estudio sobre gestión empresarial de las universidades. Además, se evidencia su importancia con el incremento experimentado a nivel mundial de organizaciones e instituciones que han implementado sistemas de ética. Sin embargo, algunos enfoques de pens...

  7. Estudo da biomassa de reactores UASB tratando efluentes de lacticínios

    OpenAIRE

    Barbosa, Marta Lains da Silva

    2009-01-01

    O metano produzido em sistemas de digestão anaeróbia (DA) é uma fonte de energia renovável, e a consolidação desta tecnologia na Europa oferece várias vantagens baseadas nos princípios de sustentabilidade ambientais. A indústria de lacticínios é uma das maiores fontes de efluentes industriais a nível europeu e a sua DA tem atraído bastante interesse devido à elevada carga orgânica que caracteriza estes efluentes. O tratamento de efluentes de lacticínios em reactores UASB com o modo de oper...

  8. Differential effects of sumoylation on the activities of CCAAT enhancer binding protein alpha (C/EBPα) p42 versus p30 may contribute in part, to aberrant C/EBPα activity in acute leukemias

    OpenAIRE

    William Hankey; Matthew Silver; Hong Sun; Terry Zibello; Nancy Berliner; Arati Khanna-Gupta

    2011-01-01

    In this study, we have examined the role of post-translational modification of the myeloid master regulator C/EBPα by small ubiquitin-related modifier (SUMO). We have used transient transfection analysis, oligonucleotide pulldown assays and chromatin immuno-precititation in all-trans retinoic acid (ATRA)-inducible promyelocytic cell lines MPRO and NB4. We demonstrate that sumoylated wild-type p42-C/EBPα is associated with negative regulation of the myeloid specific lactoferrin (LF) gene in ea...

  9. La organización de los oficios en al-Andalus a través de los manuales de "hisba"

    OpenAIRE

    García Sanjuán, Alejandro

    1997-01-01

    Como podrá comprobarse a lo largo del presente artículo, la organización corporativa de los oficios en el islam medieval ha sido objeto de una amplia polémica entre diversos autores, en buena medida provocada por la falta de acuerdo respecto al concepto de “corporación profesional”. No obstante, en lo que se refiere al caso específico de al-Andalus, este tema no ha atraído la atención que, a nuestro juicio, se merece. El objetivo de estudio es, por ello, profundizar en este asunto y revisar l...

  10. “¿Mi novio sería capaz de matarme?” Violencia en el noviazgo entre adolescentes de la Universidad Autónoma Chapingo, México

    OpenAIRE

    Verónica Vázquez García; Roberto Castro

    2008-01-01

    En este artículo analizamos la violencia en las relaciones de noviazgo en la Universidad Autónoma Chapingo (Uach), una institución mexicana dedicada a formar recursos humanos en ciencias agronómicas. La Uach posee tres características: atrae estudiantes de medios desfavorecidos de todo el país; recibe más hombres que mujeres debido a la construcción de la Agronomía como una ocupación masculina; y, funciona como una institución total en el sentido de que sus estudiantes dejan la casa paterna a...

  11. Estudio de prefactibilidad para la creación y puesta en marcha de una empresa operadora de turismo de naturaleza en Urabá

    OpenAIRE

    Gallego Moscoso, Laura; Lizcano Alonso, Adriana del Pilar; Muñoz Zuluaga, Paula Andrea

    2013-01-01

    El Gobierno Nacional tiene clara su apuesta en materia de turismo: sofisticación de la oferta, teniendo como pilar la biodiversidad que cada año atrae miles de turistas que disfrutan de los paisajes y practican actividades en las que la naturaleza es la protagonista -- Al contexto nacional se suma la visión del Gobierno del departamento de Antioquia, plasmada en su Plan de Desarrollo Turístico, que de igual manera se enfoca en el turismo especializado -- Esto constituye una oportunidad estra...

  12. Estudio de la imagen de responsabilidad social corporativa: formación e integración en el comportamiento del usuario de servicios financieros (A study of corporate social responsibility image: its formation process and its integration in banking service users behaviour)

    OpenAIRE

    Pérez Ruiz, Andrea

    2011-01-01

    RESUMEN:La responsabilidad social corporativa (RSC) es un concepto que ha atraído un especial interés de los investigadores en las últimas décadas. Sin embargo, aun hoy en día existe la necesidad de continuar profundizando en el estudio de sus beneficios como herramienta de marketing. Para cubrir este objetivo, el interés de la presente Tesis Doctoral se centra en la relación entre la imagen de RSC y el comportamiento del consumidor, basada en una amplia revisión de la literatura académica al...

  13. Breeding biology of two sympatric coots with contrasting conservation status

    OpenAIRE

    Varo, Nico

    2008-01-01

    Capsule: Red-knobbed Coots Fulica cristata and Common Coots Fulica atra have similar breeding biology except in chick survival, which was significantly lower in Red-knobbed Coots. Aims: To provide information on the breeding biology of Red-knobbed Coots in Spain and to compare this with similar data for Common Coots. Methods: During two consecutive breeding seasons, clutch size, egg size, brood size and chick survival of Red-knobbed and Common Coots were studied in nearly all of the lagoons i...

  14. The role of all-trans retinoic acid in the biology of Foxp3+ regulatory T cells

    OpenAIRE

    Liu, Zhong-Min; Wang, Kun-Peng; Ma, Jilin; Guo Zheng, Song

    2015-01-01

    Regulatory T (Treg) cells are necessary for immune system homeostasis and the prevention of autoimmune diseases. Foxp3 is specifically expressed in Treg cells and plays a key role in their differentiation and function. Foxp3+ Treg cells are consisted of naturally occurring, thymus-derived Treg (nTreg) and peripheral-induced Treg (iTreg) cells that may have different functional characteristics or synergistic roles. All-trans retinoic acid (atRA), a vitamin A metabolite, regulates a wide range ...

  15. La reconversión industrial de la siderúrgica integrada en Colombia

    OpenAIRE

    Patricia Carolina Barreto Bernal; Oscar Gutiérrez Molina; Juan Sebastián Lara Rodríguez

    2014-01-01

    La reconversión industrial en Colombia tiene su origen como iniciativa política, buscando modernizar y preparar su aparato productivo, ante la entrada de competidores atraídos por el cambio de modelo económico. Los autores pretenden explicar los principales cambios y transformaciones surgidas en el proceso de reconversión industrial del país, particularmente el caso de Acerías Paz del Río, mediante la implementación de un método hermenéutico y la técnica de análisis documental. Como resultado...

  16. La formación del mercado laboral para el sector minero (La Experiencia de Huancavelica, Perú, 1950 - 1978)

    OpenAIRE

    Heraclio Bonilla; Carmen Salazar

    1983-01-01

    Una de las caracteristicas del proceso económico peruano que aún atrae el interes de los analistas y sobre el cual no existe una explicación satisfacto- ria se refiere a la muy tardia formación de un mercado libre de la fuerza de trabajo y a la naturaleza de las dificultades que acompañó a ese proceso. Di- cho en otras palabras, el problema planteado es la resistencia ofrecida por las estructuras tradicionales a una dislocación más temprana que permitiera que las unidades domésticas perdieran...

  17. Cambios en la actividad antioxidante en frutos de mortiño (vaccinium meridionale sw.) durante su desarrollo y maduración

    OpenAIRE

    Gaviria Montoya, Carlos; Hernández Arredondo, Juan David; Lobo Arias, Mario; Medina Cano, Clara Inés; Rojano, Benjamín Alberto

    2012-01-01

    Resumen. Los frutos de mortiño (Vaccinium meridionale Sw.) han atraído el interés de los consumidores debido a su alto contenido de compuestos polifenólicos y actividad antioxidante; sin embargo, no se ha realizado ninguna evaluación sobre los cambios durante su crecimiento y maduración. En este estudio se evaluó la variación en el contenido de fenoles y antocianinas totales y de la actividad antioxidante por las metodologías TEAC-ABTS, TEAC-DPPH, FRAP y ORAC. El fruto de mortiño presentó una...

  18. Human trafficking and human (in)security : the role of the State of Myanmar as a security provider

    OpenAIRE

    Swe Zin Linn Phyu

    2012-01-01

    Dissertação de mestrado em Relações Internacionais O ser humano é confrontado com problemas de insegurança, tais como tráfico de seres humanos, migração ilegal, pobreza, degradação ambiental, pirataria e crimes transnacionais resultantes da globalização. A grande maioria das mulheres e jovens birmanesas são atraídas pelas redes de traficantes, que trabalham em grupos organizados ou individualmente. As vitimas são levadas para a Tailândia e vendidas como prostitutas. As causas e...

  19. The Function of Retinol Dehydrogenase 1 in Retinoic Acid Synthesis and Metabolic Regulation

    OpenAIRE

    Krois, Charles Robert

    2011-01-01

    Retinol dehydrogenases (RDH) convert retinol into retinal, the intermediate in the biosynthesis of retinoic acid. All-trans-retinoic acid (atRA) regulates gene transcription and/or translation through retinoic acid receptors (RARs) and PPARδ (1). To test function of Rdh1, an efficient (Vmax/Km) and widely distributed RDH (2), our lab created Rdh1 knockout (KO) mice (3). Initial study of Rdh1-KO mice determined that when fed a low or vitamin A-deficient (VAD) diet, Rdh1-KO mice gain 33% ...

  20. Consideraciones sobre la Limitación del Esfuerzo Terapéutico (LET) en pediatría: Una aproximación a los conocimientos, prácticas y actitudes en la comunidad académica y asistencial del Hospital de La Misericordia y del Departamento de Pediatría de la Universidad Nacional de Colombia

    OpenAIRE

    González Cruz, Luis Ricardo

    2014-01-01

    Los cuidados paliativos pediátricos ganan terreno en la práctica médica pero aun tienen varias limitantes para su implementación e investigación. La limitación de esfuerzos terapéuticos (LET) corresponde a un proceso (no un momento puntual) aun no bien asumido por los pedíatras. Se buscó indagar sobre los conceptos, prácticas y actitudes del personal asistencial y académico del Hospital de la Misericordia (HOMI), hospital pediátrico en Bogotá, sobre la LET y su forma de aplicarla. Para esto, ...

  1. Study of the insertion sequence IS6110 in Mycobacterium tuberculosis Beijing strains and its promoter activity

    OpenAIRE

    Alonso Ezcurra, María Henar; Otal gil Isabel

    2012-01-01

    Mycobacterium tuberculosis es el agente causal de la tuberculosis (TB). Esta enfermedad ha acompañado a la raza humana a lo largo de su historia y hoy en día sigue siendo una de las enfermedades infecciosas que causa mayor número de muertes en el mundo. Aunque se han realizado grandes avances en la lucha contra esta enfermedad, sigue siendo un problema de salud mundial. En la actualidad, una de las familias de M. tuberculosis que más atención atrae en todo el mundo es la familia Beijing, debi...

  2. Revirando A Virada

    OpenAIRE

    Oliveira, Rosenilton S.

    2014-01-01

    "Venha viver a Virada!". Anunciava o slogan da Virada Cultural. Em 2013, o evento que reúne atrações culturais que vão da música erudita ao cinema pornô, efetivou sua nona edição e, em pouco mais de 24 horas, reuniu no centro de São Paulo e em alguns outros pontos da cidade, milhares de pessoas. Alguns dos pesquisadores do Laboratório de Antropologia Urbana da Universidade de São Paulo (NAU/FFLCH-USP), mais uma vez estiveram presentes para acompanhar estes citadinos em suas deambulações em me...

  3. Levantamiento arquitectónico y estudio físico constructivo de la Iglesia de Sant Miquèu de Vielha

    OpenAIRE

    Vidal Rosó, Miquel

    2011-01-01

    El objeto del presente proyecto de final de carrera es el estudio y levantamiento arquitectónico de la iglesia de Sant Miquèu de Vielha, ésta se encuentra situada en la población de Vielha, capital de la comarca de la Val d’Aran, en el pirineo de Lleida. He decidido realizar el estudio sobre este edificio en concreto porque puede considerarse uno de los edificios más característicos y representativos de la población de Vielha. El edificio a estudiar, desde siempre me ha atraído...

  4. Del deseo al clímax : represión y expresión de la temática de sexualidad y suicidio en la literatura femenina anglonorteamericana de los siglos XIX y XX

    OpenAIRE

    Cortés Vieco, Francisco José

    2013-01-01

    La sexualidad y el suicidio son dos intrincados fenómenos físico-socio-psicológicos que, aunque determinen la existencia, el destino y la naturaleza intrínseca del individuo, se han entretejido tradicionalmente con tabú, estigma, silencio, locura, pecado y mal, hasta caer en el olvido o el más absoluto ostracismo por mandato de hegemónicos discursos oficiales. No obstante, han atraído y despertado la curiosidad de artistas y literatos a lo largo de nuestra historia, transfigurándose incluso e...

  5. Resposta de fêmeas de Encarsia formosa Gahan (Hymenoptera: Aphelinidae aos odores do hospedeiro e da planta-hospedeira em olfatômetro de quatro vias Response of female Encarsia formosa Gahan (Hymenoptera: Aphelinidae to host and plant-host odors

    Directory of Open Access Journals (Sweden)

    Kátia Maria Medeiros de Siqueira

    2003-01-01

    Full Text Available A crescente importância da mosca-branca Bemisia tabaci raça B (Hemiptera: Aleyrodidae como praga agrícola tem incentivado a busca de inimigos naturais que possam ser utilizados em programas de controle biológico. Estudou-se a atração de fêmeas de Encarsia formosa (Hymenoptera: Aphelinidae aos odores emanados pelo seu hospedeiro - a mosca-branca B. tabaci raça B - em plantas de tomate, em olfatômetro de quatro vias. O parasitóide não apresentou atração aos odores da planta de tomate nem ao complexo planta de tomate-ninfas de B. tabaci.The increasing importance of the whitefly Bemisia tabaci race B (Hemiptera: Aleyrodidae as one of the major agricultural pest of this century, has resulted in a search for natural enemies that can be used in biological control programs. The response of naive females of Encarsia formosa (Hymenoptera: Aphelinidaeto volatiles from its hostspecies: insect (B. tabacci race B and plant (Lycopersicom esculentum Mill. were tested using 4-nose olfactometre. Parasitoid was not attracted by neither or insect hostspecies volatile.

  6. Differentiation Therapy of Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Elzbieta Gocek

    2011-05-01

    Full Text Available Acute Myeloid Leukemia (AML is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA, which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL in which a PML-RARA fusion protein is generated by a t(15;17(q22;q12 chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS. Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  7. Quantitative Analysis of the Relative Transcript Levels of ABC Transporter Atr Genes in Aspergillus nidulans by Real-Time Reverse Transcription-PCR Assay

    Science.gov (United States)

    Pizeta Semighini, Camile; Marins, Mozart; Goldman, Maria Helena S.; Goldman, Gustavo Henrique

    2002-01-01

    The development of assays for quantitative analysis of the relative transcript levels of ABC transporter genes by real-time reverse transcription-PCR (RT-PCR) might provide important information about multidrug resistance in filamentous fungi. Here, we evaluate the potential of real-time RT-PCR to quantify the relative transcript levels of ABC transporter Atr genes from Aspergillus nidulans. The AtrA to AtrD genes showed different and higher levels in the presence of structurally unrelated drugs, such as camptothecin, imazalil, itraconazole, hygromycin, and 4-nitroquinoline oxide. We also verified the relative transcript levels of the Atr genes in the A. nidulans imazalil-resistant mutants. These genes displayed a very complex pattern in different ima genetic backgrounds. The imaB mutant has higher basal transcript levels of AtrB and -D than those of the wild-type strain. The levels of these two genes are comparable when the imaB mutant is grown in the presence and absence of imazalil. The imaC, -D, and -H mutants have higher basal levels of AtrA than that of the wild type. The same behavior is observed for the relative transcript levels of AtrB in the imaG mutant background. PMID:11872487

  8. Microbial modification of host long-distance dispersal capacity

    Directory of Open Access Journals (Sweden)

    Hutchings Linda

    2009-06-01

    Full Text Available Abstract Background Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour of a pest-controlling money spider, Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail, in a process termed 'ballooning'. Results We show that there is spatial heterogeneity in the prevalence of two maternally acquired endosymbiont infections within the wider E. atra meta-population and we demonstrate through several independent approaches a link between the presence of one of these endosymbionts, Rickettsia, and the tendency for long-distance movement. Conclusion This novel finding that particular endosymbionts can influence host dispersal is of broad importance given the extremely widespread occurrence of similar bacteria within arthropod communities. A bacterial phenotype that limits dispersal has the potential not only to reduce gene flow and thus contribute to degrees of reproductive isolation within species, but also to influence species distribution and thus overall community composition.

  9. Differentiation Therapy of Acute Myeloid Leukemia

    International Nuclear Information System (INIS)

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML

  10. In vitro study on arsenic sulfide (realgar)-induced apoptosis of retinoic acid susceptible or resistant acute promyelocytic leukemia cell lines

    Institute of Scientific and Technical Information of China (English)

    CHEN Si-yu; LIU Shan-xi; LI Xin-min

    2002-01-01

    Objective: To further understand the possible mechanisms of arsenic sulfide (realgar) in the treatment of acute promyelocytic leukemia (APL). Methods: All-trans retinoic acid (ATRA)-susceptible APL cell line (NB4 cells) and ATRA-resistant APL cell line (MR2 subclone) were used as models in vitro. At various times after incubated with various concentrations of realgar, NB4 and MR2 cells were observed by cell viability, cell proliferation and cell morphology; cell cycle and the expression of Annexin V were assayed by flow cytometry. Results: Cell viability and proliferation of NB4 and MR2 cells were inhibited after the treatment,to some extent, in a dose and time dependent manner. 177-711 μg/L of realgar treated NB4 and MR2 cell presented morphologically some features of apoptotic cells such as intact cell membrane, chromatin condensation and nuclear fragmentation, apoptosis body could be found by electron microscopy as well. Sub-G1 ceils andcell cycle arrest were observed by flow cytometry. The proportion of Annexin V -FITC+/PI cells, which represent apoptotic cells, was up-regulated. Conclusion: Realgar could induce apoptosis of acute promyelocytic leukemia cell despite its susceptibility to retinoic acid in the way that may be different from retinoic acid.

  11. 4-Hydroxybenzyl modification of the highly teratogenic retinoid, 4-[(1E)-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propen-1-yl]benzoic acid (TTNPB), yields a compound that induces apoptosis in breast cancer cells and shows reduced teratogenicity.

    Science.gov (United States)

    Anding, Allyson L; Nieves, Nirca J; Abzianidze, Victoria V; Collins, Michael D; Curley, Robert W; Clagett-Dame, Margaret

    2011-11-21

    Retinoids are a class of compounds with structural similarity to vitamin A. These compounds inhibit the proliferation of many cancer cell lines but have had limited medical application as they are often toxic at therapeutic levels. Efforts to synthesize retinoids with a greater therapeutic index have met with limited success. 4-[(1E)-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-propen-1-yl]benzoic acid (TTNPB) is one of the most biologically active all-trans-retinoic acid (atRA) analogues and is highly teratogenic. In this study, we show that modification of the TTNPB carboxyl group with an N-(4-hydroxyphenyl)amido (4HPTTNPB) or a 4-hydroxybenzyl (4HBTTNPB) group changes the activity of the compound in cell culture and in vivo. Unlike TTNPB, both compounds induce apoptosis in cancer cells and bind poorly to the retinoic acid receptors (RARs). Like the similarly modified all-trans-retinoic acid (atRA) analogues N-(4-hydroxyphenyl)retinamide (4-HPR/fenretinide) and 4-hydroxybenzylretinone (4-HBR), 4HBTTNPB is a potent activator of components of the ER stress pathway. The amide-linked analogue, 4HPTTNPB, is less toxic to developing embryos than the parent TTNPB, and most significantly, the 4-hydroxybenzyl-modified compound (4HBTTNPB) that cannot be hydrolyzed in vivo to the parent TTNPB compound is nearly devoid of teratogenic liability. PMID:21939267

  12. Identification of compounds that modulate retinol signaling using a cell-based qHTS assay.

    Science.gov (United States)

    Chen, Yanling; Sakamuru, Srilatha; Huang, Ruili; Reese, David H; Xia, Menghang

    2016-04-01

    In vertebrates, the retinol (vitamin A) signaling pathway (RSP) controls the biosynthesis and catabolism of all-trans retinoic acid (atRA), which regulates transcription of genes essential for embryonic development. Chemicals that interfere with the RSP to cause abnormal intracellular levels of atRA are potential developmental toxicants. To assess chemicals for the ability to interfere with retinol signaling, we have developed a cell-based RARE (Retinoic Acid Response Element) reporter gene assay to identify RSP disruptors. To validate this assay in a quantitative high-throughput screening (qHTS) platform, we screened the Library of Pharmacologically Active Compounds (LOPAC) in both agonist and antagonist modes. The screens detected known RSP agonists, demonstrating assay reliability, and also identified novel RSP agonists including kenpaullone, niclosamide, PD98059 and SU4312, and RSP antagonists including Bay 11-7085, LY294002, 3,4-Methylenedioxy-β-nitrostyrene, and topoisomerase inhibitors (camptothecin, topotecan, amsacrine hydrochloride, and idarubicin). When evaluated in the P19 pluripotent cell, these compounds were found to affect the expression of the Hoxa1 gene that is essential for embryo body patterning. These results show that the RARE assay is an effective qHTS approach for screening large compound libraries to identify chemicals that have the potential to adversely affect embryonic development through interference with retinol signaling. PMID:26820057

  13. Population Connectivity Measures of Fishery-Targeted Coral Reef Species to Inform Marine Reserve Network Design in Fiji.

    Science.gov (United States)

    Eastwood, Erin K; López, Elora H; Drew, Joshua A

    2016-01-01

    Coral reef fish serve as food sources to coastal communities worldwide, yet are vulnerable to mounting anthropogenic pressures like overfishing and climate change. Marine reserve networks have become important tools for mitigating these pressures, and one of the most critical factors in determining their spatial design is the degree of connectivity among different populations of species prioritized for protection. To help inform the spatial design of an expanded reserve network in Fiji, we used rapidly evolving mitochondrial genes to investigate connectivity patterns of three coral reef species targeted by fisheries in Fiji: Epinephelus merra (Serranidae), Halichoeres trimaculatus (Labridae), and Holothuria atra (Holothuriidae). The two fish species, E. merra and Ha. trimaculatus, exhibited low genetic structuring and high amounts of gene flow, whereas the sea cucumber Ho. atra displayed high genetic partitioning and predominantly westward gene flow. The idiosyncratic patterns observed among these species indicate that patterns of connectivity in Fiji are likely determined by a combination of oceanographic and ecological characteristics. Our data indicate that in the cases of species with high connectivity, other factors such as representation or political availability may dictate where reserves are placed. In low connectivity species, ensuring upstream and downstream connections is critical. PMID:26805954

  14. Differentiation Therapy of Acute Myeloid Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Gocek, Elzbieta; Marcinkowska, Ewa, E-mail: ema@cs.uni.wroc.pl [Department of Biotechnology, University of Wroclaw, ul Tamka 2, Wroclaw 50-137 (Poland)

    2011-05-16

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D{sub 3} (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML.

  15. Retinoid regulated macrophage cholesterol efflux involves the steroidogenic acute regulatory protein.

    Science.gov (United States)

    Manna, Pulak R

    2016-06-01

    Elimination of excess cholesteryl esters from macrophage-derived foam cells is known to be a key process in limiting plaque stability and progression of atherosclerotic lesions. We have recently demonstrated that regulation of retinoid mediated cholesterol efflux is influenced by liver X receptor (LXR) signaling in mouse macrophages (Manna, P.R. et al., 2015, Biochem. Biophys. Res. Commun., 464:312-317). The data presented in this article evaluate the importance of the steroidogenic acute regulatory protein (StAR) in retinoid mediated macrophage cholesterol efflux. Overexpression of StAR in mouse RAW 264.7 macrophages increased the effects of both all-trans retinoic acid (atRA) and 9-cis RA on cholesterol efflux, suggesting StAR enhances the efficacy of retinoic acid receptor (RAR) and/or retinoid X receptor (RXR) ligands. Additional data revealed that atRA enhances (Bu)2cAMP induced StAR and ATP-binding cassette transporter A1 protein levels. Treatment of macrophages transfected with an LXRE reporter plasmid (pLXREx3-Luc) was found to induce the effects of RAR and RXR analogs on LXR activity. PMID:27081671

  16. O Mercosul e as controvérsias sobre investimentos

    Directory of Open Access Journals (Sweden)

    Vivian Daniele Rocha Gabriel

    2015-03-01

    Full Text Available O Direito Internacional de Investimentos foi criado a fim de respaldar os investidores estrangeiros contra atos soberanos dos Estados receptores de investimentos, seja através de tratados de investimentos, seja através da arbitragem mista e da criação do ICSID. Os países do MERCOSUL mostraram-se atraídos por esse arcabouço jurídico, contudo, no século XXI, com a ascensão de novos membros no MERCOSUL, a contínua atração de investimentos e a existência de outras alternativas regionais fazem com que seja necessário repensar a estratégia do MERCOSUL em relação ao Direito dos Investimentos, e que haja um redirecionamento de seus esforços para a valorização de meios jurisdicionais já existentes para a resolução de disputas sobre investimentos.

  17. Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells.

    Science.gov (United States)

    Maniwa, Yasuhisa; Kasukabe, Takashi; Kumakura, Shunichi

    2015-08-01

    Although all-trans retinoic acid (ATRA) is a standard and effective drug used for differentiation therapy in acute promyelocytic leukemia, ATRA-resistant leukemia cells ultimately emerge during this treatment. Therefore, the development of new drugs or effective combination therapy is urgently needed. We demonstrate that the combined treatment of vitamin K2 and cotylenin A synergistically induced monocytic differentiation in HL-60 cells. This combined treatment also synergistically induced NBT-reducing activity and non-specific esterase-positive cells as well as morphological changes to monocyte/macrophage-like cells. Vitamin K2 and cotylenin A cooperatively inhibited the proliferation of HL-60 cells in short-term and long-term cultures. This treatment also induced growth arrest at the G1 phase. Although 5 µg/ml cotylenin A or 5 µM vitamin K2 alone reduced c-MYC gene expression in HL-60 cells to approximately 45% or 80% that of control cells, respectively, the combined treatment almost completely suppressed c-MYC gene expression. We also demonstrated that the combined treatment of vitamin K2 and cotylenin A synergistically induced the expression of cyclin G2, which had a positive effect on the promotion and maintenance of cell cycle arrest. These results suggest that the combination of vitamin K2 and cotylenin A has therapeutic value in the treatment of acute myeloid leukemia. PMID:26046133

  18. JENIS DAN KEPADATAN TERIPANG (Holothuroidea DI PANTAI BALI SELATAN

    Directory of Open Access Journals (Sweden)

    Ni Putu Mery Yanti

    2014-07-01

    Full Text Available The research wasaimed to theidentifyspecies and density of sea cucumbers at southernbeach of Bali are Mertasari beach, Segara beach, and Mengening beach. The identification ofspecies was conducted in the Laboratorium of EcologyDepartment of Biology, Faculty ofNatural Science and Mathematics, University of Udayana from December 2013 toJanuary 2014.A size of 1 x 1m quadrat squaretransect sampling method was employed in this research.Identification of sea cucumbers was performed based on their morphology and shape ofspicules. GSIwas used to observed reproductionphase of sea cucumber.Two species of seacucumbers found ware Holothuria atra and Holothuria sp. Holothuria atra was found atMertasari beach, Sanur village, southern of Denpasar and Segara beach, Tuban, Kuta, Badungwhile Holothuria sp. was faound atMengening beach. Segara beach showed the highestdensityof4.333 individual/m2,while Mertasari beach showed the lowest density 0.875individual/m2. GSI Value ofMertasari, Segara, andMengening beach showed the activationofphase ofI andII.Keywords: Holothuroidea, species, sea cucumber, density, GSI

  19. Acute promyelocytic leukemia after whole brain irradiation of primary brain lymphomainan HIV-infected patient

    Directory of Open Access Journals (Sweden)

    Boban A

    2009-01-01

    Full Text Available Abstract The occurrence of acute promyelocytic leukemia (APL in HIV-infected patients has been reported in only five cases. Due to a very small number of reported HIV/APL patients who have been treated with different therapies with the variable outcome, the prognosis of APL in the setting of the HIV-infection is unclear. Here, we report a case of an HIV-patient who developed APL and upon treatment entered a complete remission. A 25-years old male patient was diagnosed with HIV-infection in 1996, but remained untreated. In 2004, the patient was diagnosed with primary central nervous system lymphoma. We treated the patient with antiretroviral therapy and whole-brain irradiation, resulting in complete remission of the lymphoma. In 2006, prompted by a sudden neutropenia, we carried out a set of diagnostic procedures, revealing APL. Induction therapy consisted of standard treatment with all-trans-retinoic-acid (ATRA and idarubicin. Subsequent cytological and molecular analysis of bone marrow demonstrated complete hematological and molecular remission. Due to the poor general condition, consolidation treatment with ATRA was given in March and April 2007. The last follow-up 14 months later, showed sustained molecular APL remission. In conclusion, we demonstrated that a complete molecular APL remission in an HIV-patient was achieved by using reduced-intensity treatment.

  20. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

    Science.gov (United States)

    Yu, Zu-Yin; Xiao, He; Wang, Li-Mei; Shen, Xing; Jing, Yu; Wang, Lin; Sun, Wen-Feng; Zhang, Yan-Feng; Cui, Yu; Shan, Ya-Jun; Zhou, Wen-Bing; Xing, Shuang; Xiong, Guo-Lin; Liu, Xiao-Lan; Dong, Bo; Feng, Jian-Nan; Wang, Li-Sheng; Luo, Qing-Liang; Zhao, Qin-Shi; Cong, Yu-Wen

    2016-05-01

    All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR. PMID:26984756

  1. All-trans retinoic acid prevents the development of type 1 diabetes by affecting the levels of interferon gamma and interleukin 4 in streptozotocin-induced murine diabetes model.

    Science.gov (United States)

    Wang, Y; Zhong, Y J; Wang, Y Y; Xing, J; Wang, Z M

    2016-01-01

    The aim of this study was to explore the molecular mechanism by which all-trans retinoic acid (ATRA) prevents type 1 diabetes mellitus (T1DM). Fifty ICR mice were randomly assigned to three groups: prevention group [N = 20; mice received 10 mg/kg ATRA daily for 5 days and then 60 mg/kg streptozotocin (STZ) for 5 days]; diabetic group (N = 20, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then 60 mg/kg STZ for 5 days); and control group (N = 10, mice received 95% sterile peanut oil and 5% dimethyl sulfoxide for 5 days and then citrate buffer for 5 days). Blood glucose was measured using blood glucose test strips and serum insulin was measured by radioimmunoassay. Islets cell morphology was assessed by microscopy and ELISA was used to measure the serum levels of interferon gamma (IFN-γ) and interleukin 4 (IL- 4). In the prevention group, blood sugar levels were found to be reduced and serum insulin levels increased compared with the levels in the diabetic group (P levels of IFN-γ and increase the levels of IL-4 as well as the IFN-γ/IL-4 ratio in STZ-treated animals (P levels and increasing IL-4 levels. PMID:27050967

  2. Proton MRI as a noninvasive tool to assess elastase-induced lung damage in spontaneously breathing rats.

    Science.gov (United States)

    Quintana, Harry Karmouty; Cannet, Catherine; Zurbruegg, Stefan; Blé, François-Xavier; Fozard, John R; Page, Clive P; Beckmann, Nicolau

    2006-12-01

    Elastase-induced changes in lung morphology and function were detected in spontaneously breathing rats using conventional proton MRI at 4.7 T. A single dose of porcine pancreatic elastase (75 U/100 g body weight) or vehicle (saline) was administered intratracheally (i.t.) to male Brown Norway (BN) rats. MRI fluid signals were detected in the lungs 24 hr after administration of elastase and resolved within 2 weeks. These results correlated with perivascular edema and cellular infiltration observed histologically. Reductions in MRI signal intensity of the lung parenchyma, and increases in lung volume were detected as early as 2 weeks following elastase administration and remained uniform throughout the study, which lasted 8 weeks. Observations were consistent with air trapping resulting from emphysema detected histologically. In a separate experiment, animals were treated daily intraperitoneally (i.p.) with all-trans-retinoic acid (ATRA; 500 microg/kg body weight) or its vehicle (triglyceride oil) starting on day 21 after elastase administration and continuing for 12 days. Under these conditions, ATRA did not elicit a reversal of elastase-induced lung damage as measured by MRI and histology. The present approach complements other validated applications of proton MRI in experimental lung research as a method for assessing drugs in rat models of respiratory diseases. PMID:17029230

  3. Simultaneous measurement of electron temperature and density by a line pair method in the RFP plasma

    Science.gov (United States)

    Watanabe, Masayuki; Shimizu, S.; Ogawa, H.; Shinohara, T.

    2009-11-01

    A line-pair-method has been applied for a simultaneous measurement of the electron temperature and density in ATRAS RFP plasma. Three helium spectrum lines (668nm, 706nm, 728nm) were measured during the discharge at the same time and the electron temperature and density is estimated by using a Collision-Radiation model. To get the signal of the helium impunity line from the RFP discharge, the RFP plasma in the hydrogen gas with a few mixed helium gas was formed. In the typical ATRAS RFP discharge of the plasma current of 60kA, the electron temperature was approximately 50-150 eV and the electron density is the order of 10^18 m-3. During the discharge, the change of the temperature and density are mutually related and this correlation was the almost reverse phase. The periodically change of the temperature and density were also observed. This change synchronizes with a periodically increase of the averaged toroidal magnetic field, which is caused by the toroidal rotation of the increase of the toroidal magnetic field. This rotation, which is deeply related with dynamo effect, makes the plasma energy lose and particles also diffuse toward the plasma edge. As a result, the recycling of the particle and energy are occurred at the same time.

  4. Experimental study of retinoic acid on improving iodide uptake in MCF-7 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    FU Hong-Liang; WU Jing-Chuan; DU Xue-Liang; LI Jia-Ning; WU Zhen; ZOU Ren-Jian

    2005-01-01

    The study aims to investigate the effect of retinoic acid on the iodide uptake of MCF-7 cells and its mechanism. The iodide uptake and expression of hNIS(human sodium/iodide symporter)mRNA in the breast cancer MCF-7 cells were compared individually before and after the intervention of all-trans retinoic acid (ATRA) with the iodide uptake assay and RT-PCR. The following results are obtained: (1) when treated with all-trans retinoic acid in the concentration of 1.0 μmol/L, the capacity of iodide uptake of MCF-7 cells reached about 1.5 times of the basal state; (2) 12 h after the intervention of 1.0 μmol/L ATRA, the hNISmRNA expression of the MCF-7 cells reached maximum. The study shows that all-trans retinoic acid has the effect to improve the iodide uptake of the MCF-7 cells and this effect may result from its up-regulation of the hNISmRNA expression.

  5. Activity Analysis and Preliminary Inducer Screening of the Chicken DAZL Gene Promoter

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2015-03-01

    Full Text Available This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the DAZL gene under different inducers. Our studies showed that the DAZL core promoter region for the Suqin yellow chicken was −383 to −39 bp. The dual-luciferase® reporter showed that all-trans retinoic acid (ATRA, a retinoic acid receptor alpha agonist (tamibarotene/Am80, or estradiol (E2 could significantly enhance DAZL transcription. The in vitro inductive culture of chicken ESCs demonstrated that, with ATRA treatment, DAZL transcription peaked at 6 days and then decreased slowly; whereas, DAZL transcription was continuous and peaked at 10 days with Am80 treatment. E2 treatment significantly increased DAZL expression after 8 days. All three treatments were associated with the appearance of male germ cell (MGC-like cells on day 10. These results provide the optimum inducer screening of the DAZL gene and lay the foundation for further screening of compounds that can induce the differentiation of ESCs into MGCs in vitro.

  6. Activity analysis and preliminary inducer screening of the chicken DAZL gene promoter.

    Science.gov (United States)

    Zhang, Lei; Zhu, Rui; Zuo, Qisheng; Li, Dong; Lian, Chao; Tang, Beibei; Xiao, Tianrong; Zhang, Yani; Li, Bichun

    2015-01-01

    This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase® Reporter Assay System was used to identify the activity of the DAZL gene under different inducers. Our studies showed that the DAZL core promoter region for the Suqin yellow chicken was -383 to -39 bp. The dual-luciferase® reporter showed that all-trans retinoic acid (ATRA), a retinoic acid receptor alpha agonist (tamibarotene/Am80), or estradiol (E2) could significantly enhance DAZL transcription. The in vitro inductive culture of chicken ESCs demonstrated that, with ATRA treatment, DAZL transcription peaked at 6 days and then decreased slowly; whereas, DAZL transcription was continuous and peaked at 10 days with Am80 treatment. E2 treatment significantly increased DAZL expression after 8 days. All three treatments were associated with the appearance of male germ cell (MGC)-like cells on day 10. These results provide the optimum inducer screening of the DAZL gene and lay the foundation for further screening of compounds that can induce the differentiation of ESCs into MGCs in vitro. PMID:25807265

  7. Transcription factor C/EBP-β induces tumor-suppressor phosphatase PHLPP2 through repression of the miR-17-92 cluster in differentiating AML cells.

    Science.gov (United States)

    Yan, Y; Hanse, E A; Stedman, K; Benson, J M; Lowman, X H; Subramanian, S; Kelekar, A

    2016-07-01

    PHLPP2, a member of the PH-domain leucine-rich repeat protein phosphatase (PHLPP) family, which targets oncogenic kinases, has been actively investigated as a tumor suppressor in solid tumors. Little is known, however, regarding its regulation in hematological malignancies. We observed that PHLPP2 protein expression, but not its mRNA, was suppressed in late differentiation stage acute myeloid leukemia (AML) subtypes. MicroRNAs (miR or miRNAs) from the miR-17-92 cluster, oncomir-1, were shown to inhibit PHLPP2 expression and these miRNAs were highly expressed in AML cells that lacked PHLPP2 protein. Studies showed that miR-17-92 cluster regulation was, surprisingly, independent of transcription factors c-MYC and E2F in these cells; instead all-trans-retinoic acid (ATRA), a drug used for terminally differentiating AML subtypes, markedly suppressed miR-17-92 expression and increased PHLPP2 protein levels and phosphatase activity. Finally, we demonstrate that the effect of ATRA on miR-17-92 expression is mediated through its target, transcription factor C/EBPβ, which interacts with the intronic promoter of the miR-17-92 gene to inhibit transactivation of the cluster. These studies reveal a novel mechanism for upregulation of the phosphatase activity of PHLPP2 through C/EBPβ-mediated repression of the miR-17-92 cluster in terminally differentiating myeloid cells. PMID:26868909

  8. All-Trans Retinoic Acid Induces Expression of a Novel Intergenic Long Noncoding RNA in Adult rat Primary Hippocampal Neurons.

    Science.gov (United States)

    Kour, Sukhleen; Rath, Pramod C

    2016-02-01

    Around 90% of the mammalian genome undergoes pervasive transcription into various types of small and long regulatory noncoding RNAs, whereas only ∼ 1.5% codes for proteins. Long noncoding RNAs (lncRNAs) constitute diverse classes of sense- and antisense transcripts that are abundantly expressed in the mammalian central nervous system (CNS) in cell type- and developmental stage-specific manners. They are implicated in brain development, differentiation, neuronal plasticity, and other cognitive functions. Mammalian brain requires the vitamin A metabolite all-trans retinoic acid (atRA) for its normal development, differentiation, and cell-fate determination. However, its role in adult brain function is less understood. Here, we report atRA-mediated transcriptional upregulation of endogenous expression of a novel long intergenic noncoding RNA-rat brain expressed (LINC-RBE) in cultured primary hippocampal neurons from adult rat. We have previously reported LINC-RBE as an intergenic, simple repeat sequence containing lncRNA highly expressed in the rat brain. This is a first-time report of involvement of atRA in transcriptional upregulation of lncRNA expression in rat hippocampal neurons. Therefore, it may be involved in regulation of brain function and disease. PMID:26572536

  9. ESTUDIO DE ALGUNOS GÉNEROS MICROBIANOS ASOCIADOS A DIFERENTES VARIEDADES DE TRIGO (Triticum aestivum L. EN SUELO FERRALÍTICO ROJO

    Directory of Open Access Journals (Sweden)

    Annia Hernández

    2002-01-01

    Full Text Available Se estudiaron los géneros bacterianos predominantes en la rizosfera de cuatro variedades de trigo (Triticum aestivum L. crecido en un suelo Ferralítico Rojo. También se evaluó la quimioatracción de algunas rizobacterias hacia los exudados radicales de este cultivo. Se utilizó el Modelo Espermosférico para el aislamiento y los tubos colectores y la cámara de quimiotaxis modificada para la evaluación del efecto quimiotáctico de los exudados radicales. Los resultados obtenidos demostraron que en las variedades Gang y Caeté, Pseudomonas es la población dominante, siendo Pseudomonas (Burkholderia cepacia la especie más fuertemente atraída por los exudados radicales a los 14 días y 40 minutos de exposición. En las variedades Culiacam y Antisama, es el género Azospirillum el predominante en la rizosfera, siendo esta especie la más fuertemente atraída por los exudados radicales a los 14 días y 60 minutos de exposición. Esta investigación permite la aplicación de biofertilizantes a base de los géneros microbianos predominantes en la rizosfera del trigo, potenciando su actividad sin alterar la biología del suelo.

  10. Identification of Tumor Progression-Related Genes in Astrocytoma cell Lines

    Institute of Scientific and Technical Information of China (English)

    Yi Zeng; Zhong Yang; Chao You; Yangyun Han

    2008-01-01

    OBJECTIVE To identify progression-related genes that lead to astrocytoma progression from a low to a high grade by analyzing the gene expression profiles from different tumor grades, and all-trans retinoic acid-treated astrocytoma cell lines.METHODS In this study, all-trans retinoic acid(ATRA) was used to induce differentiation of SHG-44 cells.Then,by using a cDNA microarray, we compared gene expression profiling in different grades of astrocytoma cell lines(CHG-5,WHo Grade II and SHG-44,WHO Grade IV)and in ATRA-induced differentiation in SHG-44 cells.A panel of overlapped genes that might be related to tumor progression was identified,and the cell line individual variation was avoided as well. RESUIJTS In the 31 overlapped genes,the stable over-expression of MDM2 and UGB as well as the repression of SOD2,G3BP, and CSTB in parental SHG-44 ceils was observed and their possible roles in tumor progression were discussed.Moreover, validation of some differentially expressed genes was confirmed by Northern blots.CONCLUSl0N The overlapped genes reported in this study might relate to progression of astrocytoma.Further study of progression-related genes may be helpful to explore the genetic pathways that are involved in astrocytoma progress from a low to a high grade.

  11. Retinoid receptor signaling and autophagy in acute promyelocytic leukemia.

    LENUS (Irish Health Repository)

    Orfali, Nina

    2014-05-15

    Retinoids are a family of signaling molecules derived from vitamin A with well established roles in cellular differentiation. Physiologically active retinoids mediate transcriptional effects on cells through interactions with retinoic acid (RARs) and retinoid-X (RXR) receptors. Chromosomal translocations involving the RARα gene, which lead to impaired retinoid signaling, are implicated in acute promyelocytic leukemia (APL). All-trans-retinoic acid (ATRA), alone and in combination with arsenic trioxide (ATO), restores differentiation in APL cells and promotes degradation of the abnormal oncogenic fusion protein through several proteolytic mechanisms. RARα fusion-protein elimination is emerging as critical to obtaining sustained remission and long-term cure in APL. Autophagy is a degradative cellular pathway involved in protein turnover. Both ATRA and ATO also induce autophagy in APL cells. Enhancing autophagy may therefore be of therapeutic benefit in resistant APL and could broaden the application of differentiation therapy to other cancers. Here we discuss retinoid signaling in hematopoiesis, leukemogenesis, and APL treatment. We highlight autophagy as a potential important regulator in anti-leukemic strategies.

  12. αvβ3 imaging can accurately distinguish between mature teratoma and necrosis in 18F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

    International Nuclear Information System (INIS)

    We assessed whether imaging αvβ3 integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles).18F-Fluorodeoxyglucose (18F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of αvβ3 expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [99mTc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse αvβ3 expression were performed. Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for 18F-FDG [mean standardised uptake value (SUVmean) = 0.48 ± 0.05] compared to untreated embryonal carcinoma (SUVmean = 0.92 ± 0.13) (p = 0.005). αvβ3 imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 ± 1.57) from necrosis (tumour to muscle ratio = 1.3 ± 0.26) (p = 0.0002). Immunohistochemistry studies showed that αvβ3 integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma. Imaging αvβ3 integrin accurately distinguished mature teratoma from necrosis following cisplatin-based treatment in human NSGCT xenografts. (orig.)

  13. MicroRNA-10a is reduced in breast cancer and regulated in part through retinoic acid

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short non-coding RNA molecules that play a critical role in mRNA cleavage and translational repression, and are known to be altered in many diseases including breast cancer. MicroRNA-10a (miR-10a) has been shown to be deregulated in various cancer types. The aim of this study was to investigate miR-10a expression in breast cancer and to further delineate the role of retinoids and thyroxine in regulation of miR-10a. Following informed patient consent and ethical approval, tissue samples were obtained during surgery. miR-10a was quantified in malignant (n = 103), normal (n = 30) and fibroadenoma (n = 35) tissues by RQ-PCR. Gene expression of Retinoic Acid Receptor beta (RARβ) and Thyroid Hormone receptor alpha (THRα) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T4) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3. The level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log10 Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log10 RQ, p < 0.001) and benign tissues (2.6(0.17) Log10 RQ, p < 0.05). The levels of both RARβ and THRα gene expression were also found to be decreased in breast cancer patients compared to controls (p < 0.001). A significant positive correlation was determined between miR-10a and RARβ (r = 0.31, p < 0.001) and also with THRα (r = 0.32, p < 0.001). In vitro stimulation assays revealed miR-10a expression was increased in both T47D and SK-BR-3 cells following addition of ATRA (2 fold (0.7)). While T4 alone did not stimulate miR-10a expression, the combination of T4 and ATRA was found to have a positive synergistic effect. The data presented supports a potential tumour suppressor role for miR-10a in breast cancer, and highlights retinoic acid as a positive regulator of the micro

  14. Identification and characterization of the retinoic acid response elements in the human RIG1 gene promoter

    International Nuclear Information System (INIS)

    The expression of retinoic acid-induced gene 1 (RIG1), a class II tumor suppressor gene, is induced in cells treated with retinoids. RIG1 has been shown to express ubiquitously and the increased expression of this gene appears to suppress cell proliferation. Recent studies also demonstrated that this gene may play an important role in cell differentiation and the progression of cancer. In spite of the remarkable regulatory role of this protein, the molecular mechanism of RIG1 expression induced by retinoids remains to be clarified. The present study was designed to study the molecular mechanism underlying the all-trans retinoic acid (atRA)-mediated induction of RIG1 gene expression. Polymerase chain reaction was used to generate a total of 10 luciferase constructs that contain various fragments of the RIG1 5'-genomic region. These constructs were then transfected into human gastric cancer SC-M1 and breast cancer T47D cells for transactivation analysis. atRA exhibited a significant induction in luciferase activity only through the -4910/-5509 fragment of the 5'-genomic region of RIG1 gene relative to the translation initiation site. Further analysis of this promoter fragment indicated that the primary atRA response region is located in between -5048 and -5403 of the RIG1 gene. Within this region, a direct repeat sequence with five nucleotide spacing, 5'-TGACCTctattTGCCCT-3' (DR5, -5243/-5259), and an inverted repeat sequence with six nucleotide spacing, 5'-AGGCCAtggtaaTGGCCT-3' (IR6, -5323/-5340), were identified. Deletion and mutation of the DR5, but not the IR6 element, abolished the atRA-mediated activity. Electrophoretic mobility shift assays with nuclear extract from atRA-treated cells indicated the binding of retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers specifically to this response element. In addition to the functional DR5, the region contains many other potential sequence elements that are required to maximize the at

  15. Retinoic acid signalling is activated in the postischemic heart and may influence remodelling.

    Directory of Open Access Journals (Sweden)

    Dusan Bilbija

    Full Text Available BACKGROUND: All-trans retinoic acid (atRA, an active derivative of vitamin A, regulates cell differentiation, proliferation and cardiac morphogenesis via transcriptional activation of retinoic acid receptors (RARs acting on retinoic acid response elements (RARE. We hypothesized that the retinoic acid (RA signalling pathway is activated in myocardial ischemia and postischemic remodelling. METHODS AND FINDINGS: Myocardial infarction was induced through ligating the left coronary artery in mice. In vivo cardiac activation of the RARs was measured by imaging RARE-luciferase reporter mice, and analysing expression of RAR target genes and proteins by real time RT-PCR and western blot. Endogenous retinoids in postinfarcted hearts were analysed by triple-stage liquid chromatography/tandem mass spectrometry. Cardiomyocytes (CM and cardiofibroblasts (CF were isolated from infarcted and sham operated RARE luciferase reporter hearts and monitored for RAR activity and expression of target genes. The effect of atRA on CF proliferation was evaluated by EdU incorporation. Myocardial infarction increased thoracic RAR activity in vivo (p<0.001, which was ascribed to the heart through ex vivo imaging (p = 0.002 with the largest signal 1 week postinfarct. This was accompanied by increased cardiac gene and protein expression of the RAR target genes retinol binding protein 1 (p = 0.01 for RNA, p = 0,006 for protein and aldehyde dehydrogenase 1A2 (p = 0.04 for RNA, p = 0,014 for protein, while gene expression of cytochrome P450 26B1 was downregulated (p = 0.007. Concomitantly, retinol accumulated in the infarcted zone (p = 0.02. CM and CF isolated from infarcted hearts had higher luminescence than those from sham operated hearts (p = 0.02 and p = 0.008. AtRA inhibited CF proliferation in vitro (p = 0.02. CONCLUSION: The RA signalling pathway is activated in postischemic hearts and may play a role in regulation of damage and

  16. CaCO3 dissolution by holothurians (sea cucumber): a case study from One Tree Reef, Great Barrier Reef

    Science.gov (United States)

    Schneider, K.; Silverman, J.; Kravitz, B.; Woolsey, E.; Eriksson, H.; Schneider-Mor, A.; Barbosa, S.; Rivlin, T.; Byrne, M.; Caldeira, K.

    2012-12-01

    Holothurians (sea cucumbers) are among the largest and most important deposit feeder in coral reefs. They play a role in nutrient and CaCO3 cycling within the reef structure. As a result of their digestive process they secrete alkalinity due to CaCO3 dissolution and organic matter degradation forming CO2 and ammonium. In a survey at station DK13 on One Three Reef we found that the population density of holothurians was > 1 individual m-2. The dominant sea cucumber species Holothuria leucospilota was collected from DK13. The increase in alkalinity due to CaCO3 dissolution in aquaria incubations was measured to be 47±7 μmol kg-1 in average per individual. Combining this dissolution rate with the sea cucumbers concentrations at DK13 suggest that they may account for a dissolution rate of 34.9±17.8 mmol m-2 day-1, which is equivalent to about half of night time community dissolution measured in DK13. This indicates that in reefs where the sea cucumber population is healthy and protected from fishing they can be locally important in the CaCO3 cycle. Preliminary result suggests that the CaCO3 dissolution rates are not affected by the chemistry of the sea water they are incubated in. Measurements of the empty digestive track volume of two sea cucumbers H. atra and Stichopus herrmanni were 36 ± 4 ml and 151 ± 14 ml, respectively. Based on these measurements it is estimated that these species process 19 ± 2kg and 80 ± 7kg CaCO3 sand yr-1 per individual, respectively. The annual dissolution rates of H. atra and S. herrmanni are 6.5±1.9g and 9.6±1.4g, respectively, suggest that 0.05±0.02% and 0.1±0.02% of the CaCO3 processed through their gut annually is dissolved. During the incubations the CaCO3 dissolution was 0.07±0.01%, 0.04±0.01% and 0.21±0.05% of the fecal casts for H. atra, H. leucospilota and S. herrmanni, respectively. Our result that the primary parameter determining the CaCO3 dissolution by sea cucumber is the amount of carbonate send in their gut

  17. Characterization of protective human CD4CD25 FOXP3 regulatory T cells generated with IL-2, TGF-β and retinoic acid.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available BACKGROUND: Protective CD4+CD25+ regulatory T cells bearing the Forkhead Foxp3 transcription factor can now be divided into three subsets: Endogenous thymus-derived cells, those induced in the periphery, and another subset induced ex-vivo with pharmacological amounts of IL-2 and TGF-β. Unfortunately, endogenous CD4+CD25+ regulatory T cells are unstable and can be converted to effector cells by pro-inflammatory cytokines. Although protective Foxp3+CD4+CD25+ cells resistant to proinflammatory cytokines have been generated in mice, in humans this result has been elusive. Our objective, therefore, was to induce human naïve CD4+ cells to become stable, functional CD25+ Foxp3+ regulatory cells that were also resistant to the inhibitory effects of proinflammatory cytokines. METHODOLOGY/PRINCIPAL FINDINGS: The addition of the vitamin A metabolite, all-trans retinoic acid (atRA to human naïve CD4+ cells suboptimally activated with IL-2 and TGF-β enhanced and stabilized FOXP3 expression, and accelerated their maturation to protective regulatory T cells. AtRA, by itself, accelerated conversion of naïve to mature cells but did not induce FOXP3 or suppressive activity. The combination of atRA and TGF-β enabled CD4+CD45RA+ cells to express a phenotype and trafficking receptors similar to natural Tregs. AtRA/TGF-β-induced CD4+ regs were anergic and low producers of IL-2. They had potent in vitro suppressive activity and protected immunodeficient mice from a human-anti-mouse GVHD as well as expanded endogenous Tregs. However, treatment of endogenous Tregs with IL-1β and IL-6 decreased FOXP3 expression and diminished their protective effects in vivo while atRA-induced iTregs were resistant to these inhibitory effects. CONCLUSIONS/SIGNIFICANCE: We have developed a methodology that induces human CD4(+ cells to rapidly become stable, fully functional suppressor cells that are also resistant to proinflammatory cytokines. This methodology offers a practical

  18. {alpha}{sub v}{beta}{sub 3} imaging can accurately distinguish between mature teratoma and necrosis in {sup 18}F-FDG-negative residual masses after treatment of non-seminomatous testicular cancer: a preclinical study

    Energy Technology Data Exchange (ETDEWEB)

    Aide, Nicolas [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Centre Francois Baclesse, Service de Medecine Nucleaire, Caen (France); Briand, Melanie; Dutoit, Soizic; Deslandes, Edwiges; Poulain, Laurent [Francois Baclesse Cancer Centre and Caen University, Bioticla Team, EA1772, IFR 146 ICORE, GRECAN, Caen (France); Bohn, Pierre; Rouvet, Jean; Modzelewski, Romain; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital and QuantIF- LITIS (EA4108), Department of Nuclear Medicine, Rouen (France); Lasnon, Charline [Caen University Hospital and Francois Baclesse Cancer Centre, PET Unit, Caen (France); Chasle, Jacques [Francois Baclesse Cancer Centre and Caen University, Pathology Department, Caen (France); Vela, Antony [Francois Baclesse Cancer Centre and Caen University, Radiophysics Unit, Caen (France); Carreiras, Franck [Universite de Cergy Pontoise, UFR Sciences et Techniques, ERRMECe, EA 1391, Institut des materiaux, Cergy-Pontoise (France)

    2011-02-15

    We assessed whether imaging {alpha}{sub v}{beta}{sub 3} integrin could distinguish mature teratoma from necrosis in human non-seminomatous germ cell tumour (NSGCT) post-chemotherapy residual masses. Human embryonal carcinoma xenografts (six/rat) were untreated (controls) or treated to form mature teratomas with low-dose cisplatin and all-trans retinoic acid (ATRA) over a period of 8 weeks. In another group, necrosis was induced in xenografts with high-dose cisplatin plus etoposide (two cycles).{sup 18}F-Fluorodeoxyglucose ({sup 18}F-FDG) small animal positron emission tomography (SA PET) imaging was performed in three rats (one control and two treated for 4 and 8 weeks with cisplatin+ATRA). Imaging of {alpha}{sub v}{beta}{sub 3} expression was performed in six rats bearing mature teratomas and two rats with necrotic lesions on a microSPECT/CT device after injection of the tracer [{sup 99m}Tc]HYNIC-RGD [6-hydrazinonicotinic acid conjugated to cyclo(Arg-Gly-Asp-D-Phe-Lys)]. Correlative immunohistochemistry studies of human and mouse {alpha}{sub v}{beta}{sub 3} expression were performed. Cisplatin+ATRA induced differentiation of the xenografts. After 8 weeks, some glandular structures and mesenchymal cells were visible; in contrast, control tumours showed undifferentiated tissues. SA PET imaging showed that mature teratoma had very low avidity for {sup 18}F-FDG [mean standardised uptake value (SUV{sub mean}) = 0.48 {+-} 0.05] compared to untreated embryonal carcinoma (SUV{sub mean} = 0.92 {+-} 0.13) (p = 0.005). {alpha}{sub v}{beta}{sub 3} imaging accurately distinguished mature teratoma (tumour to muscle ratio = 4.29 {+-} 1.57) from necrosis (tumour to muscle ratio = 1.3 {+-} 0.26) (p = 0.0002). Immunohistochemistry studies showed that {alpha}{sub v}{beta}{sub 3} integrin expression was strong in the glandular structures of mature teratoma lesions and negative in host stroma. Imaging {alpha}{sub v}{beta}{sub 3} integrin accurately distinguished mature teratoma from

  19. New approaches for the desing of chiral catalysts. Application in carbonylation reactions.

    OpenAIRE

    Muñoz Moreno, Bianca Karelia

    2007-01-01

    Actualmente, el interés industrial de los productos carbonilados ha atraído la atención de los científicos hacia el desarrollo de nuevos sistemas catalíticos eficientes. La reacción de alcoxicarbonilación de vinil arenos ha sido considerada una ruta alternativa para la obtención de ácidos 2-aril propiónicos, la clase más importante de antiinflamatorios no esteroides. Por otro lado, los copolímeros de monóxido de carbono y olefinas son materiales de gran interés industrial debido a su aplica...

  20. Socialinės pedagoginės pagalbos komandos narių atrankos kriterijai

    OpenAIRE

    Kvieskienė, Giedrė; Indrašienė, Valdonė; Merfeldaitė, Odeta

    2006-01-01

    Šiandieninėje visuomenėje, patiriančioje globalizacijos procesų pasekmes, vaikų ir jaunimo socializacijos problemos tampa vis sudėtingesnės, todėl joms spręsti nebeužtenka vieno klasės auklėtojo kompetencijos ir pastangų. Tai reiškia, kad siekiant bendrojo lavinimo mokyklose kompleksiškai spręsti socialines pedagogines problemas būtina socialinės pedagoginės pagalbos komanda. Straipsnyje aptariama bendrojo lavinimo mokyklos socialinės pedagoginės pagalbos komandos sudėtis, komandos narių atra...

  1. Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia.

    Science.gov (United States)

    Iaccarino, Licia; Ottone, Tiziana; Divona, Mariadomenica; Cicconi, Laura; Cairoli, Roberto; Voso, Maria Teresa; Lo-Coco, Francesco

    2016-03-01

    Acute promyelocytic leukaemia (APL) is characterized by the PML/RARA fusion transcript. PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). We analysed the prevalence of PML mutations in 32 patients with de novo or therapy-related APL (t-APL; n = 5), treated with ATO. We identified one ATO-resistant t-APL patient, who presented a PML A216T mutation in both the rearranged and unrearranged PML alleles, and two mutations in the rearranged RARA gene. In this patient, subclones with different PML and RARA mutations acquired clonal dominance during the disease course, probably leading to treatment resistance. PMID:26728337

  2. Una aproximación a la predicción del valor de acciones en la bolsa de valores aplicando técnicas de Data Mining

    OpenAIRE

    Espinosa Muñoz, Javier Isaac

    2015-01-01

    La predicción del valor de las acciones en la bolsa de valores ha sido un tema importante en el campo de inversiones, que por varios años ha atraído tanto a académicos como a inversionistas. Esto supone que la información disponible en el pasado de la compañía que cotiza en bolsa tiene alguna implicación en el futuro del valor de la misma. Este trabajo está enfocado en ayudar a un persona u organismo que decida invertir en la bolsa de valores a través de gestión de compra o venta de acciones ...

  3. Incidencia del síndrome de Burnout en sacerdotes católicos lationamericanos y su relación con la inteligencia emocional

    OpenAIRE

    López Herrera, Helena

    2010-01-01

    [ES]Burnout es una palabra en inglés que significa “Quemado” o “Desgastado”. Este concepto se ha utilizado cuando una persona se siente agotada de su profesión u ocupación. Es un problema que alcanza tales magnitudes, que ha atraído la atención de los científicos de la conducta humana, quienes han identificado síntomas típicos de esta condición: dificultad para dormir, malestares somáticos (pérdida de peso, dolores de cabeza, perturbaciones gastrointestinales, fatiga crónica, depresión, entre...

  4. Caracterización bioquímica de la porfiria cutánea tardía, hepatopatía porfirica.

    OpenAIRE

    Herrero Mateu, Carmen

    1980-01-01

    [spa] En el año 1971 y atraída por la gran personalidad del Prof. J. Piñol Aguadé, inicié el estudio de la Especialidad de Dermatología en la Cátedra por él dirigida. De este modo, me encontré en una Escuela profundamente interesada en las enfermedades producidas por alteraciones en el metabolismo de las porfirinas. Esto era debido a que el profesor Piñol seguía con sumo interés a los pacientes porfíricos y mostraba constantemente su preocupación por los problemas clínicos y patogénicos que p...

  5. Depressão na esclerose multipla forma remitente-recorrente

    OpenAIRE

    Mendes Maria Fernanda; Tilbery Charles Peter; Balsimelli Silvia; Moreira Marcos Aurélio; Barão-Cruz Ana Maria

    2003-01-01

    A possibilidade de correlação entre depressão e esclerose múltipla (EM) é conhecida há muitos anos, porém os estudos de prevalência não são conclusivos. No nosso meio a prevalência deste sintoma na EM permanece desconhecida. O objetivo deste estudo é verificar a prevalência da depressão em pacientes com EM, estudando a sua correlação com a incapacidade funcional, o sexo, a idade e o tempo de doença. Foram avaliados 84 pacientes com EM remitente-recorrente (EMRR). A depressão foi avaliada atra...

  6. Mutual exclusivity analysis of genetic and epigenetic drivers in melanoma identifies a link between p14ARF and retinoic acid receptor β signaling

    DEFF Research Database (Denmark)

    Dahl, Christina; Christensen, Claus; Jonsson, Goran;

    2013-01-01

    patterns. We found statistically significant mutual exclusivity among components of each of the p16INK4A-CDK4-RB, RAS-RAF-MEK-ERK and PI3K-AKT pathways. In addition, we found an inverse correlation between promoter hypermethylation of RARB (encoding retinoic acid receptor β (RARβ)) and CDKN2A alterations...... affecting p14ARF (P < 0.0001), suggesting a functional link between RARβ signaling and the melanoma-suppressive activities of p14ARF. We show that all-trans retinoic acid (ATRA) can increase the expression of p14ARF in primary human melanocytes, and that the steady-state levels of p14ARF in these cells are...

  7. Therapeutic strategies targeting cancer stem cells.

    Science.gov (United States)

    Ning, Xiaoyan; Shu, Jianchang; Du, Yiqi; Ben, Qiwen; Li, Zhaoshen

    2013-04-01

    Increasing studies have demonstrated a small proportion of cancer stem cells (CSCs) exist in the cancer cell population. CSCs have powerful self-renewal capacity and tumor-initiating ability and are resistant to chemotherapy and radiation. Conventional anticancer therapies kill the rapidly proliferating bulk cancer cells but spare the relatively quiescent CSCs, which cause cancer recurrence. So it is necessary to develop therapeutic strategies acting specifically on CSCs. In recent years, studies have shown that therapeutic agents such as metformin, salinomycin, DECA-14, rapamycin, oncostatin M (OSM), some natural compounds, oncolytic viruses, microRNAs, cell signaling pathway inhibitors, TNF-related apoptosis inducing ligand (TRAIL), interferon (IFN), telomerase inhibitors, all-trans retinoic acid (ATRA) and monoclonal antibodies can suppress the self-renewal of CSCs in vitro and in vivo. A combination of these agents and conventional chemotherapy drugs can significantly inhibit tumor growth, metastasis and recurrence. These strategies targeting CSCs may bring new hopes to cancer therapy. PMID:23358473

  8. 雄黄治疗维甲酸耐药急性早幼粒细胞白血病临床研究

    Institute of Scientific and Technical Information of China (English)

    关键平; 袁炜; 杨浩; 宋春利; 王梦昌

    2002-01-01

    目的观察诱导凋亡剂雄黄对耐维甲酸(ATRA)的急性早幼粒细胞白血病(APL)的治疗效果及毒副作用.方法对比应用雄黄治疗APL2 0例前后结果.结果完全缓解(CR)17例,部分缓解(PR)1例,总有效率(CR +PR)90%.结论雄黄对ATRA耐药的APL仍有较高的缓解率,二者无交叉耐药,毒性小,适用于临床推广应用.

  9. Estudio de diseño y plan de marketing de un nuevo verdejo frizzante de bodegas Rodriguez Sanzo

    OpenAIRE

    Calvo Gómez, Diego

    2015-01-01

    Dada la difícil situación del mercado de vino en España, donde cada vez se consume menos vino, sobre todo la gente joven, que no se siente atraída por él y beben otras bebidas alcohólicas como la cerveza principalmente; se busca un nuevo producto que les sea más atractivo. Se decidió elaborar un vino verdejo frizzante, por lo de moda que se está poniendo este tipo de productos y así conseguir llegar a un nicho de población que no suele ser consumidor habitual de vinos tranquilos convencion...

  10. Immunomodulatory effects of honey cannot be distinguished from endotoxin

    DEFF Research Database (Denmark)

    Timm, Michael; Bartelt, Stine; Hansen, Erik Wind

    2008-01-01

    In recent years, the use of honey has re-emerged as a remedy for wound treatment. Effects of honey have been related to the presence of an unidentified component that induces release of inflammatory cytokines from monocytic cells. The present study was intended to further characterize the reported...... in vitro effects of honey. Our results show that natural honeys induce interleukin-6 release from Mono Mac 6 cells as well as release of reactive oxygen species from all-trans retinoic acid (ATRA) differentiated HL-60 cells. The natural honeys contained substantial amounts of endotoxin, and the...... responses observed in the cell based assays were similar to the responses induced by endotoxin alone. In addition, we determined that the immunomodulatory component present in the natural honeys was retained in the ultra filtrated fraction with a molecular weight greater than 20 kDa. The component was...

  11. Materiales nanoestructurados céramicos como vehículo para la liberación de principios activos

    OpenAIRE

    Marlene Lariza Andrade Guel; Lourdes Díaz Jiménez; Dora Cortés Hernández

    2013-01-01

    Los materiales nanoestructurados han atraído especial atención debido a sus propiedades químicas y físicas que permiten nuevas aplicaciones en campos de la medicina y farmacología como vehículos para la liberación de principios activos que ayudan a transportarlos al sitio de interés controlando la dosificación. Algunos materiales nanoestructurados como dióxido de titanio TiO2, dióxido de zirconio ZrO2, dióxido de silicio SiO2 o hidróxidos dobles laminares, destacan por sus propiedades y aplic...

  12. El desarrollo de habilidades lingüísticas en el marco de la alfabetización digital : una investigación con la lectura de "La isla del Tesoro"

    OpenAIRE

    Garre Marín, Raúl

    2015-01-01

    Con esta tesis doctoral se pretende incidir en la relación que el uso de las tecnologías de la información y de la comunicación y de formatos por los que los jóvenes se sienten atraídos (videojuegos, cine, cómics) tiene con el desarrollo de las habilidades lingüísticas del alumnado, frente al uso de formatos analógicos tradicionales. Se sostiene la idea de que, ante las nuevas formas de lectura y escritura impuestas en la sociedad por el masificado uso de las tecnologías de la información y d...

  13. Flotação com amina: a importância da qualidade da água Amine flotation: the importance of the water quality

    OpenAIRE

    Viviane da Silva Pinheiro; Carlos Adolpho Magalhães Baltar; José Yvan Pereira Leite

    2012-01-01

    Enquanto há disponibilidade de sítios na superfície mineral, a adsorção da amina é não específica, motivada pela atração eletrostática com a superfície. Espécies catiônicas dissolvidas na água competem com o íon coletor pelos sítios negativos da superfície mineral. Esse fato evidencia a importância da composição química da água no resultado de uma flotação com amina. Estudou-se a flotação de quartzo, com amina, usando-se três diferentes águas: (1) uma água dura proveniente de Currais Novos (R...

  14. Revisão do gênero Mecocephala Dallas, 1851 (Heteroptera, Pentatomidae

    Directory of Open Access Journals (Sweden)

    Cristiano Feldens Schwertner

    2002-01-01

    Full Text Available Revision of the genus Mecocephala Dallas, 1851 (Heteroptera, Pentatomidae. The genus Mecocephala Dallas, 1851 is revised, and some taxonomic and geographical distribution data are evaluated. The following species are considered to belong to this genus: M. acuminata Dallas, 1851 = M. holmbergi Pirán, 1969 syn. nov., M. curculionoides Pirán, 1959, M. bonariensis sp. nov., M. magna sp. nov., M. maldonadensis sp. nov., and M. zikani sp. nov.; their distribution is restricted to southern Neotropical Region. Other species, formerly placed in Mecocephala, are considered, respectively: M. rubripes Berg, 1894 incertae sedis, M. darwini Kirkaldy, 1909 incertae sedis, M. atra Bergroth, 1914 incertae sedis, Paramecocephala uruguayensis (Pirán, 1970 comb. nov., Paramecocephala fusca (Haglund, 1868 comb. nov. A key to the species is presented.

  15. Esterificação heterogênea de ácidos graxos livres em óleos residuais de fritura / Heterogeneous esterification of free fatty acids in waste frying oils

    OpenAIRE

    Camila da Silva; Djessica Tatiana Raspe; Carolina Fernanda Sengling Cebin; Talita Amabile da Silva Colonelli

    2012-01-01

    ResumoO biodiesel (ésteres de ácidos graxos) tem atraído considerável atenção como combustível renovável, biodegradável e não tóxico. Tal ponto justifica o crescente interesse no desenvolvimento de tecnologias referentes à produção deste biocombustível em diversos países e no âmbito nacional. Com a grande variedade de substratos para a produção deste biocombustível, aumenta-se o interesse no estudo da reação de esterificação, como um processo prévio a transesterificação quando os substratos a...

  16. Medida da satisfação em relacionamento de casal Measure of the satisfaction in couple relationship

    OpenAIRE

    João Fernando Rech Wachelke; Alexsandro Luiz de Andrade; Roberto Moraes Cruz; Robson Brino Faggiani; Jean Carlos Natividade

    2004-01-01

    O objetivo deste estudo é descrever a construção e validação de uma escala de satisfação em relacionamento de casal, composta por subescalas capazes de medir aspectos componentes da satisfação com relacionamento. Para constituir a Escala Fatorial da Satisfação em Relacionamento de Casal foram elaborados nove itens, no formato escala de Likert de 5 pontos, divididos em dois fatores após a realização da análise dos componentes principais e análise fatorial, Satisfação com Atração Física e Sexua...

  17. Contrarios y aprendizaje : preferencia por las diferencias salientes entre objetos

    OpenAIRE

    Llach Carles, Sílvia; Ribot i Mundet, Maria Dolors de

    2010-01-01

    A partir de la hipótesis de que los contrarios son un elemento adecuado para las tareas de aprendizaje, en este estudio se ha investigado la respuesta de niños y adultos ante una serie de estímulos que se han agrupado en más opuestos y menos opuestos. La finalidad de este trabajo es investigar si los sujetos analizados se sienten más atraídos por los objetos que muestran una relación de oposición mayor que los que no la muestran. Los resultados evidencian que los niños escogen más los contrar...

  18. O Turismo, o Turista e a (Pós)Modernidade

    OpenAIRE

    Fortuna, Carlos; Ferreira, Claudino

    1996-01-01

    O turismo é um fenómeno que tem atraído um notável esforço de análise sociológica nos últimos anos. Recorrendo a um conjunto de contributos recentes da sociologia, em geral, e das sociologias da cultura, do lazer e do turismo, em particular, a comunicação comenta algumas das orientações que se têm revelado heuristicamente mais valiosas para a análise do fenómeno turístico. Procura-se, sobretudo, delinear os principais factores que ajudam à compreensão das práticas e das experiê...

  19. Atividade e moléculas antioxidantes de cogumelos silvestres comestíveis do género Agaricus

    OpenAIRE

    Martins, Anabela; Pereira, Eliana; Barros, Lillian; Isabel C. F. R. Ferreira

    2012-01-01

    Os cogumelos contêm vários compostos antioxidantes nomeadamente, compostos fenólicos (e.g. ácidos fenólicos), tocoferóis e carotenóides. Entre as substâncias biologicamente ativas presentes nos cogumelos, os compostos fenólicos têm atraído muita atenção devido às suas excelentes propriedades como antioxidantes e ao seu potencial anti-inflamatório ou antitumoral [1,2]. Neste trabalho, foi avaliado o potencial antioxidante de seis espécies silvestres comestíveis do género Agaricus: Agaricus bis...

  20. Arsenic trioxide: impact on the growth and differentiation of cancer cells and possible use in cancer therapy

    Directory of Open Access Journals (Sweden)

    Ewelina Hoffman

    2013-08-01

    Full Text Available Arsenic trioxide (As2O3 has recently been identified as an effective drug in different types of cancer therapy. It is a useful pharmacological agent in acute promyelocytic leukemia (APL treatment, especially the form that is resistant to conventional chemotherapy with all-trans retinoic acid (ATRA. What is more, laboratory data suggest that As2O3 is also active when it comes to several solid tumor cell lines. However, the mechanism of action is not fully understood. As2O3 in high doses triggers apoptosis, while in lower concentrations it induces partial differentiation. The As2O3 mechanism of action involves effects on mitochondrial transmembrane potential which lead to apoptosis. It also acts on the activity of JNK kinase, glutathione, caspases, NF-ĸB nuclear factor or pro- and antiapoptotic proteins. This publication presents the current knowledge about the influence of arsenic trioxide in cancer cells.

  1. Acute Promyelocytic Leukemia Presenting with Severe Marrow Fibrosis

    Directory of Open Access Journals (Sweden)

    Harsh Shah

    2015-01-01

    Full Text Available We report a case of acute promyelocytic leukemia (APL presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA- containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

  2. Proceso de transformación del territorio rural del distrito de santa marta

    Directory of Open Access Journals (Sweden)

    Antonio Navarro Hernández

    2014-02-01

    Full Text Available Através del tiempo, el área rural del Distrito de Santa Marta ha sido objeto de sucesivas ocupaciones por grupos poblacionales que atraídos por la oferta natural de sus recursos, procuraronla satisfacción de sus necesidades usufructuando de la misma con sistemas de producción que si hien contribuyeron al desarrollo económicos local, en la mayoría de las veces lesionaron la dinámica ambiental del entorno, dando lugar a alteraciones que se sienten más allá del medio en donde se realiza la explotación de tales recursos.

  3. Malária e aspectos hematológicos em moradores da área de influência dos futuros reservatórios das hidrelétricas de Santo Antônio e Jirau, Rondônia, Brasil Malaria and hematological aspects among residents to be impacted by reservoirs for the Santo Antônio and Jirau Hydroelectric Power Stations, Rondônia State, Brazil

    OpenAIRE

    Tony Hiroshi Katsuragawa; Roberto Penna de Almeida Cunha; Daniele Cristina Apoluceno de Souza; Luiz Herman Soares Gil; Rafael Bastos Cruz; Alexandre de Almeida e Silva; Mauro Shugiro Tada; Luiz Hildebrando Pereira da Silva

    2009-01-01

    Em Rondônia, prevê-se a construção de mais duas usinas hidrelétricas (UHE) no rio Madeira, a montante da cidade de Porto Velho, Rondônia, Brasil (de Santo Antônio e Jirau). O objetivo deste trabalho foi analisar a prevalência da malária antes do início da implantação das obras civis e fazer considerações sobre os impactos da doença com o ingresso de milhares de trabalhadores e agregados atraídos pelas oportunidades de emprego e comércio. Os resultados obtidos mostram que a malária se faz pres...

  4. Avian influenza in wild waterfowl and shorebirds in the Donana National Park: Serological survey using the enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Astorga, R J; Leon, L; Cubero, M J; Arenas, A; Maldonado, A; Tarradas, M C; Perea, A

    1994-06-01

    The indirect ELISA was used to detect antibodies to influenzavirus A in the sera of wildfowl from the Donana National Park. Of the 712 birds examined, 44 (6.2%) were seropositive. Positive birds belonged to 10 of the 13 species studied. Infection rates varied widely: spoonbill (Platalea leucorodia, 32.2%), mallard (Anas platyrhynchos, 9.9%), gadwall (Anas strepera, 8.6%), red-crested pochard (Netta rufina, 8.1%), pochard (Aythya ferina, 6.4%), shoveler (Anas clypeata, 5%), great crested grebe (Podiceps cristatus, 4.3%), avocet (Recurvirostra avosetta, 3.1%), grey heron (Ardea cinerea, 3.1%) and coot (Fulica atra, 0.8%). Although infection rates were not high, the wide range of avian species susceptible to influenzavirus A suggests circulation of the virus amongst wildfowl at Donana. PMID:18671098

  5. Marca e Imagem de um País: Considerações sobre a Copa do Mundo de 2014 e a Promoção do Brasil.

    OpenAIRE

    Marco Antonio Ocke

    2013-01-01

    O marketing de lugares com foco na promoção da imagem de cidades, estados e países enfoca a utilização das atividades de marketing como forma de contribuir com o desenvolvimento socioeconômico da região captando recursos e investimentos através da construção de uma imagem forte e a conseqüente atração de seus públicos de interesse. Como metodologia, o artigo parte de uma revisão da literatura da gestão de imagem e marca-país, passando pelo estudo de casos das Copas do Mundo de Futebol da FIFA...

  6. El mundo de la prensa rosa: análisis del discurso escrito en la revista ¡Hola!

    OpenAIRE

    Roy-Orenes, Chloé

    2012-01-01

    Hoy en día, vivimos en una sociedad cada vez más atraída por los medios de comunicación como la televisión, el cine, la radio y la prensa, lo que los especialistas denominan mass media o medios de comunicación de masas. Básicamente, diremos que unos emisores mínimos transmiten mensajes a una mayoría de receptores, la denominada sociedad de masas. En España, en los inicios de los años 40 del siglo xx, nació el género periodístico denominado prensa rosa, entendiendo por este nombre la que se de...

  7. Lichens from Antalya, Cankiri, Konya and Nevsehir Provinces (Turkey).

    Science.gov (United States)

    Yazici, K; Aslan, A; Etayo, J; Giordani, P

    2008-09-15

    A contribution to the lichen flora of Turkey is performed. A total of 171 lichen taxa (including 2 subspecies and 2 varieties) and 1 lichenicolous fungus are determined from 14 localities in Antalya, Cankiri, Konya and Nevşehir provinces of Turkey. Caloplaca scrobiculata H. Magn. is new to Turkey. Besides Caloplaca scrobiculata H. Magn. and Xanthoria sorediata (Vain.) Poelt were found for the second time in Asia. Carbonea vitellinaria (Nyl.) Hertel was found to grow on Candelariella vitellina (Hoffm.) Müll. Arg. while Muellerella pymaea (Körb.) D. Hawksw. var. athallina (Müll. Arg.) Triebel (lichenicolous fungus) on Tephromela atra (Huds.) Hafellner as parasitic. All lichen taxa found in Cankiri are new to this province (92 intraspecific taxa), while 39 new to Nevşehir, 8 new to Konya and 5 new to Antalya provinces. For every each taxon, the habitat pattern and distribution data are presented. PMID:19137828

  8. La nueva prefectura de Bamberg, Alemania

    Directory of Open Access Journals (Sweden)

    Haindl, Friedrich F.

    1968-10-01

    Full Text Available This building has two basements, and five storeys. The lower floors contain the standard installations and services, and underground car park and the registry. The ground floor and higher storeys are devoted to offices, and a dining room and lecture hall are situated on the top floor. The building has an attractively simple aspect.El inmueble consta de: dos sótanos, planta baja, y cuatro plantas de altura. Los niveles inferiores contienen: los cuartos de las instalaciones del edificio, aparcamiento subterráneo, etc.; y el Registro. La planta baja y las cuatro superiores albergan los despachos; y la cuarta, además, aloja un comedor y una sala de conferencias. El edificio atrae por su elegante sencillez.

  9. [Characterization of Campylobacter spp. from wild birds].

    Science.gov (United States)

    Glünder, G

    1989-02-01

    Bacteria of the genus Campylobacter were isolated from 28 Rooks (Corvus frugilegus), 1 Red Kite (Milvus milvus), 1 Lapwing (Vanellus vanellus), 1 Coot (Fulica atra), 1 Common Moorhen (Gallinula chloropus) and 1 Northern Mallard (Anas platyrhynchos). Altogether, C. jejuni biovar 1, was isolated 19x, C. jejuni biovar 2 8x and C. coli 5x. Among C. jejuni biovar 1 and 2 there were 5 isolates tolerating a content of 1.5% NaCl in the medium. H2S proof of 3 C. jejuni biovar 2 and 1 C. coli isolates resulted positive or negative dependent on incubation time of the used bacterial inoculum. Concerning Rooks the findings indicate that nestlings are more often infected with campylobacters than older birds. Only 1 campylobacter isolate could be recovered from altogether 54 birds of prey although 16 Buzzards (Buteo buteo) were investigated as nestlings. PMID:2930449

  10. Reacciones de formación de enlaces C-C catalizadas por metales de transición y factores que les afectan

    OpenAIRE

    Noverges Pedro, Bárbara

    2015-01-01

    La síntesis y funcionalización de compuestos carbonílicos ha atraído la atención de los químicos a lo largo del tiempo ya que el grupo carbonilo es una función muy versátil en química orgánica y está presente en numerosos compuestos con actividad biológica. Por su parte, las reacciones de acoplamiento cruzado de dos y tres componentes son metodologías que actualmente se aplican a nivel tanto académico como industrial debido a que requieren condiciones suaves de reacción, la extracción de los ...

  11. Morphological and acoustic characters of Cicadatra platyptera Fieber, 1876

    Directory of Open Access Journals (Sweden)

    Abbas Mol

    2013-04-01

    Full Text Available Acoustic and morphological characters are very important to distinguish species of Cicadidae. In this study, the morphological and acoustic characters of Cicadatra platyptera Fieber, 1876 (Hemiptera, Cicadidae collected from Turkey were analysed. The external morphological structures of two species were drawn and photographs of some specimens were taken. We evaluated taxonomically important morphological characters such as body shape, colors, patterns, structure, and genital structure. We evaluated measurements of external morphological structures and acoustics characters of C. platyptera from Turkey, partly with statistical analyses. Morphological characters were compared and differentiated from the closely related species, C. atra. The distribution in Turkey including previous records and the material examined were shown on a map, and the distribution in Palearctic Region was given.

  12. Cryptic PML-RARα positive acute promyelocytic leukemia with unusual morphology and cytogenetics

    Directory of Open Access Journals (Sweden)

    Goyal Manu

    2010-10-01

    Full Text Available Acute Promyelocytic Leukemia (APL is different from other forms of acute myeloid leukemia (AML, to the reason being the potential devastating coagulopathy and the sensitivity to all-trans retinoic acid (ATRA and arsenic trioxide (As 2 O 3 . We hereby present a case of APL, morphologically distinct from the hypergranular APL; however, the flow cytometry revealed a characteristic phenotype showing dim CD45, bright CD13, bright CD33 and dim CD117 positivity. These were negative for CD34, HLA-DR, B-lymphoid and T-lymphoid lineage markers. Conventional cytogenetics revealed a distinct karyotype of a male with translocation t(4;15(q34.2:q26.3. However, interphase florescence-in-situ hybridization (FISH revealed PML/RARA fusion signal on chromosome 15 in 90% cells. The cryptic translocations may be missed on conventional cytogenetics, however, need to be picked by other techniques as FISH.

  13. Arsenic in the cerebrospinal fluid of a patient receiving arsenic trioxide for relapsed acute promyelocytic leukemia with CNS involvement.

    Science.gov (United States)

    Knipp, Sabine; Gattermann, Norbert; Schapira, Marc; Käferstein, Herbert; Germing, Ulrich

    2007-11-01

    We report on a 42-year-old patient whose relapse of acute promyelocytic leukaemia (APL) included meningeal infiltration. Since he had previously experienced ATRA syndrome, he received arsenic trioxide (ATO) plus intrathecal therapy with cytarabine, prednisone, and methotrexate. We measured the concentration of arsenic in his cerebrospinal fluid (CSF). Arsenic showed a peak CSF concentration of 0.008 mg/l (0.11 micromol/l) and a nadir of 0.002 mg/l (0.027 micromol/l), both representing about 14% of blood levels. ATO thus crosses the blood-CSF-barrier when administered intravenously, but the concentration in CSF is probably not sufficient for treatment of meningeal leukemia. PMID:17416415

  14. Do paradigma molecular ao impacto no prognóstico: uma visão da leucemia promielocítica aguda From the molecular model to the impact on prognosis: an overview on acute promyelocytic leukemia

    OpenAIRE

    Rafael Henriques Jácomo; Lorena Lobo de Figueiredo-Pontes; Eduardo Magalhães Rego

    2008-01-01

    A leucemia promielocítica aguda (LPA) é um modelo da aplicabilidade clínica dos conhecimentos moleculares fisiopatológicos. Caracteriza-se por alterações genéticas recorrentes que envolvem o gene do receptor alfa do ácido retinóico. A conseqüência é uma proteína com sensibilidade reduzida ao ligante, com bloqueio da diferenciação mielóide. Entretanto, doses suprafisiológicas do ácido all-trans-retinóico (ATRA) são capazes de suplantar esta deficiência, e este é o princípio fundamental do trat...

  15. Prevenção primária de doenças cardiovasculares na obesidade infantojuvenil: efeito anti-inflamatório do exercício físico Early prevention of cardiovascular diseases in juvenile obesity: the anti-inflammatory effect of physical exercise

    OpenAIRE

    Márcia Braz Rossetti; Raquel Rodrigues Britto; Rocksane de Carvalho Norton

    2009-01-01

    A pandemia da obesidade juvenil e do sedentarismo está relacionada com o maior risco de doenças cardiovasculares no futuro. Ambas com fisiopatologia inflamatória, essas condições têm atraído significativa atenção científica. O início dos eventos que agridem o endotélio vascular pode ocorrer na infância, porém, sinais clínicos da aterosclerose geralmente só aparecem na fase adulta. O tecido adiposo é hoje reconhecido por seu papel ativo, induzindo a produção de citocinas pró e anti-inflamatóri...

  16. Nepotismo e poder na Arquidiocese de Braga (1245-1374)

    OpenAIRE

    Costa, Maria Antonieta Moreira da

    2005-01-01

    O estudo do nepotismo no seio da Igreja Católica da Idade Média tem atraído alguns investigadores alemães, ingleses e italianos, mas no caso português são poucos os autores que mencionam esta prática, dedicando-lhe apenas vagas referências em obras de carácter geral. Actualmente, o conhecimento do uso deste costume pode trazer à luz do dia uma outra realidade para além da tradicional história política e institucional do Estado Pontifício. Pode revelar-nos outros canais de exercício do poder e...

  17. La educación laica y el proyecto educativo velasquista en el Ecuador, 1930-1950

    OpenAIRE

    Rosemarie Terán Najas; Guadalupe Soasti Toscano

    2006-01-01

    Este estudio analiza la política educativa de Velasco Ibarra durante sus dos primeros gobiernos 0934-1935 y 1944-1947) Y las tensiones que mantuvo con la educación laica, instituida décadas atrás por la Revolución Liberal. Con este pro- pósito, el artículo examina la función que la educación tuvo en el ideario velasquista, empeñado en la reconstitución del orden moral de la sociedad. El ensayo interroga el proyecto de despolitización de la educación y de respaldo a la educación ...

  18. Mosquitoes of the mangrove forests of India: part six--Kundapur, Karnataka and Kannur, Kerala.

    Science.gov (United States)

    Rajavel, A R; Natarajan, R; Vaidyanathan, K

    2006-12-01

    Mosquitoes of 26 species belonging to 16 subgenera and 11 genera were recorded in the Kundapur mangroves of Karnataka, and 17 species belonging to 11 subgenera and 7 genera were recorded in the mangroves of Kannur, Kerala along the west coast of India. Genera recorded were Aedes, Anopheles, Armigeres, Culex, Heizmannia, Lutzia, Mansonia, Ochlerotatus, Tripteroides, Uranotaenia, and Verrallina. Species common to both mangrove forests were Ae. albopictus, Ae. vittatus, An. jamesi, Ar. subalbatus, Cx. gelidus, Cx. infantulus, Cx. pseudovishnui, Cx. sitiens, Cx. tritaeniorhynchus, Oc. wardi, Ur. atra, and Ve. luguhris. Tree holes and swamp pools were the common larval habitats, with more species occurring in tree holes in Kundapur than in Kannur. Adults of Ae. albopictus, Ae. vittatus, Ar. aureolineatus, Ar. subalbatus, Cx. bitaeniorhynchus, Cx. sitiens, Ma. uniformis, and Ve. lugubris bloodfed on humans. PMID:17304922

  19. Mechanism of retinoid receptors in inhibiting proliferation and inducing apoptosis of human melanoma cell line A375

    Institute of Scientific and Technical Information of China (English)

    NIU Xin-wu; PENG Zhen-hui; FENG Jie; MA Hui-qun; LIU Chao; YUAN Jing-yi

    2005-01-01

    @@ Malignant melanoma is a common cancer of skin. Its incidence is growing rapidly in recent years,1 however, there is no effective therapy for this cancer. Retinoids are metabolites or derivatives of vitamin A. They are essential for growth, differentiation, and maintenance of epithelial tissues.2 Previous studies showed that retinoids could inhibit growth of many kinds of malignant tumor cell lines and induce its apoptosis,3,4 including malignant melanoma cell lines.5 Some retinoids have therapeutic action to malignant melanoma, such as all-trans retinoic acid (ATRA) and 13-cis-RA.6,7 Retinoids take effects mainly through two kinds of nuclear receptors, retinoic acid receptor (RAR) and retinoic acid X receptor (RXR). In this study, we have investigated the effects of diverse retinoids and receptor agonists in inhibiting proliferation and inducing apoptosis of human melanoma cell line A375.

  20. Dissolução e reativação de relacionamentos cliente-empresa: estudo exploratório

    OpenAIRE

    Lopes, Luísa; Brito, Carlos Henrique; Alves, Helena

    2012-01-01

    Os mercados apresentam hoje em dia elevados níveis de competição que, com frequência, dão origem a menores índices de lealdade por parte dos clientes. Isto significa que o sucesso empresarial depende não só da atração e retenção de clientes, mas também da prevenção e gestão do abandono (churn) e da recuperação de clientes perdidos (win-back). Este estudo tem por objetivo explorar a dinâmica dos relacionamentos com o cliente na fase pós-dissolução. Com base numa revisão de literatura, em conte...

  1. El Valor de una Obra de Arte: Estrategias de Comunicación para Influenciar su Valor de Mercado

    OpenAIRE

    Batllori Lloveras, Gloria

    2016-01-01

    En los últimos años el ambiente de los mercados financieros ha cambiado drásticamente con la venida de nuevas tecnologías y la expansión económica. La sofisticación de los mercados financieros ha atraído la atención del público hacia los nuevos instrumentos y prácticas financieras, las obras de arte que se ven ahora como una inversión alternativa. La proliferación y sofisticación de los mercados de arte ha sido objeto de muchos estudios académicos que han ido analizando el funcionamiento...

  2. La pulverización electrostática de agroquímicos: teoría, evaluaciones y aplicaciones en el sector agrícola

    OpenAIRE

    Aristizábal Torres, Iván Darío

    2008-01-01

    Resumen: La pulverización electrostática es una técnica para la aplicación de productos químicos mediante la cual se transfieren cargas eléctricas a las gotas atomizadas para que éstas sean atraídas por un blanco biológico, lográndose mayor cobertura y deposición del producto asperjado, disminuyendo la dosis requerida para el tratamiento y reduciendo la pérdida de producto químico arrojado al ambiente. Los conceptos utilizados en la fumigación electrostática no son nuevos, por ejemplo, los au...

  3. La Universidad como espacio de mediación cultural

    Directory of Open Access Journals (Sweden)

    Willem FRIJHOFF

    2010-03-01

    Full Text Available RESUMEN: Los organizadores de este congreso me han concedido el tremendo honor de situar mi conferencia al final de nuestros trabajos, incluso recortando el tiempo disponible hasta un punto extremo. Me atrae la tentación de entregar un breve resumen de lo que se ha dicho y tratado, y ello porque algunas de las contribuciones que aquí se han presentado cosquillean, incluso provocan hasta un grado difícil de aguantar la conciencia profesional del historiador que soy. No se me ha pedido preparar una síntesis o una réplica. Por eso no lo haré. Al menos en la forma debida, porque tampoco puedo escabullirme del todo. ¿No es acaso la historia, como decía mi compatriota, el eminente historiador de la cultura que era Johan Huizinga, «una perpétua discusión»?

  4. Adaptación para multiples GPU de un simulador de actividad eléctrica en el corazón

    OpenAIRE

    García Mollá, Víctor Manuel; Vidal Maciá, Antonio Manuel; Liberos Mascarell, Alejandro; Climent, Andreu M.

    2013-01-01

    La simulación de la actividad eléctrica del corazón se calcula mediante la resolución de un gran sistema de ecuaciones diferenciales ordinarias, que necesita una enorme cantidad de tiempo de computación. Sin embargo, en los últimos años se están introduciendo, en el ámbito de la computación de alto rendimiento, las unidades de procesamiento gráfico (GPU). Estos potentes dispositivos han atraído a grupos de investigación que requieren simular la actividad eléctrica del corazón. El grupo de inv...

  5. EVALUACIÓN DE UNA FORMULACIÓN ATRACTICIDA PARA CONTROL DE Cydia pomonella (L. (Lepidoptera: Tortricidae EN MANZANOS EN EL ESTADO DE WASHINGTON, EEUU Assessment of an attracticide formulation to control Cydia pomonella (L. (Lepidoptera: Tortricidae in apple orchards in Washington State, USA.

    Directory of Open Access Journals (Sweden)

    Tomislav Curkovic S.

    2003-07-01

    Full Text Available Se evaluó la actividad de un atracticida (Sirene®CM: 0,16% codlemone + 6% permetrina en el control y atracción de machos de Cydia pomonella. Los machos fueron atraídos por un período prolongado (> 80 días hacia las trampas con el atracticida. Sólo una pequeña proporción ( 2,5 m.Cydia pomonella control and male attraction of an attracticide (Sirene®CM: 0.16% codlemone + 6% permethrin were evaluated. The attracticide had a long-lasting attraction (> 80 days for males to regular traps. Only a small proportion of males ( 2.5 m.

  6. Retinoid-like activity and teratogenic effects of cyanobacterial exudates.

    Science.gov (United States)

    Jonas, Adam; Buranova, Veronika; Scholz, Stefan; Fetter, Eva; Novakova, Katerina; Kohoutek, Jiri; Hilscherova, Klara

    2014-10-01

    Retinoic acids and their derivatives have been recently identified by chemical analyses in cyanobacteria and algae. Given the essential role of retinoids for vertebrate development this has raised concerns about a potential risk for vertebrates exposed to retinoids during cyanobacterial blooms. Our study focuses on extracellular compounds produced by phytoplankton cells (exudates). In order to address the capacity for the production of retinoids or compounds with retinoid-like activity we compared the exudates of ten cyanobacteria and algae using in vitro reporter gene assay. Exudates of three cyanobacterial species showed retinoid-like activity in the range of 269-2,265 ng retinoid equivalents (REQ)/L, while there was no detectable activity in exudates of the investigated algal species. The exudates of one green alga (Desmodesmus quadricaudus) and the two cyanobacterial species with greatest REQ levels, Microcystis aeruginosa and Cylindrospermopsis raciborskii, were selected for testing of the potential relation of retinoid-like activity to developmental toxicity in zebrafish embryos. The exudates of both cyanobacteria were indeed provoking diverse teratogenic effects (e.g. tail, spine and mouth deformation) and interference with growth in zebrafish embryos, while such effects were not observed for the alga. Fish embryos were also exposed to all-trans retinoic acid (ATRA) in a range equivalent to the REQ concentrations detected in exudates by in vitro bioassays. Both the phenotypes and effective concentrations of exudates corresponded to ATRA equivalents, supporting the hypothesis that the teratogenic effects of cyanobacterial exudates are likely to be associated with retinoid-like activity. The study documents that some cyanobacteria are able to produce and release retinoid-like compounds into the environment at concentrations equivalent to those causing teratogenicity in zebrafish. Hence, the characterization of retinoid-like and teratogenic potency should be

  7. JWA,a novel microtubule associate protein,participates cell differentiation signal pathways and also functions as a modulator of amino acid transportation in PC12 cells

    Institute of Scientific and Technical Information of China (English)

    ZhouJW; QunLA

    2002-01-01

    JWA,a novel putative cytoskeleton associated and retinoic acid responsible gene,primarily cloned from ex vivo cultured human tracheal bonchial epithelial cells (1998,GenBank:AF070523).Very little is known of its critical biological function although several homologues of JWA have been identified recently.Our previous data have shown that JWA is widely distributed in human tissues and not only responses to differentiating agents such as all trans retinoic acid (ATRA),13-cis retinoid acid(13-cis RA) and 12-O-tetradecanoyl phorbol-13-acetate(TPA),but actively responsible to environmental stress.In this study,in one hand,we use immuno-fluorescentmicroscopy and immunoprecipitation assay investigated the relationship between JWA and microtubule under treatments of depolymerizing agents (cochicine and nocodizol) and cool-shock.In another hand,we identified and analyzed the promoter sequence of JWA and its structure-based function in regulation of cell differentiation and apoptosis by ATRA,TPA,N-4-hydroxyphenyl-retinamide(4HPR),arsenic trioxide(As2O3) and cytosine arabinoside(Ara C) in NB4 and HL-60) cell lines,and responses to ervironmental stress.In addition,our accumulated evidences showed that JWA might be a stronger moulator which functions amino acids transportation in PC12 cells.It is suggested that JWA might involve in a crosstalk signal pathways in vivo,in vitro and ex vivo systems.Surprisingly,a proposed fusion-size JWA protein was found in both HL-60 cells and fresh APL cells and it might be a novel biomarker for the both.It may give us new insight in understanding the molecular mechanisms in both generation and development of human myeloid leukemia.

  8. Bebês: o irresistível poder da graciosidade. Um estudo sobre o significado evolutivo dos traços infantis Babies: the irresistible power of cuteness. A study concerning the evolutionary function of infantile traits

    Directory of Open Access Journals (Sweden)

    Monique Leitão

    2010-04-01

    Full Text Available Os bebês, em geral, despertam ternura e comportamentos de cuidado nas pessoas. O objetivo deste trabalho foi discutir a atração provocada pelos traços infantis, tendo como referencial teórico os quatro níveis de explicação de Tinbergen. Do ponto de vista dos mecanismos que desencadeiam essa atração neonatal, avaliamos a importância da aparência do infante para eliciar as respostas de cuidado parental. Considerando a função adaptativa desta característica, discutimos os processos evolutivos que moldaram as preferências pelos atributos infantis, além da história filogenética do favoritismo pelos sinais morfológicos de filhotes. Apresentamos, ainda, dados sobre o desenvolvimento deste traço comportamental ao longo da vida. Tomadas em conjunto, estas informações provêem uma análise de por que achamos os bebês tão irresistíveis.Babies generally elicit tenderness and caretaking behaviors on people. The aim of this study is to discuss the attraction towards babyish features, taking Tinbergen's four questions as a theoretical benchmark. Concerning the mechanisms implicated in this neonatal attraction, we evaluated the importance of children´s morphology on eliciting parental responses. Considering the adaptive function of this characteristic, we discuss the evolutionary process that shaped the preferences towards infantile traits as well as the phylogeny of the preference towards infant´s morphological traits. It was also presented data about the development of this behavioral trait across life span. The information provided here suggests a reason why we find babies such irresistible creatures.

  9. Co-expression of t(15;17 and t(8;21 in a Case of Acute Promyelocytic Leukemia: Review of the Literature

    Directory of Open Access Journals (Sweden)

    Burak Uz

    2013-12-01

    Full Text Available Additional chromosomal abnormalities in acute myelogenous leukemia have been identified as one of the most important prognostic factors. Favorable chromosomal changes such as t(8;21, inv(16, and t(15;17 are associated with higher rates of complete remission and event-free survival. Translocation (15;17 characterizes acute promyelocytic leukemia (APL (French- American-British class M3 in almost all patients. Secondary chromosomal abnormalities are also present in approximately 23%-29% of patients with newly diagnosed APL. The prognostic implications of t(8;21 and other secondary cytogenetic aberrations in APL are reviewed here. We present a 47-year-old woman diagnosed with APL whose initial cytogenetic analysis included both t(8;21 and t(15;17. The initial induction chemotherapy included 3 days of idarubicin (12 mg/m2/day and daily all-trans retinoic acid (ATRA; 45 mg/m2/day. At the sixth week of treatment, a control bone marrow biopsy was found to be normocellular, t(15;17 bcr3 and t(8;21 were negative, and t(15;17 bcr1 fusion transcripts were reduced from 5007 (1.78525699% copies per 1 μg RNA to 40 (0.00062020% with real-time quantitative polymerase chain reaction. Consolidation with 4 days of idarubicin (5 mg/m2/day, ATRA (45 mg/m2/day for 15 days, and cytarabine (1 g/m2/day for 4 days was then started. However, the patient became pancytopenic and had neutropenic fever after consolidation treatment. Unfortunately, she died 3 months after the time of APL diagnosis, due to acute respiratory distress syndrome-like respiratory problems and multiorgan dysfunction requiring respiratory support and hemodialysis.

  10. Pulmonary Administration of GW0742, a High-Affinity Peroxisome Proliferator-Activated Receptor Agonist, Repairs Collapsed Alveoli in an Elastase-Induced Mouse Model of Emphysema.

    Science.gov (United States)

    Ozawa, Chihiro; Horiguchi, Michiko; Akita, Tomomi; Oiso, Yuki; Abe, Kaori; Motomura, Tomoki; Yamashita, Chikamasa

    2016-01-01

    Pulmonary emphysema is a disease in which lung alveoli are irreversibly damaged, thus compromising lung function. Our previous study revealed that all-trans-retinoic acid (ATRA) induces the differentiation of human lung alveolar epithelial type 2 progenitor cells and repairs the alveoli of emphysema model mice. ATRA also reportedly has the ability to activate peroxisome proliferator-activated receptor (PPAR) β/δ. A selective PPARβ/δ ligand has been reported to induce the differentiation of human keratinocytes during wound repair. Here, we demonstrate that treatment using a high-affinity PPARβ/δ agonist, GW0742, reverses the lung tissue damage induced by elastase in emphysema-model mice and improves respiratory function. Mice treated with elastase, which collapsed their alveoli, were then treated with either 10% dimethyl sulfoxide (DMSO) in saline (control group) or GW0742 (1.0 mg/kg twice a week) by pulmonary administration. Treatment with GW0742 for 2 weeks increased the in vivo expression of surfactant proteins A and D, which are known alveolar type II epithelial cell markers. GW0742 treatment also shortened the average distance between alveolar walls in the lungs of emphysema model mice, compared with a control group treated with 10% DMSO in saline. Treatment with GW0742 for 3 weeks also improved tissue elastance (cm H2O/mL), as well as the ratio of the forced expiratory volume in the first 0.05 s to the forced vital capacity (FEV 0.05/FVC). In each of these experiments, GW0742 treatment reversed the damage caused by elastase. In conclusion, PPARβ/δ agonists are potential therapeutic agents for pulmonary emphysema. PMID:27150147

  11. Main-Chain and Side-Chain Sequence-Regulated Vinyl Copolymers by Iterative Atom Transfer Radical Additions and 1:1 or 2:1 Alternating Radical Copolymerization.

    Science.gov (United States)

    Soejima, Takamasa; Satoh, Kotaro; Kamigaito, Masami

    2016-01-27

    Main- and side-chain sequence-regulated vinyl copolymers were prepared by a combination of iterative atom transfer radical additions (ATRAs) of vinyl monomers for side-chain control and 1:1 or 2:1 alternating radical copolymerization of the obtained side-chain sequenced "oligomonomers" and vinyl comonomers for main-chain control. A complete set of sequence-regulated trimeric vinyl oligomers of styrene (S) and/or methyl acrylate (A) were first synthesized via iterative ATRAs of these monomers to a halide of monomeric S or A unit (X-S or X-A) under optimized conditions with appropriate ruthenium or copper catalysts, which were selected depending on the monomers and halides. The obtained halogen-capped oligomers were then converted into a series of maleimide (M)-ended oligomonomers with different monomer compositions and sequences (M-SSS, M-ASS, M-SAS, M-AAS, M-SSA, M-ASA, M-SAA, M-AAA) by a substitution reaction of the halide with furan-protected maleimide anion followed by deprotection of the furan units. These maleimide-ended oligomonomers were then radically copolymerized with styrene or limonene to enable the 1:1 or 2:1 monomer-sequence regulation in the main chain and finally result in the main- and side-chain sequence-regulated vinyl copolymers with high molecular weights in high yield. The properties of the sequence-regulated vinyl copolymers depended on not only the monomer compositions but also the monomer sequences. The solubility was highly affected by the outer monomer units in the side chains whereas the glass transition temperatures were primarily affected by the two successive monomer sequences. PMID:26761148

  12. Identification and characterization of nucleolin as a COUP-TFII coactivator of retinoic acid receptor β transcription in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Lacey M Litchfield

    Full Text Available INTRODUCTION: The orphan nuclear receptor COUP-TFII plays an undefined role in breast cancer. Previously we reported lower COUP-TFII expression in tamoxifen/endocrine-resistant versus sensitive breast cancer cell lines. The identification of COUP-TFII-interacting proteins will help to elucidate its mechanism of action as a transcriptional regulator in breast cancer. RESULTS: FLAG-affinity purification and multidimensional protein identification technology (MudPIT identified nucleolin among the proteins interacting with COUP-TFII in MCF-7 tamoxifen-sensitive breast cancer cells. Interaction of COUP-TFII and nucleolin was confirmed by coimmunoprecipitation of endogenous proteins in MCF-7 and T47D breast cancer cells. In vitro studies revealed that COUP-TFII interacts with the C-terminal arginine-glycine repeat (RGG domain of nucleolin. Functional interaction between COUP-TFII and nucleolin was indicated by studies showing that siRNA knockdown of nucleolin and an oligonucleotide aptamer that targets nucleolin, AS1411, inhibited endogenous COUP-TFII-stimulated RARB2 expression in MCF-7 and T47D cells. Chromatin immunoprecipitation revealed COUP-TFII occupancy of the RARB2 promoter was increased by all-trans retinoic acid (atRA. RARβ2 regulated gene RRIG1 was increased by atRA and COUP-TFII transfection and inhibited by siCOUP-TFII. Immunohistochemical staining of breast tumor microarrays showed nuclear COUP-TFII and nucleolin staining was correlated in invasive ductal carcinomas. COUP-TFII staining correlated with ERα, SRC-1, AIB1, Pea3, MMP2, and phospho-Src and was reduced with increased tumor grade. CONCLUSIONS: Our data indicate that nucleolin plays a coregulatory role in transcriptional regulation of the tumor suppressor RARB2 by COUP-TFII.

  13. Deficiency of retinaldehyde dehydrogenase 1 induces BMP2 and increases bone mass in vivo.

    Directory of Open Access Journals (Sweden)

    Shriram Nallamshetty

    Full Text Available The effects of retinoids, the structural derivatives of vitamin A (retinol, on post-natal peak bone density acquisition and skeletal remodeling are complex and compartment specific. Emerging data indicates that retinoids, such as all trans retinoic acid (ATRA and its precursor all trans retinaldehyde (Rald, exhibit distinct and divergent transcriptional effects in metabolism. Despite these observations, the role of enzymes that control retinoid metabolism in bone remains undefined. In this study, we examined the skeletal phenotype of mice deficient in retinaldehyde dehydrogenase 1 (Aldh1a1, the enzyme responsible for converting Rald to ATRA in adult animals. Bone densitometry and micro-computed tomography (µCT demonstrated that Aldh1a1-deficient (Aldh1a1(-/- female mice had higher trabecular and cortical bone mass compared to age and sex-matched control C57Bl/6 wild type (WT mice at multiple time points. Histomorphometry confirmed increased cortical bone thickness and demonstrated significantly higher bone marrow adiposity in Aldh1a1(-/- mice. In serum assays, Aldh1a1(-/- mice also had higher serum IGF-1 levels. In vitro, primary Aldh1a1(-/- mesenchymal stem cells (MSCs expressed significantly higher levels of bone morphogenetic protein 2 (BMP2 and demonstrated enhanced osteoblastogenesis and adipogenesis versus WT MSCs. BMP2 was also expressed at higher levels in the femurs and tibias of Aldh1a1(-/- mice with accompanying induction of BMP2-regulated responses, including expression of Runx2 and alkaline phosphatase, and Smad phosphorylation. In vitro, Rald, which accumulates in Aldh1a1(-/- mice, potently induced BMP2 in WT MSCs in a retinoic acid receptor (RAR-dependent manner, suggesting that Rald is involved in the BMP2 increases seen in Aldh1a1 deficiency in vivo. Collectively, these data implicate Aldh1a1 as a novel determinant of cortical bone density and marrow adiposity in the skeleton in vivo through modulation of BMP signaling.

  14. Inactivation of Vibrio cholerae O1 El Tor inoculated into Peruvian ''choro'' mussels (Aulacomya ater) and two species of clams (Argopecten purpuratus and Gari solida) using medium-dose irradiation

    International Nuclear Information System (INIS)

    The radiation decimal reduction dose (D10) for Vibrio cholerae O1 biotype El Tor inoculated through the natural feeding system into three species of bivalve mollusks from the Peruvian Pacific coast: ''choro'' mussels (Aulacome ater), ''abanico'' clams (Argopecten purpuratus), and common clams (Gari solida), was determined in vivo. The D10 value obtained in vivo was 0.14 kGy in all mollusks tested. Concurrent studies conducted to determine the potential use of irradiation to extend the microbiological shelf-life of the mollusks during post-irradiation storage at 0-1 deg. C indicated that a dose of 1.0 kGy was optimal for choro mussels and abanico clams, whereas 2.0 kGy produced the best results when treating common clams. Shelf-life extension thus achieved was 31 days for choro mussels, 16 days for abanico clams, and 21 days for common clams. Non-irradiated control samples of all mollusks spoiled after 17 days of refrigerated storage. There were no significant (p<.05) adverse effects from the application of the optimal radiation treatments on the sensory characteristics (i.e. appearance, odor, flavor, and texture) of the mollusks. Total volatile basic nitrogen (VBN) and pH values were examined for use as indexes of seafood freshness. (author)

  15. Study of apoptotic mechanisms induced by all-trans retinoic acid and its 13-cis isomer on cellular lines of human hepato carcinoma Hep3B and HepG2

    International Nuclear Information System (INIS)

    Two cellular lines of liver cancer (Hep3B and HepG2) were incubated during different periods of time with some concentrations of two retinoic acid isomers (ATRA and 13-cis AR) and with 5-fu chemotherapeutic agents, cisplatin and paclitaxel. It was determined if these substances leaded cytotoxicity, apoptosis and if they modified the expression of different genes related to cellular death by apoptosis, in order to explain the hepatocellular carcinoma resistance to these drugs. HepG2 cells showed more resistance than Hep3B cells to 72 hours of treatment, as much ATRA as the 13-cis AR were toxic and produced apoptosis in two cellular lines. This type of cellular death seems to be mediated by a decrease in Bcl-xL concentration in Hep3B cells treated with both retinoids an increase in bax concentration in HepG2 cells treated with 13-cis AR. It were observed 3 and 8 proteolysis of procaspase in Hep3B cells, suggesting extrinsic via activation of the apoptosis, while cellular death in HepG2 cells seems to be independent of caspases. Cisplatin and paclitaxel leaded cytotoxicity to 48 hours of treatment, with significant differences between two cellular lines only in case of paclitaxel. Hep3B cells treated with cisplatin and HepG2 cells treated with paclytaxel suffered apoptosis. 5-FU produced toxicity only when it was used to high concentrations and the mechanism of cellular death induced by this agent seems to be primarily necrosis in Hep3B cells and apoptosis in HepG2. There was decrease in the Bcl-xL concentration in two cellular lines when it was treated with cisplatin and in HepG2 cells treated with 5-FU. Bax concentration there no was modified with no treatment. Activation of the 3 caspases seems to happen only in HepG2 cells with 5-FU and paclytaxel. These two agents, also, decreased the survivin concentration of HepG2 cells. Treatments of the three drugs produced an increase in the expression of this gen in Hep3B cells, which might explain partially the resistance

  16. 人工饲料“富蛇康”养殖蛇蛇肉营养成分比较分析%Comparative Analysis on Meaty Nutrient Contents of Breeding Snake with Artificial Feed “FUSHEKANG”

    Institute of Scientific and Technical Information of China (English)

    蓝洲; 李其斌; 张剑锋; 冯德进; 宁宗; 王威

    2015-01-01

    目的:为了解人工饲料养殖蛇蛇肉的营养成分。方法检测由人工饲料“富蛇康”养殖的眼镜蛇和滑鼠蛇成商品蛇蛇肉的营养成分,如蛋白质、脂肪、氨基酸、糖、微量元素的含量,并与传统养殖方法(用小鸡、小白鼠等小动物喂养)的蛇以及野生蛇蛇肉营养成分进行比较分析。结果“富蛇康”养殖的眼镜蛇及滑鼠蛇蛇肉的蛋白质、脂肪、氨基酸、糖以及矿物质元素硒、铬、镁、铁、锌等含量与野生及传统养殖眼镜蛇和滑鼠蛇相比,除了脂肪和铁的含量偏高外其余无明显差异。结论“富蛇康”是价廉、物美、安全的蛇饲料,富蛇康养殖眼镜蛇及滑鼠蛇蛇肉与传统养殖及野生蛇蛇肉的营养价值大致相同。%Objective To understand the artificial feed breeding the snakes and its nutrients . Methods The snake meat nutrients content such as protein ,fat ,amino acid ,sugar ,and trace elements were be test and compared the nutrients of snake (Naj a naja atra and Ptyas mucosus) that breeding by artificial feed (Fushekang) with the snakes of traditional breeding method (with the chicken ,mice and other small animal feed) and wild snakes . Re‐sults The snake protein ,fat ,amino acid ,sugar and minerals element selenium ,chromium ,magnesium ,iron ,zinc content of breeding snake by artificial feed (Fushekang ) and compared to traditional breeding snake ,in addition to high fat and iron content no obvious difference was found between the rest of them . Conclusion Artificial feed (Fushekang) is a cheap ,safe snake feed ,breeding the snake of Naj a naj a atra and Ptyas mucosus which meat nu‐tritional value are the same as traditional breeding and wild snake .

  17. Música, comportamento social e relações interpessoais Music, social behavior and interpersonal relationships

    Directory of Open Access Journals (Sweden)

    Beatriz Ilari

    2006-04-01

    Full Text Available O objetivo desta investigação foi verificar o papel da música na atração interpessoal, escolha de parceiros e relacionamentos afetivos. Cinqüenta adultos não-músicos escolheram possíveis parceiros através de classificados pessoais, descreveram as características de ouvintes de 7 gêneros musicais diferentes e responderam a questões referentes ao uso da música em seus relacionamentos afetivos. Embora a música não tenha tido um efeito direto sobre a atração interpessoal e a escolha de parceiros, ela aparentou ter alguns efeitos indiretos nas relações interpessoais. Alguns estereótipos de personalidade associados aos gêneros musicais foram encontrados, sugerindo que o gosto musical pode influenciar na escolha de parceiros. Além disso, emergiram quatro categorias relacionadas ao uso da música no contexto das relações interpessoais: objetivos de excitação, fundo acústico, facilitadora de atividades que promovem a aproximação e artefato mnemônico. Os dados desta investigação reforçam a idéia de que a música exerce um papel importante nas relações interpessoais.The purpose of this study was to investigate the effects of music on interpersonal relationships by means of attraction, choice of partners, and romantic relationships. Fifty adult non-musicians chose potential partners in newspaper ads, described the characteristics of listeners of 7 different musical styles, and answered open-ended questions related to the uses of music in interpersonal relationships of a romantic nature. Although music did not seem to impact interpersonal attraction and choice of partners directly, it was found to impact social bonding in indirect ways. Personality types associated with musical styles emerged, suggesting that musical taste influences interpersonal relationships. Additionally, four categories related to the uses of music in the context of interpersonal relationships emerged including arousal goals, background, facilitator

  18. Nrf2 facilitates repair of radiation induced DNA damage through homologous recombination repair pathway in a ROS independent manner in cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jayakumar, Sundarraj; Pal, Debojyoti; Sandur, Santosh K., E-mail: sskumar@barc.gov.in

    2015-09-15

    Highlights: • Nrf2 inhibition in A549 cells led to attenuated DNA repair and radiosensitization. • Influence of Nrf2 on DNA repair is not linked to its antioxidant function. • Nrf2 influences DNA repair through homologous recombination (HR) repair pathway. • Many genes involved in HR pathway show ARE sequences in their upstream region. - Abstract: Nrf2 is a redox sensitive transcription factor that is involved in the co-ordinated transcription of genes involved in redox homeostasis. But the role of Nrf2 in DNA repair is not investigated in detail. We have employed A549 and MCF7 cells to study the role of Nrf2 on DNA repair by inhibiting Nrf2 using all-trans retinoic acid (ATRA) or by knock down approach prior to radiation exposure (4 Gy). DNA damage and repair analysis was studied by γH2AX foci formation and comet assay. Results suggested that the inhibition of Nrf2 in A549 or MCF7 cells led to significant slowdown in DNA repair as compared to respective radiation controls. The persistence of residual DNA damage even in the presence of free radical scavenger N-acetyl cysteine, suggested that the influence of Nrf2 on DNA repair was not linked to its antioxidant functions. Further, its influence on non-homologous end joining repair pathway was studied by inhibiting both Nrf2 and DNA-PK together. This led to synergistic reduction of survival fraction, indicating that Nrf2 may not be influencing the NHEJ pathway. To investigate the role of homologous recombination repair (HR) pathway, RAD51 foci formation was monitored. There was a significant reduction in the foci formation in cells treated with ATRA or shRNA against Nrf2 as compared to their respective radiation controls. Further, Nrf2 inhibition led to significant reduction in mRNA levels of RAD51. BLAST analysis was also performed on upstream regions of DNA repair genes to identify antioxidant response element and found that many repair genes that are involved in HR pathway may be regulated by Nrf2

  19. Pressure gradient of a two-region solid-liquid flow in horizontal wells; Gradiente de presion de un flujo bifasico solido-liquido de dos regiones en pozos horizontales

    Energy Technology Data Exchange (ETDEWEB)

    Salazar Mendoza, R.; Garcia Gutierrez, A. [Centro Nacional de Investigacion y Desarrollo Tecnologico (CENIDET), Cuernavaca, Morelos (Mexico); Espinosa Paredes, G. [Universidad Autonoma Metropolitana-Iztapalapa, Mexico, D.F. (Mexico)

    2005-12-01

    relacion de la altura del lecho estacionario y del diametro de la tuberia, y esta se basa en una aproximacion discreta hacia atras de diferencias finitas explicitas. El sistema fisico simulado se basa en una aproximacion discreta hacia atras de diferencias finitas explicitas. El sistema fisico simulado es una tuberia horizontal de 4.135 m de longitud y 0.0508 m de diametro. Se usa una cuadricula unidimensional de malla centrada de 10 nodos. Los resultados numericos se compararon con datos experimentales encontrandose una comparacion satisfactoria entre los perfiles medidos y los simulados.

  20. Black carbon simulations using a size- and mixing-state-resolved three-dimensional model: 2. Aging timescale and its impact over East Asia

    Science.gov (United States)

    Matsui, H.

    2016-02-01

    This study evaluates the aging timescale and the cloud condensation nuclei (CCN) activity of black carbon (BC) over East Asia and its outflow region using a size- and mixing-state-resolved three-dimensional model, the Weather Research and Forecasting model with chemistry (WRF-chem) with the Aerosol Two-dimensional bin module for foRmation and Aging Simulation (ATRAS) and the Model for Simulating Aerosol Interactions and Chemistry (MOSAIC). The WRF-chem/ATRAS-MOSAIC model explicitly calculates BC aging (condensation and coagulation) and removal processes, with 12 size and 10 BC mixing state bins (128 bins in total). The model reveals large spatial and temporal variability of the BC aging timescale and the CCN activity of BC-containing particles over East Asia (spring 2009) with their strong size and supersaturation dependence. The BC aging timescale differs from 0.19 to 3.1 days (period and domain average at an altitude of 1 km), depending on the choice of size (mass or number) and supersaturation (1.0% or 0.1%). As a result, almost 100% of BC-containing particles are CCN-active at a supersaturation of 1.0%, whereas 20-50% of BC-containing particles are CCN-inactive at a supersaturation of 0.1%, with a strong size dependence. These results show the importance of resolving BC aging processes and their dependence on size and supersaturation in models for more accurate simulations of BC concentrations and their distribution and lifetime. A sensitivity simulation without resolving BC mixing state shows the underestimation of total BC mass concentrations by 5-10% and the BC mass concentrations in the CCN-inactive particles (at a supersaturation of 0.1%) by 40-60% over the outflow region (at 150°E), compared with the simulation resolving BC mixing state. Because BC aging speed is very slow at 150°E and eastward, the change in BC mass and its CCN activity by resolving BC mixing state will continue over long distances and may have a large impact on BC transport from East