WorldWideScience

Sample records for aulacomya atra atra

  1. Biomarkers of environmental stress in gills of ribbed mussel Aulacomya atra atra (Nuevo Gulf, Northern Patagonia).

    Science.gov (United States)

    Giarratano, Erica; Gil, Mónica N; Malanga, Gabriela

    2014-09-01

    In this study, we assessed in gills of native ribbed mussels Aulacomya atra atra from three sites within Nuevo Gulf (Northern Patagonia) several biomarkers such as reactive oxygen species (ROS), lipid radicals (LR), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST) and metallothionein (MT). Furthermore, concentrations of main trace metals (Fe, Al, Zn, Cu, Cd and Pb) were quantified in mussel tissue. Results showed significant induction of SOD, GST, MT and MDA, as well as, higher concentration of Fe, Al and Cd in winter than in summer. The high MDA content measured in mussels from Folías Wreck seemed to be caused by the very high levels of Fe that would come from the corrosion of the vessel. Mussels from the control site Punta Cuevas presented the lowest levels of Cd and the highest of Al in winter. Despite positive correlations were found between Al and GST and MT, no spatial differentiation was detected in those biomarkers. On the other hand, MT was only related to Al been most likely influenced by environmental variables than by the trace metals. It has to be highlighted that the relationship detected among water temperature, nutrients and antioxidant responses in gills is probably related to the fact that this tissue is in direct contact with water and it is sensitive to its fluctuations. Taking into account that mussel gill is a tissue actively proliferating and the first target of contaminants present in water, so that changes in its antioxidant system can provide an earlier warning signal than in other tissues.

  2. Assessment of antioxidant responses and trace metal accumulation by digestive gland of ribbed mussel Aulacomya atra atra from Northern Patagonia.

    Science.gov (United States)

    Giarratano, Erica; Gil, Mónica N; Malanga, Gabriela

    2013-06-01

    Seasonal and spatial variability of trace metal concentrations and of a battery of antioxidant parameters were evaluated in digestive gland of the ribbed mussel Aulacomya atra atra. Fe, Al and Cu accumulated in tissue exhibited maximum values in winter, coinciding partially with the highest labile concentrations of Fe and Cu in sediment. Metals, as other pollutants, are known to influence the oxidative status of organisms and antioxidant enzymes have been often proposed as biomarkers of contaminant effects. Seasonal variations of trace metals did not appear to influence those of biochemical parameters, which generally showed an opposite trend with higher enzymatic activities in summer when trace metal concentrations were lower. Organisms from Punta Cuevas (control site) showed higher induction of reactive oxygen species production than those from both considered impacted sites, suggesting the possibility of some biochemical adaptation in organisms or a higher modulation of environmental and physiological factors on antioxidant responses than levels of trace metals. This study, which is the first in the area in this matter, showed that seasonal variations of potential biomarkers should be incorporated into interpretation of long-term biomonitoring studies in this marine coastal ecosystem.

  3. Bioactive compounds from Holothuria atra of Indian ocean.

    Science.gov (United States)

    Dhinakaran, Devaraj Isaac; Lipton, Aaron Premnath

    2014-01-01

    The sea cucumber (Holothuria atra) extracts have been evaluated for the presence of bioactive compounds and various biological activities. The methanol extracts showed anti proliferative activities against the Hela and MCF-7 cell lines. Similarly the inhibitory effects of Herpes simplex virus 1 and 2 cells were detected using the plaque reduction assay. The extracts of H. atra were purified using the silica gel column chromatography. The active fractions collected were observed for antimicrobial activity. The GC-MS analysis showed the availability of 59 compounds. The active bioactive compounds found in the H. atra were analyzed and their structure was identified using the (1)HNMR and (13)C NMR experiments.

  4. Cytoprotective Effects of Lysophospholipids from Sea Cucumber Holothuria atra.

    Directory of Open Access Journals (Sweden)

    Yoshifumi Nishikawa

    Full Text Available Lysophospholipids are important signaling molecules in animals and metazoan cells. They are widely distributed among marine invertebrates, where their physiological roles are unknown. Sea cucumbers produce unique lysophospholipids. In this study, two lysophospholipids were detected in Holothuria atra for the first time, lyso-platelet activating factor and lysophosphatidylcholine, with nuclear magnetic resonance and liquid chromatography-time-of-flight mass spectrometric analyses. The lipid fraction of H. atra contained lyso-platelet activating factor and lysophosphatidylcholine, and inhibited H2O2-induced apoptosis in the macrophage cell line J774A.1. The antioxidant activity of the lysophospholipid-containing lipid fraction of H. atra was confirmed with the oxygen radical absorbance capacity method. Our results suggest that the lysophospholipids from H. atra are potential therapeutic agents for the inflammation induced by oxidative stress.

  5. ATRA AS A POTENTIAL ANTIMETASTATIC AGENT IN COLORECTAL ADENOCARCINOMA

    Directory of Open Access Journals (Sweden)

    Robert Edwards

    2014-01-01

    Full Text Available The family of Retinoic acid compounds have long been the subject of intense study and interest as chemo prophylactic agents. This dates back to their therapeutic effect in leukoplakia Where ATRA was shown to lead to the reversal of premalignant lesions and Subsequent reports on their use in metastatic colorectal adenocarcinoma and a vast array of other malignant disorders as well as adjuvant treatment of loco regional head and neck and colorectal adenocarcinoma. All-trans retinoic acid has transformed the treatment and outcome of patients with acute promyelocytic leukemia by differentiating leukemic promyelocytes into mature cells. Retinoid Receptor knock out mouse models also serve as excellent proof for the critical role of retinoids in embryogenesis, specifically their vital role in heart and blood vessel development, CNS specification, fetal lung development and proper limb morphogenesis. Here we show the results of our first phase of in vitro studies of the interaction of ATRA with the Gut homing Receptor, CCR9. Hypoxia up regulates CCR9 expression in CCIC, while ATRA down regulates CCR9 expression in hypoxic CCIC. In contrast, HT29 cells express significantly less CCR9 which is up regulated by hypoxia and further enhanced by ATRA treatment. We conclude that CCIC (representing a colon cancer stem-like line respond differently to ATRA treatment Vs. a less stem-like, more differentiated cancer cell line such as HT-29. These results support a potential clinical use of ATRA early in the natural history of CRC in order to abort or slow down the process of metastasis in colorectal adenocarcinoma which is the ultimate killer of such patients. They also signify the critical significance of the time window and intratumoral heterogeneity in the final outcome of our intervention with ATRA in the treatment of CRC.

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Toxicity effects of water extracts of Holothuria atra Jaeger in mice

    Institute of Scientific and Technical Information of China (English)

    Ridzwan Bin Hashim; Nurul Alia Azizan; Zaitunnatakin Zamli; Farah Hanis Zulkipli; Nurzafirah Mazlan; Osama Yousef Althunibat

    2014-01-01

    Objective:To determine lethal median dose (LD50) and histopathological toxicity of water extract of Holothuria atra (H. atra) in mice. Methods: The behavioral changes, mortality and histopathology examination on liver were assessed in mice 14 d after the administration (i.p.) of H. atra water extract. Seven doses (10, 20, 30, 50, 100, 150 and 200 mg/kg) of H. atra were used. The control group was treated with normal saline. Results:In the acute study in mice, the water extracts of H. atra caused dose-dependent general behavior adverse affects and mortality. The main behavioral sign of toxicity was hypoactivity, noticed immediately after administration of the extract which was more obvious at the higher doses and persisted until death. Mortality increased with increasing doses, the calculated LD50 was 41 mg/kg in mice. The liver toxicity was confirmed by histopathological examination, which indicated the presence of abnormal hepatocytes with a distorted shape and undefined cell lining as well as enlarged nuclei in low doses groups. High doses groups indicated a more prominent distortion of the polyhedral hepatocytes with undefined cell lining, massive cytoplasm, pyknotic, karyorhexis and karyolytic nuclei (necrosis of hepatocytes). Control group showed polyhedral hepatocytes with defined cell lining arranged in cords and normal round nuclei, with granular cytoplasm. Conclusions: Because of the relatively low LD50 value in the acute study in mice, it may be concluded that the H. atra water extract is toxic.

  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. Receptor-mediated delivery of all-trans-retinoic acid (ATRA) to hepatocytes from ATRA-loaded poly(N-p-vinylbenzyl-4-o-{beta}-D-galactopyranosyl-D-gluconamide) nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Seog-Jin [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Moon, Hyun-Seuk [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Guo, Ding-Ding [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ; Kim, Sang-Heon [Korea Institute of Science and Technology, Seoul 136-791 (Korea, Republic of) ; Akaike, Toshihiro [Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama 226-8501 (Japan); Cho, Chong-Su [School of Agricultural Biotechnology, Seoul National University, Seoul 151-742 (Korea, Republic of) ]. E-mail: chocs@plaza.snu.ac.kr

    2006-01-15

    All-trans-retinoic acid (ATRA) plays a role in regulating CYP26 gene expression in hepatocytes. Poly(N-p-vinylbenzyl-4-o-{beta}-D-galactopyranosyl-D-gluconamide) (PVLA) nanoparticles have been used as hepatocyte-specific targeting candidates. The objective of this study was to investigate receptor-mediated delivery of ATRA using PVLA nanoparticles. ATRA-loaded PVLA nanoparticles were confirmed by {sup 1}H-nuclear magnetic resonance ({sup 1}H-NMR) and powder X-ray diffraction (XRD). In the {sup 1}H-NMR study, the proton signals of ATRA disappeared in the spectrum of ATRA-loaded PVLA nanoparticles in D{sub 2}O, whereas in dimethylsulfoxide-d{sub 6}, the spectrum seemed like an addition of the respective spectrum of each of the pure components. The crystalline peaks of ATRA disappeared in the XRD pattern of ATRA-loaded PVLA nanoparticles after ATRA was loaded into PVLA nanoparticles. In the measurement of size distribution, diameter of PVLA and ATRA-loaded PVLA nanoparticles in aqueous solution was 6.9 and 61.2 nm in number average, respectively. Flow cytometric analysis showed that the internalization of FITC-PVLA nanoparticles by hepatocytes in the absence of a competitive inhibitor was larger than preincubated with galactose. In reverse transcription-polymerase chain reaction (RT-PCR) analysis, ATRA-loaded PVLA nanoparticles induced CYP26A1 gene in hepatocytes in the absence of a competitive inhibitor but not preincubated with galactose. The results indicate that the ATRA-loaded PVLA nanoparticle can induce CYP26A1 gene in aqueous phase by an asialoglycoprotein receptor (ASGPR)-mediated delivery system.

  11. ATRA (all-trans-retinoic acid) syndrome in acute promyelocytic leukemia: clinical and radiologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Keon Ha; Goo, Jin Mo; Im, Jung Gi; Chung, Myung Jin; Do, Kyung Hyun; Park, Seon Yang [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Seo, Joon Beom [Gachon Univ. Medical School, Gil Medical Center, Seoul (Korea, Republic of)

    2001-03-01

    To describe the clinical and radiologic findings of all-trans-retinoic acid (ATRA) syndrome in acute promyelocytic leukemia. Among 21 patients with acute promyelocytic leukemia who were treated with all-trans-retinoic acid between 1995 and 1998, we retrospectively evaluated the cases of four with ATRA syndrome. Two were male and two were female, and their mean age was 58 years. The clinical and radiologic findings of chest radiography (n=4) and HRCT (n=1) were analyzed. Between seven and 13 days after ATRA treatment, dry cough, dyspnea and high fever developed in all patients. The WBC count in peripheral blood was significantly higher [2.9-25.3(mean, 10.8)-fold] than before ATRA treatment, and in all patients, chest radiography revealed ill-defined consolidation and pleural effusion. Kerley's B line (n=3) and hilar enlargement (n=3) were also seen, and in one patient, HRCT demonstrated septal line thickening. Among four patients treated with prednisolone and Ara-C, three recovered and one died. In acute promyelocytic patients treated with all-trans-retinoic acid, radiologic findings of ill-de-fined consolidation, pleural effusion, hilar prominence and Kerley's B line may suggest ATRA syndrome. The early diagnosis of this will improve the patients' prognosis.

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

    OpenAIRE

    2011-01-01

    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 ATR...

  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. Discovery of Salamandra atra aurorae (Trevisan, 1982 on the Altopiano di Vezzena, Trentino (Northeastern Italy

    Directory of Open Access Journals (Sweden)

    Wouter Beukema

    2008-05-01

    Full Text Available Aurora’s Alpine Salamander is a limited distributed subspecies endemic to the Altopiano di Asiago, Veneto. In the current paper the occurrence of Salamandra atra aurorae is described for the Altopiano di Vezzena, Trentino. The aim of this paper is to review the distribution as well as to comment on the conservational status of the subspecies in Trentino.

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

    Science.gov (United States)

    Akter, Jesmin; Takatori, Atsushi; Islam, Md Sazzadul; Nakazawa, Atsuko; Ozaki, Toshinori; Nagase, Hiroki; Nakagawara, Akira

    2014-10-10

    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.

  16. LG-362B targets PML-RARα and blocks ATRA resistance of acute promyelocytic leukemia.

    Science.gov (United States)

    Wang, X; Lin, Q; Lv, F; Liu, N; Xu, Y; Liu, M; Chen, Y; Yi, Z

    2016-07-01

    Acute promyelocytic leukemia (APL) is a M3 subtype of acute myeloid leukemia (AML). Promyelocytic leukemia (PML)-retinoic acid receptor α (RARα) translocation generally occurs in APL patients and makes APL unique both for diagnosis and treatment. However, some conventional drugs like all-transretinoic acid (ATRA) and arsenic trioxide (ATO), as the preferred ones for APL therapy, induce irreversible resistance and responsible for clinical failure of complete remission. Herein, we screened a library of novel chemical compounds with structural diversity and discovered a novel synthetic small compound, named LG-362B, specifically inhibited the proliferation of APL and induced apoptosis. Notably, the differentiation arrest was also relieved by LG-362B in cultured APL cells and APL mouse models. Moreover, LG-362B overcame the ATRA resistance on cellular differentiation and transplantable APL mice. These positive effects were driven by caspases-mediated degradation of PML-RARα when treated with LG-362B, making it specific to APL and reasonable for ATRA resistance relief. We propose that LG-362B would be a potential candidate agent for the treatment of the relapsed APL with ATRA resistance in the future.

  17. ATRA inhibits experimental liver metastasis of gastric cancer cells in nude mice

    Institute of Scientific and Technical Information of China (English)

    Yu Qiang Chen; Qiao Wu; Zheng Ming Chen; Fu Chen; Wen Jin Su

    2000-01-01

    AIM To study the effects of ATRA on experimental liver metastasis of gastric cancer cells.METHODS MGc80-3 and SGC-7901 cells were injectied into spleen subcapsule of nude mice, who weresubsequently administrated with ATRA every other day. Food-intake and body weight of mice were measuredweekly. After six weeks, the nude mice were executed, tumors in spleen and liver were examinedpathologically, microtumor vessel density (MVD) was accounted by immunohistochemical method and serumCEA was measured by radioimmunoassay.RESULTS Nude mice administrated with ATRA, the growth of spleen tumor and its metastatic ability toliver were inhibited, the metastatic rate was decreased by 33.3% (MGc80-3) and 50.0% (SGC-7901). SpleenMVD and liver MVD were reduced by 28.6% and 22.9% (MGc80-3), 23.7% and 37.6% (SGC-7901),respectively. The serum CEA was lowered by 43.4% (MGc80-3).CONCLUSION ATRA can effectively inhibit the experimental liver metastasis of gastric cancer cells,which is relavant with the decrease of MVD and CEA.

  18. Malignancy: Case Report: Acute Promyelocytic Leukemia in Late Pregnancy. Successful Treatment with All-Trans-Retinoic Acid (ATRA) and Chemotherapy.

    Science.gov (United States)

    Delgado-Lamas, JOSÉ LUIS; Garcés-Ruiz, OSCAR MIGUEL

    2000-01-01

    The use of all-transretinoic acid (ATRA) in APL is a great advance in the treatment of acute leukemia, driving the maturation steps until adult form. The effect of this medication in pregnant women with APL is being a safe and effective treatment only after the first trimester of pregnancy. If used in the first three months, it can cause fetus malformations due to its potent teratogenicity. The two patients we reported here, gave birth to normal children, yet they received ATRA. After a week with ATRA treatment, fibrinogen level improved and "D" dimers decreased, so as observed slowly maturation of leukemic leucocytes. ATRA used at the same time with chemotherapy; such as Cytarabine and Idarrubicine seems highly useful for induction and long term control of disease. One short discussion about the findings and compare with those found in the literature are presented.

  19. Acute Promyelocytic Leukemia in Late Pregnancy. Successful Treatment with All-Trans-Retinoic Acid (ATRA) and Chemotherapy.

    Science.gov (United States)

    Delgado-Lamas, J L; GarcéS-Ruiz, O M

    1999-01-01

    The use of all-transretinoic acid (ATRA) in APL is a great advance in the treatment of acute leukemia, driving the maturation steps until adult form. The effect of this medication in pregnant women with APL is being a safe and effective treatment only after the first trimester of pregnancy. If used in the first three months, it can cause fetus malformations due to its potent teratogenicity. The two patients we reported here, gave birth to normal children, yet they received ATRA. After a week with ATRA treatment, fibrinogen level improved and "D" dimers decreased, so as observed slowly maturation of leukemic leucocytes. ATRA used at the same time with chemotherapy; such as Cytarabine and Idarrubicine seems highly useful for induction and long term control of disease. One short discussion about the findings and compare with those found in the literature are presented.

  20. Atrações e prazeres visuais em um pornô feminino

    Directory of Open Access Journals (Sweden)

    Mariana Baltar

    2015-08-01

    Full Text Available 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 associado ao campo da pornografia feminista empreendido com apoio do Swedish Film Institut.

  1. 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.

  2. Toxicity effects of water extracts of Holothuria atra Jaeger in mice

    Institute of Scientific and Technical Information of China (English)

    Ridzwan; Bin; Hashim; Nurul; Alia; Azizan; Zaitunnatakin; Zamli; Farah; Hanis; Zulkipli; Nurzafirah; Mazlan; Osama; Yousef; Althunibat

    2014-01-01

    Objective:To determine lethal median dose(LD50) and histopalhological toxicity of water extract of Hololhuria atra(H,atra) in mice.Methods:The behavioral changes,mortality and histopathology examination on liver were assessed in mice 14 d after the administration(i.p.) of H.atra water extract.Seven doses 110,20,30,50.100.150 and 200 mg/kg) of H.atra were used.The control group was treated with normal saline,Results:In the acute study in mice,the water extracts of H,atra caused dose-dependent general behavior adverse affects and mortality.The main behavioral sign of toxicity was hypoactivity,noticed immediately after administration of the extract which was more obvious at the higher doses and persisted until death.Mortality increased with increasing doses,the calculated LD50was 41 mg/kg in mice.The liver toxicity was confirmed by histopalhological examination,which indicated the presence of abnormal hepatocytes with a distorted shape and undefined cell lining as well as enlarged nuclei in low doses groups.High doses groups indicated a more prominent distortion of the polyhedral hepatocytes with undefined cell lining,massive cytoplasm,pvknotic.karyorhexis and karyolytie nuclei(necrosis of hepatocytes).Control group showed polyhedral hepatocytes with defined cell lining arranged in cords and normal round nuclei,with granular cytoplasm.Conclusions:Because of the relatively low LD50 value in the acute study in mice,it may be concluded that the H.atra water extract is toxic.

  3. ATRA inhibits the proliferation of DU145 prostate cancer cells through reducing the methylation level of HOXB13 gene.

    Directory of Open Access Journals (Sweden)

    Zhiwei Liu

    Full Text Available All-trans retinoic acid (ATRA has been widely investigated for treatments of many cancers including prostate cancer. HOXB13, silenced in androgen receptor-negative (AR(- prostate cancer cells, plays a role in AR(- prostate cancer cell growth arrest. In this study we intended to elucidate the mechanisms that are involved in the proliferation inhibition of AR(- prostate cancer cells triggered by ATRA. We discovered that ATRA was able to induce the growth arrest and to increase HOXB13 expression in AR(- prostate cancer cells. Both EZH2 and DNMT3b participated in the repression of HOXB13 expression through an epigenetic mechanism involving DNA and histone methylation modifications. Specifically, EZH2 recruited DNMT3b to HOXB13 promoter to form a repression complex. Moreover, ATRA could upregulate HOXB13 through decreasing EZH2 and DNMT3b expressions and reducing their interactions with the HOXB13 promoter. Concurrently, the methylation level of the HOXB13 promoter was reduced upon the treatment of ATRA. Results from this study implicated a novel effect of ATRA in inhibition of the growth of AR(- resistant human prostate cancer cells through alteration of HOXB13 expression as a result of epigenetic modifications.

  4. EFFECT OF ARSENIC TRIOXIDE OR ATRA ON PRIMARY APL CELL OR HL-60 CELLS AND THEIR VALUE ANALYSIS IN HYPERLEUKOCYTOSIS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To detect the effect of arsenic trioxide or ATRA on APL cells or HL-60 cells and to investigate the mechanism of the hyperleukocytosis and detect the cross resistance between ATRA and arsenic trioxide. Methods: The number of promyelocytes or more matured granulocytes were counted by regular method, MTT test was used to measure the proliferation of HL-60 cells or APL cells, flow cytometry analysis to measure the apoptosis, NBT method to detect the differentiation of HL-60 cells or APL cells. Results: The proliferation of primary APL cells or HL-60 cells could be inhibited in vitro by either arsenic trioxide or ATRA, which could induce obvious apoptosis or obvious differentiation of primary APL cells or HL-60 cells. Inhibition of proliferation or apoptosis of ATRA resistant HL-60 cells were achieved by exposure toarsenic trioxide in vitro. On the other hand, the results of in vivo treatment showed that arsenic trioxide also induce of hyperleukocytosis. Conclusion: The results indicated that the hyperleukocytosis induced by ATRA is not contributed to the mechanism of more differentiation than apoptosis, there was not cross resistance between ATRA and arsenic trioxide.

  5. 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.

  6. Effect of ATRA on Contents of liver Retinoids, Oxidative Stress and Hepatic Injury in Rat Model of Extrahepatic Cholestasis

    Institute of Scientific and Technical Information of China (English)

    JIANG Haiyan; DAN Zili; WANG Hui; LIN Jusheng

    2007-01-01

    The effects of all-trans-retinoic acid (ATRA) administration on the concentration of retinoids (RA and vitamin A) in liver, oxidative stress and the hepatic injury in a rat model of com-mon bile duct ligation (CBDL)-induced liver injury were investigated. Female rats were subjected to a sham (n=5) or CBDL (n=48). Two weeks after operation, rats undergoing CBDL were randomized to receive treatment with either ATRA at three different doses (0.1, 1.5, 7.5 mg/kg) dissolved in bean oil or only bean oil every day over a 4-week experimental period. Rats were killed and blood samples were collected from the heart for determination of the serum transaminase. The contents of retinoids in rat liver were detected by using HPLC. Malondialdehyde (MDA), glutathione (GSH) and superox-ide dismutase (SOD) levels in liver were determined by a spectrophotometric method according to the instruction of the kits. Liver pathologic changes were observed under the light microscopy and electron microscopy. The results showed that compared with sham-operated group, the levels of reti-noids in the liver tissue were significantly decreased in the CBDL group (P<0.01). ATRA (0.1 mg/kg) administration in CBDL rats partially restored the contents of retinoids (P<0.05). Liver RA and vita-min A contents in CBDL group were significantly increased after ATRA (1.5 and 7.5 mg/kg) sup-plementation as compared with sham-operated group (P<0.05). However, in ATRA-treated CBDL group, hepatic GSH level and SOD activity, depressed by CBDL, and hepatic MDA level, increased by CBDL were returned to those in sham-operated group (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER). Treatment with ATRA could reduce levels of serum transaminase as compared with sham-operated group, more greatly in 1.5 and 7.5 mg/kg ATRA-treated groups than in 0.1 mg

  7. 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.; Chung, H.; Smith, D.L. [Argonne National Lab., IL (United States)] [and others

    1997-04-01

    The ATR-A1 irradiation experiment in the Advanced Test Reactor (ATR) was a collaborative U.S./Japan effort to study at low temperatures 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 was completed on May 5, 1996, as planned, after achieving an estimated neutron damage of 4.7 dpa in vanadium. The capsule has since been kept in the ATR water canal for the required radioactivity cool-down. Planning is underway for disassembly of the capsule and test specimen retrieval.

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

    OpenAIRE

    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

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Low-dose ATRA Supplementation Abolishes PRM Formation in Rat Liver and Ameliorates Ethanol-induced Liver Injury

    Institute of Scientific and Technical Information of China (English)

    PAN Zhihong; DAN Zili; FU Yu; TANG Wangxian; LIN Jusheng

    2006-01-01

    The effects of all-trans-retinoic acid (ATRA) in low doses supplementation on concentrations of polar retinoid metabolites (PRM) and retinoids in the ethanol-fed rat liver, and on hepatocyte injury were investigated. The rat model of alcoholic liver disease (ALD) was induced by intragastric infusion of ethanol, and then the rats were administrated with ATRA in two different doses (150 μg/kg body weight and 1.5 mg/kg body weight) for 4 weeks. Concentrations of retinoids in rat liver and plasma were determined by using HPLC. Liver tissues pathologic changes were observed under the light microscopy and electron microscopy. The serum transaminases concentrations were measured. The results showed that the HPLC analysis of retinoids revealed that retinoids (vitamin A,RA, retinyl palmitate) concentrations in ethanol-fed rat liver and RA concentration in ethanol-fed rat plasma were markedly diminished (P<0.01) after ethanol feeding for 12 weeks. Furthermore, obvious peaks of PRM were formed in livers of ethanol-fed rats. ATRA 150 μg/kg supplementation in ethanol-fed rats for 4 weeks raised RA concentration in both liver and plasma, and also raised vitamin A concentration in liver to control levels, partially restored retinyl palmitate concentration (P<0.05) in liver. ATRA 1.5 mg/kg supplementation raised not only RA concentrations in liver and plasma but also retinyl palmitate concentrations in liver. However, the vitamin A concentration in liver of ATRA-supplemented rats (1.5 mg/kg) was higher than that of controls (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling,steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER).ATRA treatment greatly decreased levels of serum transaminases as compared with the only ethanol-fed group (P<0.05). It was concluded that low-dose ATRA treatment could restore retinoids concentrations and abolish the PRM formation

  13. Sirenophila ovis-atra a new species of maritime Teloschistaceae from the Southern Hemisphere

    DEFF Research Database (Denmark)

    Søchting, Ulrik; Søgaard, Majbrit Zeuthen; Sancho, Leopoldo G.

    2016-01-01

    A new species, Sirenophila ovis-atra is described from maritime rocks of southern Patagonia, the Falkland Islands and Macquarie Island, where it grows in the upper part of the black ‘Verrucaria-zone’, most often on members of the genus Hydropunctaria. It is so far the only known species of Sireno...

  14. [Acute promyelocytic leukemia (APL) resulting in broad cerebral infarction during all-trans retinoic acid (ATRA) treatment].

    Science.gov (United States)

    Ikeda, Y; Yoshinaga, K; Iki, S; Ohbayashi, Y; Urabe, A

    1994-02-01

    A 27-year-old woman visited Kanto Teishin Hospital complaining of fever and petechiae in September, 1992. Her fetus had suddenly died in the uterus two weeks before (in the sixth month of pregnancy). Total white blood cell (WBC) count was 3.2 x 10(3)/microliters with 80% promyelocytes. Bone marrow was hypercellular with 90% promyelocytes. Disseminated intravascular coagulation (DIC) was recognized. She was diagnosed as having acute promyelocytic leukemia (APL), and treatment with daily oral administration of all-trans retinoic acid (ATRA) (70 mg/body/day) was begun. On day 4, hemiplegia and aphasia appeared. Broad cerebral infarction was suspected from computed tomography. On day 9, the WBC count increased rapidly, standard chemotherapy was added and she achieved complete remission. ATRA is known to have stimulatory effects on the differentiation of APL cells, but some reports have described thromboembolic events during the administration of ATRA. In this case, ATRA might have affected coagulability resulting in cerebral infarction.

  15. Binding of a biosynthetic intermediate to AtrA modulates the production of lidamycin by Streptomyces globisporus.

    Science.gov (United States)

    Li, Xingxing; Yu, Tengfei; He, Qing; McDowall, Kenneth J; Jiang, Bingya; Jiang, Zhibo; Wu, Linzhuan; Li, Guangwei; Li, Qinglian; Wang, Songmei; Shi, Yuanyuan; Wang, Lifei; Hong, Bin

    2015-06-01

    The control of secondary production in streptomycetes involves the funneling of environmental and physiological signals to the cluster-situated (transcriptional) regulators (CSRs) of the biosynthetic genes. For some systems, the binding of biosynthetic products to the CSR has been shown to provide negative feedback. Here we show for the production of lidamycin (C-1027), a clinically relevant antitumor agent, by Streptomyces globisporus that negative feedback can extend to a point higher in the regulatory cascade. We show that the DNA-binding activity of the S. globisporus orthologue of AtrA, which was initially described as a transcriptional activator of actinorhodin biosynthesis in S. coelicolor, is inhibited by the binding of heptaene, a biosynthetic intermediate of lidamycin. Additional experiments described here show that S. globisporus AtrA binds in vivo as well as in vitro to the promoter region of the gene encoding SgcR1, one of the CSRs of lidamycin production. The feedback to the pleiotropic regulator AtrA is likely to provide a mechanism for coordinating the production of lidamycin with that of other secondary metabolites. The activity of AtrA is also regulated by actinorhodin. As AtrA is evolutionarily conserved, negative feedback of the type described here may be widespread within the streptomycetes.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Therapeutic effect of all-trans-retinoic acid (at-RA on an autoimmune nephritis experimental model: role of the VLA-4 integrin

    Directory of Open Access Journals (Sweden)

    Lucio-Cazaña Javier

    2007-01-01

    Full Text Available Abstract Background Mercuric chloride (HgCl2 induces an autoimmune nephritis in the Brown Norway (BN rats characterized by anti-glomerular basement membrane antibodies (anti-GBM Ab deposition, proteinuria and a severe interstitial nephritis, all evident at day 13 of the disease. We assessed the effects of all-trans retinoic acid (at-RA in this experimental model. At-RA is a vitamin A metabolite which has shown beneficial effects on several nephropathies, even though no clear targets for at-RA were provided. Methods We separated animals in four different experimental groups (HgCl2, HgCl2+at-RA, at-RA and vehicle. From each animal we collected, at days 0 and 13, numerous biological samples: urine, to measure proteinuria by colorimetry; blood to determine VLA-4 expression by flow citometry; renal tissue to study the expression of VCAM-1 by Western blot, the presence of cellular infiltrates by immunohistochemistry, the IgG deposition by immunofluorescence, and the cytokines expression by RT-PCR. Additionally, adhesion assays to VCAM-1 were performed using K562 α4 transfectant cells. ANOVA tests were used for statistical significance estimation. Results We found that at-RA significantly decreased the serum levels of anti-GBM and consequently its deposition along the glomerular membrane. At-RA markedly reduced proteinuria as well as the number of cellular infiltrates in the renal interstitium, the levels of TNF-α and IL-1β cytokines and VCAM-1 expression in renal tissue. Moreover, we reported here for the first time in an in vivo model that at-RA reduced, to basal levels, the expression of VLA-4 (α4β1 integrin induced by mercury on peripheral blood leukocytes (PBLs. In addition, using K562 α4 stable transfectant cells, we found that at-RA inhibited VLA-4 dependent cell adhesion to VCAM-1. Conclusion Here we demonstrate a therapeutic effect of at-RA on an autoimmune experimental nephritis model in rats. We report a significant reduction of the

  1. 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.

  2. 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.

  3. 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.

  4. Decitabine and SAHA-Induced Apoptosis Is Accompanied by Survivin Downregulation and Potentiated by ATRA in p53-Deficient Cells

    Directory of Open Access Journals (Sweden)

    Barbora Brodská

    2014-01-01

    Full Text Available While p53-dependent apoptosis is triggered by combination of methyltransferase inhibitor decitabine (DAC and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA in leukemic cell line CML-T1, reactive oxygen species (ROS generation as well as survivin and Bcl-2 deregulation participated in DAC + SAHA-induced apoptosis in p53-deficient HL-60 cell line. Moreover, decrease of survivin expression level is accompanied by its delocalization from centromere-related position in mitotic cells suggesting that both antiapoptotic and cell cycle regulation roles of survivin are affected by DAC + SAHA action. Addition of subtoxic concentration of all-trans-retinoic acid (ATRA increases the efficiency of DAC + SAHA combination on viability, apoptosis induction, and ROS generation in HL-60 cells but has no effect in CML-T1 cell line. Peripheral blood lymphocytes from healthy donors showed no damage induced by DAC + SAHA + ATRA combination. Therefore, combination of ATRA with DAC and SAHA represents promising tool for therapy of leukemic disease with nonfunctional p53 signalization.

  5. 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.

  6. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra

    Directory of Open Access Journals (Sweden)

    Cao-Xin Chen

    2015-01-01

    Full Text Available Cardiotoxin (CTX from Naja naja atra venom (NNAV reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis.

  7. The antineoplastic effect of Naja Naja atra venom on S180 bearing mice and its mechanism

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM:To observe the antineoplastic effect of Naja Naja atra venom (NNAV) on S180 bearing mice and to study the possible antineoplastic mechanism. METHODS:We observed the effect of NNAV on tumor weight、plasma nitric oxide content、plasma endothelin content and spleen index in S180 bearing mice with different concentration and different period by means of injecting into abdomen. RESULTS:Treatment with NNAV solution of different concentration could markedly inhibit S180 growth (especially in the low concentration group and by long period) and rate of inhibiting ranged from 21 63% to 49.25%; the plasma nitric oxide content, the plasma endothelin content and NO/ET ratio in tumor bearing mice were obviously higher than those of the normal control group, while after treatment with NNAV solution, the plasma nitric oxide level, the plasma endothelin level and NO/ET ratio could be reduced markedly, and it was noticed that NO/ET ratio in the group with highest inhibiting rate was most close to that of the normal control group. The spleen index was obviously increased after treatment with NNAV solution.CONCLUSION:The antineoplastic effect of NNAV on S180 bearing mice is best in long period by means of injecting into abdomen with low concentration. The mechanism of the antineoplastic effect of NNAV may be related to lowering the plasma nitric oxide and endothelin level, regulating the NO/ET ratio and enhancing the immune response.

  8. L-amino acid oxidase from Naja atra venom activates and binds to human platelets

    Institute of Scientific and Technical Information of China (English)

    Rui Li; Shaowen Zhu; Jianbo Wu; Wanyu Wang; Qiumin Lu; Kenneth J.Clemetson

    2008-01-01

    An L-amino acid oxidase (LAAO),NA-LAAO,was purified from the venom of Naja atra.Its N-terminal sequence shows great similarity with LAAOs from other snake venoms.NALAAO dose-dependently induced aggregation of washed human platelets.However,it had no activity on platelets in platelet-rich plasma.A low concentration of NA-LAAO greatly promoted the effect of hydrogen peroxide,whereas hydrogen peroxide itself had little activation effect on platelets.NA-LAAO induced tyrosine phosphorylation of a number of platelet proteins including Src kinase,spleen tyrosine kinase,and phospholipase C γ2.Unlike convulxin,Fc receptor γ chain and T lymphocyte adapter protein are not phosphorylated in NA-LAAO activated platelets,suggesting an activation mechanism different from the glycoprotein VI pathway.Catalase inhibited the platelet aggregation and platelet protein phosphorylation induced by NA-LAAO.NA-LAAO bound to fixed platelets as well as to platelet lysates of Western blots.Furthermore,affinity chromatography of platelet proteins on an NA-LAAO Sepharose 4B column isolated a few platelet membrane proteins,suggesting that binding of NA-LAAO to the platelet membrane might play a role in its action on platelets.

  9. All-trans retinoic acid (ATRA)-induced apoptosis is preceded by G1 arrest in human MCF-7 breast cancer cells.

    Science.gov (United States)

    Mangiarotti, R; Danova, M; Alberici, R; Pellicciari, C

    1998-01-01

    In this study the effects of all-trans retinoic acid (ATRA) on cell cycle and apoptosis of MCF-7 human breast cancer cells were investigated to elucidate the mechanisms underlying the antineoplastic potential of this retinoid in breast cancer. The antiproliferative effect of ATRA was evaluated by DNA content measurements and dual-parameter flow cytometry of bromodeoxyuridine (BrdU) incorporation and of the expression of cell cycle-related proteins (Ki-67 as proliferation marker and statin as quiescence marker) vs DNA content. Apoptosis was also studied by flow cytometry of either DNA content or Annexin V labelling. After 10(-6) M ATRA treatment, the fraction of S-phase cells decreased significantly, and cells accumulated in the G0/G1 range of DNA contents. Dual-parameter flow cytograms showed a decrease in the percentage of Ki-67-labelled cells (after 10 days, only 20% of the cells were still positive for Ki-67 compared with 95% in controls), while the fraction of statin-positive cells increased slightly. From 3 days of treatment onwards, apoptosis was found to occur. These results show that ATRA-induced inhibition of MCF-7 cell growth is related to two mechanisms, i.e. the block of cell proliferation, mostly in a pre-S phase, and the induction of apoptosis. These results should be taken into account when attempting to design treatment programmes that associate ATRA with antineoplastic compounds of different cell cycle specificity.

  10. 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.

  11. Development of an aerosol microphysical module: Aerosol Two-dimensional bin module for foRmation and Aging Simulation (ATRAS

    Directory of Open Access Journals (Sweden)

    H. Matsui

    2014-04-01

    Full Text Available Number concentrations, size distributions, and mixing states of aerosols are essential parameters for accurate estimation of aerosol direct and indirect effects. In this study, we develop an aerosol module, designated Aerosol Two-dimensional bin module for foRmation and Aging Simulation (ATRAS, that can represent these parameters explicitly by considering new particle formation (NPF, black carbon (BC aging, and secondary organic aerosol (SOA processes. A two-dimensional bin representation is used for particles with dry diameters from 40 nm to 10 μm to resolve both aerosol size (12 bins and BC mixing state (10 bins for a total of 120 bins. The particles with diameters from 1 to 40 nm are resolved using an additional 8 size bins to calculate NPF. The ATRAS module is implemented in the WRF-chem model and applied to examine the sensitivity of simulated mass, number, size distributions, and optical and radiative parameters of aerosols to NPF, BC aging and SOA processes over East Asia during the spring of 2009. BC absorption enhancement by coating materials is about 50% over East Asia during the spring, and the contribution of SOA processes to the absorption enhancement is estimated to be 10–20% over northern East Asia and 20–35% over southern East Asia. A clear north-south contrast is also found between the impacts of NPF and SOA processes on cloud condensation nuclei (CCN concentrations: NPF increases CCN concentrations at higher supersaturations (smaller particles over northern East Asia, whereas SOA increases CCN concentrations at lower supersaturations (larger particles over southern East Asia. Application of ATRAS to East Asia also shows that the impact of each process on each optical and radiative parameter depends strongly on the process and the parameter in question. The module can be used in the future as a benchmark model to evaluate the accuracy of simpler aerosol models and examine interactions between NPF, BC aging, and SOA

  12. 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.

  13. Combination of interferon alpha with either Ara-C or ATRA in vitro reduces the selective action of interferon against CML CFU-GM.

    Science.gov (United States)

    Marley, S B; Davidson, R J; Goldman, J M; Gordon, M Y

    2000-08-01

    Although interferon (IFN)-alpha has no specific inhibitory effect on the plating efficiency of granulocyte-macrophage colony-forming cells (CFU-GM) from patients with chronic myeloid leukaemia (CML), it does selectively inhibit the replating ability (secondary colony formation) of CML CFU-GM. Thus, amplification of CFU-GM may be a target for IFN-alpha and other agents used in the treatment of CML. Here we examined whether cytarabine (Ara-C) or all-trans retinoic acid (ATRA) exert similar effects and whether they might in combination with IFN-alpha enhance its efficacy. We found that Ara-C preferentially inhibits the formation of CML CFU-GM compared to normal CFU-GM, but this inhibition was not increased by addition of IFN-alpha. When Ara-C was added to cultures containing IFN-alpha, the inhibition of replating by CML progenitors was abrogated. ATRA increased significantly the plating efficiency of normal CFU-GM. The addition of IFN-alpha to ATRA had no effect on CML or normal colony numbers. However, addition of ATRA to cultures containing IFN-alpha reversed the selective inhibition of CML CFU-GM replating seen in cultures containing IFN-alpha alone. In four IFN-alpha/Ara-C experiments, secondary CML patient-derived colonies were examined by fluorescence in situ hybridisation (FISH). All of them were Ph chromosome positive. No significant effects on CFU-GM production were observed when CML primitive haemopoietic progenitor cells were investigated in a delta (delta) assay. Thus we conclude that combining IFN-alpha with Ara-C or ATRA neutralises the effect of IFN-alpha on CML CFU-GM. This observation provides a rationale for treating patients with alternating courses of IFN-alpha and Ara-C or ATRA, rather than giving either of these two agents in combination with IFN-alpha.

  14. Effect of ATRA on the expression of HOXA5 gene in K562 cells and its relationship with cell cycle and apoptosis.

    Science.gov (United States)

    Liu, Wen-Jun; Zhang, Teng; Guo, Qu-Lian; Liu, Chun-Yan; Bai, Yong-Qi

    2016-05-01

    Leukemia is the most common malignant disease in children with high incidence and mortality rates, and a poor treatment effect. The aim of the present study was to examine the changes in the expression of homeobox (Hox) A5 gene and its relationship with cell cycle and apoptosis through the intervention of human K562 myeloid leukemia cell line by all-trans retinoic acid (ATRA), to analyze the role of HOXA5 in the pathogenesis and development process of myeloid leukemia. The optimal concentration of ATRA to be used with K562 cells was determined using a cell counting kit‑8 (CCK‑8). After 24, 72 and 48 h following treatment of K562 cells with 10 µmol/l ATRA, cell cycle events and apoptosis were measured using flow cytometry. HOXA5 mRNA and protein expression in K562 cells was assessed by RT‑PCR and western blot analysis, and the relationship between HOXA5 expression and cell cycle and apoptosis was analyzed. The HOXA5 mRNA and protein expression levels were increased following treatment with ATRA in K562 cells. Apoptosis was increased significantly. The cell cycle was inhibited in G0/G1 phase. Cell proliferation was also inhibited. HOXA5 mRNA and protein expression rates positively correlated with cell apoptosis and the increased percentage and cell cycle of the G0/G1 phase. However, HOXA5 negatively correlated with the reduced percentage of S stage. In conclusion, the expression of HOXA5 in cells was increased following treatment with ATRA in K562 cells, in a time-dependent manner. Additionally, ATRA may inhibit the proliferation of K562 cells and promote apoptosis by upregulating the HOXA5 mRNA and protein expression.

  15. Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom

    Directory of Open Access Journals (Sweden)

    Zhi-Hui Ding

    2014-01-01

    Full Text Available Previous studies reported the oral administration of Naja naja atra venom (NNAV reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

  16. Ameliorating Adriamycin-Induced Chronic Kidney Disease in Rats by Orally Administrated Cardiotoxin from Naja naja atra Venom.

    Science.gov (United States)

    Ding, Zhi-Hui; Xu, Li-Min; Wang, Shu-Zhi; Kou, Jian-Qun; Xu, Yin-Li; Chen, Cao-Xin; Yu, Hong-Pei; Qin, Zheng-Hong; Xie, Yan

    2014-01-01

    Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180  μ g/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.

  17. 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.

  18. Celastrol inhibits lung infiltration in differential syndrome animal models by reducing TNF-α and ICAM-1 levels while preserving differentiation in ATRA-induced acute promyelocytic leukemia cells.

    Directory of Open Access Journals (Sweden)

    Li-min Xu

    Full Text Available All-trans retinoic acid (ATRA is a revolutionary agent for acute promyelocytic leukemia (APL treatment via differentiation induction. However, ATRA treatment also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1 expression, which can cause clinical complications, including a severe situation known as differentiation syndrome (DS which can cause death. Therefore, it is of clinical significance to find a strategy to specifically blunt inflammatory effects while preserving differentiation. Here we report that the natural compound, celastrol, could effectively block lung infiltrations in DS animal models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4 cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF-α and IL-1β secretion, though treatment showed no effects on IL-8 and MCP-1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no obvious effects on ATRA-induced NB4 differentiation, as determined by morphology, enzymes, and surface markers. Our results show that celastrol is a promising and unique agent for managing the side effects of ATRA application on APL, and suggest that hyper-inflammatory ability is accompanied by, but not necessary for, APL differentiation. Thus we offered an encouraging novel strategy to further improve differentiation therapy.

  19. Upregulation of CD54 and downregulation of HLA‑ABC contribute to the novel enhancement of the susceptibility of HL-60 cells to NK cell-mediated cytolysis induced by ATRA plus VPA.

    Science.gov (United States)

    Zou, Huijuan; Li, Lianlian; Han, Yang; Ma, Ruiping; Liao, Qiong; Tian, Jing; Zhang, Xiaoyu; Ren, Xia; Song, Guanhua; Guo, Qiang; Li, Xia; Ding, Huifang; Jiang, Guosheng

    2017-01-01

    Enhancement of the susceptibility of HL-60 cells to NK cell-mediated cytolysis induced by all-trans-retinoic acid (ATRA) plus valproate (VPA) was evaluated. In addition to the synergistic effect of ATRA plus VPA on HL-60 cells, the optimal concentration of 1 mM VPA plus 0.5 µM ATRA increased the cytotoxic sensitivity of HL-60 cells to NK cells. The expression of the activated receptors NKp30 and NKG2D on NK-92 cells was higher compared with the levels noted for the other receptors, and the expression of NKG2D ligands MICA/B on HL-60 cells was not significantly upregulated in the ATRA plus VPA goup compared with the control. Moreover, it was observed that the ligands of NKp30 on HL-60 cells presented the same variation trend. As to the co-stimulatory and adhesion molecules on NK-92 and their ligands on HL-60 cells post exposure to ATRA and VPA alone or their combination, there was no obvious change in the expression of CD112, CD48 and CD70 on the HL-60 cells. However, the expression of CD54 on HL-60 cells was significantly upregulated. In contrast, the expression of NKG2A ligands HLA-ABC on HL-60 cells was obviously downregulated. In addition, the expression of HLA-E on the HL-60 cells in the group treated with ATRA plus VPA was not significantly increased. In conclusion, the combination of VPA and ATRA not only induced the differentiation of HL-60 cells, but also induced enhancement of the sensitivity of HL-60 cells to NK cells by downregulating the expression of HLA-ABC and upregulating the expression of CD54, but not MICA/MICB. The results provide experimental and theoretical basis for the clinical combination of a low-dose of ATRA plus VPA for the treatment of leukemia.

  20. The Impact of ATRA on Shaping Human Myeloid Cell Responses to Epithelial Cell-Derived Stimuli and on T-Lymphocyte Polarization

    Directory of Open Access Journals (Sweden)

    Arunima Chatterjee

    2015-01-01

    Full Text Available Vitamin A plays an essential role in the maintenance of gut homeostasis but its interplay with chemokines has not been explored so far. Using an in vitro model system we studied the effects of human colonic epithelial cells (Caco2, HT-29, and HCT116 derived inflammatory stimuli on monocyte-derived dendritic cells and macrophages. Unstimulated Caco2 and HT-29 cells secreted CCL19, CCL21, and CCL22 chemokines, which could attract dendritic cells and macrophages and induced CCR7 receptor up-regulation by retinoic-acid resulting in dendritic cell migration. The chemokines Mk, CXCL16, and CXCL7 were secreted by all the 3 cell lines tested, and upon stimulation by IL-1β or TNF-α this effect was inhibited by ATRA but had no impact on CXCL1, CXCL8, and CCL20 secretion in response to IL-1β. In the presence of ATRA the supernatants of these cells induced CD103 expression on monocyte-derived dendritic cells and when conditioned by ATRA and cocultured with CD4+ T-lymphocytes they reduced the proportion of Th17 T-cells. However, in the macrophage-T-cell cocultures the number of these effector T-cells was increased. Thus cytokine-activated colonic epithelial cells trigger the secretion of distinct combinations of chemokines depending on the proinflammatory stimulus and are controlled by retinoic acid, which also governs dendritic cell and macrophage responses.

  1. Regulation of CD11b transcription by decreasing PRC2 and increased acH4 level during ATRA-induced HL-60 differentiation

    Institute of Scientific and Technical Information of China (English)

    Huarong Tang; Fangping Chen; Qian Tan; Sanqin Tan; Linxin Liu; Fan Zhang

    2009-01-01

    Polycomb repressive complex 2 (PRC2),which mediates trimethylation of lysine 27 on histone H3 (K27me3),plays an important role in many types of stem cell differentiation.Here,we try to reveal how PRC2,PRC2-mediated repressive histone marker H3K27me3,and active histone marker histone H4 acetylation (acH4) regulate the CD11b transcription during all-trans retinoic acid (ATRA)-induced HL-60 leukemia cell differentiation.By using quantitative real-time polymerase chain reaction (qPCR) and western blot analysis,we found that the mRNA and protein expression levels of two members of PRC2 were decreased during ATRA-induced HL-60 differentiation,respectively.When treated with ATRA for 72 h,the EZH2 and SUZ12 mRNA levels were decreased to 35% and 38% of the control group,respectively.At the same time,the granulocytic mature surface marker CD11b expression was increased significantly at mRNA level detected by qPCR and protein level detected by flow cytometry.By using chromatin immunoprecipita-tion assay,we compared the local changes in SUZ12 binding and PRC2-mediated H3K27me3 at the promo-ter of CD11b during ATRA-induced HL-60 differ-entiation.Both the levels of SUZ12 binding and PRC2-mediated H3K27me3 at the promoter of CD11b were decreased for 4.1 and 3.8 folds,respectively.And we also found the increase in the acH4 level up to 4 folds after 72 h of ATRA treatment.These results suggested that the histone modification including PRC2-mediated repressive histone marker H3K27me3 and active histone marker acH4 may involve in CD11b transcription during HL-60 leukemia cells reprogram-ming to terminal differentiation.

  2. 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

    2016-01-01

    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 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 1H-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 anti-cancer agent. Our exciting observations suggest that the combinatorial approach might be an effective way to combat HCC. PMID:26079152

  3. 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.

  4. Crystallographic observation of pH-induced conformational changes in the Amyelois transitella pheromone-binding protein AtraPBP1.

    Directory of Open Access Journals (Sweden)

    Eric di Luccio

    Full Text Available The navel orangeworm, Amyelois transitella is a major agricultural pest causing large losses in a variety of tree crops. Control of this insect pest may be achieved by interfering with olfactory pathways to block detection of female-produced sex pheromones and consequently, disrupt mating. The first component of this pathway is the pheromone-binding protein AtraPBP1, which recognizes the pheromone and presents it to the odorant receptor housed in a sensory neuron of the male antennae. Release of the ligand depends on a pH-induced conformational change associated with the acidity of the membrane surface. To characterize this conformational change and to understand how pheromones bind, we have determined the high resolution crystal structures of AtraPBP1 in complex with two main constituents of the sex pheromone, i.e., (11Z,13Z-hexadecadienal and (11Z,13Z-hexadecadienol. Comparison with the structure of the unliganded form demonstrates a large ∼90° movement of the C-terminal helix which is observed in other pheromone- or odorant-binding proteins accompanied by an unpredicted 37° displacement of the N-terminal helix. Molecular dynamic trajectories suggest that the conformational change of the α1 helix facilitates the movement of the C-terminal helix.

  5. AChE and EROD activities in two echinoderms, Holothuria leucospilota and Holoturia atra (Holothuroidea), in a coral reef (Reunion Island, South-western Indian Ocean).

    Science.gov (United States)

    Kolasinski, Joanna; Taddei, Dorothée; Cuet, Pascale; Frouin, Patrick

    2010-01-01

    AChE and EROD activities were investigated in two holothurian species, Holothuria leucospilota and Holoturia atra, from a tropical coral reef. These organisms were collected from 3 back-reef stations, where temperature and salinity were homogeneous. The activity levels of both AChE and EROD varied significantly between the two species, but were in the range of values determined in other echinoderm species. AChE activity levels were higher in the longitudinal muscle than in the tentacle tegument. Among the several tissues tested, the digestive tract wall exhibited higher EROD activity levels. Sex did not influence AChE and EROD activity levels in both species. Animal biomass and EROD activity levels were only correlated in the tegument tissue of H. atra, and we hypothesize a possible influence of age. EROD activity did not show intraspecific variability. A significant relationship was found between AChE activity and Cuvierian tubules time of expulsion in Holothuria leucospilota. Individuals collected at the southern site presented both lower AChE activity levels and Cuvierian tubules time of expulsion, indicating possible neural disturbance. More information on holothurians biology and physiology is needed to further assess biomarkers in these key species. This study is the first of its kind performed in the coastal waters of Reunion Island and data obtained represent reference values.

  6. El valor adaptativo de la emoción: ¿Por qué nos atrae la información negativa?

    Directory of Open Access Journals (Sweden)

    Fernando Gordillo

    2010-12-01

    Full Text Available Continuamente estamos sometidos a un enorme flujo de información a la que no podemos prestar atención en su totalidad, y que debe ser filtrada por un mecanismo básico. El contenido emocional de la información es clave en este proceso, de manera que aquello que es potencialmente peligroso atrae nuestra atención para poder ser afrontado con prontitud, al mismo tiempo que nos permite un mejor recuerdo de la información que nos será de utilidad en situaciones similares. En este sentido, podríamos decir que la atracción por lo negativo es un requerimiento adaptativo de alerta y prevención.

  7. Effect of cyclic AMP and acridine orange on the enzymatic reduction of usnic acid in the lichen Usnea aurantiaco-atra (Jacq. Bory

    Directory of Open Access Journals (Sweden)

    C. Vicente

    2014-01-01

    Full Text Available A fluorescence-detection HPLC procedure has been applied to identify and quantify acridine orange in lichen samples. The dye accumulates in thalli of the lichen Usnea aurantiaco-atra and, in part, it is recovered from protamine-precipitated nucleic acids extracted from the samples. A supply of exogenous cyclic AMP reverses the uptake of acridine orange by thallus samples and its binding to nucleic acids. The dye impedes neither the loss of endogenously-produced cyclic AMP by thallus samples nor inhibits the uptake of that exogenously supplied. However, part of the endogenously produced cyclic AMP is secreted to the incubation medium in which phosphodiesterase activity has never been detected. Since the synthesis of D-usnic acid: NAD+(H oxido-reductase is impeded by acridine orange, oxidative catabolism of usnic acid is inhibited in thalli floated on the dye. Cyclic AMP reverses this effect.

  8. Extrusion of the C-terminal helix in navel orangeworm moth pheromone-binding protein (AtraPBP1) controls pheromone binding.

    Science.gov (United States)

    Xu, Wei; Xu, Xianzhong; Leal, Walter S; Ames, James B

    2011-01-07

    The navel orangeworm, Amyelois transitella (Walker), is an agricultural insect pest that can be controlled by disrupting male-female communication with sex pheromones, a technique known as mating disruption. Insect pheromone-binding proteins (PBPs) provide fast transport of hydrophobic pheromones through aqueous sensillar lymph and promote sensitive delivery of pheromones to receptors. Here we present a mutational analysis on a PBP from A. transitella (AtraPBP1) to evaluate how the C-terminal helix in this protein controls pheromone binding as a function of pH. Pheromone binds tightly to AtraPBP1 at neutral pH, but the binding is much weaker at pH below 5. Deletion of the entire C-terminal helix (residues 129-142) causes more than 100-fold increase in pheromone-binding affinity at pH 5 and only a 1.5-fold increase at pH 7. A similar pH-dependent increase in pheromone binding is also seen for the H80A/H95A double mutant that promotes extrusion of the C-terminal helix by disabling salt bridges at each end of the helix. The single mutants (H80A and H95A) also exhibit pheromone binding at pH below 5, but with ∼2-fold weaker affinity. NMR and circular dichroism data demonstrate a large overall structural change in each of these mutants at pH 4.5, indicating an extrusion of the C-terminal helix that profoundly affects the overall structure of the low pH form. Our results confirm that sequestration of the C-terminal helix at low pH as seen in the recent NMR structure may serve to block pheromone binding. We propose that extrusion of these C-terminal residues at neutral pH (or by the mutations in this study) exposes a hydrophobic cleft that promotes high affinity pheromone binding.

  9. c-myc but not Hif-1α-dependent downregulation of VEGF influences the proliferation and differentiation of HL-60 cells induced by ATRA.

    Science.gov (United States)

    Song, Guanhua; Li, Yanmei; Zhang, Zhiyong; Ren, Xia; Li, Hongjiang; Zhang, Wen; Wei, Ruoying; Pan, Sufei; Shi, Lulu; Bi, Kehong; Jiang, Guosheng

    2013-06-01

    Vascular endothelial growth factor (VEGF) plays an important role in solid tumor growth, progression and metastasis as well as in the proliferation and differentiation of hematological malignancies. However, the molecular mechanism that modulates VEGF expression and secretion in leukemia cells has not yet to be elucidated. The purpose of the present study was to investigate the role of the signal pathway in modulating the expression of VEGF in HL-60 cells. Specific siRNAs targeting VEGF were transfected into HL-60 cells and the VEGF expression was measured with reverse transcription-polymerase chain reaction (RT-PCR) and western blot assay. The cell proliferation of HL-60 cells was detected by the cell counting kit-8 (CCK-8) assay and the differentiation of HL-60 cells induced by all-trans-retinoic acid (ATRA) was detected by the RT-PCR assay and flow cytometry assay for CD11b. The upstream transcription factors that were related to VEGF expression such as P53, SP-1, c-jun, VHL, cox-2, c-myc and stat3 were detected by RT-PCR assay. In addition, the chromatin immunoprecipitation (ChIP) assay was used to reveal the role of c-myc by binding the target gene VEGF. The results demonstrated the hypoxia-inducible factor 1α-related signaling pathway, not the same as in solid tumors, might not play a key role in modulating VEGF expression. c-myc contributes to the modulation of VEGF expression by targeting the promoter of VEGF, which was indicated by the ChIP assay. In conclusion, our data demonstrate that VEGF plays an important role in the differentiation and proliferation of HL-60 cells; c-myc-dependent downregulation of VEGF induced by ATRA contributes to the differentiation of HL-60 cells.

  10. 全反式维甲酸治疗急性早幼粒细胞白血病耐药机制的研究进展%Advancement about the drug resistance of ATRA in curing acute promyelocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    唐善浩; 裴仁治

    2009-01-01

    全反式维甲酸(ATRA)治疗急性早幼粒细胞白血病(APL)的耐药机制至今还未完全清楚,它涉及到很多方面的学说,其中基因、蛋白质以及细胞信号传导途径等方面的研究目前越来越成为科学家们研究的热点.%The mechanism of drug resistance about ATRA curing acute promyelocytic leukemia involves many aspects and was not understood completely now. Among them, gene, protein and cell signal conduction way have become hot points that scientists are focusing on recently.

  11. Transient dilated cardiomyopathy in a newborn exposed to idarubicin and all-trans-retinoic acid (ATRA) early in the second trimester of pregnancy.

    Science.gov (United States)

    Siu, B L; Alonzo, M R; Vargo, T A; Fenrich, A L

    2002-01-01

    Acute promyelocytic leukemia was diagnosed in a 28-year-old pregnant woman at 13 gestational weeks. She was immediately started on idarubicin and all-trans-retinoic acid (ATRA) and achieved remission after her fourth cycle of treatment. Serial fetal ultrasonograms throughout pregnancy did not reveal any intrauterine growth retardation or other obvious malformations. The mother delivered a term (36.7 gestational weeks), 2720-gram female neonate. The infant was admitted to the intermediate care nursery for observation due to transient mild respiratory distress during the peripartum period. Because of right ventricular hypertrophy on an electrocardiogram, an echocardiogram was performed on the first day of life which showed moderate dilation of the right atrium and right ventricle with mildly depressed function, two small secundum atrial septal defects, and a small patent ductus arteriosus. The neonate remained hemodynamically stable and no arrhythmias were detected. The remainder of the hospital course was uneventful. When reassessed 1-1/2 months later, she was doing well and did not show any signs of congestive heart failure. A repeat echocardiogram at that time demonstrated complete resolution of the right heart enlargement and closure of the ductus arteriosus with persistence of the small and hemodynamically insignificant secundum atrial septal defects.

  12. Effect of ATRA and ATO on the expression of tissue factor in NB4 acute promyelocytic leukemia cells and regulatory function of the inflammatory cytokines TNF and IL-1β.

    Science.gov (United States)

    Dunoyer-Geindre, Sylvie; Rivier-Cordey, Anne-Sophie; Tsopra, Olga; Lecompte, Thomas; Kruithof, Egbert K O

    2017-03-25

    The characteristic hemorrhages of acute promyelocytic leukemia (APL) are caused in part by the high expression of tissue factor (TF) on leukemic cells, which also produce TNF and IL-1β, proinflammatory cytokines known to increase TF in various cell types. Exposure of NB4 cells, an APL cell line, to all-trans retinoic acid (ATRA) or arsenic trioxide (ATO) rapidly and strongly reduced TF mRNA. Both drugs also reduced TNF mRNA, but later, and moreover increased IL-1β mRNA. The effect on procoagulant activity of cells and microparticles, as measured with calibrated automated thrombography, was delayed and only partial at 24 h. TNF and IL-1β inhibition reduced TF mRNA and activity only partially. Inhibition of the inflammatory signaling intermediate p38 reduced TF mRNA by one third but increased TNF and IL-1β mRNA. NF-κB inhibition reduced, within 1 h, TF and TNF mRNA but did not change IL-1β mRNA, and rapidly and markedly reduced cell survival, with procoagulant properties still being present. In conclusion, although we provide evidence that TNF, IL-1β, and their signaling intermediates have a regulatory function on TF expression by NB4 APL cells, the effect of ATRA and ATO on TF can only partially be accounted for by their impact on these cytokines.

  13. 全反式维甲酸联合顺铂对A549细胞增殖及PDCD5和TP53 mRNA表达的影响%Effects of ATRA combined with cisplatin on A549 cell proliferation and expression of PDCD5 and TP53 mRNA

    Institute of Scientific and Technical Information of China (English)

    刘红; 李海燕; 李伟国; 康燕; 陈红杰; 黄永杰; 王静

    2013-01-01

    目的 观察全反式维甲酸(ATRA)联合顺铂对肺癌A549细胞增殖的影响,探索ATRA应用的最适浓度,研究各组肺癌A549细胞PDCD5、TP53基因表达情况.方法 以不同浓度的ATRA(10-5 mol/L、10-6 mol/L、10-7 mol/L)与顺铂(10-2 μmol/L)联合作用于肺癌A549细胞,采用MTT法检测细胞增殖情况.利用RT-PCR检测ATRA、顺铂作用于肺癌细胞A549细胞后,凋亡相关基因PDCD5、TP53 mRNA的表达.结果 ①MTT研究可观察到,在24 h、48 h、72 h各时间点,ATRA组、顺铂组及两药联合组A549细胞增殖率与阴性对照组比较明显降低(P<0.05);在同一时间点,ATRA不同的浓度间,抑制率随浓度的增加而增加(P<0.05).②与阴性对照组相比,药物干预组PDCD5、TP53mRNA含量明显增加(P<0.05).结论 ATRA对肺癌A549的生长具有抑制作用,有明显的浓度和时间依赖性;ATRA及其与顺铂联用,可以诱导PDCD5及TP53的mRNA的表达.PDCD5与TP53的表达呈正相关.%Objective To observe the functions of all-trans retinoic acid (ATRA) combined with cisplatin on proliferation of A549 cells and to explore the optimal concentration of ATRA and the expressions of PDCD5,TP53 genes of A549 cells in different groups.Methods A549 cells were treated by different concentrations of ATRA (10-5 mol/L,10-6 mol/L,10-7 mol/L) and cisplatin (10-2 μmol/L).MTT assay was used to detect cell proliferation in different groups.The expressions of PDCD5 and TP53 mRNA were detected by RT-PCR.Results ①MTT assay showed the cell proliferation rate in ATRA group,cisplatin group,and two-drug group was lower than that in control group (P <0.05) in 24 h,48 h,and 72 h after treatment.At the same time-point,cell inhibition rate increased with the increase of the concentration of ATRA (P <0.05).②Compared with control group,mRNA of PDCD5 and TP53 in groups treated with drugs increased (P <0.05).Conclusions The growth of lung cancer A549 cells can be inhibited by ATRA in a concentration

  14. 全反式维甲酸和5-Fu对胃癌细胞端粒酶活性和细胞生长的影响%The effects of ATRA and 5-Fu on telomerase activity and cell growth of gastric cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    朱兆华; 夏忠胜; 何守搞

    2000-01-01

    目的观察ATRA,5-Fu单独和联合应用对体外培养的胃癌细胞端粒酶活性及细胞生长的影响.方法分别用ATRA,5-Fu单独和联合处理胃癌MGC-803细胞,采用MTT法测定细胞活力,采用端粒重复序列扩增法测定端粒酶活性.结果胃癌细胞活力随ATRA,5-Fu浓度增高、作用时间的延长其细胞活力逐渐下降,ATRA d1,d3,d 5的IC50分别为>40μmol/L,(20~40)μmol/L,(10~20)μmol/L;5-Fu d1,d3,d5的IC50分别为>25μmol/L,(2~5)μmol/L,(2~5)μmol/L;40μmol/L ATRA,5μmol/L 5-Fu及40μmol/LATRA+5μmol/L 5-Fu处理胃癌细胞3 d其细胞活力分别为46%,47%,8%(P<0.01),端粒酶活性分别为45.68%(P<0.01),100.00%,46.10%(P<0.01).结论ATRA,5-Fu均能抑制胃癌细胞的生长,其抑制作用具有时间和浓度依赖性,且二者合用具有协同抑制作用;ATRA能抑制胃癌细胞端粒酶活性,而5-Fu对胃癌细胞端粒酶活性无影响,二者合用对胃癌细胞端粒酶活性无协同抑制作用.抑制端粒酶活性可能是ATRA抗癌机制之一.

  15. 眼镜蛇毒对大鼠脊髓Nestin和BDNF表达的影响%Effects of naja naja atra venom on nestin and BDNF expression in spinal cor d of rats

    Institute of Scientific and Technical Information of China (English)

    王继胜; 丁见; 吴锋; 熊克仁

    2013-01-01

    Objective:To observe the effects of naja naja atra venom on the expression of nestin and brain-derived Neorotrophin factors(BDNF)in the spinal cord of rats.Metho ds: Twenty-four rats were randomly divided into groups of normal controls,administration of either normal saline or snake venom( n=8 for each) .Poisoning rat models were developed by in-jection of the crude venom of cobra at dosage of 0 .5 μl/kg via left poste-rior limb,and killed in 30 min.Immunohistochemical technique was used to detect the expression of nestin and BDNF in lumbar spinal cord . Results:The number of nestin and BDNF positive cells were increased significantly in the anterior horn and posterior horn of the gray matter in lumbar spinal cord in rats treated with the naja naja atra venom as com-pared with the controls and saline management group(P<0.05),and the cells presented with darker coloration,whereas the average gray value of nestin and BDNF was notably decreased in the snake venom treated ani-mals than the normal controls and saline groups(P<0.05).Conclusion:The nestin and BDNF expression were upregulated in the gray matter in spinal cord of rats treated with naja naja atra venom,suggesting that this protein and the factor may be involved in compensatory repair of the in-jured spinal cord.%目的:观察眼镜蛇毒对大鼠脊髓Nestin和BDNF表达的影响。方法:24只大鼠随机分为正常对照组、生理盐水组和眼镜蛇毒组,每组8只。眼镜蛇粗毒以0.5μl/kg注入左后肢内侧复制蛇伤模型,30 min后处死动物,采用免疫组织化学方法,检测脊髓腰段Nestin 和BDNF的表达。结果:眼镜蛇毒组大鼠脊髓腰段前角和后角Nestin和BDNF阳性神经元数量较正常对照组、生理盐水组均明显增多(P <0.05),且着色较深,眼镜蛇毒组脊髓Nestin和BDNF平均灰度值较正常对照组、生理盐水组表达均明显降低(P <0.05)。结论:眼镜蛇毒致伤后,脊髓灰质Nestin

  16. The Effects of All-Trans Retinoic Acid (ATRA) on the Expression of Ski in Cultured Rat Mesangial Cells Treated by TGF-β1%Ski在全反式维甲酸抑制TGF-β1诱导的系膜细胞增殖中的作用

    Institute of Scientific and Technical Information of China (English)

    苏宝凤; 王晓花; 张莉; 于莹; 陈晓岚

    2013-01-01

    目的 探讨全反式维甲酸(ATRA)对转化生长因子(TGF)-β1诱导的大鼠系膜细胞增殖及Ski表达的影响.方法 不同浓度ATRA预处理大鼠HBZY-I系膜细胞(为各剂量ATRA组)24 h后再加TGF-β1(10 μg/L)培养24 h.CCK-8法检测细胞增殖情况;Real-time PCR法检测Ski mRNA的表达;Western blot检测Ski蛋白的表达;激光共聚焦荧光显微镜检测Ski蛋白的亚细胞定位.并与正常对照组及TGF-β1组比较.结果 与正常对照组相比,TGF-β1组系膜细胞增殖明显,且Ski mRNA及蛋白表达升高(P<0.05);与TGF-β1组相比,ATRA能够呈剂量依赖性地抑制TGF-β1的促增殖作用,ATRA 10 μmol/L组Ski mRNA及蛋白表达量明显增高.ATRA组Ski蛋白主要定位于大鼠系膜细胞核,其细胞核荧光信号强度较TGF-β1组明显增强,细胞浆中荧光信号强度较TGF-β1组减弱.结论 ATRA可通过上调大鼠系膜细胞Ski表达,抑制其向核外转位,从而抑制TGF-β1诱导的系膜细胞增殖.%Objective To investigate the effects of all-trans retinoic acid (ATRA) on the expression of Ski in cultured rat mesangial cells treated by transforming growth factor (TGF-β1).Methods The mesangial cells were pre-treated with different concentrations of ATRA for 24 h, and then stimulated with TGF-β1 (10 μg/L) for 24 h.The cell proliferation was detected by CCK-8 method.The Ski mRNA expression was determined by real time-PCR.The protein expression of Ski was determined by Western blot analyses.The localization of Ski was observed by confocal fluorescence microscopy.Results Compared with the control group, TGF-β1 significantly enhanced the proliferation and the expression of Ski mRNA and protein in rat mesangial cells (P < 0.05).ATRA significantly inhibited mesangial cell proliferation induced by TGF-β1 in a dose-dependent manner.In ATRA groups, Ski mRNA and protein were increased significantly.Additionally, Ski protein was mainly localized in nucleus, and fluorescence intensity was

  17. ATRA对三阴性乳腺癌细胞CDH1表达的影响%Effect of ATRA on CDH1 Expression in Triple-negative Breast Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    陈卓荣; 沈三弟; 黄湛; 赵欣; 雷睿文

    2012-01-01

    目的 探讨全反式维甲酸(ATRA)对三阴性乳腺癌(TNBC)细胞系MDA-MB-231的CDH1表达的影响及可能机制.方法 实验分空白对照组(control)、5-杂氮-2'-脱氧胞苷(5-Aza-CdR)组及ATRA组,分别用甲基化特异性PCR(MSP)、逆转录PCR(RT-PCR)方法检测MDA-MB-231细胞CDH1基因启动子区甲基化状态及mRNA表达情况.结果 空白对照组MDA-MB-231细胞CDH1基因启动子区处于甲基化状态,CDH1mRNA无表达,而5-Aza-CdR组与ATRA组CDH1基因启动子区处于非甲基化状态,CDH1 mRNA表达明显上调,且两组之间无明显差别.结论 ATRA能够通过去甲基化机制上调MDA-MB-231细胞CDH1基因的表达.

  18. A Gestão de Pessoas e as Estratégias de Atração, Desenvolvimento e Retenção de Profissionais: O Caso Petrobras

    Directory of Open Access Journals (Sweden)

    Nildes Pitombo Leite

    2013-12-01

    Full Text Available Este estudo de caso, ancorado na abordagem qualitativa e com nível de análise organizacional, investigou a gestão de pessoas dentro de unidades com estruturas organizacionais remotas (i.e., longe dos centros urbanos e não remotas da PETROBRAS – Petróleo Brasileiro S/A. A pesquisa foi realizada em três plataformas marítimas, três bases e na unidade operacional da selva Amazônica, envolvendo 31 respondentes, entre diretores, gerentes, profissionais de RH, supervisores e coordenadores. Esses respondentes são representativos para o nível de análise escolhido, bem como para a estratégia de pesquisa. Seu foco esteve voltado para dois problemas principais, considerados igualmente relevantes: Como gerenciar pessoas em unidades distantes das principais sedes da organização? Como gerenciar essas pessoas de modo a assegurar os objetivos estratégicos de atrair, desenvolver e reter o capital humano valorizado nessas unidades? A coleta dos dados primários foi feita por meio de entrevistas em profundidade e observações; a dos dados secundários, por meio de análise de documentos. Trabalhou-se com as estratégias das análises de conteúdo, documental e reflexiva. Seus resultados indicaram as especificidades de políticas e práticas de gestão de pessoas, oriundas das estratégias de atração, desenvolvimento e retenção de profissionais nessas unidades, especificidades essas que representam contribuição para a área de gestão de pessoas. DOI:10.5585/riae.v12i4.2043

  19. Atração de miracídios de Schistosoma mansoni por hospedeiros invertebrados: comportamento de miracídios frente a girinos de Hyla fuscovaria Miracidia attraction to invertebrate hosts: miracidia behavior in the presence of Hyla fuscovaria girina

    Directory of Open Access Journals (Sweden)

    Beatriz de C. Brasio

    1985-02-01

    Full Text Available Analisou-se a atração de miracídios de Schistosoma mansoni das linhagens BH e SJ frente a seus vetores simpátricos e alopátricos tendo-se em consideração a possibilidade da presença de substâncias quimiotáxicas emanadas dos moluscos. Estudou-se também o comportamento desses miracídios frente a girinos de Hyla fuscovaria. Foi verificado que houve atração dos miracídios pelos moluscos vetores e que essa atração foi mais evidente quando a larva era colocada frente ao seu hospedeiro simpátrico.As observações realizadas no decorrer da experiência demonstraram a presença de substâncias miraxonais emanadas pelos moluscos.Miracidia tropism to suitable hosts is a subject of much controversy. In this work, we try to determine the possible specificity of Schistosoma mansoni miracidia attraction and also the degree of this specificity. To this end an experiment was carried out to determine the probability of attraction in a given experimental set up, to H. fuscovaria girina or to one of two susceptible snail species. Two strains of S. mansoni were employed and also the corresponding snail species. A specially designed apparatus consisting of two circular glass chambers joined by an open channel was used. One of the girina or a snail was placed in one of the chambers (randomly chosen. In the channel a known number of miracidia were deposited and the count of miracidia in each of the three compartments (the two chambers and the channel was recorded. The experiment was carried out under strong or subdued lighting. Statistical and ad-hoc exploratory data analysis have shown that: a the miracidia, when exposed to only one species of snail, show more attraction to the sympatric snail host; bone strain of miraciadia showed more attraction under strong lighting; the other strain behaved the opposite way, with stronger attraction under weak liht; c the girina did not attract the miracidia; this seems to imply that sone chemiotropism is present

  20. Atração miraxonal exercida por Biomphalaria straminea, Lymnaea columella e Physa sp, sobre miracídios de Schistosoma mansoni da linhagem BH The miraxonal attraction exercised by Biomphalaria straminea, Lymnaea columella and Physa sp over miracidia of Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Luiz A. Magalhães

    1991-02-01

    Full Text Available Utilizando-se um artefato de vidro composto de duas câmaras unidas por um canal, testamos a atração miraxonal exercida por Biomphalaria straminea, Lymnaea columella e Physa sp, sobre larvas de Schistosoma mansoni da linhagem BH. Os moluscos, ou suas águas de condicionamento (SCW, foram colocados aleatoriamente em uma das câmaras, contendo o restante do artefato somente água declorada. Dez miracídios foram depositados no centro do canal. O comportamento dos miracídios foi observado por 15 min. Foram feitas dez replicações de cada experimento, utilizando-se espécimens de moluscos e miracídios diferentes. Verificou-se que todos os moluscos e suas SCW exerceram atração miraxonal, sendo que Physa sp atraiu mais que Lymnaea columella. Foi isolado um único exemplar de B. straminea que exerceu efeito repulsivo sobre os miracídios de S. mansoni.The attraction exercised over Schistosoma mansoni miracidia by Biomphalaria straminea, Lymnaea columella and Physa sp using a specially designed apparatus consisting of two circular glass chambers joined by an open channel were studied. The molluscs or their snail-conditioned water (SCW was placed in one of the chambers (randomly chosen. In the channel ten miracidia was deposited and the count of miracidia in each of the three compartments (the two chambers and the channel was recorded during fifteen minutes. Ten replications of each experiment with different specimens of molluscs and miracidia were made. Statistical and ad-hoc exploratory data analysis showed that: a the three species of molluscs and their SCW attract the miracidia; b Physa sp attract more miracidia then L. columella. There was an isolated single B. straminea specimen that had a repulsive effect to the miracidia.

  1. Pacientes adultos con recidiva de leucemia promielocítica aguda (LPA) o leucemia promielocítica aguda refractaria después de haber sido tratados con ácido trans retinóico total (ATRA) y trióxido de arsénico (ATO) (en combinación o secuencialmente). | EU Clinical Trials Register [EU Clinical Trials Register

    Lifescience Database Archive (English)

    Full Text Available aroteno en pacientes con leucemia promielocítica aguda que hayan recibido terapia previa con ATRA y trióxido...ondition(s) being investigated Pacientes adultos con recidiva de leucemia promielocítica aguda (LPA) o leucemia...dultos con recidiva de LPA o LPA refractaria. E.2.2Secondary objectives of the trial Determinar las tasas de estado libre de leucemia...nicamente significativa y que se considera que no guarda relación con la leucemia

  2. 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

  3. 全反式维甲酸与紫杉醇、阿霉素联合诱导HL-60细胞凋亡的研究%Studies on the apoptosis using ATRA in combination with taxol and ADR in HL-60 cell lines

    Institute of Scientific and Technical Information of China (English)

    尤学芬; 丁润生; 谢玉娟; 姚登福; 陆德炎

    2007-01-01

    目的:探讨全反式维甲酸(ATRA)分别与紫杉醇(Taxol)、阿霉素(ADR)单独或联合孵育HL-60细胞株能否增强凋亡诱导作用,并进一步研究bcl-2基因及家族bax、bcl-x基因在此过程中的作用.方法:①用台盼兰拒染法观察细胞生长活力;②在光镜和电镜下观察细胞形态变化;③用流式细胞仪(FCM)检测药物孵育前后细胞凋亡率(AP)的变化;④用RT-PCR法检测药物孵育前后bcl-2基因及其家族bax、bcl-x基因的表达水平.结果:①ATRA能增强Taxol和ADR对HL-60细胞的生长抑制作用;②ATRA能增强HL-60细胞对Taxol和ADR诱导的细胞凋亡;③在ATRA与Taxol、ADR联合诱导的HL-60细胞凋亡中,bcl-2、bcl-xl基因表达下降,bax、bcl-xs基因表达增加.结论:ATRA能增加Taxol和ADR对HL-60细胞的生长抑制作用及凋亡诱导作用,bcl-2基因及家族bax、bcl-x基因参与了ATRA与Taxol、ADR联合诱导细胞凋亡的调控.

  4. Effect of Atra on the Expression of CyclinD3 and Lipoprotein-associated phospholipase A2 in injury nidus of carotid endothelium in rabbits%ARTA对兔颈动脉内膜损伤病灶CydinD3及LP-PLA2的影响

    Institute of Scientific and Technical Information of China (English)

    胡真真; 董果雄; 张社华; 张滨; 姚如永

    2012-01-01

    目的 观察全反式维甲酸(ARTA)对兔颈动脉内膜损伤与修复病灶内膜增生和细胞周期素CyclinD3及炎性相关因子LP-PLA2表达的影响和机制.方法 将54只健康新西兰大白兔随机分为9组(n=6):正常对照组(A、B、C)、高脂饮食组(A、B、C)、治疗组(A、B、C).普通饮食后正常对照组仅暴露颈动脉;高脂饮食组,暴露颈动脉并损伤内膜;治疗组用ARTA灌胃,其他操作同高脂饮食组.术后1周、2周、4周处死A、B、C组动物,对病变血管行形态学观察和测定,分别用ELISA和免疫组化方法检测颈动脉内膜损伤与修复病灶中LP-PLA2和CyclinD3的表达水平.结果 ①正常对照组LP-PLA2仅有微量表达.CyclinD3胞浆呈弱阳性表达,胞核呈阴性表达.②高脂饮食组在术后7天内膜开始增生,28天后明显增生,出现泡沫细胞、脂质条纹、管腔狭窄.LP-PLA2和CyclinD3表达水平较正常组显著增高.③治疗组LP-PLA2和CyclinD3表达水平明显低于高脂饮食组(P<0.05).内膜的增生和管腔的狭窄显著减轻(P<0.05).结论 ARTA可以通过抑制LP-PLA2和CyclinD3的表达,抑制内膜的炎症反应和血管平滑肌细胞的增生,从而抑制颈动脉内膜损伤病灶的过度增生和管腔狭窄.%Objective To observe the influence of all-trans retinoic acid( ATRA) on the process of neointimal formation and the expression of CyclinD3 and Lipoprotein-associated phos pholipase A2 in injury nidus of carotid endothelium in rabbits. Methods Fifty-six healthy male New-Zealand rabbits were randomly divided in to 9 groups(=6): normal control groups(A, B, C), high-fat groups(A, B, C), treatment groups(A, B, C). There were 6 rabbits in each group. The normal control groups were fed with conventional chow, and underwent surgery without endothelium injury. The high-fat groups were fed with high cholesterol chowand. subjected to the carotid endothelial injury by air desiccation. The treatment groups were administered ATRA

  5. Composição e diversidade de Scarabaeoidea (Coleoptera atraídos por armadilha de luz em área rural no norte do Paraná, Brasil Composition and diversity of Scarabaeoidea (Coleoptera attracted by light trap in the rural areas of Northern Paraná

    Directory of Open Access Journals (Sweden)

    Daniele C. Ronqui

    2006-03-01

    Full Text Available No Estado do Paraná, as áreas mais devastadas são aquelas com potencial agrícola e as ações de inferência no meio raramente são precedidas do estudo faunístico que permitam avaliar a diversidade e abundância dos animais das áreas atingidas. Este trabalho objetivou catalogar a escarabeoideofauna atraída por armadilha de luz na área rural do município de Tamarana, Paraná e contribuir com o conhecimento ecológico de espécies deste grupo. As coletas foram realizadas em duas propriedades, utilizando armadilha de luz modelo Luiz de Queiroz modificada. Estas tiveram periodicidade quinzenal de março de 2002 a abril de 2001. Foram capturados 2.447 espécimens, distribuídos em 10 famílias, 24 gêneros e 67 espécies. As três espécies mais abundantes também foram as mais freqüentes: Aphodius lividus (Olivier, 1789, Melolonthidae sp. 1 e Ataenius sp. 5. A maior abundância de A. lividus ocorreu no outono, durante o mês de abril, enquanto que Melolonthidae sp. 1 e Ataeucus sp. 5 foram mais abundantes em outubro e novembro. A maioria das espécies foram representadas por poucos indivíduos (H'=1,74 e as espécies apareceram de maneira uniforme (J'=0,95; S=0,20. Ocorreu um maior número de famílias que estavam representadas por poucos indivíduos. Houve predominância das famílias que apresentam hábitos alimentares detritívoros - Aphodiidae, Scarabaeidae, Hybosoridae e fitófagos - Melolonthidae, Dynastidae e Rutelidae. Para os grupos de hábito detritívoro, foram coletados 25 espécies, num total de 1.422 espécimes.The most devastated environments in the State of Paraná are those with great agricultural potential, and most human interference actions on the environment are seldom preceded by a careful study of the fauna, which would reveal the diversity and abundance of animals in these areas. This study aimed to describe the Scarabaeoidea fauna attracted by light traps in rural areas of the Tamarana County, Paraná, Brazil, and

  6. 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

  7. Unhatched and Hatched Eggshells of the Chinese CobraNaja atra

    Institute of Scientific and Technical Information of China (English)

    Zheng WANG; Longhui LIN; Xiang JI

    2014-01-01

    Changes in structure and composition of the eggshell resulting from embryonic mobilization of minerals from the eggshell are found in all oviparous reptiles studied thus far. In this study, we measured samples of unhatched and hatched eggshells of the Chinese cobraNaja atrato determine the percentage of ash and the phase composition of calcium carbonate. The mean percentage of ash was signiifcantly higher in unhatched eggshells (24.6%) than in hatched eggshells (22.3%). The dominant phase in unhatched eggshells was the calcite form of calcium carbonate. In addition to the peaks of calcite, a few small peaks were found to be caused by the aragonite and vaterite phases of calcium carbonate, implying that there are small amounts of aragonite and vaterite in the eggshell. The concentration of the various phases calculated from the intensity of the X-ray diffraction spectra allowed the estimation that percentages of calcite, aragonite and vaterite were about 92%, 4% and 4%, respectively. Hatched eggshells produced similar spectral characteristics as unhatched eggshells, with one exception. The dominant phase composition in the hatched eggshell was also calcite, but the amount of the aragonite phase had a marked increase. Our study adds evidence that embryonic mobilization of minerals from the eggshell may result in changes in structure of the eggshell.

  8. Allogeneic stem cell transplantation for advanced acute promyelocytic leukemia in the ATRA and ATO era.

    Science.gov (United States)

    Ramadan, Safaa M; Di Veroli, Ambra; Camboni, Agnese; Breccia, Massimo; Iori, Anna Paola; Aversa, Franco; Cupelli, Luca; Papayannidis, Cristina; Bacigalupo, Andrea; Arcese, William; Lo-Coco, Francesco

    2012-11-01

    The role of allogeneic stem cell transplant in advanced acute promyelocytic leukemia patients who received standard first- and second-line therapy is still unknown. We report the outcome of 31 acute promyelocytic leukemia patients (median age 39 years) who underwent allogeneic transplant in second remission (n=15) or beyond (n=16). Sixteen patients were real-time polymerase chain reaction positive and 15 negative for PML/RARA pre-transplant. The 4-year overall survival was 62% and 31% for patients transplanted in second remission and beyond, respectively (P=0.05), and 64% and 27% for patients with pre-transplant negative and positive real-time polymerase chain reaction, respectively (P=0.03). The 4-year cumulative incidence of relapse was 32% and 44% for patients transplanted in second remission and beyond, respectively (P=0.37), and 30% and 47% for patients transplanted with negative and positive real-time polymerase chain reaction, respectively (P=0.30). Transplant-related mortality was 19.6%. In conclusion, allogeneic transplant is effective in advanced acute promyelocytic leukemia in the all-trans-retinoic acid and arsenic trioxide era, and should be considered once relapse is diagnosed.

  9. Sügis 2012. Haridusteadus seab atra vaole / Virve Liivanõmm

    Index Scriptorium Estoniae

    Liivanõmm, Virve

    2012-01-01

    Tartu ülikoolis saavad alates 2018. a. lektoritena tööd ainult doktoritöö kaitsnud. Lektorite praegusest haridusseisust TLÜ kasvatusteaduste instituudis ja psühholoogiaprofessor Mati Heidmetsa visioon lektorite kvalifikatsiooninõuetest. TLÜ kasvatusteaduste instituudi algõpetuse osakonna juhataja, didaktika aluste ja matemaatikadidaktika lektor on oma instituudi värskeim doktor

  10. 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.

  11. 中国商业经济学会储运研究分会章程%ATRA Constitution

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ 第一章 总则 第一条 本会名称为:中国商业经济学会储运研究分会(英文名:Warehousing and Transportation Research Association of China Commercial Economy Sociery,缩写:WTRA).

  12. First report of long term measurements of the MGGL laboratory in the M\\'atra mountain range

    CERN Document Server

    Barnaföldi, G G; Cieslar, M; Dávid, E; Dobróka, M; Fenyvesi, E; Gráczer, Z; Hamar, G; Huba, G; Kis, Á; Kovács, R; Lemperger, I; Lévai, P; Molnár, J; Nagy, D; Novák, A; Oláh, L; Pázmándi, P; Piri, D; Rosinska, D; Starecki, T; Suchenek, M; Surányi, G; Szalai, S; Varga, D; Vasúth, M; Ván, P; Vásárhelyi, B; Wesztergom, V; Wéber, Z

    2016-01-01

    Matra Gravitational and Geophysical Laboratory (MGGL) has been established near Gy\\"ongy\\"osoroszi, Hungary in 2015, in the cavern system of an unused ore mine. The Laboratory is located at 88~m below the surface, with the aim to measure and analyse the advantages of the underground installation of third generation gravitational wave detectors. Specialized instruments have been installed to measure seismic, infrasound, electromagnetic noise, and the variation of the cosmic muon flux. In the preliminary (RUN-0) test period, March-August 2016, data collection has been accomplished. In this paper we describe the research potential of the MGGL, list the installed equipments and summarize the experimental results of RUN-0. A novel theoretical framework of noise damping in rock masses is also introduced. Here we report RUN-0 data, that prepares systematic and synchronized data collection of the next run period.

  13. 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 i...

  14. ¿Estan los paises europeos dando pasos atras? El caso de España y las politicas neoinjustas

    Directory of Open Access Journals (Sweden)

    Fernando Garcia Quero

    2014-01-01

    Full Text Available Este artículo aborda la crisis económica actual desde la óptica de sus consecuencias sobre la pérdida de derechos humanos en las sociedades supuestamente más desarrolladas del mundo. Situándose en el caso concreto de España, el objetivo principal del trabajo es mostrar y analizar el enorme retroceso que como resultado de la implantación paulatina de unas políticas neoinjustas, se está produciendo en los derechos humanos de segunda generación. Para ello se diferencian dos periodos históricos con implicaciones muy distintas para los derechos de la ciudadanía: el de consolidación de los Estados de Bienestar europeos (1945-1975; y el que abarca de mediados de los años 70 hasta la actualidad. Mediante un análisis documental y bibliográfico, el principal hallazgo al que se llega en este trabajo es la existencia de una relación bidireccional de retroalimentación entre un Estado de Bienestar fuerte y el cumplimiento de los derechos humanos, siendo imposible, como manifiesta la coyuntura actual española, un Estado cada vez más débil y una mejora en los derechos humanos. Se concluye que la dinámica seguida durante las últimas décadas está llevando a España a un escenario muy precario, que solo puede ser revertido a través de una ciudadanía activa que recupere su poder en las decisiones estatales.

  15. 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.

  16. 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.

  17. 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

  18. Branding de países e atração de investimento direto estrangeiro : o papel do soft power

    OpenAIRE

    Santos, Ana Cristina Leitão

    2013-01-01

    Mestrado em Marketing Nas últimas décadas, deu-se uma mudança no paradigma internacional e na maneira como os países se interrelacionam. Estas relações, cada vez mais económicas, exigem uma nova abordagem por parte dos países. Neste sentido, o conceito de soft power de Joseph Nye, enquanto poder de atracção de um país e que pode ser encontrado na sua cultura, valores e políticas externas, ao invés de hard power, considerado como poder de coerção e que pode ser económico ou militar, ganha u...

  19. Representação social de sujeitos alcoolistas acerca da atração e da dependência do uso de álcool

    Directory of Open Access Journals (Sweden)

    Silvio Eder Dias da Silva

    2015-06-01

    Full Text Available Introdução: O consumo de álcool está relacionado a vários fatores sendo considerados fatores de risco, sem restrição de classe, idade ou sexo. A família, o meio de interação social e as propagandas são três de vários fatores que podem influenciar o consumo de bebidas alcoólicas. O risco familiar e grupo de envolvimentos são considerados importantes critérios de vulnerabilidade ao alcoolismo. Este estudo objetivou conhecer a representação social do alcoolista sobre a de sua dependência química e analisar as implicações dessa representação social para o cuidado de si. Metodologia: É um estudo é do tipo descritivo e exploratório, com base na Teoria das Representações Sociais, realizado em um Centro de Atenção Psicossocial - Álcool e Drogas, em Belém-PA, com 31 sujeitos que estavam em tratamento por dependência química. Resultados: Com a análise dos dados obtivemos resultados de duas unidades temáticas: A influência parental no interesse pelo alcoolismo que mostra o meio familiar como importante influenciador para que o sujeito inicie a beber e Fatores que influenciaram o alcoolismo na adolescência em que se mostram as características da adolescência como influenciador da experimentação do álcool. Conclusão: Durante as entrevistas, pôde-se entender que, desde o início de suas vidas, os sujeitos que se tornaram alcoólatras estiveram expostos a um meio social com integrantes alcoolista, que gerou entusiasmo para uma vida cotidiana voltada para o uso do álcool; os depoimentos expressam que a família e o período da adolescência configuraram importantes fatores para sua realidade atual.

  20. 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.

  1. Uji Sitotoksik Ekstrak Etanol dan Fraksi n-Heksana serta Etil Asetat Teripang Jenis Holothuria atra Jaeger Metode Brine Shrimp Lethality Test (BSLT)

    OpenAIRE

    Gultom, Ester Lia

    2016-01-01

    Sea cucumbers are one of marine invertebrate animals that are consumed by Asian and used in traditional Chinese medicine to enhance the body's immunity against various diseases. Therapeutic effects and benefits of medication of sea cucumber such as antifungal, antibacterial, anti-inflammatory, anticancer, antitumor, and other activities are associated by the bioactive compounds in sea cucumbers, particularly triterpene glycosides. The purpose of this study was testing and assessing the LC50 o...

  2. Recent Progress in Visible-Light Photoredox-Catalyzed Intermolecular 1,2-Difunctionalization of Double Bonds via an ATRA-Type Mechanism.

    Science.gov (United States)

    Courant, Thibaut; Masson, Géraldine

    2016-08-19

    Radical difunctionalizations of alkenes constitute an efficient method for the construction of complex organic molecules. This synopsis focuses on visible-light catalysis, a recent and very promising technological refinement of this class of transformations. Examples taken from the literature illustrate the use of a variety of (metallic or nonmetallic) systems, which allow us to leverage the energy of readily available visible-light radiation to efficiently create some of the most commonly looked for types of bonds (C-X, C-O, C-N, and C-C) under mild conditions and starting from unsaturated substrates.

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

    Science.gov (United States)

    Binkowski, Łukasz J; Sawicka-Kapusta, Katarzyna; Szarek, Józef; Strzyżewska, Emilia; Felsmann, Mariusz

    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.

  4. 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.

  5. 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.

  6. Encontro às escuras: sobre a atração entre as pessoas. O que mantém as pessoas unidas? (em um Projeto

    Directory of Open Access Journals (Sweden)

    Antonio Mendes Silva Filho

    2015-10-01

    Full Text Available Em toda história humana, nunca houve período com demanda tão elevada por profissionais qualificados como o atual. Os rumos da economia mundial não são, unicamente, ditados pelas nações desenvolvidas. O século 21 é centrado no conhecimento e respectiva capacidade de inovação promovida pelas pessoas, i.e., organizações (afinal, uma organização é feita de pessoas. Este é fator determinante no destino da humanidade. O futuro e respectivo domínio dependerão, primariamente, do conhecimento e a capacidade de inovação tem sido o principal propulsor deste avanço. Entretanto, para que isso aconteça numa escala maior, as pessoas são esperadas trabalharem juntas, em equipe, como um time. Mas, o que mantém as pessoas juntas perseguindo e trabalhando em pró de uma meta comum? O que poderia mover pessoas diferentes se unirem após um ‘encontro às escuras’? Este artigo discute essas questões que são determinantes ao cotidiano das pessoas e organizações, especulando e apontando respostas.

  7. Educando a Estudiantes con Diversidades Linguisticas y Culturales (Educating Linguistically and Culturally Diverse Students). Que Ningun Nino se Quede Atras (No Child Left Behind).

    Science.gov (United States)

    Office of English Language Acquisition, Language Enhancement, and Academic Achievement for Limited English Proficient Students (ED), Washington, DC.

    The brochure, written in Spanish, briefly outlines the U.S. Department of Education's most recent policy on educating students with diverse linguistic and cultural backgrounds. It states the Department's mission, describes today's student population, and outlines the role of the Office of English Language Acquisition, Language Enhancement and…

  8. 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.

  9. 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.

  10. 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…

  11. 眼镜蛇毒细胞毒素缓释微球制备及体外性质研究%Preparation and characterization of poly (lactide-co-glycolide acid) microspheres containing cytotoxin from Naja Naja Atra venom

    Institute of Scientific and Technical Information of China (English)

    陈志奎; 林礼务; 林琦; 庄权权; 何以敉; 薛恩生

    2008-01-01

    目的 研究眼镜蛇毒细胞毒素(Cytotoxin, CTX)聚乳酸/羟基乙酸缓释微球的制备方法,考察其一般性质、体外释药特性及生物学活性.方法 采用色谱方法纯化眼镜蛇CTX, MTT方法检测细胞毒活性,复乳-溶剂挥发法制备载药微球,考察微球表面形态、粒径、包封率、载药率、体外释药行为及释放眼镜蛇CTX细胞毒活性.结果 纯化眼镜蛇CTX具有明显的细胞毒作用,对肝癌HepG2细胞12,24h的IC50分别为1.43,1.12μg/mL,对L02肝细胞12,24h的IC50分别为1.37,1.01μg/mL.微球表面光滑圆整,粒径2.1~7.8μm,包封率和载药率分别为(74.10±9.92)%和(0.72±0.09)%,30d药物累积释放84.3%,释放眼镜蛇CTX保持较好的生物学活性.结论 采用复乳.溶剂挥发法可制备具有较高包封率,良好缓释效果,保持完整生物学活性的眼镜蛇CTX缓释微球.

  12. 眼镜蛇毒细胞毒素对S180荷瘤小鼠抗肿瘤作用的研究%The Antitumor Role of Naja Naja Atra Venom Cytotoxin in S180-bearing Mice

    Institute of Scientific and Technical Information of China (English)

    张锦宏; 曾军; 谢天炽; 郭芝刚

    2012-01-01

    目的:探讨眼镜蛇毒细胞毒素(Cytotoxin,CTX) 对S180 荷瘤小鼠的抗肿瘤作用.方法:采用昆明小鼠S180 实体瘤模型,通过腹腔注射CTX,观察CTX 对S180 小鼠的肿瘤重量、亚显微结构、凋亡率和pro-caspase-3 表达量的变化.结果:CTX 对S180 肿瘤细胞的生长表现出明显抑制作用.0.2、0.4、0.8 mg/kg CTX 剂量组的抑瘤率分别为23.8%、54.1%、63.2%;透射电子显微镜和流式细胞仪检测显示S180 肿瘤细胞发生凋亡;免疫印迹结果显示pro-caspase-3 蛋白表达降低,提示caspase-3 被激活.结论:CTX 通过诱导细胞凋亡来抑制S180 肿瘤细胞的生长.

  13. Cloning, Expression of Cytotoxin(CTX) from Chinase Cobra(Naja Naja Atra)%舟山眼镜蛇毒细胞毒素的克隆及原核表达

    Institute of Scientific and Technical Information of China (English)

    陈瑜; 王玥; 黄燕愉; 许云禄

    2010-01-01

    目的 构建舟山眼镜蛇毒细胞毒素(Cytotoxin,CTX)原核表达载体(pET42α(+)-CTX),并在大肠杆菌中表达CTX重组蛋白.方法 从舟山眼镜蛇毒中分离纯化细胞毒素(CTX),测定N-末端氨基酸序列并据此设计引物,以提取的舟山眼镜蛇毒腺总RNA为模板,通过RT-PCR方法扩增细胞毒素基因序列(CTX cDNA).将CTX cDNA定向克隆到原核表达载体pET42α(+)中,双酶切图谱、PCR和DNA测序鉴定,转化宿主菌E.coli BL21(DE3),异丙基硫代-β-D半乳糖苷(IPTG)诱导,SDS-PAGE凝胶电泳分析表达产物,GSTrap FF亲和层析纯化融合蛋白CTX;Western-blotting鉴定.结果 成功合成CTX cDNA,并构建原核表达质粒pET42α(+)/GST-CTX,在大肠杆菌E.coli BL21(DE3)中表达融合蛋白CTX,SDS-PAGE凝胶浓度扫描显示表达量占菌体总蛋白的28.9%,western-blotting证实纯化蛋白为重组CTX融合蛋白(rCTX).结论 成功构建CTX基因的原核表达载体,并在大肠杆菌中表达,获得rCTX具有眼镜蛇毒CTX的抗原性.

  14. Pós-graduação na educação física brasileira: a atração (fatal) para a biodinâmica

    OpenAIRE

    2011-01-01

    O objetivo do trabalho foi caracterizar academicamente a educação física no Brasil. Primeiro, fez-se um paralelo entre os eventos desse processo ocorridos nos Estados Unidos e no Brasil. A seguir, os programas de pós-graduação brasileiros foram analisados do ponto de vista de suas áreas de concentração e de sua vinculação com o corpo docente, as linhas e os projetos de pesquisa. Educação física é o termo predominante na denominação da maioria dos programas brasileiros, diferentemente dos Esta...

  15. Ten Facts Every Parent Should Know about the No Child Left Behind Act = Diez datos que cada padre debe saber sobre La Ley. Que Ningun Nino Se Quede Atras.

    Science.gov (United States)

    Department of Education, Washington, DC.

    The No Child Left Behind Act (NCLB) is President George W. Bush's education reform law passed by Republicans and Democrats in Congress. This flier, in both English and Spanish, details 10 facts concerning NCLB to inform parents as to the goals of the Act and how they will affect their child's school. The flier highlights how the Act: (1) gives…

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

    Science.gov (United States)

    Arteaga, Maria Francisca; Mikesch, Jan-Henrik; Qiu, Jihui; Christensen, Jesper; Helin, Kristian; Kogan, Scott C; Dong, Shuo; So, Chi Wai Eric

    2013-03-18

    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 identified the histone demethylase PHF8 as a coactivator that is specifically recruited by RARα fusions to activate expression of their downstream targets upon ATRA treatment. Forced expression of PHF8 resensitizes ATRA-resistant APL cells, whereas its downregulation confers resistance. ATRA sensitivity depends on the enzymatic activity and phosphorylation status of PHF8, which can be pharmacologically manipulated to resurrect ATRA sensitivity to resistant cells. These findings provide important molecular insights into ATRA response and a promising avenue for overcoming ATRA resistance.

  17. Prevention and Reversal of Diabetes by All-Trans Retinoid Acid and Exendin-4 in NOD Mice

    Directory of Open Access Journals (Sweden)

    Jyuhn-Huarng Juang

    2014-01-01

    Full Text Available It has been shown that all-trans retinoid acid (ATRA hinders the development of autoimmune diabetes by inducing immune tolerance status. Meanwhile, exendin-4 increases beta-cell function and mass. Thus, we hypothesized that ATRA and exendin-4 combination therapy would prevent and reverse autoimmune diabetes. NOD/scid mice were intravenously transferred with splenocytes isolated from 12-week-old female NOD mice. After adoptive transfer, mice were treated with vehicle, ATRA (0.5 mg/mouse intraperitoneally every other day, exendin-4 (3 μg/kg subcutaneously twice daily, or combination for 6 weeks. Compared with vehicle, ATRA (P=0.022 and ATRA plus exendin-4 (P=0.013 treatment delayed the onset of diabetes. The pancreatic insulin content in mice treated with ATRA (P=0.013 and exendin-4 (P<0.02 was significantly higher than that of control mice. All but one spontaneous diabetic NOD mouse treated with ATRA and/or exendin-4 remained persistent hyperglycemic. ATRA and/or exendin-4 treatment did not alter their blood glucose levels and survival. Our results indicate that, before the onset of autoimmune diabetes, ATRA and exendin-4 treatment alone preserves pancreatic beta cells; ATRA and ATRA plus exendin-4 treatment delays the onset of autoimmune diabetes. However, after the onset of autoimmune diabetes, ATRA and/or exendin-4 treatment is unable to reverse hyperglycemia or improve survival.

  18. 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

  19. Bayesian network meta-analysis comparing five contemporary treatment strategies for newly diagnosed acute promyelocytic leukaemia.

    Science.gov (United States)

    Wu, Fenfang; Wu, Di; Ren, Yong; Duan, Chongyang; Chen, Shangwu; Xu, Anlong

    2016-07-26

    Acute promyelocytic leukemia (APL) is a curable subtype of acute myeloid leukemia. The optimum regimen for newly diagnosed APL remains inconclusive. In this Bayesian network meta-analysis, we compared the effectiveness of five regimens-arsenic trioxide (ATO) + all-trans retinoic acid (ATRA), realgar-indigo naturalis formula (RIF) which contains arsenic tetrasulfide + ATRA, ATRA + anthracycline-based chemotherapy (CT), ATO alone and ATRA alone, based on fourteen randomized controlled trials (RCTs), which included 1407 newly diagnosed APL patients. According to the results, the ranking efficacy of the treatment, including early death and complete remission in the induction stage, was the following: 1. ATO/RIF + ATRA; 2. ATRA + CT; 3. ATO, and 4. ATRA. For long-term benefit, ATO/RIF + ATRA significantly improved overall survival (OS) (hazard ratio = 0.35, 95%CI 0.15-0.82, p = 0.02) and event-free survival (EFS) (hazard ratio = 0.32, 95%CI 0.16-0.61, p = 0.001) over ATRA + CT regimen for the low-to-intermediate-risk patients. Thus, ATO + ATRA and RIF + ATRA might be considered the optimum treatments for the newly diagnosed APL and should be recommended as the standard care for frontline therapy.

  20. Genital ulcers after treatment with all-trans-retinoic acid in a child with acute promyelocytic leukemia.

    Science.gov (United States)

    Unal, Selma; Gümrük, Fatma; Cetin, Mualla; Hiçsönmez, Gönül

    2005-01-01

    All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers in adult patients. The authors report genital ulcers that developed in a child with APL after ATRA treatment. An 8-year-old girl with APL was treated with ATRA for 21 days and after discontinuation of ATRA treatment she developed genital ulcers. Systemic and local antibiotic pomades were applied and the lesions improved within 15 days. In conclusion, genital ulcers may develop in children with APL as a complication of ATRA treatment and physicians should be alert to this possibility.

  1. 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.

  2. Granulocyte colony-stimulating factor potentiates differentiation induction by all-trans retinoic acid and arsenic trioxide and enhances arsenic uptake in the acute promyelocytic leukemia cell line HT93A.

    Science.gov (United States)

    Iriyama, Noriyoshi; Yuan, Bo; Hatta, Yoshihiro; Horikoshi, Akira; Yoshino, Yuta; Toyoda, Hiroo; Aizawa, Shin; Takeuchi, Jin

    2012-11-01

    The effects of arsenic trioxide (ATO), all-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF), alone or in combination, were investigated by focusing on differentiation, growth inhibition and arsenic uptake in the acute promyelocytic leukemia (APL) cell line HT93A. ATO induced differentiation at low concentrations (0.125 µM) and apoptosis at high concentrations (1-2 µM). Furthermore, ATRA induced greater differentiation than ATO. No synergistic effect of ATRA and ATO was found on differentiation. G-CSF promoted differentiation-inducing activities of both ATO and ATRA. The combination of ATRA and G-CSF showed maximum differentiation and ATO addition was not beneficial. Addition of 1 µM ATRA and/or 50 ng/ml G-CSF to ATO did not affect apoptosis compared to ATO treatment alone. ATRA induced expression of aquaporin-9 (AQP9), a transmembrane transporter recognized as a major pathway of arsenic uptake, in a time- and dose-dependent manner. However, treatment with 1 µM ATRA decreased arsenic uptake by 43.7% compared to control subject. Although G-CSF addition did not enhance AQP9 expression in the cells, the reduced arsenic uptake was recovered to the same level as that in controls. ATRA decreased cell viability and addition of 50 ng/ml G-CSF to ATRA significantly increased the number of viable cells compared with that in ATRA alone treated cells. G-CSF not only promotes differentiation-inducing activities of both ATRA and ATO, but also makes APL cells vulnerable to increased arsenic uptake. These observations provide new insights into combination therapy using these three agents for the treatment of APL.

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

    Science.gov (United States)

    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 credited widely as a mechanism of ethanol toxicity. Here, we analyze the effects of ethanol on retinoid concentrations in vivo during normal vitamin A nutriture, using sensitive and analytically robust assays. Ethanol either increased or had no effect on atRA, regardless of changes in retinol and retinyl esters. Acute ethanol (3.5 g/kg) increased atRA in adult hippocampus (1.6-fold), liver (2.4-fold), and testis (1.5-fold). Feeding dams a liquid diet with 6.5% ethanol from embryonic day 13 (e13) to e19 increased atRA in fetal hippocampus (up to 20-fold) and cortex (up to 50-fold), depending on blood alcohol content. One-month feeding of the 6.5% ethanol diet increased atRA in adult hippocampus (20-fold), cortex (2-fold), testis (2-fold), and serum (10-fold). Tissue-specific increases in retinoid dehydrogenase mRNAs and activities, extrahepatic retinol concentrations, and atRA catabolism combined to produce site-specific effects. Because a sustained increase in atRA has deleterious effects on the central nervous system and embryo development, these data suggest that superphysiological atRA contributes to ethanol pathological conditions, including cognitive dysfunction and fetal alcohol syndrome.—Kane, M. A., Folias, A. E., Wang, C., Napoli, J. L. Ethanol elevates physiological all-trans-retinoic acid levels in select loci through altering retinoid metabolism in multiple loci: a potential mechanism of ethanol toxicity. PMID:19890016

  4. 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).

  5. Interon-gamma Enhances the Antitumor Effect of All-trans Retinoic Acid on Hepatocellular Carcinoma Cells by Inhibiting the Expression of Nuclear Factor-kappaB

    Institute of Scientific and Technical Information of China (English)

    YIN Yuan-qin; WANG Xiao-hua; MA Ping; FU Liye; HANG Tao; WANG Yang

    2008-01-01

    Objective:To explore the combination effects of all-trans retinoic acid(ATRA)with interferon-gamma(IFN-γ)on human hepatocarcinoma cell line SMMC-7721 and the mechanism of action.Methods:SMMC-7721 cells were divided into treated group and control group.The cells were treated with ATRA or ATRA+IFN-γ in the former and added with PBS in the latter.The inhibition rate of SMMC-7721 cell proliferation was detected by MTT,the cell change in morphology was observed by electron microscope.The apoptosis was detected by flow cytometry and the expression changes of nuclear factor-kappaB(NF-κB)was analyzed by Western blotting when the SMMC-7721 cells were treated with ATRA and IFN-γ.Results:The SMMC-7721 cell proliferation was suppressed and apoptosis was induced after the cells were treated with ATRA treatment,and these effects were enhanced when ATRA was combined with IFN-γ.The expression of NF-κB was reduced after SMMC-7721 cell was treated with ATRA,and reduced significantly when the cells were treated with the combination of ATRA and IFN-γ.Conclusion:IFN-γ can enhance the inhibiting effects of ATRA on cell proliferation and inducing apoptosis on SMMC-7721 cell and these effects might be mediated by inhibiting the expression of NF-κB.

  6. A Complicated Case of Acute Promyelocytic Leukemia in the Second Trimester of Pregnancy Successfully Treated with All-trans-Retinoic Acid.

    Science.gov (United States)

    Agarwal, Kanika; Patel, Megha; Agarwal, Vandana

    2015-01-01

    A 40-year-old female at 26-week gestation was diagnosed with acute promyelocytic leukemia (APL) after an abnormal prenatal lab workup showed pancytopenia. She was treated with all-trans-retinoic acid (ATRA), idarubicin, and dexamethasone. After day one of treatment, she developed differentiation syndrome, which was treated with dexamethasone. At 30-week gestation, she had preterm premature rupture of membranes and delivered by cesarean section because of the fetus' breech presentation. Despite ATRA's potential for teratogenicity, a viable infant was born without apparent anomalies. Postpartum, she underwent consolidation treatment with ATRA and arsenic trioxide (ATO). The patient continued ATRA therapy after delivery and is currently in remission.

  7. Outcome of pregnancy in women treated with all-trans retinoic acid; a case report and review of literature.

    Science.gov (United States)

    Valappil, Saudabi; Kurkar, Micheal; Howell, Rosemary

    2007-10-01

    All-trans-retinoic acid (ATRA) has been proved to be an effective treatment for acute promyelocytic leukemia (APL), inducing remission in more than 90% of cases. Treatment of APL in pregnancy is controversial as the use of ATRA has been questioned due to the teratogenic effect of retinoids. We report a case of pregnancy in a woman exposed to ATRA during the first trimester. The baby was born healthy, without any anomalies. Review of all reported cases of the use of ATRA in pregnancy revealed no serious adverse outcomes or congenital anomalies although only very few cases had exposure in the first trimester.

  8. Scrotal ulceration following all-trans retinoic acid therapy for acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Illias Tazi

    2011-01-01

    Full Text Available All-trans retinoic acid (ATRA induces complete remission in most cases of acute promyelocytic leukemia. Toxicity of ATRA has been shown to be mild, consisting of headache, dry skin, dermatitis, and gastrointestinal disorders. We describe a case of scrotal ulceration with ATRA use in a Moroccan patient, an occurrence that has been rarely reported in the medical literature. The pathogenesis of scrotal ulceration remains unknown. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

  9. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

    Science.gov (United States)

    Platzbecker, Uwe; Avvisati, Giuseppe; Cicconi, Laura; Thiede, Christian; Paoloni, Francesca; Vignetti, Marco; Ferrara, Felicetto; Divona, Mariadomenica; Albano, Francesco; Efficace, Fabio; Fazi, Paola; Sborgia, Marco; Di Bona, Eros; Breccia, Massimo; Borlenghi, Erika; Cairoli, Roberto; Rambaldi, Alessandro; Melillo, Lorella; La Nasa, Giorgio; Fiedler, Walter; Brossart, Peter; Hertenstein, Bernd; Salih, Helmut R; Wattad, Mohammed; Lübbert, Michael; Brandts, Christian H; Hänel, Mathias; Röllig, Christoph; Schmitz, Norbert; Link, Hartmut; Frairia, Chiara; Pogliani, Enrico Maria; Fozza, Claudio; D'Arco, Alfonso Maria; Di Renzo, Nicola; Cortelezzi, Agostino; Fabbiano, Francesco; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Amadori, Sergio; Mandelli, Franco; Ehninger, Gerhard; Schlenk, Richard F; Lo-Coco, Francesco

    2017-02-20

    Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 10(9)/L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

  10. Treatment of newly diagnosed and relapsed acute promyelocytic leukemia with intravenous liposomal all-trans retinoic acid.

    Science.gov (United States)

    Douer, D; Estey, E; Santillana, S; Bennett, J M; Lopez-Bernstein, G; Boehm, K; Williams, T

    2001-01-01

    A novel intravenous liposomal formulation of all-trans retinoic acid (ATRA) was evaluated in 69 patients with acute promyelocytic leukemia (APL): 32 new diagnoses, 35 relapses, and 2 oral ATRA failures. Liposomal ATRA (90 mg/m(2)) was administered every other day until complete remission (CR) or a maximum of 56 days. Treatment following CR was liposomal ATRA with or without chemotherapy. In an intent-to-treat (ITT) analysis of all patients, CR rates were 62%, 70%, and 20% in newly diagnosed, group 1 first relapses (ATRA naive or off oral ATRA more than or equal to 1 year), or group 2 relapses (second or subsequent relapse or first relapses off oral ATRA less than 1 year), respectively. In 56 evaluable patients (receiving 4 or more doses), CR rates for the same groups were 87% (20 of 23), 78% (14 of 18), and 23% (3 of 13). Remission failure in newly diagnosed patients was not from resistant disease. Several patients in CR became polymerase chain reaction (PCR) negative for promyelocytic leukemia/retinoic acid receptor-alpha (PML/RARalpha) after liposomal ATRA alone. Toxicity was generally mild, most commonly headaches (67. 5%). Eighteen patients (26%) had ATRA syndrome develop during induction. One-year survival of ITT patients was 62%, 56%, and 20% for newly diagnosed, group 1, and group 2, respectively. The medium duration of CR has not yet been reached and was 18 and 5.5 months in the same groups. These results demonstrate that liposomal ATRA is effective in inducing CR in newly diagnosed or group 1 APL patients. It provides a reliable dosage of ATRA for patients with APL unable to swallow or absorb medications and can induce molecular remissions without chemotherapy.

  11. All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats.

    Science.gov (United States)

    Zhang, Chao; Kong, Xiaohong; Ning, Guangzhi; Liang, Zhipin; Qu, Tongjun; Chen, Feiran; Cao, Daigui; Wang, Tianyi; Sharma, Hari S; Feng, Shiqing

    2014-04-01

    Laminectomy is a widely accepted treatment for lumbar disorders, and epidural fibrosis (EF) is a common complication. EF is thought to cause post-operative pain recurrence after laminectomy or discectomy. All-trans retinoic acid (ATRA) has shown anti-fibrotic, anti-inflammatory, and anti-proliferative functions. The object of this study was to investigate the effects of ATRA on the prevention of EF in post-laminectomy rats. In vitro, the anti-fibrotic effect of ATRA was demonstrated with cultured fibroblasts count, which comprised of those that were cultured with/without ATRA. In vivo, rats underwent laminectomy at the L1-L2 levels. We first demonstrated the beneficial effects using 0.05% ATRA compared to vehicle (control group). We found that a higher concentration of ATRA (0.1%) achieved dose-dependent results. Hydroxyproline content, Rydell score, vimentin-positive cell density, fibroblast density, inflammatory cell density and inflammatory factor expression levels all suggested better outcomes in the 0.1% ATRA rats compared to the other three groups. Presumably, these effects involved ATRA's ability to suppress transforming growth factor (TGF-β1) and interleukin (IL)-6 which was confirmed with reverse-transcriptase polymerase chain reaction (RT-PCR). Finally we demonstrated that ATRA down-regulated nuclear factor (NF)-κB by immunohistochemistry and western blotting for p65 and inhibition of κB (IκBα), respectively. Our findings indicate that topical application of ATRA can inhibit fibroblast proliferation, decrease TGF-β1 and IL-6 expression level, and prevent epidural scar adhesion in rats. The highest concentration employed in this study (0.1%) was the most effective. ATRA suppressed EF through down-regulating NF-κB signaling, whose specific mechanism is suppression of IκB phosphorylation and proteolytic degradation.

  12. 力达霉素产生菌球孢链霉菌C-1027中atrA同源基因的克隆及分析%Cloning and Analyses of atrA Homologous Gene atrA-gl Involved in Lidamycin Producing Strain Streptomyces globisporus C-1027

    Institute of Scientific and Technical Information of China (English)

    李光伟; 王丽非; 王松梅; 洪斌

    2010-01-01

    目的:在天蓝色链霉菌Streptomyces coelicolor A3(2)中多效性调节因子AtrA(AtrA-c)可通过激活放线紫红素途径特异性的调节因子ActⅡ-ORF4的转录来控制放线紫红素的产生.在灰色链霉菌Sreptomyces griseus NBRCl3350和阿维链霉菌Streptomyces avermitilis MA-4680中也发现了AtrA-c编码基因(atrA-c)的同源基因,分别影响链霉素和阿维菌素的生物合成.为探索球孢链霉菌C-1027(Sreptomyces globisporus C-1027)中是否存在AtrA,克隆球孢链霉菌C-1027中atrA基因并进行生物信息学分析,为进一步确定其对力达霉素产生的调控作用及调控机制奠定基础.方法:采用在球孢链霉菌C-1027中异源表达AtrA-c,来确定AtrA-c对力达霉素产量的影响;通过southern blot分析来判断在球孢链霉菌C-1027基因组中是否有atrA-c同源基因;PCR扩增方法获得球孢链霉菌c-1027atrA基因(atrA-gl)并测序;通过多种生物信息学软件来分析atrA-gl及其与旁侧基因的组织结构、对已发现的AtrA蛋白进行同源性比对及亲缘关系分析.结果:在球孢链霉菌C-1027中异源表达天蓝色链霉菌AtrA-c蛋白,发现其对力达霉素的产量有影响.以atrA-c为探针,通过Southern blot分析显示球孢链霉菌C-1027基因组中存在atrA-c的同源基因.PCR扩增得到球孢链霉菌c-1027的atrA基因的全序列以及该基因上下游的旁侧序列(GenBank/EMBI/DDRJ登录号GU723707).通过对球孢链霉菌C-1027、天蓝色链霉菌A3(2)、灰色链霉菌NBRCl3350以及阿维链霉菌MA-4680 AtrA蛋白序列进行同源性分析发现,4种AtrA蛋白编码氨基酸序列一致性达到65%~87%,相似性高达70%~89%.并且,球孢链霉菌C-1027 atrA基因与相邻基因形成的组织结构与天蓝色链霉菌和灰色链霉菌完全一致.根据蛋白质同源性绘制进化树,发现球孢链霉菌AtrA蛋白与灰色链霉菌AtrA蛋白亲缘关系最近.结论:确定在球孢链霉菌C-1027中存在atrA同源基因并影响力达霉素的产量,克隆了首个力达霉素生物合成基因簇外的调节基因--atrA基因,通过生物信息学分析初步推测了该基因的功能,为进一步研究.AtrA-gl对力达霉素途径特异性级联调控网络的调控关系奠定了基础.

  13. In vitro cytotoxicity following specific activation of a bladder cancer-associated monoclonal antibody conjugated to a cytotoxin from Naja Naja Atra%中华眼镜蛇细胞毒素及其偶联膀胱癌单克隆抗体的体外抑制膀胱癌细胞增殖的实验研究

    Institute of Scientific and Technical Information of China (English)

    王剑松; 丁明霞; 李翀; 谢蜀生; 王婉瑜; 徐鸿毅

    2007-01-01

    目的 从中华眼镜蛇的四种细胞毒素(cytotoxins,CTXs)中筛选活性最强的一种与膀胱癌单克隆抗体构建成免疫毒素(immunotoxin IT),并研究IT的体外抑制膀胱癌细胞增殖的活性.方法 [3H]-TdR掺入法检测CTXs对膀胱癌细胞株的抑制增殖作用,用双功能偶联剂将CTX-12与:BDI-1连接成IT,并用SDS-聚丙烯酰胺凝胶电泳、DAB染色法和[3H]-TdR掺入法鉴定和检测IT的活性.结果 四种CTXs对BIU-87和EJ细胞株均有抑制增殖的活性,CTX-12与BDI-1能够连接成IT,IT对BIU-87和EJ细胞株具有特异性结合性.且IT仍具有抑制肿瘤细胞增殖的活性,其BIU-87,EJ和Lovo细胞作用6h的IC50分别为97.12,85.28和193.4mg/L,而作用半小时更换培养液培养至6h的IC50分别为94.64,81.28和865mg/L.结论 四种CTXs对膀胱癌细胞株均有抑制增殖的活性,CTX-12与BDI-1连接的IT具有特异性抑制增殖的活性,IT和四种CTXs都有潜力成为新的抗膀胱癌药物.

  14. Pós-graduação na educação física brasileira: a atração (fatal para a biodinâmica Graduate studies in Brazilian physical education: the (fatal attraction to biodynamics

    Directory of Open Access Journals (Sweden)

    Edison de Jesus Manoel

    2011-08-01

    Full Text Available O objetivo do trabalho foi caracterizar academicamente a educação física no Brasil. Primeiro, fez-se um paralelo entre os eventos desse processo ocorridos nos Estados Unidos e no Brasil. A seguir, os programas de pós-graduação brasileiros foram analisados do ponto de vista de suas áreas de concentração e de sua vinculação com o corpo docente, as linhas e os projetos de pesquisa. Educação física é o termo predominante na denominação da maioria dos programas brasileiros, diferentemente dos Estados Unidos, onde se privilegia cinesiologia. A análise das áreas de concentração dos programas de pós-graduação permitiu-nos identificar três subáreas: biodinâmica, sociocultural e pedagógica. A biodinâmica sobressai-se pela dimensão do corpo docente e pela quantidade de linhas e projetos de pesquisa, sempre mais numerosos em comparação com as subáreas sociocultural e pedagógica. Tal hegemonia expressa a valorização atribuída às pesquisas orientadas pelas ciências naturais em detrimento daquelas fundamentadas pelas ciências humanas e sociais, além da dificuldade em problematizar a intervenção, particularmente no âmbito da escola. Esse quadro guarda semelhança com a realidade norte-americana, haja vista que acadêmicos norte-americanos das subáreas sociocultural e pedagógica apontam os obstáculos para compatibilizar suas concepções teóricas e metodológicas com os modos hegemônicos de pensamento, investigação e ação no campo da cinesiologia. Tanto os acontecimentos nos Estados Unidos quanto a caracterização acadêmica predominante nos programas de pós-graduação no Brasil indicam a forte presença da biodinâmica em prejuízo da educação física, no que ela compreende e agrega, sobretudo, como prática social e pedagógica de longa data.The present work aimed at the academic characterization of physical education in Brazil. First, a parallel was made between the history of academic characterization of physical education in North America and in Brazil. Next, the analysis of the areas comprehended by graduate study programs was carried out in the field around Brazil. A survey was done considering the field of concentration and its interface and links with the size of faculty, with research lines and with research projects. Physical education is the most preferred term to name the majority of the Brazilian graduate programs in contrast with the United States where Kinesiology is preferred. The analysis of the field of concentration yields three main subfields: biodynamics, sociocultural and pedagogical. Biodynamics takes precedence as one considers the size of the faculty and the number of research lines and projects always greater than the same variables in comparison with sociocultural and pedagogical subfields. This hegemony reflects a trend in which natural sciences-oriented research is privileged over human and social sciences-oriented research and difficulty in valuing the intervention, especially in schooling. This portrait resembles what happens in the US as some North American scholars from the sociocultural and pedagogical subfields have also identified difficulties in making their theoretical and methodological conceptions compatible with the hegemonic modes of thinking and investigation in kinesiology.

  15. Pós-graduação na educação física brasileira: a atração (fatal) para a biodinâmica Graduate studies in Brazilian physical education: the (fatal) attraction to biodynamics

    OpenAIRE

    2011-01-01

    O objetivo do trabalho foi caracterizar academicamente a educação física no Brasil. Primeiro, fez-se um paralelo entre os eventos desse processo ocorridos nos Estados Unidos e no Brasil. A seguir, os programas de pós-graduação brasileiros foram analisados do ponto de vista de suas áreas de concentração e de sua vinculação com o corpo docente, as linhas e os projetos de pesquisa. Educação física é o termo predominante na denominação da maioria dos programas brasileiros, diferentemente dos Esta...

  16. 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.

  17. All-trans retinoic acid with daunorubicin or idarubicin for risk-adapted treatment of acute promyelocytic leukaemia : a matched-pair analysis of the PETHEMA LPA-2005 and IC-APL studies

    NARCIS (Netherlands)

    Sanz, Miguel A.; Montesinos, Pau; Kim, Haesook T.; Ruiz-Argueelles, Guillermo J.; Undurraga, Maria S.; Uriarte, Maria R.; Martinez, Lem; Jacomo, Rafael H.; Gutierrez-Aguirre, Homero; Melo, Raul A. M.; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Fagundes, Evandro M.; Vellenga, Edo; Holowiecka, Alexandra; Gonzalez-Huerta, Ana J.; Fernandez, Pascual; De la Serna, Javier; Brunet, Salut; De Lisa, Elena; Gonzalez-Campos, Jose; Ribera, Jose M.; Krsnik, Isabel; Ganser, Arnold; Berliner, Nancy; Ribeiro, Raul C.; Lo-Coco, Francesco; Lowenberg, Bob; Rego, Eduardo M.

    2015-01-01

    Front-line treatment of acute promyelocytic leukaemia (APL) consists of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. In this setting, a comparison of idarubicin and daunorubicin has never been carried out. Two similar clinical trials using ATRA and chemotherapy for newly diag

  18. 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.

  19. 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.

  20. 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 id...

  1. [A neonate born to a mother with acute promyelocytic leukemia treated by all-trans retinoic acid].

    Science.gov (United States)

    Maeda, M; Tyugu, H; Okubo, T; Yamamoto, M; Nakamura, K; Dan, K

    1997-09-01

    We report a female neonate delivered in week 32 of gestation by a mother who had acute promyelocytic leukemia (APL) treated by all-trans retinoic acid (ATRA). APL was diagnosed in week 29 of gestation and was treated with ATRA from week 30. Physical examination and laboratory tests showed no abnormalities at birth. The girl has since shown normal development, with no peripheral blood abnormalities at 2 years old. Hypersegmented neutrophils, which often appear during ATRA treatment, were seen in the peripheral blood of the mother and cord blood but not peripheral blood of the neonate on the day of birth. ATRA is known to cross the placenta, and has been revealed to be teratogenic in animal studies. There have been eight neonates born to the mothers with APL who were treated with ATRA during pregnancy. All infants, including this one, have shown normal growth without any complications.

  2. Direct protein-protein interactions and substrate channeling between cellular retinoic acid binding proteins and CYP26B1.

    Science.gov (United States)

    Nelson, Cara H; Peng, Chi-Chi; Lutz, Justin D; Yeung, Catherine K; Zelter, Alex; Isoherranen, Nina

    2016-08-01

    Cellular retinoic acid binding proteins (CRABPs) bind all-trans-retinoic acid (atRA) tightly. This study aimed to determine whether atRA is channeled directly to cytochrome P450 (CYP) CYP26B1 by CRABPs, and whether CRABPs interact directly with CYP26B1. atRA bound to CRABPs (holo-CRABP) was efficiently metabolized by CYP26B1. Isotope dilution experiments showed that delivery of atRA to CYP26B1 in solution was similar with or without CRABP. Holo-CRABPs had higher affinity for CYP26B1 than free atRA, but both apo-CRABPs inhibited the formation of 4-OH-RA by CYP26B1. Similar protein-protein interactions between soluble binding proteins and CYPs may be important for other lipophilic CYP substrates.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. All-trans retinoic acid enhances bystander effect of suicide gene therapy in the treatment of breast cancer.

    Science.gov (United States)

    Kong, Heng; Liu, Xia; Yang, Liucheng; Qi, Ke; Zhang, Haoyun; Zhang, Jingwen; Huang, Zonghai; Wang, Hongxian

    2016-03-01

    All-trans retinoic acid (ATRA) has been shown to enhance the expression of connexin 43 (Cx43) and the bystander effect (BSE) in suicide gene therapy. These in turn improve effects of suicide gene therapies for several tumor types. However, whether ATRA can improve BSE remains unclear in suicide gene therapy for breast cancer. In the present study, MCF-7, human breast cancer cells were treated with ATRA in combination with a VEGFP-TK/CD gene suicide system developed by our group. We found that this combination enhances the efficiency of cell killing and apoptosis of breast cancer by strengthening the BSE in vitro. ATRA also promotes gap junction intercellular communication (GJIC) in MCF-7 cells by upregulation of the connexin 43 mRNA and protein in MCF-7 cells. These results indicate that enhancement of GJIC by ATRA in suicide gene system might serve as an attractive and cost-effective strategy of therapy for breast cancer cells.

  6. 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.``

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Molecular mechanism of inhibitory effects of C-phycocyanin combined with all-trans-retinoic acid on the growth of HeLa cells in vitro.

    Science.gov (United States)

    Yang, Fan; Li, Bing; Chu, Xian-Ming; Lv, Cong-Yi; Xu, Ying-Jie; Yang, Peng

    2014-06-01

    We studied the effects of all-trans-retinoic acid (ATRA), C-phycocyanin (C-PC), or ATRA+C-PC on the growth of cervical cells (HeLa cells), cell cycle distribution, and apoptosis. The anticancer mechanism of the drug combination was revealed. MTT assay was adopted to determine the effects of C-PC and ATRA on the growth of HeLa cells. The expression quantities of cyclin-dependent kinase (CDK) 4, cyclin D1, Bcl-2, caspase-3, and CD59 were determined by in situ hybridization, immunofluorescence, immunohistochemistry staining, Western blot, and RT-PCR. TUNEL assay was adopted to determine the cellular apoptosis levels. Both C-PC and ATRA could inhibit the growth of HeLa cells, and the combination of ATRA+C-PC functioned cooperatively to induce apoptosis in HeLa cells. The dosage of ATRA was reduced when it cooperated with C-PC to reduce the toxicity. ATRA treated with C-PC could induce more cell cycle arrests than the single drug used by decrease in cyclin D1 and CDK4 expression. The combination of the two drugs could upregulate caspase-3 and downregulate the Bcl-2 gene and induce cell apoptosis. Moreover, the combination therapy has an important immunological significance in decreased expression of the CD59 protein. Singly, C-PC or ATRA could inhibit the growth of HeLa cells, and the effects of treatment were further enhanced in the combination group. In combination with C-PC, the dosage of ATRA was effectively reduced. The C-PC + ATRA combination might take effect by inhibiting the progress of the cell cycle, inducing cell apoptosis and promoting complement-mediated cytolysis.

  9. Inhibition effects of all trans-retinoic acid on the growth and angiogenesis of esophageal squamous cell carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    LU Tai-ying; LI Wen-cai; CHEN Ren-yin; FAN Qing-xia; WANG Liu-xing; WANG Rui-lin; LU Shi-xin; MENG Hui

    2011-01-01

    Background The potential application of retinoic acid receptor activators,such as all trans-retinoic acid (ATRA),for treating various cancers have been studied both pre-clinically and clinically.Whether ATRA has an anticancer effect on human esophageal squamous cancer cell (ESCC) is still unknown.We have explored the anticancer effect of ATRA in ESCC,and in this study,the effects of ATRA on levels and patterns of expression of the vascular endothelial growth factor (VEGF) signal transduction pathway in transplantable tumor growth of the human ESCC cell line,EC9706,in nude mice.Methods The animal model of the ESCC xenograft was made by subcutaneous implantation of tumor cells into nude mice.Reverse transcription-polymerase chain reaction (RT-PCR),Western blotting and immunohistochemical assays were used to detect the expression of the VEGF signal transduction pathway in ESCC xenograft tissues.Results Compared to the control group,the tumor inhibition rates in the low dose ATRA,high dose ATRA,and 5-FU groups were 83.21%,88.32%,91.02%,respectively.The protein and mRNA levels of VEGF were down-regulated after being treated with ATRA and 5-FU compared to the control group (P <0.05).The study also revealed that ATRA specifically down-regulated VEGF and the component of the VEGF signal transduction pathway of CD31,CD34,and CD105 (component of the TGF-β receptor) in ESCC xenograft tissues (P <0.05).Conclusions ATRA can significantly inhibit tumor growth and has anticancer effects on transplantable tumor growth of human ESCC cell line EC9706 in nude mice.These findings indicate that ATRA specifically down regulated VEGF and the components of VEGF signal transduction,which may be an important mechanism responsible for the neoangiogenesis inhibition of ESCC cells.

  10. Effect of all-trans retinoic acid 0n drug sensitivity and expression of survivin in LoVo cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background All-trans retinoic acid(ATRA)can influence the tumor cell proliferation cycle,and some chemotherapeutic drugs are cycle specific.In this study,we hypothesize that ATRA can enhance chemotherapeutic drug sensitivity by affecting the cell cycle of tumor cells.Methods The cell cycle of LoVo cells was evaluated using flow cytometry(FCM).Cell viability was analyzed using the MTT assay.The morphologic changes in the treated LoVo cells were measured with acridine orange (AO)/ethidium bromide(EB)staining.Expression of survivin in LoVo cells was analyzed by immunofluorescence assay.Results After LoVo cells were treated with ATRA,the G0/G1 ratio of the tumor cells increased and the cell ratio of Sand G2/M-phase decreased.Viability of the cells decreased significantly after combined treatment with ATRA and 5-fluorouracil(5-FU)or mitomycin c(MMC) and was evaluated by fluorescence microscopy.Expression level of survivin in the tumor cells decreased after ATRA combination treatment.Conclusions ATRA enhances drug sensitivity of the LoVo cell line to cell cycle-specific agents and inhibits the expression of survivin in LoVo cells.The combination of ATRA and 5-FU or MMC promoted cell apoptosis,and the mechanism involved in apoptosis may be related to inhibition of survivin gene expression.

  11. Retinoic acids acting through retinoid receptors protect hippocampal neurons from oxygen-glucose deprivation-mediated cell death by inhibition of c-jun-N-terminal kinase and p38 mitogen-activated protein kinase.

    Science.gov (United States)

    Shinozaki, Y; Sato, Y; Koizumi, S; Ohno, Y; Nagao, T; Inoue, K

    2007-06-15

    Retinoic acids (RAs), including all-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA), play fundamental roles in a variety of physiological events in vertebrates, through their specific nuclear receptors: retinoic acid receptor (RAR) and retinoid X receptor (RXR). Despite the physiological importance of RA, their functional significance under pathological conditions is not well understood. We examined the effect of ATRA on oxygen/glucose-deprivation/reperfusion (OGD/Rep)-induced neuronal damage in cultured rat hippocampal slices, and found that ATRA significantly reduced neuronal death. The cytoprotective effect of ATRA was observed not only in cornu ammonis (CA) 1 but also in CA2 and dentate gyrus (DG), and was attenuated by selective antagonists for RAR or RXR. By contrast, in the CA3 region, no protective effects of ATRA were observed. The OGD/Rep also increased phosphorylated forms of c-jun-N-terminal kinase (P-JNK) and p38 (P-p38) in hippocampus, and specific inhibitors for these kinases protected neurons. ATRA prevented the increases in P-JNK and P-p38 after OGD/Rep, as well as the decrease in NeuN and its shrinkage, all of which were inhibited by antagonists for RAR or RXR. These findings suggest that the ATRA signaling via retinoid receptors results in the inhibition of JNK and p38 activation, leading to the protection of neurons against OGD/Rep-induced damage in the rat hippocampus.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Severe stomatitis and ileocecal perforation developed after all-trans retinoic acid monotherapy in an HLA-B51-positive patient with acute promyelocytic leukemia.

    Science.gov (United States)

    Kimura, Kenji; Takeuchi, Masahiro; Hasegawa, Nagisa; Togasaki, Emi; Shimizu, Ryoh; Kawajiri, Chika; Muto, Tomoya; Tsukamoto, Shokichi; Takeda, Yusuke; Ohwada, Chikako; Sakaida, Emiko; Sakai, Shio; Mimura, Naoya; Ota, Satoshi; Iseki, Tohru; Nakaseko, Chiaki

    2016-06-01

    A 34-year-old man who had been referred to our hospital was diagnosed with acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA), oral administration, was initiated. On day 25, he developed fever and respiratory distress with bilateral pulmonary infiltrates, suggesting differentiation syndrome (DS) caused by ATRA. These symptoms showed amelioration after discontinuing ATRA and initiating methylprednisolone. ATRA was re-started on day 29 at half the original dose because of residual APL blasts. The patient subsequently developed fever, severe stomatitis, and oropharyngeal ulcers, which persisted even after discontinuing ATRA. On day 48, he suddenly developed severe abdominal pain with free air, observable on an abdominal X-ray, and underwent emergency ileocecal resection. Pathological examination of the resected ileocecal intestines revealed multiple ulcers and perforations. No leukemic cell infiltration was observed. In this case, only ATRA was administered for APL treatment. These findings suggest that ileocecal ulcerations and perforations, as well as oropharyngeal ulcers, might have been caused by DS or ATRA. Furthermore, DNA typing of the HLA-B locus revealed that the patient had HLA-B51 associated with Behçet's disease. Therefore, hypercytokinemia with DS might have induced Behçet's disease-like symptoms, including stomatitis and ileocecal perforation, complications that are particularly observed in patients with HLA-B51.

  15. RETINOIC ACID DOWN-REGULATES BONE MORPHOGENETIC PROTEIN 7 EXPRESSION IN RAT WITH CLEFT PALATE

    Institute of Scientific and Technical Information of China (English)

    Lei Guo; Yu-yan Zhao; Shi-liang Zhang; Kui Liu; Xiao-yu Gao

    2008-01-01

    Objective To evaluate the effects of retinoic acid (RA) on expression of bone morphogenetic protein 7 (BMP-7)in rat fetus with cleft palate, and the effects of RA on proliferation and apoptosis of osteoblasts. Methods All-trans RA (ATRA) was used to induce congenital cleft palate in Wistar rat. BMP-7 mRNA expres-sion in maxillary bone tissue of fetal rats was measured by Northern blotting analysis. Flow cytometry and MTT assay were used to measure the apoptosis and proliferation of ATRA-treated MC-3T3-E1 cells. BMP-7 mRNA and protein ex-pressions in ATRA-treated MC-3T3-E1 cells were detected by RT-PCR and Western blotting analysis.Results ATRA could induce cleft palate of rat fetus. The incidence rate of cleft palate induced by 100 mg/kg AT-RA (45.5%) was significantly higher than 50 mg/kg ATRA (12.5%, P<0.05). BMP-7 mRNA expression de-creased in maxillary bone tissue of rat fetus with cleft palate. MC-3T3-E1 cells proliferation treated with 1 × 10-6 mol/L ATRA decreased by 60%, the cell apoptosis increased by 2 times. BMP-7 mR.NA and protein levels in MC-3T3-E1cells treated with 1 × 10-6 mol/L ATRA decreased by 60% and 80%, respectively, compared with ATRA-untreated ceils (P<0.05).Conclusions BMP-7 may play an important role in embryonic palate development RA may possess the ability to down-regulate cell proliferation through regulation of BMP-7 gene expression.

  16. Transcriptome profiling and genome-wide DNA binding define the differential role of fenretinide and all-trans RA in regulating the death and survival of human hepatocellular carcinoma Huh7 cells.

    Science.gov (United States)

    Hu, Ying; Liu, Hui-Xin; He, Yuqi; Fang, Yaping; Fang, Jianwen; Wan, Yu-Jui Yvonne

    2013-04-01

    Fenretinide is significantly more effective in inducing apoptosis in cancer cells than all-trans retinoic acid (ATRA). The current study uses a genome-wide approach to understand the differential role fenretinide and ATRA have in inducing apoptosis in Huh7 cells. Fenretinide and ATRA-induced gene expressions and DNA bindings were profiled using microarray and chromatin immunoprecipitation with anti-RXRα antibody. The data showed that fenretinide was not a strong transcription regulator. Fenretinide only changed the expressions of 1 093 genes, approximately three times less than the number of genes regulated by ATRA (2 811). Biological function annotation demonstrated that both fenretinide and ATRA participated in pathways that determine cell fate and metabolic processes. However, fenretinide specifically induced Fas/TNFα-mediated apoptosis by increasing the expression of pro-apoptotic genes i.e., DEDD2, CASP8, CASP4, and HSPA1A/B; whereas, ATRA induced the expression of BIRC3 and TNFAIP3, which inhibit apoptosis by interacting with TRAF2. In addition, fenretinide inhibited the expression of the genes involved in RAS/RAF/ERK-mediated survival pathway. In contrast, ATRA increased the expression of SOSC2, BRAF, MEK, and ERK genes. Most genes regulated by fenretinide and ATRA were bound by RXRα, suggesting a direct effect. This study revealed that by regulating fewer genes, the effects of fenretinide become more specific and thus has fewer side effects than ATRA. The data also suggested that fenretinide induces apoptosis via death receptor effector and by inhibiting the RAS/RAF/ERK pathway. It provides insight on how retinoid efficacy can be improved and how side effects in cancer therapy can be reduced.

  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. Physiological and receptor-selective retinoids modulate interferon gamma signaling by increasing the expression, nuclear localization, and functional activity of interferon regulatory factor-1.

    Science.gov (United States)

    Luo, Xin M; Ross, A Catharine

    2005-10-28

    Synergistic actions between all-trans-retinoic acid (atRA) and interferon gamma (IFNgamma) on modulation of cellular functions have been reported both in vitro and in vivo. However, the mechanism of atRA-mediated regulation of IFNgamma signaling is poorly understood. In this study, we have used the human lung epithelial cell line A549 to examine the effect of atRA on IFNgamma-induced expression of IFN regulatory factor-1 (IRF-1), an important transcription factor involved in cell growth and apoptosis, differentiation, and antiviral and antibacterial immune responses. At least 4 h of pretreatment with atRA followed by suboptimal concentrations of IFNgamma induced a faster, higher, and more stable expression of IRF-1 than IFNgamma alone. Actinomycin D completely blocked the induction of IRF-1 by the combination, suggesting regulation at the transcriptional level. Further, we found that activation of signal transducer and activator of transcription-1 was induced more dramatically by atRA and IFNgamma than by IFNgamma alone. Expression of IFNgamma receptor-1 on the cell surface was also increased upon atRA pretreatment. Experiments using receptor-selective retinoids revealed that ligands for retinoic acid receptor-alpha (RARalpha), including atRA, 9-cis-retinoic acid, and Am580, sequentially increased the levels of IFNgamma receptor-1, activated signal transducer and activator of transcription-1, and IRF-1 and that an RARalpha antagonist was able to inhibit the effects of atRA and Am580. In addition, atRA pretreatment affected the transcriptional functions of IFNgamma-induced IRF-1, increasing its nuclear localization and DNA binding activity as well as the transcript levels of IRF-1 target genes. These results suggest that atRA, an RARalpha ligand, regulates IFNgamma-induced IRF-1 by affecting multiple components of the IFNgamma signaling pathway, from the plasma membrane to the nuclear transcription factors.

  19. All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2.

    Science.gov (United States)

    Wheelwright, Matthew; Kim, Elliot W; Inkeles, Megan S; De Leon, Avelino; Pellegrini, Matteo; Krutzik, Stephan R; Liu, Philip T

    2014-03-01

    A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the mechanism is unclear. In this study, we demonstrate that vitamin A-triggered antimicrobial activity against M. tuberculosis requires expression of NPC2. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D3), the biologically active forms of vitamin A and vitamin D, respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Stimulation of primary human monocytes with ATRA did not result in expression of the antimicrobial peptide cathelicidin, which is required for 1,25D3 antimicrobial activity. In contrast, ATRA triggered a reduction in the total cellular cholesterol concentration, whereas 1,25D3 did not. Blocking ATRA-induced cellular cholesterol reduction inhibits antimicrobial activity as well. Bioinformatic analysis of ATRA- and 1,25D3-induced gene profiles suggests that NPC2 is a key gene in ATRA-induced cholesterol regulation. Knockdown experiments demonstrate that ATRA-mediated decrease in total cellular cholesterol content and increase in lysosomal acidification are both dependent upon expression of NPC2. Expression of NPC2 was lower in caseous tuberculosis granulomas and M. tuberculosis-infected monocytes compared with normal lung and uninfected cells, respectively. Loss of NPC2 expression ablated ATRA-induced antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated antimicrobial mechanism against M. tuberculosis requires NPC2-dependent expression and function, indicating a key role for cellular cholesterol regulation in the innate immune response.

  20. Nicotinamide attenuates aquaporin 3 overexpression induced by retinoic acid through inhibition of EGFR/ERK in cultured human skin keratinocytes.

    Science.gov (United States)

    Song, Xiuzu; Xu, Aie; Pan, Wei; Wallin, Brittany; Kivlin, Rebecca; Lu, Shan; Cao, Cong; Bi, Zhigang; Wan, Yinsheng

    2008-08-01

    The most common adverse effects that are related to all-trans retinoic acid (atRA) treatment are irritation and dryness of the skin. atRA therapy is reported to impair barrier function as achieved by trans-epidermal water loss (TEWL). Treatment with nicotinamide prior to initiation of atRA therapy provides additional barrier protection and thus reduces susceptibility of retinoic acid. Our previous studies showed that atRA upregulates aquaporin 3 (AQP3) in cultured human skin keratinocytes and fibroblasts. Others have demonstrated that in atopic dermatitis, overexpression of AQP3 is linked to elevated TEWL and that nicotinamide treatment reduces skin TEWL. In this study, we observed that while atRA upregulates AQP3 expression in cultured human skin keratinocytes (HaCaT cells), nicotinamide attenuates the effect of atRA in a concentration-dependent manner. atRA treatment induces EGFR and ERK activation. PD153035, an EGFR inhibitor, and U0126, an ERK inhibitor, inhibit atRA-induced upregulation of AQP3. Nicotinamide also inhibits atRA-induced activation of EGFR/ERK signal transduction and decreases water permeability by downregulating AQP3 expression. Collectively, our results indicate that the effect of atRA on AQP3 expression is at least partly mediated by EGFR/ERK signaling in cultured human skin keratinocytes. Nicotinamide attenuates atRA-induced AQP3 expression through inhibition of EGFR/ERK signal transduction and eventually decreases water permeability and water loss. Our study provides insights into the molecular mechanism through which nicotinamide reverses the side effects of dryness in human skin after treatment with atRA.

  1. Characterization and performance of short cationic antimicrobial peptide isomers.

    Science.gov (United States)

    Juba, Melanie; Porter, Devin; Dean, Scott; Gillmor, Susan; Bishop, Barney

    2013-07-01

    Cationic antimicrobial peptides (CAMPs) represent an ancient defense mechanism against invading bacteria, with peptides such as the cathelicidins being essential elements of vertebrate innate immunity. CAMPs are typically associated with broad-spectrum antimicrobial potency and limited bacterial resistance. The cathelicidin identified from the elapid snake Naja atra (NA-CATH) contains a semi-conserved repeated 11-residue motif (ATRA motif) with a sequence pattern consistent with formation of an amphipathic helical conformation. Short peptide amides (ATRA-1, -1A, -1P, and -2) generated based on the pair of ATRA motifs in NA-CATH exhibited varied antimicrobial potencies. The small size of the ATRA peptides, coupled with their varied antimicrobial performances, make them interesting models to study the impact various physico-chemical properties have on antimicrobial performance in helical CAMPs. Accordingly, the D- and L-enantiomers of the peptide ATRA-1A, which in earlier studies had shown both good antimicrobial performance and strong helical character, were investigated in order to assess the impact peptide stereochemistry has on antimicrobial performance and interaction with chiral membranes. The ATRA-1A isomers exhibit varied potencies against four bacterial strains, and their conformational properties in the presence of mixed zwitterionic/anionic liposomes are influenced by anionic lipid content. These studies reveal subtle differences in the properties of the peptide isomers. Differences are also seen in the abilities of the ATRA-1A isomers to induce liposome fusion/aggregation, bilayer rearrangement and lysing through turbidity studies and fluorescence microscopy. The similarities and differences in the properties of the ATRA-1A isomers could aid in efforts to develop D-peptide-based therapeutics using high-performing L-peptides as templates.

  2. Synergistic effect of all-trans-retinoic acid and arsenic trioxide on growth inhibition and apoptosis in human hepatoma, breast cancer, and lung cancer cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Le-Min Lin; Bao-Xin Li; Jian-Bing Xiao; Dan-Hua Lin; Bao-Feng Yang

    2005-01-01

    AIM: To investigate the effect of all-trans-retinoic acid (ATRA) on arsenic trioxide (As2O3)-induced apoptosis of human hepatoma, breast cancer, and lung cancer cells in an attempt to find a better combination therapy for solid tumors.METHODS: Human hepatoma cell lines HepG2, Hep3B,human breast cancer cell line MCF-7, and human lung adenocarcinoma cell line AGZY-83-a were treated with As2O3 together with ATRA. Cell survival fraction was determined by MTT assay, cell viability and apoptosis were measured by annexin V-fluorescein isothiocyanate (FITC) and PI staining, and intracellular glutathione (GSH)and glutathione-S-transferase (GST) activities were determined using commercial kits.RESULTS: Cytotoxicity of ATRA was low. ATRA (0.1, 1,and 10 μmol/L) could synergistically potentiate As2O3 to exert a dose-dependent inhibition of growth and to induce apoptosis in each of the cell lines. HepG2 and Hep3B with low intracellular GSH or GST activities were remarkably sensitive to As2O3 or As2O3+ATRA, while AGZY-83-a with higher GSH or GST activities was less sensitive to As2O3or As2O3+ATRA. Treatment with 2 μmol/L As2O3 for 72 h significantly decreased intracellular GSH and GST levels in each of the cell lines, and 1 μmol/L ATRA alone reduced minimal intracellular GSH and GST levels. ATRA potentiated the effect of As2O3 on intracellular GSH levels, but intracellular GST levels were not significantly affected by the combination of As2O3 and ATRA for 72 h as compared to As2O3 alone.CONCLUSION: ATRA can strongly potentiate As2O3-induced growth-inhibition and apoptosis in each of the cell lines, and two drugs can produce a significant synergic effect. The sensitivity to As2O3 or As2O3+ATRA is inversely proportional to intracellular GSH or GST levels in each of the cell lines. The GSH redox system may be the possible mechanism by which ATRA synergistically potentiates As2O3 to exert a dose-dependent inhibition of growth and to induce apoptosis.

  3. Incidence of secondary neoplasms in patients with acute promyelocytic leukemia treated with all-trans retinoic acid plus chemotherapy or with all-trans retinoic acid plus arsenic trioxide.

    Science.gov (United States)

    Eghtedar, Alireza; Rodriguez, Ildefonso; Kantarjian, Hagop; O'Brien, Susan; Daver, Naval; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Kadia, Tapan; Pierce, Sherry; Cortes, Jorge; Ravandi, Farhad

    2015-05-01

    The incidence and pattern of secondary neoplasms in patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA)-containing regimens is not well described. We compared 160 patients with APL treated with ATRA plus idarubicin (n = 54) or ATRA plus arsenic trioxide (ATO) (n = 106) for the incidence of secondary cancers per unit time of follow-up. Median follow-up times for the two cohorts were 136 and 29 months, respectively. Nine patients developed secondary cancers in the chemotherapy group. These included two breast cancers, three myelodysplastic syndromes/acute myeloid leukemia, one vulvar cancer, one prostate cancer, one colon cancer and one soft tissue sarcoma. A melanoma and one pancreatic cancer developed in the ATO group. We conclude that treatment of patients with APL using the non-chemotherapy regimen of ATRA plus ATO is not associated with a higher incidence of secondary cancers (p = 0.29) adjusted for unit time of exposure.

  4. Description and DNA barcoding of three new species of Leohumicola from South Africa and the United States

    NARCIS (Netherlands)

    Nguyen, H.D.T.; Seifert, K.A.

    2008-01-01

    Three new species of Leohumicola (anamorphic Leotiomycetes) are described using morphological characters and phylogenetic analyses of DNA barcodes. Leohumicola levissima and L. atra were isolated from soils collected after forest fires in Crater Lake National Park, United States. Leohumicola incrust

  5. 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......-treated CAOV3 cells was the result of an increased protein stability. Moreover, Rb2/p130 exhibited a decreased ubiquitination following ATRA treatment. Because phosphorylation frequently mediates ubiquitination of proteins, we examined the serine/threonine phosphatase activity in our CAOV3 cells following ATRA...... treatment. A significant increase in Ser/Thr phosphatase activity was found, which correlated with a rise in the level of protein phosphatase 2A (PP2A) catalytic subunit-alpha. In addition, co-immunoprecipitation and glutathione S-transferase pull-down studies demonstrated that PP2A and Rb2/p130 associate...

  6. 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"

  7. COMPARISON OF CLINICAL OBSERVATIONS BETWEEN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA TREATED WITH ALL-TRANS RETINOIC ACID AND CHEMOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    张芬琴; 吴立德; 李秀松; 孙关林; 蔡敬仁; 王振义

    1992-01-01

    Clinical observations were retrospectively compared between 2 matched groups of patients with acute promyelocytic leukemia (APL) each 20. The first group were treated with chemotherapy, the other with all-tram retinoic acid (ATRA) alone at a dose of 45-60mg/M~2/d. The complete remission (CR) rate of ATRA group was significantly higher than that of chemotherapy (90% vs 55%). The time for obtaining CR as well as the duration of fever and hospitalization were shorter and the amount of blood transfused was less in the former than in the latter group. Seven cases were complicated by DIC and 4 died in the group of chemotherapy, while no case was by of DIC or death in the ATRA group. The mechanism was discussed. ATRA is an alternative effective drug for remission induction therapy in APL with high rate of CR.

  8. Genital Ulcer Development in Patients with Acute Promyelocytic Leukaemia Treated with All-Trans Retinoic Acid: A Case Series

    Directory of Open Access Journals (Sweden)

    Mohammed Al Huneini

    2013-05-01

    Full Text Available We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid (ATRA for the treatment of acute promyelocytic leukemia (APL. Between October 2007 and March 2010, three males and one female (age range 19-35 years were identified to have genital ulcers after being prescribed all-trans retinoic acid (ATRA as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted.

  9. 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.

  10. 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.

  11. 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...

  12. 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

    affecting p14ARF (P melanocytes, and that the steady-state levels of p14ARF in these cells...... are regulated via RARβ. Furthermore, we show that the ability of ATRA to induce senescence is reduced in p14ARF-depleted melanocytes, and we provide proof-of-concept that ATRA can induce irreversible growth arrest in melanoma cells with an intact RARβ-p14ARF axis, independent of p16INK4A and p53 status...

  13. Síndrome da diferenciação na leucemia promielocítica aguda: patogênese e fatores de risco

    OpenAIRE

    2008-01-01

    Differentiation syndrome is a treatment complication which can occur in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) or arsenic trioxide (ATO), which is characterized by enhanced leukocyte transmigration. Several cellular and molecular mechanisms participate in differentiation syndrome development. This review discusses the changes in expression of adhesion molecules induced during ATRA and ATO treatments and their possible implications in the pathog...

  14. All-trans retinoic acid potentiates cisplatin-induced kidney injury in rats: impact of retinoic acid signaling pathway.

    Science.gov (United States)

    Elsayed, Abdelrahman M; Abdelghany, Tamer M; Akool, El-Sayed; Abdel-Aziz, Abdel-Aziz H; Abdel-Bakky, Mohamed S

    2016-03-01

    Cisplatin (cis-diammine dichloroplatinum (II), CDDP) is a widely used drug for treatment of various types of cancers. However, CDDP-induced nephrotoxicity remains the main dose-limiting side effect. Retinoids are a group of vitamin A-related compounds that exert their effects through retinoid receptors activation. In this study, we investigated the effect of CDDP treatment on retinoic acid receptor-α (RAR-α) and retinoid X receptor-α (RXR-α) expression. In addition, we investigated the possible modulatory effects of RAR agonist, all-trans retinoic acid (ATRA), on CDDP-induced nephrotoxicity. Rats were treated with saline, DMSO, CDDP, ATRA, or CDDP/ATRA. Twenty-four hours after the last ATRA injection, rats were killed; blood samples were collected; kidneys were dissected; and biochemical, immunohistochemical, and histological examinations were performed. Our results revealed that CDDP treatment significantly increased serum levels of creatinine and urea, with concomitant decrease in serum albumin. Moreover, reduced glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities were significantly reduced with concurrent increase in kidney malondialdehyde (MDA) content following CDDP treatment. Furthermore, CDDP markedly upregulated tubular RAR-α, RXR-α, fibrin, and inducible nitric oxide synthase (iNOS) protein expression. Although administration of ATRA to control rats did not produce marked alterations in kidney function parameters, administration of ATRA to CDDP-treated rats significantly exacerbated CDDP-induced nephrotoxicity. In addition, CDDP/ATRA co-treatment significantly increased RAR-α, RXR-α, fibrin, and iNOS protein expression compared to CDDP alone. In conclusion, we report, for the first time, the crucial role of retinoid receptors in CDDP-induced nephrotoxicity. Moreover, our findings indicate that co-administration of ATRA with CDDP, although beneficial on the therapeutic effects, their deleterious effects on

  15. 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

    2016-06-14

    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.

  16. In Situ Catalyst Modification in Atom Transfer Radical Reactions with Ruthenium Benzylidene Complexes.

    Science.gov (United States)

    Lee, Juneyoung; Grandner, Jessica M; Engle, Keary M; Houk, K N; Grubbs, Robert H

    2016-06-08

    Ruthenium benzylidene complexes are well-known as olefin metathesis catalysts. Several reports have demonstrated the ability of these catalysts to also facilitate atom transfer radical (ATR) reactions, such as atom transfer radical addition (ATRA) and atom transfer radical polymerization (ATRP). However, while the mechanism of olefin metathesis with ruthenium benzylidenes has been well-studied, the mechanism by which ruthenium benzylidenes promote ATR reactions remains unknown. To probe this question, we have analyzed seven different ruthenium benzylidene complexes for ATR reactivity. Kinetic studies by (1)H NMR revealed that ruthenium benzylidene complexes are rapidly converted into new ATRA-active, metathesis-inactive species under typical ATRA conditions. When ruthenium benzylidene complexes were activated prior to substrate addition, the resulting activated species exhibited enhanced kinetic reactivity in ATRA with no significant difference in overall product yield compared to the original complexes. Even at low temperature, where the original intact complexes did not catalyze the reaction, preactivated catalysts successfully reacted. Only the ruthenium benzylidene complexes that could be rapidly transformed into ATRA-active species could successfully catalyze ATRP, whereas other complexes preferred redox-initiated free radical polymerization. Kinetic measurements along with additional mechanistic and computational studies show that a metathesis-inactive ruthenium species, generated in situ from the ruthenium benzylidene complexes, is the active catalyst in ATR reactions. Based on data from (1) H, (13)C, and (31)P NMR spectroscopy and X-ray crystallography, we suspect that this ATRA-active species is a RuxCly(PCy3)z complex.

  17. All-trans-retinoic acid inhibits tumour growth of malignant pleural mesothelioma in mice.

    Science.gov (United States)

    Tabata, C; Tabata, R; Hirayama, N; Yasumitsu, A; Yamada, S; Murakami, A; Iida, S; Tamura, K; Terada, T; Kuribayashi, K; Fukuoka, K; Nakano, T

    2009-11-01

    Malignant pleural mesothelioma (MPM) is an aggressive malignant tumour of mesothelial origin associated with asbestos exposure. Because MPM has limited response to conventional chemotherapy and radiotherapy, the prognosis is very poor. Several researchers have reported that cytokines such as interleukin (IL)-6 play an important role in the growth of MPM. Previously, it was reported that all-trans-retinoic acid (ATRA) inhibited the production and function of IL-6 and transforming growth factor (TGF)-beta1 in experiments using lung fibroblasts. We investigated whether ATRA had an inhibitory effect on the cell growth of MPM, the origin of which was mesenchymal cells similar to lung fibroblasts, using a subcutaneous xenograft mouse model. We estimated the tumour growth and performed quantitative measurements of IL-6, TGF-beta1 and platelet-derived growth factor (PDGF) receptor (PDGFR)-beta mRNA levels both of cultured MPM cells and cells grown in mice with or without the administration of ATRA. ATRA significantly inhibited MPM tumour growth. In vitro studies disclosed that the administration of ATRA reduced 1) mRNA levels of TGF-beta1, TGF-beta1 receptors and PDGFR-beta, and 2) TGF-beta1-dependent proliferation and PDGF-BB-dependent migration of MPM cells. These data may provide a rationale to explore the clinical use of ATRA for the treatment of MPM.

  18. Genital ulcers during treatment with ALL-trans retinoic acid for acute promyelocytic leukemia.

    Science.gov (United States)

    Fukuno, Kenji; Tsurumi, Hisashi; Goto, Hideko; Oyama, Masami; Tanabashi, Shinobu; Moriwaki, Hisataka

    2003-11-01

    Scrotal ulcer is a unique adverse effect of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). The pathogenesis of scrotal ulceration remains unknown. We describe genital ulcers that developed in four patients with APL who were undergoing ATRA therapy (45 mg/m2 per day p.o.). Two of the patients were female, in whom this condition is quite rare. Genital ulcers with concomitant fever appeared between 17 and 32 days of therapy in all four patients. Genital ulcers healed in three of the patients while another patient developed Fournier's gangrene and underwent left testectomy. Ulcer healing was brought by either local or intravenous corticosteroids. Intravenous dexamethasone actually enabled continued ATRA administration in one patient, while ATRA was discontinued in other two patients. If corticosteroids cannot control progression of genital ulcers nor concomitant fever, ATRA administration should be discontinued so as not to induce Fournier's gangrene nor retionic acid syndrome. Our experience indicates the importance of recognizing genital ulcers associated with ATRA in order that appropriate countermeasures can be taken.

  19. Isocitrate dehydrogenase 1 mutations prime the all-trans retinoic acid myeloid differentiation pathway in acute myeloid leukemia.

    Science.gov (United States)

    Boutzen, Héléna; Saland, Estelle; Larrue, Clément; de Toni, Fabienne; Gales, Lara; Castelli, Florence A; Cathebas, Mathilde; Zaghdoudi, Sonia; Stuani, Lucille; Kaoma, Tony; Riscal, Romain; Yang, Guangli; Hirsch, Pierre; David, Marion; De Mas-Mansat, Véronique; Delabesse, Eric; Vallar, Laurent; Delhommeau, François; Jouanin, Isabelle; Ouerfelli, Ouathek; Le Cam, Laurent; Linares, Laetitia K; Junot, Christophe; Portais, Jean-Charles; Vergez, François; Récher, Christian; Sarry, Jean-Emmanuel

    2016-04-04

    Acute myeloid leukemia (AML) is characterized by the accumulation of malignant blasts with impaired differentiation programs caused by recurrent mutations, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients. These mutations result in the production of the oncometabolite (R)-2-hydroxyglutarate (2-HG), leading to a hypermethylation phenotype that dysregulates hematopoietic differentiation. In this study, we identified mutant R132H IDH1-specific gene signatures regulated by key transcription factors, particularly CEBPα, involved in myeloid differentiation and retinoid responsiveness. We show that treatment with all-trans retinoic acid (ATRA) at clinically achievable doses markedly enhanced terminal granulocytic differentiation in AML cell lines, primary patient samples, and a xenograft mouse model carrying mutant IDH1. Moreover, treatment with a cell-permeable form of 2-HG sensitized wild-type IDH1 AML cells to ATRA-induced myeloid differentiation, whereas inhibition of 2-HG production significantly reduced ATRA effects in mutant IDH1 cells. ATRA treatment specifically decreased cell viability and induced apoptosis of mutant IDH1 blasts in vitro. ATRA also reduced tumor burden of mutant IDH1 AML cells xenografted in NOD-Scid-IL2rγ(null)mice and markedly increased overall survival, revealing a potent antileukemic effect of ATRA in the presence of IDH1 mutation. This therapeutic strategy holds promise for this AML patient subgroup in future clinical studies.

  20. All-trans-Retinoic Acid Ameliorated High Fat Diet-Induced Atherosclerosis in Rabbits by Inhibiting Platelet Activation and Inflammation

    Directory of Open Access Journals (Sweden)

    Birong Zhou

    2012-01-01

    Full Text Available Background. All-trans-retinoic acid (atRA is effective for many proliferative diseases. We investigated the protective effects of atRA against atherosclerosis. Methods. Rabbits were randomly allocated to receive basal diet or an HFD for 4 weeks. HFD group then received rosuvastatin (3 mg/day, atRA (5 mg/kg/day, or the same volume of vehicle, respectively, for next 8 weeks. Results. HFD group showed increases in plasma lipids and aortic plaque formation. P-selectin expression and fibrinogen binding on platelets or deposition on the intima of the aorta also increased significantly as did the levels of TNF-α, IL-6, and fibrinogen in plasma. After 8 weeks of treatment with atRA, there was a significant decrease in plasma lipids and improvement in aortic lesions. AtRA also inhibited the expression of P-selectin and fibrinogen binding on platelets and deposition on the intima of the aorta. Conclusion. AtRA can ameliorate HFD-induced AS in rabbits by inhibiting platelet activation and inflammation.

  1. Inhalation administration of all-trans-retinoic acid for treatment of elastase-induced pulmonary emphysema in Fischer 344 rats.

    Science.gov (United States)

    March, Thomas H; Cossey, Patricia Y; Esparza, Dolores C; Dix, Kelly J; McDonald, Jacob D; Bowen, Larry E

    2004-01-01

    A past study demonstrated that all-trans-retinoic acid (ATRA) treatment by intraperitoneal injection in a rat model of elastase-induced emphysema caused tissue regeneration as evidenced by a decrease in alveolar size and lung volume and an increase in alveolar number. We postulated that treatment with this retinoid by nose-only inhalation exposure would be a more efficient means of targeting damaged lung tissue. Emphysema was induced in male Fischer 344 rats by intratracheal instillation of pancreatic elastase (0.5 IU/g body weight). Four weeks after elastase instillation, animals were treated once daily, 4 days/week, for 3 weeks by exposing them nose-only to aerosolized ATRA (target concentration-time of 3000 or 15,000 mg-min/m3) or by injecting them intraperitoneally with ATRA in cottonseed oil (0.5 or 2.5 mg/kg). Based on estimates of particle deposition in the respiratory tract, inhalation doses were chosen to be consistent with injected doses. Lungs were fixed by inflation with formalin (constant pressure for 6 hours followed by >48 hours of immersion) and were embedded in paraffin. Sections were evaluated by histopathology and stereology. Inhalation exposure to ATRA at both aerosol concentrations caused significant elevations of ATRA in the lung, whereas only the high-dose injection treatment was associated with an elevation of lung ATRA. The mean ATRA concentration from lungs of rats in the high-dose inhalation exposure groups as measured by liquid chromatography--mass spectrometry was approximately 12-fold greater than that of high-dose injection-treated rats. Elastase instillation caused increased lung volumes, irregular alveolar air space enlargement, and fragmentation and attenuation of alveolar septa. Neither inhaled nor injected ATRA reduced the enlarged lung volumes associated with this emphysema model. Stereology demonstrated that alveolar air space enlargement in ATRA-treated rats was similar to that in sham-treated emphysematous animals. Thus

  2. 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

  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. All-trans-retinoic Acid Modulates the Plasticity and Inhibits the Motility of Breast Cancer Cells: ROLE OF NOTCH1 AND TRANSFORMING GROWTH FACTOR (TGFβ).

    Science.gov (United States)

    Zanetti, Adriana; Affatato, Roberta; Centritto, Floriana; Fratelli, Maddalena; Kurosaki, Mami; Barzago, Maria Monica; Bolis, Marco; Terao, Mineko; Garattini, Enrico; Paroni, Gabriela

    2015-07-17

    All-trans-retinoic acid (ATRA) is a natural compound proposed for the treatment/chemoprevention of breast cancer. Increasing evidence indicates that aberrant regulation of epithelial-to-mesenchymal transition (EMT) is a determinant of the cancer cell invasive and metastatic behavior. The effects of ATRA on EMT are largely unknown. In HER2-positive SKBR3 and UACC812 cells, showing co-amplification of the ERBB2 and RARA genes, ATRA activates a RARα-dependent epithelial differentiation program. In SKBR3 cells, this causes the formation/reorganization of adherens and tight junctions. Epithelial differentiation and augmented cell-cell contacts underlie the anti-migratory action exerted by the retinoid in cells exposed to the EMT-inducing factors EGF and heregulin-β1. Down-regulation of NOTCH1, an emerging EMT modulator, is involved in the inhibition of motility by ATRA. Indeed, the retinoid blocks NOTCH1 up-regulation by EGF and/or heregulin-β1. Pharmacological inhibition of γ-secretase and NOTCH1 processing also abrogates SKBR3 cell migration. Stimulation of TGFβ contributes to the anti-migratory effect of ATRA. The retinoid switches TGFβ from an EMT-inducing and pro-migratory determinant to an anti-migratory mediator. Inhibition of the NOTCH1 pathway not only plays a role in the anti-migratory action of ATRA; it is relevant also for the anti-proliferative activity of the retinoid in HCC1599 breast cancer cells, which are addicted to NOTCH1 for growth/viability. This effect is enhanced by the combination of ATRA and the γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester, supporting the concept that the two compounds act at the transcriptional and post-translational levels along the NOTCH1 pathway.

  5. 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.

  6. 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.

  7. Retinoic acid receptor agonists regulate expression of ATP-binding cassette transporter G1 in macrophages.

    Science.gov (United States)

    Ayaori, Makoto; Yakushiji, Emi; Ogura, Masatsune; Nakaya, Kazuhiro; Hisada, Tetsuya; Uto-Kondo, Harumi; Takiguchi, Shunichi; Terao, Yoshio; Sasaki, Makoto; Komatsu, Tomohiro; Iizuka, Maki; Yogo, Makiko; Uehara, Yoshinari; Kagechika, Hiroyuki; Nakanishi, Tsuyoshi; Ikewaki, Katsunori

    2012-04-01

    ABC transporter G1 (ABCG1) plays a pivotal role in HDL-mediated cholesterol efflux and atherogenesis. We investigated whether, and how, retinoic acid receptors (RARs) regulate ABCG1 expression in macrophages. All-trans retinoic acid (ATRA), an RAR ligand, increased ABCG1 protein levels and apoA-I/HDL-mediated cholesterol efflux from the macrophages. Both ATRA and other RAR agonists, TTNPB and Am580, increased major transcripts driven by promoter B upstream of exon 5, though minor transcripts driven by promoter A upstream of exon 1 were only increased by ATRA. The stimulatory effects of ATRA on ABCG1 expression were completely abolished in the presence of RAR/RXR antagonists but were only partially canceled in the presence of an LXR antagonist. Adenovirus with overexpressed oxysterol sulfotransferase abolished the LXR pathway, as previously reported, and ATRA-responsiveness in ABCA1/ABCG1 expressions were respectively attenuated by 38 and 22% compared to the control virus. Promoter assays revealed that ABCG1 levels were regulated more by promoter B than promoter A, and ATRA activated promoter B in a liver X receptor-responsive element (LXRE)-dependent manner. Further, LXRE-B in intron 7, but not LXRE-A in intron 5, enhanced ATRA responsiveness under overexpression of all RAR isoforms-RARα/β/γ. In contrast, the activation of promoter B by TTNPB depended on LXRE-B and RARα, but not on RARβ/γ. Finally, chromatin immunoprecipitation and gel-shift assays revealed a specific and direct repeat 4-dependent binding of RARα to LXRE-B. In conclusion, RAR ligands increase ABCA1/G1 expression and apoA-I/HDL-mediated cholesterol efflux from macrophages, and modulate ABCG1 promoter activity via LXRE-dependent mechanisms.

  8. 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.

  9. 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.

  10. Epigenetic priming of AML blasts for all-trans retinoic acid-induced differentiation by the HDAC class-I selective inhibitor entinostat.

    Directory of Open Access Journals (Sweden)

    Nadja Blagitko-Dorfs

    Full Text Available All-trans retinoic acid (ATRA has only limited single agent activity in AML without the PML-RARα fusion (non-M3 AML. In search of a sensitizing strategy to overcome this relative ATRA resistance, we investigated the potency of the HDAC class-I selective inhibitor entinostat in AML cell lines Kasumi-1 and HL-60 and primary AML blasts. Entinostat alone induced robust differentiation of both cell lines, which was enhanced by the combination with ATRA. This "priming" effect on ATRA-induced differentiation was at least equivalent to that achieved with the DNA hypomethylating agent decitabine, and could overall be recapitulated in primary AML blasts treated ex vivo. Moreover, entinostat treatment established the activating chromatin marks acH3, acH3K9, acH4 and H3K4me3 at the promoter of the RARβ2 gene, an essential mediator of retinoic acid (RA signaling in different solid tumor models. Similarly, RARβ2 promoter hypermethylation (which in primary blasts from 90 AML/MDS patients was surprisingly infrequent could be partially reversed by decitabine in the two cell lines. Re-induction of the epigenetically silenced RARβ2 gene was achieved only when entinostat or decitabine were given prior to ATRA treatment. Thus in this model, reactivation of RARβ2 was not necessarily required for the differentiation effect, and pharmacological RARβ2 promoter demethylation may be a bystander phenomenon rather than an essential prerequisite for the cellular effects of decitabine when combined with ATRA. In conclusion, as a "priming" agent for non-M3 AML blasts to the differentiation-inducing effects of ATRA, entinostat is at least as active as decitabine, and both act in part independently from RARβ2. Further investigation of this treatment combination in non-M3 AML patients is therefore warranted, independently of RARβ2 gene silencing by DNA methylation.

  11. Effects of TrkB-BDNF signal pathway on synthesis and secretion of vascular endothelial growth factor in human neuroblastoma cells%TrkB-BDNF信号通路对神经母细胞瘤细胞分泌血管内皮生长因子的影响

    Institute of Scientific and Technical Information of China (English)

    李坤霞; 李爱敏; 张继红

    2011-01-01

    Objective To study the effects of TrkB-BDNF signal pathway on the synthesis and secretion of vascular endothelial growth factor (VEGF) in human neuroblastoma cells (NB). Methods TrkB protein expression in SY5Y cells before and after all-trans-retinoicacid (ATRA) treatment was detected by Western blot. p-TrkB protein expression in SY5Y cells before and after the treatment of ATRA along with BDNF was also detected by Western blot. VEGF concentrations in the SY5Y cell culture supernatants were measured using ELISA after the treatment with ATRA, BDNF, tyrosine kinase inhibitor K252a and PI3k inhibitor LY294002. Results TrkB protein was undetectable in SY5Y cells before ATRA treatment. After the treatment of 1, 10 and 100 nM/L ATRA for five days, TrkB protein was expressed in SY5Y cells and the TrkB protein level increased with the increasing ATRA concentration. p-TrkB protein was not expressed in SY5Y cells treated only with 10 nM/L ATRA, but it was detectable after the treatment of ATRA along with BDNF. VEGF concentrations in the group treated with ATRA + BDNF were significantly higher than those in the untreated control and the ATRA alone treatment groups ( P < 0.01 ). VEGF concentrations in the K252a pretreated ATRA + BDNF group were significantly lower than those in the group treated with ATRA + BDNF ( P < 0.05 ). VEGF concentrations in the LY294002 treatment group (ATRA + LY294002 + BDNF group) were also significantly lower than those in the group treated with ATRA + BDNF ( P < 0. 01 ). Conclusions Activation of TrkB-BDNF signal pathway may increase the synthesis and secretion of VEGF in human NB cells. The synthesis and secretion of VEGF can be inhibited by blocking TrkB-BDNF signal pathway with K252a or blocking the TrkB-BDNF downstream signal pathway PI3K/Akt with LY294002.%目的:探讨TrkB-BDNF信号通路对神经母细胞瘤(NB)细胞SH-SYSY分泌血管内皮生长因子(VEGF)的影响.方法:Western blot方法检测全反式维甲酸(ATRA

  12. Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells.

    Science.gov (United States)

    Falanga, A; Consonni, R; Marchetti, M; Locatelli, G; Garattini, E; Passerini, C G; Gordon, S G; Barbui, T

    1998-07-01

    All-trans-retinoic acid (ATRA) downregulates the expression of two cellular procoagulants, tissue factor (TF) and cancer procoagulant (CP), in human promyelocytic leukemia cells. To evaluate whether or not changes of the procoagulant activities (PCAs) may share mechanisms with the ATRA-induced cyto-differentiation process, we have characterized the effect of ATRA on the TF and CP expression by NB4 cells, an ATRA maturation-inducible cell line, and two NB4-derived cell lines resistant to ATRA-induced maturation, the NB4. 306 and NB4.007/6 cells. Next, we evaluated the effect on the PCAs of the NB4 parental cells of three synthetic retinoid analogues, ie: AM580 (selective for the retinoic acid receptor [RAR] alpha), capable to induce the granulocytic differentiation of NB4 cells; and CD2019 (selective for RARbeta) and CD437 (selective for RARgamma), both lacking this capability. Cells were treated with either ATRA or the analogues (10(-6) to 10(-8) mol/L) for 96 hours. The effect on cell differentiation was evaluated by morphologic changes, cell proliferation, nitro blue tetrazolium reduction assay, and flow cytometry analysis of the CD33 and CD11b surface-antigen expression. PCA was first measured in 20 mmol/L Veronal Buffer cell extracts by the one-stage clotting assay of normal and FVII-deficient plasmas. Further TF and CP have been characterized and quantified in cell-sample preparations by chromogenic and immunological assays. In the first series of experiments, ATRA downregulates both TF and CP in NB4 parental cells, as expected. However, in the differentiation-resistant cell lines, it induced a significant loss of TF but had little or no effect on CP. In a second series of experiments, in the NB4 parental cells, the RARalpha agonist (AM580) induced cell maturation and reduced 91% CP expression, whereas CD437 and CD2019 had no cyto-differentiating effects and did not affect CP levels. On the other hand, in the same cells the TF expression was reduced by ATRA

  13. Cloning and functional studies of a splice variant of CYP26B1 expressed in vascular cells.

    Directory of Open Access Journals (Sweden)

    Ali Ateia Elmabsout

    Full Text Available BACKGROUND: All-trans retinoic acid (atRA plays an essential role in the regulation of gene expression, cell growth and differentiation and is also important for normal cardiovascular development but may in turn be involved in cardiovascular diseases, i.e. atherosclerosis and restenosis. The cellular atRA levels are under strict control involving several cytochromes P450 isoforms (CYPs. CYP26 may be the most important regulator of atRA catabolism in vascular cells. The present study describes the molecular cloning, characterization and function of atRA-induced expression of a spliced variant of the CYP26B1 gene. METHODOLOGY/PRINCIPAL FINDINGS: The coding region of the spliced CYP26B1 lacking exon 2 was amplified from cDNA synthesized from atRA-treated human aortic smooth muscle cells and sequenced. Both the spliced variant and full length CYP26B1 was found to be expressed in cultured human endothelial and smooth muscle cells, and in normal and atherosclerotic vessel. atRA induced both variants of CYP26B1 in cultured vascular cells. Furthermore, the levels of spliced mRNA transcript were 4.5 times higher in the atherosclerotic lesion compared to normal arteries and the expression in the lesions was increased 20-fold upon atRA treatment. The spliced CYP26B1 still has the capability to degrade atRA, but at an initial rate one-third that of the corresponding full length enzyme. Transfection of COS-1 and THP-1 cells with the CYP26B1 spliced variant indicated either an increase or a decrease in the catabolism of atRA, probably depending on the expression of other atRA catabolizing enzymes in the cells. CONCLUSIONS/SIGNIFICANCE: Vascular cells express the spliced variant of CYP26B1 lacking exon 2 and it is also increased in atherosclerotic lesions. The spliced variant displays a slower and reduced degradation of atRA as compared to the full-length enzyme. Further studies are needed, however, to clarify the substrate specificity and role of the CYP26B1

  14. 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.

  15. Acute promyelocytic leukemia and pregnancy.

    Science.gov (United States)

    Giagounidis, A A; Beckmann, M W; Giagounidis, A S; Aivado, M; Emde, T; Germing, U; Riehs, T; Heyll, A; Aul, C

    2000-04-01

    In acute promyelocytic leukemia (APL), the use of all-trans-retinoic acid (ATRA) as a differentiating agent induces complete remission in a high percentage of patients. In pregnancy, however, this drug bears the risk of severe teratogenicity to the child. We report the case of a 23-yr-old woman at 21 weeks' gestation suffering from APL. She was treated with ATRA (45 mg/m2) for 40 d and two courses of standard chemotherapy. The mother achieved complete remission within 22 d of treatment. Fetal development was normal, and a healthy premature girl was born in the 35th week of pregnancy. In a review of the literature we have identified 14 cases of APL in pregnancy treated with ATRA alone or in combination with chemotherapy. ATRA has been used as early as in the 3rd week of gestation and in no case have malformations or other teratogenic effects occurred. Side-effects, however, ranged from fetal cardiac arrhythmias to induction of labour. Although known to exhibit severe teratogenic effects during the first trimester of pregnancy, ATRA seems to be reasonably safe during the second and third trimesters in the treatment of APL. However, careful obstetric follow-up is mandatory regarding fetal cardiac complications.

  16. 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.

  17. Characterization of a negative regulator AveI for avermectin biosynthesis in Streptomyces avermitilis NRRL8165.

    Science.gov (United States)

    Chen, Lei; Lu, Yinhua; Chen, Jun; Zhang, Weiwen; Shu, Dan; Qin, Zhongjun; Yang, Sheng; Jiang, Weihong

    2008-08-01

    A transcriptional activator for actinorhodin biosynthesis, AtrA, was previously characterized in Streptomyces coelicolor A3(2), and an orthologue of atrA, named aveI, is identified in the Streptomyces avermitilis NRRL8165 genome (Uguru et al., Mol Microbiol, 58:131-150, 2005). In this study, genetic and functional characterization of aveI gene was reported. Deletion of aveI gene led to increased biosynthesis of avermectin B1a by about 16-fold. The increased synthesis of avermectin B1a was suppressed by complementation with either aveI gene or its orthologue gene atrA from S. coelicolor, suggesting AveI and AtrA shared the similar functionality and were negative regulators for avermectin biosynthesis in S. avermitilis. However, when aveI was introduced into S. coelicolor on a multi-copy plasmid, the production of actinorhodin was significantly increased, indicating that aveI had a positive effect on actinorhodin biosynthesis in S. coelicolor, the same as its orthologue atrA. Electrophoretic mobility shift assays revealed AveI can bind specifically to the promoter region of actII-ORF4 in vitro but not that of aveR. Although its mechanism still needs to be defined, the species-differential regulation by the same regulator may represent an example of the evolutional strategy that enables bacteria to adapt the existing molecular machinery to a variety of functionalities for growth and survival.

  18. 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.

  19. Vitamin A increases nerve growth factor and retinoic acid receptor beta and improves diabetic neuropathy in rats.

    Science.gov (United States)

    Hernández-Pedro, Norma; Granados-Soto, Vinicio; Ordoñez, Graciela; Pineda, Benjamin; Rangel-López, Edgar; Salazar-Ramiro, Aleli; Arrieta, Oscar; Sotelo, Julio

    2014-09-01

    All-trans retinoic acid (ATRA) promotes the endogenous expression of both nerve growth factor (NGF) and retinoic acid receptor beta (RAR-β). We have previously shown that the administration of ATRA partly reverts the damage induced by diabetic neuropathy (DN). In this investigation, we evaluated the effects of vitamin A, a commercial, inexpensive compound of retinoic acid, on the therapy of DN. A total of 70 rats were randomized into 4 groups. Group A was the control, and groups B, C, and D received a total dose of 60 mg/kg streptozotocin intraperitoneally. When signs of DN developed, groups C and D were treated either with vitamin A (20,000 IU) or with ATRA 25 mg/kg for 60 days. Plasma glucose, contents of NGF, thermal and nociceptive tests, and RAR-β expression were evaluated. All diabetic rats developed neuropathy. The treatment with vitamin A and ATRA reverted similarly the sensorial disturbances, which was associated with increased contents of NGF and RAR-β expression. Our results indicate that the administration of vitamin A has the same therapeutic effect as ATRA on peripheral neuropathy and suggest its potential therapeutic use in patients with diabetes.

  20. Elevated TrkA receptor expression is associated with all-trans retinoic acid-induced neuroblastoma differentiation.

    Science.gov (United States)

    Gao, Q; Chen, C F; Dong, Q; Hou, L; Chen, X; Zhi, Y L; Li, X; Lu, H T; Zhang, H Y

    2015-10-27

    Neuroblastoma is the most common and one of the deadliest among pediatric tumors; however, a subset of infants with neuroblastoma display spontaneous regression. The mechanism of spontaneous regression remains to be elucidated. TrkA plays an essential role in the differentiation and functionality of neurons; abundant TrkA expression is associated with favorable prognosis of neuroblastoma. All-trans retinoic acid (ATRA), a first-line drug for acute promyelocytic leukemia (APL) treatment, has been shown to induce differentiation and inhibit cell growth. Neuroblastoma tissues in our hospital inpatient were collected, primary cell culture was performed, and the cells were separated and purified to be cell line. Trypan blue exclusion was used to count the numbers of cells alive, morphological changes were observed under the phase-contrast microscope. RT-PCR was used to determine the expression level of TrkA. In this study, a human neuroblastoma cell line was successfully established; in addition, we demonstrated that ATRA induces growth arrest and promotes the differentiation of neuroblastoma cells. In addition, ATRA was shown to significantly increase the levels of TrkA mRNA expression. Therefore, we concluded that the elevated expression of the TrkA receptor is associated with ATRA-induced growth arrest and differentiation o neuroblastoma cells. The results of this study provide a theoretical basis for the clinical application of differentiation-inducing ATRA for neuroblastoma therapy.

  1. Gangrenous cheilitis associated with all-trans retinoic acid therapy for acute promyelocytic leukemia.

    Science.gov (United States)

    Tanaka, Mariko; Fukushima, Noriyasu; Itamura, Hidekazu; Urata, Chisako; Yokoo, Masako; Ide, Masaru; Hisatomi, Takashi; Tomimasu, Rika; Sueoka, Eisaburo; Kimura, Shinya

    2010-01-01

    A 67-year-old Japanese woman who presented with erythema on the abdomen and pancytopenia was found to have acute promyelocytic leukemia (APL). A skin biopsy revealed invasion of APL cells. She was started on induction treatment with all-trans retinoic acid (ATRA) at 45 mg/m(2). On day 4, the leukemic cell number had increased to over 1.0 x 10(9)/L. Consequently, chemotherapy with idarubicin and cytarabine was initiated. On day 10, dryness of the lips appeared. The lower lip swelled and developed painful black eschars. A high fever was also present. Despite discontinuing ATRA on day 20 and administering antibiotics, an anti-fungal agent and valaciclovir, these signs did not improve. Histopathologically, the biopsied lip revealed infiltration of neutrophils and vasculitis. The patient was given ATRA on days 29 and 30 due to an increase in APL cell numbers, after which the gangrenous cheilitis extended over the whole lip. On day 49, the patient was started on re-induction treatment with arsenic trioxide. She achieved complete remission and the gangrenous cheilitis slowly healed over the following 8 weeks. Since the clinical features of the gangrenous cheilitis in this case were similar to those of ATRA-associated scrotal ulcers, it appears that activated neutrophils derived from differentiated APL cells may have caused the gangrenous cheilitis. Physicians should be alert to the development of gangrenous cheilitis during treatment with ATRA.

  2. An Improved Method for Directional Differentiation and Efficient Production of Neurons from Embryonic Stem Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yufeng; FANG Feng; DONG Yongsui; LI Ge; ZHEN Hong; YI Wenlong; XIANG Zhidan

    2005-01-01

    To establish a method of directional differentiation and efficient production of neurons from embryonic stem cells (ES cells) in vitro, based on the 4-/4+ protocol described by Bain, a new method was established to induce ES cells differentiating into neurons by means of three-step differentiation using all-trans retinoic acid (ATRA) combined with astrocyte-conditioned medium (ACM) in Vitro. The totipotency of ES cells was identified by observation of cells' morphology and formations of teratoma in immunocompromised mice. The cells' differentiation was evaluated continuously by the detection of the specific cellular markers of neural stem ceils, neurons and astrocytes,including nestin, NSE and GFAP using immunohistochemistry assay. The NSE positive cells' ratio of the differentiated cells was determined by flow cytometry. It was found that the transparent circular clusters surrounding embryoid bodies induced with combining induction protocol formed just after 24 h and gradually enlarged later. This phenomenon could not be observed in EBs induced only by ATRA. The NSE positive cells' ratio irthe cells induced with ATRA and ACM was higher than that of the cells induced by ATRA at different time points of differentiation, and finally reached up to 73.5 % among the total differentiated population. It was concluded that ES cells could be induced into neurons with high purity and yield by means of inducing method combining with ATRA and ACM.

  3. 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

    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 immunity...

  4. 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.

  5. A Complicated Case of Acute Promyelocytic Leukemia in the Second Trimester of Pregnancy Successfully Treated with All-trans-Retinoic Acid

    Directory of Open Access Journals (Sweden)

    Kanika Agarwal

    2015-01-01

    Full Text Available A 40-year-old female at 26-week gestation was diagnosed with acute promyelocytic leukemia (APL after an abnormal prenatal lab workup showed pancytopenia. She was treated with all-trans-retinoic acid (ATRA, idarubicin, and dexamethasone. After day one of treatment, she developed differentiation syndrome, which was treated with dexamethasone. At 30-week gestation, she had preterm premature rupture of membranes and delivered by cesarean section because of the fetus’ breech presentation. Despite ATRA’s potential for teratogenicity, a viable infant was born without apparent anomalies. Postpartum, she underwent consolidation treatment with ATRA and arsenic trioxide (ATO. The patient continued ATRA therapy after delivery and is currently in remission.

  6. Purification and characterization of Ophiophagus hannah cytotoxin-like proteins.

    Science.gov (United States)

    Chang, Long-Sen; Chen, Ku-Chung; Lin, Shinne-Ren; Huang, Hsien-Bin

    2006-09-15

    Three cytotoxin-like proteins from the venom of Ophiophagus hannah were isolated by a combination of ion exchange chromatography and reverse phase HPLC. Amino acid sequence analysis revealed that these proteins all consisted of 63 amino acids and shared approximate 50% and 56% sequence identity with Naja naja atra cardiotoxins and cardiotoxin-like basic proteins (CLBPs), respectively. CD spectra revealed that their secondary structure was dominated with beta-sheet as those noted with cardiotoxins and CLBPs. O. hannah cytotoxin-like protein exhibited a cell-lytic activity on SK-N-SH cells, but its activity was more weak than that noted for N. naja atra cardiotoxin 3. Alternatively, apoptotic cell death was induced by the addition of N. naja atra CLBP. Based on the sequence information with the toxin molecules, the functional residues and regions related to the differential activity with O. hannah cytotoxin-like protein, cardiotoxin and CLBP are discussed.

  7. Apoptosis of Glioblastoma U251 Cells Induced by Carmustine Combined All-trans Retinoic Acid via Regulating Cyclin E and p27kip 1

    Institute of Scientific and Technical Information of China (English)

    QI Bin; WEIJun; HU Guo-zhang; YANG Hong-fa; BI Chun-hua; SUN Zhi-gang; TIAN Yu

    2011-01-01

    The effect and mechanism of carmustine(BCNU) combined with all-trans retinoic acid(ATRA) on the apoptosis of human glioblastoma U251 cells were investigated by means of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay,flow cytometry,reverse transcription-polymerase chain reaction(RT-PCR) and Western blot analysis.The results show that BCNU or ATRA shows time- and dose-dependent inhibition effects on human glioblastoma U251 cells and the combination of BCNU with ATRA shows an synergistic inhibition effect on human glioblastoma U251 cells,and the combined BCNU and ATRA can significantly inhibit the proliferation of human glioblastoma U251 cells,and induce the apoptosis of them,making the cells arrest in the stage of G1 phase,the stage of S and G2 phases decline,the rate of the apoptosis of human glioblastoma U251 cells increase,the corresponding mRNA expression of cyclin E and cyclin-dependent kinase 2(CDK2) downregulated and the corresponding mRNA expression of p27kip 1 unregulated.In addition,the combined BCNU and ATRA reduced the protein expression of nuclear factor kappa B(NF-kB).Taken together,these results suggest that the treatment of human glioblastoma U251 cells with a combination application of ATRA and BCNU can exert synergistic effect,the course of this kind of combination chemotherapy may likely be associated with multiple molecular mechanisms for apoptosis,furthermore,the cyclin E and p27kip 1 should be considered as novel targets for controlling the growth of glioblastoma cells.

  8. Development of a validated UPLC method for simultaneous estimation of both free and entrapped (in solid lipid nanoparticles) all-trans retinoic acid and cholecalciferol (vitamin D3) and its pharmacokinetic applicability in rats.

    Science.gov (United States)

    Kumar, Manoj; Sharma, Gaurav; Singla, Dinesh; Singh, Sukhjeet; Sahwney, Sudhir; Chauhan, Anurag S; Singh, Gagandeep; Kaur, Indu Pal

    2014-03-01

    A sensitive ultra-performance liquid chromatography (UPLC) method was developed for simultaneous estimation of all-trans retinoic acid (ATRA) and cholecalciferol (vitamin D3) in rat plasma. The method was validated over the linear range of 1.0-5000ng/ml (r(2)=0.999) for both vitamins with a limit of detection of 0.5ng/ml. Chromatographic separation was achieved using liquid-liquid extraction (LLE) on an Acquity BEH RP 18 column (2.1mm×50mm, I.D. 1.7μm), with mobile phase comprising of acetonitrile:methanol:water (90:8:2, v/v/v), at a flow rate of 0.20ml/min and a total run time of 5min. Intra and inter-day variability (RSD) was ≤3.1%, and the accuracy varied between 95.4-99.9% and 95.3-101.1% respectively, for ATRA and 98.5-100.8% and 99.3-101.7%, respectively for vitamin D3. High recovery of ≥96.0% for ATRA and ≥87.80% for vitamin D3 was achieved. ATRA and vitamin D3 were stable in plasma under different storage and processing conditions. The method was applied to estimate the total drug content and entrapment efficiency of ATRA and vitamin D3 loaded solid lipid nanoparticles (SLNs). Concentration of these two agents was determined in rat plasma after simultaneous subcutaneous administration in free form or when loaded into SLNs thus establishing pharmacokinetic application of the developed procedure. Results indicated an improvement in AUC0-∞ by 5.4 times and 29.4 times for ATRA and vitamin D3, respectively, upon their incorporation into SLNs. Simultaneous administration of these two vitamins and their improved and prolonged bioavailability has scope for their use in treatment and control of tuberculosis.

  9. 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

  10. Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid.

    Science.gov (United States)

    Silvis, Anne M; McCormick, Michael L; Spitz, Douglas R; Kiningham, Kinsley K

    2016-04-01

    Neuroblastoma is the most common extra-cranial solid tumor in childhood; and patients in stage IV of the disease have a high propensity for tumor recurrence. Retinoid therapy has been utilized as a means to induce differentiation of tumor cells and to inhibit relapse. In this study, the expression of a common neuronal differentiation marker [neurofilament M (NF-M)] in human SK-N-SH neuroblastoma cells treated with 10μM all-trans retinoic acid (ATRA) showed significantly increased expression in accordance with reduced cell number. This was accompanied by an increase in MitoSOX and DCFH2 oxidation that could be indicative of increased steady-state levels of reactive oxygen species (ROS) such as O2(•-) and H2O2, which correlated with increased levels of MnSOD activity and immuno-reactive protein. Furthermore PEG-catalase inhibited the DCFH2 oxidation signal to a greater extent in the ATRA-treated cells (relative to controls) at 96h indicating that as the cells became more differentiated, steady-state levels of H2O2 increased in the absence of increases in peroxide-scavenging antioxidants (i.e., glutathione, glutathione peroxidase, and catalase). In addition, ATRA-induced stimulation of NF-M at 48 and 72h was enhanced by decreasing SOD activity using siRNA directed at MnSOD. Finally, treatment with ATRA for 96h in the presence of MnSOD siRNA or PEG-catalase inhibited ATRA induced increases in NF-M expression. These results provide strong support for the hypothesis that changes in steady-state levels of O2(•-) and H2O2 significantly contribute to the process of ATRA-induced differentiation in neuroblastoma, and suggest that retinoid therapy for neuroblastoma could potentially be enhanced by redox-based manipulations of superoxide metabolism to improve patient outcome.

  11. 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.

  12. 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.

  13. A role for paclitaxel in the combination chemotherapy of acute myeloblastic leukaemia: preclinical cell culture studies.

    Science.gov (United States)

    Curtis, J E; Minkin, S; Minden, M D; McCulloch, E A

    1996-11-01

    Paclitaxel dose responses in culture have been investigated alone and in association with cytosine arabinoside (ARA-C) and all-trans retinoic acid (ATRA), with the objective of identifying a role for paclitaxel in the treatment of acute myeloblastic leukaemia (AML). Initial studies were done to determine if paclitaxel dose responses of AML blast cell precursors were altered by regulatory compounds known to modify the dose responses of ARA-C. In contrast to ARA-C, paclitaxel dose responses were independent of cell culture method, the growth factors G-CSF and GM-CSF, and the ligands all-trans retinoic acid (ATRA) and hydrocortisone. Most blast cell populations were sensitive to paclitaxel; compared with normal marrow progenitors the dose responses were markedly heterogenous with some more, and others less, sensitive. Remission marrow progenitor paclitaxel responses resembled those of AML blasts in heterogeneity. The cell culture model tested the effect of pacliataxel and ATRA on the ARA-C dose responses of OCI/ AML-5; paclitaxel exposure was either before or after ARA-C to test for an effect of schedule; ATRA was added to the MEC cultures after paclitaxel and ARA-C. Repeat experiments were done to test three dose levels each of paclitaxel and ATRA. When paclitaxel was given after ARA-C, synergism was found for all but one of the dose combinations tested; only three examples of synergy were seen when paclitaxel preceded ARA-C. The studies justify trials combining ARA-C, paclitaxel and ATRA using a schedule suggested by the cell culture findings.

  14. 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.

  15. All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study.

    Science.gov (United States)

    Schlenk, Richard F; Lübbert, Michael; Benner, Axel; Lamparter, Alexander; Krauter, Jürgen; Herr, Wolfgang; Martin, Hans; Salih, Helmut R; Kündgen, Andrea; Horst, Heinz-A; Brossart, Peter; Götze, Katharina; Nachbaur, David; Wattad, Mohammed; Köhne, Claus-Henning; Fiedler, Walter; Bentz, Martin; Wulf, Gerald; Held, Gerhard; Hertenstein, Bernd; Salwender, Hans; Gaidzik, Verena I; Schlegelberger, Brigitte; Weber, Daniela; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut

    2016-12-01

    The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m(2), days 6-8; 15 mg/m(2), days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).

  16. Polydimethylsiloxane (PDMS) modulates CD38 expression, absorbs retinoic acid and may perturb retinoid signalling.

    Science.gov (United States)

    Futrega, Kathryn; Yu, Jianshi; Jones, Jace W; Kane, Maureen A; Lott, William B; Atkinson, Kerry; Doran, Michael R

    2016-04-21

    Polydimethylsiloxane (PDMS) is the most commonly used material in the manufacture of customized cell culture devices. While there is concern that uncured PDMS oligomers may leach into culture medium and/or hydrophobic molecules may be absorbed into PDMS structures, there is no consensus on how or if PDMS influences cell behaviour. We observed that human umbilical cord blood (CB)-derived CD34(+) cells expanded in standard culture medium on PDMS exhibit reduced CD38 surface expression, relative to cells cultured on tissue culture polystyrene (TCP). All-trans retinoic acid (ATRA) induces CD38 expression, and we reasoned that this hydrophobic molecule might be absorbed by PDMS. Through a series of experiments we demonstrated that ATRA-mediated CD38 expression was attenuated when cultures were maintained on PDMS. Medium pre-incubated on PDMS for extended durations resulted in a time-dependant reduction of ATRA in the medium and increasingly attenuated CD38 expression. This indicated a time-dependent absorption of ATRA into the PDMS. To better understand how PDMS might generally influence cell behaviour, Ingenuity Pathway Analysis (IPA) was used to identify potential upstream regulators. This analysis was performed for differentially expressed genes in primary cells including CD34(+) haematopoietic progenitor cells, mesenchymal stromal cells (MSC), and keratinocytes, and cell lines including prostate cancer epithelial cells (LNCaP), breast cancer epithelial cells (MCF-7), and myeloid leukaemia cells (KG1a). IPA predicted that the most likely common upstream regulator of perturbed pathways was ATRA. We demonstrate here that ATRA is absorbed by PDMS in a time-dependent manner and results in the concomitant reduced expression of CD38 on the cell surface of CB-derived CD34(+) cells.

  17. All-trans-retinoic acid reduces BACE1 expression under inflammatory conditions via modulation of nuclear factor κB (NFκB) signaling.

    Science.gov (United States)

    Wang, Ruishan; Chen, Shaoya; Liu, Yingchun; Diao, Shiyong; Xue, Yueqiang; You, Xiaoqing; Park, Edwards A; Liao, Francesca-Fang

    2015-09-11

    Insulin resistance and neuroinflammation have emerged as two likely key contributors in the pathogenesis of Alzheimer disease (AD), especially in those sporadic AD cases compromised by diabetes or cardiovascular disease. Amyloid-β (Aβ) deposition and its associated inflammatory response are hallmarks in sporadic AD brains. Elevated expression and activity of β-secretase 1 (BACE1), the rate-limiting enzyme responsible for the β-cleavage of amyloid precursor proteins to Aβ peptides, are also observed in sporadic AD brains. Previous studies have suggested that there is therapeutic potential for retinoic acid in treating neurodegeneration based on decreased Aβ. Here we discovered that BACE1 expression is elevated in the brains of both Tg2576 transgenic mice and mice on high fat diets. These conditions are associated with a neuroinflammatory response. We found that administration of all-trans-retinoic acid (atRA) down-regulated the expression of BACE1 in the brains of Tg2576 mice and in mice fed a high fat diet. Moreover, in LPS-treated mice and cultured neurons, BACE1 expression was repressed by the addition of atRA, correlating with the anti-inflammatory efficacy of atRA. Mutations of the NFκB binding site in BACE1 promoter abolished the suppressive effect of atRA. Furthermore, atRA disrupted LPS-induced nuclear translocation of NFκB and its binding to BACE1 promoter as well as promoting the recruitment of the corepressor NCoR. Our findings indicate that atRA represses BACE1 gene expression under inflammatory conditions via the modulation of NFκB signaling.

  18. 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.

  19. 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)

  20. All-trans retinoic acid promotes TGF-β-induced Tregs via histone modification but not DNA demethylation on Foxp3 gene locus.

    Directory of Open Access Journals (Sweden)

    Ling Lu

    Full Text Available BACKGROUND: It has been documented all-trans retinoic acid (atRA promotes the development of TGF-β-induced CD4(+Foxp3(+ regulatory T cells (iTreg that play a vital role in the prevention of autoimmune responses, however, molecular mechanisms involved remain elusive. Our objective, therefore, was to determine how atRA promotes the differentiation of iTregs. METHODOLOGY/PRINCIPAL FINDINGS: Addition of atRA to naïve CD4(+CD25(- cells stimulated with anti-CD3/CD28 antibodies in the presence of TGF-β not only increased Foxp3(+ iTreg differentiation, but maintained Foxp3 expression through apoptosis inhibition. atRA/TGF-β-treated CD4(+ cells developed complete anergy and displayed increased suppressive activity. Infusion of atRA/TGF-β-treated CD4(+ cells resulted in the greater effects on suppressing symptoms and protecting the survival of chronic GVHD mice with typical lupus-like syndromes than did CD4(+ cells treated with TGF-β alone. atRA did not significantly affect the phosphorylation levels of Smad2/3 and still promoted iTreg differentiation in CD4(+ cells isolated from Smad3 KO and Smad2 conditional KO mice. Conversely, atRA markedly increased ERK1/2 activation, and blockade of ERK1/2 signaling completely abolished the enhanced effects of atRA on Foxp3 expression. Moreover, atRA significantly increased histone methylation and acetylation within the promoter and conserved non-coding DNA sequence (CNS elements at the Foxp3 gene locus and the recruitment of phosphor-RNA polymerase II, while DNA methylation in the CNS3 was not significantly altered. CONCLUSIONS/SIGNIFICANCE: We have identified the cellular and molecular mechanism(s by which atRA promotes the development and maintenance of iTregs. These results will help to enhance the quantity and quality of development of iTregs and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.

  1. 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.

  2. 酪氨酸激酶受体B-脑源性神经营养因子信号传导通路对神经母细胞瘤细胞分泌血管内皮生长因子及基质金属蛋白酶-9的影响%Effects of tyrosine kinase receptor B-brain-derived neurotrophic factor signal pathway on the secretion of vascular endothelial growth factor and matrix metalloproteinase-9 of neuroblastoma

    Institute of Scientific and Technical Information of China (English)

    刘建英; 高惠敏; 李爱敏; 蔡维艳; 初清

    2013-01-01

    目的 探讨酪氨酸激酶受体B(tyrosine kinase receptor B,TrkB)-脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)信号传导通路对神经母细胞瘤(neuroblastoma,NB)细胞SH-SY5Y分泌血管内皮生长因子(vascular endothelial growth factor,VEGF)及基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的影响.方法 用全反式维甲酸(all-trans retinoic acid,ATRA)诱导SH-SY5Y细胞表达TrkB,加入外源性BDNF,从而激活TrkB-BDNF信号传导通路及其3条下游信号通路.再用特异性酪氨酸激酶抑制剂K252a阻断TrkB-BDNF信号传导通路;用磷脂酰肌醇-3激酶(phosphatidylinositol 3-hydrox y kinase,PBK)抑制剂LY294002、磷脂酶C抑制剂U73122、丝裂原活化蛋白激酶抑制剂U0126分别阻断TrkB-BDNF的3条相应下游信号传导通路.采用酶联免疫吸附法检测细胞培养上清液中VEGF及MMP-9含量.结果 ATRA+ BDNF组VEGF[(485.89±109.99) pg/ml]及MMP-9[(15.73±1.72) pg/ml]含量明显高于对照组及ATRA组(P <0.05);ATRA+ BDNF+ K252a组VEGF[(272.42±86.33) pg/ml]及MMP-9[(5.25±1.44) pg/ml]含量明显低于ATRA+ BDNF组(P<0.05),与对照组及ATRA组比较差异无统计学意义(P>0.05);ATRA+ BDNF+ LY294002组VEGF[(314.12±24.68) pg/ml]及MMP-9[(4.91±1.08) pg/ml]含量明显低于ATRA+ BDNF组(P<0.05),与对照组及ATRA组比较差异无统计学意义(P >0.05);ATRA+ BDNF+ U73122组VEGF[(444.08±64.49) pg/ml]及MMP-9[(13.28±3.38) pg/ml]含量与ATRA+ BDNF组比较差异无统计学意义(P>0.05).ATRA+ BDNF+ U0126组VEGF[(429.97±19.95) pg/ml]及MMP-9[(13.96±4.45) pg/ml]含量与ATRA+ BDNF组比较差异无统计学意义(P>0.05).结论 激活TrkB-BDNF信号传导通路可促进NB细胞合成、分泌VEGF及MMP-9.TrkB-BDNF信号传导通路可能通过进一步激活其下游PI3 K/Akt通路来促进VEGF及MMP-9的合成及分泌,用K252a阻断TrkB-BDNF信号通路、LY294002阻断其下游PI3K通路均可有效抑制NB细胞合成及分泌VEGF及MMP-9

  3. 78 FR 7387 - Continuation of 2008 Farm Bill-Dairy Forward Pricing Program

    Science.gov (United States)

    2013-02-01

    ... producers and cooperative associations of producers may enter into forward price contracts under the Dairy... September 30, 2015. However, passage of the ATRA that was signed into law on January 2, 2013, revised the... and cooperative associations of producers to voluntarily enter into forward price contracts...

  4. Effects of all-trans-retinoic acid on the expression and tyrosine phosphorylation of gap junction connexin 43 in HeLa cell line and its significance

    Institute of Scientific and Technical Information of China (English)

    CHEN Bi-liang; MA Xiang-dong; XIN Xiao-yan; WANG De-tang; WANG Chun-mei

    2001-01-01

    Objective: To investigate the signal transduction mechanism of gap junctional genes connexin43 in human cervical carcinogenesis. Methods: Human cervical carcinoma cell line HeLa was cultured and treated by all-trans-retinoic acid (ATRA). Flow cytometer (FCM) was employed to detect expression of Cx43 protein in HeLa cells. Fluo-3 AM loading and laser scanning confocal microscope (LSCM) were used to measure the concentrations of intracellular calcium ([Ca2+]i) in HeLa cells. Phosphorylation on tyrosine of connexin43 protein was examined by immunoblot. Results: The positive rate of Cx43 protein increased from 1.9% in untreated HeLa cells to 26.3% in RA-treated HeLa cells as shown by FCM. [Ca2+]i was 35.73 nmol/L in untreated HeLa cells which was increased to 58.16 nmol/L in ATRA-treated cells.Immunoblot showed that ATRA-treated HeLa cells had phosphorylation on tyrosine in Cx43 protein whereas untreated cells had not. Conclusions: Carcinogenesis of human cervical carcinoma is related with the abnormal expression of cx43gene and disorder of signal transduction manifested as the decrease of [Ca2+]i and post-translation phosphorylation on tyrosine of Cx43 protein. The anti-tumor effect of ATRA in HeLa cells might be due to the up-regulation of cx43 gene and its signal transduction pathway.

  5. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: Further improvements in treatment outcome

    NARCIS (Netherlands)

    M.A. Sanz (Miguel Angel); P. Montesinos (Pau); C. Rayón (Chelo); A. Holowiecka (Aleksandra); J. De La Serna (Javier); G. Milone (Gustavo); E. de Lisa (Elena); S. Brunet (Salut); V. Rybio (Vicente); J.M. Ribera (Josep Maria); C. Rivas (Concha); I. Krsnik (Isabel); J.M. Bergua (Juan Miguel); J.D. González (José David); J. Díaz-Mediavilla (Joaquín); R. Rojas (Rafael); F. Manso (Félix); G.J. Ossenkoppele (Gert); B. Löwenberg (Bob)

    2010-01-01

    textabstractA risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMALPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements i

  6. Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: Long-term outcome of the LPA 99 multicenter study by the PETHEMA Group

    NARCIS (Netherlands)

    M.A. Sanz (Miguel Angel); P. Montesinos (Pau); E. Vellenga (Edo); C. Rayón (Consuelo); J. de Serna (Javier); R. Parody (Ricardo); J.M. Bergua (Juan Miguel); A. León (Angel); S. Negri (Silvia); M. González (Marcos); C. Rivas (Concha); J. Esteve (Jordi); G. Milone (Gustavo); E. Amutio (Elena); S. Brunet (Salut); J. García-Laraña; D. Colomer (Dolors); M.J. Calasanz (Maria); C. Chillón (Carmen); E. Barragán (Eva); P. Bolufer (Pascual); B. Löwenberg (Bob)

    2008-01-01

    textabstractA previous report of the Programa de Estudio y Tratamiento de las Hemopatfas Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leu

  7. Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy : long-term outcome of the LPA 99 multicenter study by the PETHEMA Group

    NARCIS (Netherlands)

    Sanz, Miguel A.; Montesinos, Pau; Vellenga, Edo; Rayon, Consuelo; de la Serna, Javier; Parody, Ricardo; Bergua, Juan M.; Leon, Angel; Negri, Silvia; Gonzalez, Marcos; Rivas, Concha; Esteve, Jordi; Milone, Gustavo; Gonzalez, Jose D.; Amutio, Elena; Brunet, Salut; Garcia-Larana, J.; Colomer, Dolors; Calasanz, Maria J.; Chillon, Carmen; Barragan, Eva; Bolufer, Pascual; Lowenberg, Bob

    2008-01-01

    A previous report of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leukemia result

  8. Food supply and seasonal variation in breeding success: An experiment in the European coot

    NARCIS (Netherlands)

    Brinkhof, M.W.G.; Cavé, A.J.

    1997-01-01

    We investigated experimentally the seasonal role of food supply in brood survival of the European coot Fulica atra. For two breeding seasons, individual pairs were offered supplemental food the first ten days after their young hatched. Under natural conditions this period was largely responsible for

  9. 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.

  10. Experiment list: SRX014758 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available SRX014758 hg19 Histone H3K27me3 Blood NB-4 Primary Tissue=Blood|Site of Extraction=Bone Marrow|Tissue Diagno...sis=Leukemia 15859913,93.5,4.4,416 GSM468188: H3K27me3 ChIP-seq NB4 24hoursATRA, JM

  11. Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival.

    Science.gov (United States)

    Perrotta, Ida; Perri, Mariarita; Santoro, Marta; Panza, Salvatore; Caroleo, Maria C; Guido, Carmela; Mete, Annamaria; Cione, Erika; Aquila, Saveria

    2015-01-01

    Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.

  12. Antiproliferative Effects of Drugs on Endothelial and Osteoblastic Cells and Altered Release of Angioregulatory Mediators by Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Hilde Kvestad

    2014-01-01

    Full Text Available The combined use of the histone deacetylase inhibitor valproic acid (VPA, the retinoic acid receptor-α agonist all-trans retinoic acid (ATRA, and the deoxyribonucleic acid polymerase-α inhibitor cytarabine (Ara-C is now considered for disease-stabilizing treatment of acute myeloid leukemia (AML. Leukemogenesis and leukemia cell chemoresistance seem to be supported by neighbouring stromal cells in the bone marrow, and we have therefore investigated the effects of these drugs on primary human endothelial cells and the osteoblastic Cal72 cell line. The results show that VPA and Ara-C have antiproliferative effects, and the antiproliferative/cytotoxic effect of Ara-C was seen at low concentrations corresponding to serum levels found during low-dose in vivo treatment. Furthermore, in functional assays of endothelial migration and tube formation VPA elicited an antiangiogenic effect, whereas ATRA elicited a proangiogenic effect. Finally, VPA and ATRA altered the endothelial cell release of angiogenic mediators; ATRA increased levels of CXCL8, PDGF-AA, and VEGF-D, while VPA decreased VEGF-D and PDGF-AA/BB levels and both drugs reduced MMP-2 levels. Several of these mediators can enhance AML cell proliferation and/or are involved in AML-induced bone marrow angiogenesis, and direct pharmacological effects on stromal cells may thus indirectly contribute to the overall antileukemic activity of this triple drug combination.

  13. All-trans retinoic acid in acute promyelocytic leukemia in late pregnancy.

    Science.gov (United States)

    Stentoft, J; Nielsen, J L; Hvidman, L E

    1994-09-01

    All-trans retinoic acid (ATRA) was used in a case of acute promyelocytic leukemia (APL) in late pregnancy. A very prompt maternal risk reduction was achieved with subsequent complete remission and spontaneous delivery of two live children in whom no fetal damage seems to have occurred.

  14. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Directory of Open Access Journals (Sweden)

    Yifei Zhong

    Full Text Available Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs: RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1 in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN. Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  15. Novel retinoic acid receptor alpha agonists for treatment of kidney disease.

    Science.gov (United States)

    Zhong, Yifei; Wu, Yingwei; Liu, Ruijie; Li, Zhengzhe; Chen, Yibang; Evans, Todd; Chuang, Peter; Das, Bhaskar; He, John Cijiang

    2011-01-01

    Development of pharmacologic agents that protect podocytes from injury is a critical strategy for the treatment of kidney glomerular diseases. Retinoic acid reduces proteinuria and glomerulosclerosis in multiple animal models of kidney diseases. However, clinical studies are limited because of significant side effects of retinoic acid. Animal studies suggest that all trans retinoic acid (ATRA) attenuates proteinuria by protecting podocytes from injury. The physiological actions of ATRA are mediated by binding to all three isoforms of the nuclear retinoic acid receptors (RARs): RARα, RARβ, and RARγ. We have previously shown that ATRA exerts its renal protective effects mainly through the agonism of RARα. Here, we designed and synthesized a novel boron-containing derivative of the RARα-specific agonist Am580. This new derivative, BD4, binds to RARα receptor specifically and is predicted to have less toxicity based on its structure. We confirmed experimentally that BD4 binds to RARα with a higher affinity and exhibits less cellular toxicity than Am580 and ATRA. BD4 induces the expression of podocyte differentiation markers (synaptopodin, nephrin, and WT-1) in cultured podocytes. Finally, we confirmed that BD4 reduces proteinuria and improves kidney injury in HIV-1 transgenic mice, a model for HIV-associated nephropathy (HIVAN). Mice treated with BD4 did not develop any obvious toxicity or side effect. Our data suggest that BD4 is a novel RARα agonist, which could be used as a potential therapy for patients with kidney disease such as HIVAN.

  16. The impact of medical education and networking on the outcome of leukemia treatment in developing countries. The experience of International Consortium on Acute Promyelocytic Leukemia (IC-APL)

    NARCIS (Netherlands)

    E.M. Rego (Eduardo); H.T. Kim (Haesook); G. Ruiz-Argüelles (Guillermo); M.R. Uriarte (Maria del Rosario); R.H. Jacomo (Rafael); H. Gutiérrez-Aguirre (Homero); R.A. Melo (Raul); H.N.S. Bittencourt (Henrique); R. Pasquini (Ricardo); K. Pagnano (Katia); E.M. Fagundes (Evandro); M.d.L. Chauffaille (Maria de Lourdes); C.S. Chiattone (Carlos); L. Martinez (Lem); L.A. Meillón (Luis); D. Gómez-Almaguer (David); H.C. Kwaan (Hau); J. Garcés-Eisele (Javier); R. Gallagher (Robert); C.M. Niemeyer (Charlotte); B. Löwenberg (Bob); R.C. Ribeiro (Raul); F. Lo-Coco (Francesco); M.A. Sanz (Miguel Angel)

    2012-01-01

    textabstractObjectives: Several clinical trials conducted in Europe and US reported favorable outcomes of patients with APL treated with the combination of all trans retinoic acid (ATRA) and anthracyclines. Nevertheless, the results observed in developing countries with the same regimen was poorer,

  17. 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

  18. 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

  19. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial.

    Science.gov (United States)

    Burnett, A K; Hills, R K; Grimwade, D; Jovanovic, J V; Craig, J; McMullin, M F; Kell, J; Wheatley, K; Yin, J A L; Hunter, A; Milligan, D; Russell, N H

    2013-04-01

    Two hundred eighty-five patients, median age 42, with PML-RARα-positive acute promyelocytic leukaemia were randomised to Ara-C-containing 'Medical Research Council (MRC) Chemotherapy'+ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified 'Spanish') therapy. MRC treatment comprised four courses with ATRA in courses 1-2. Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1-3. In course 3 patients were randomised to gemtuzumab ozogamicin (GO) or not. The Spanish arm received 24-month maintenance. Patients were sequentially molecularly monitored. Quality of life was assessed at baseline, 3, 6, 9, 12, 24 months. Remission rates were similar in both arms (93%): cumulative incidence of haematological relapse (CIHR) was 6% at 5 years; 5 patients relapsed molecularly. Survival post relapse was 80%. There were more deaths in remission in the MRC arm (4% vs 10%: P=0.2). The overall 5-year relapse-free and overall survival was similar between arms (81% vs 82% and 84% vs 83%, respectively). More supportive care and hospitalisation (81.8 vs 63 days, P10 × 10(9)/l) was not prognostic overall, or within treatment arms. Both approaches deliver similar results with minor differences in quality of life. MRC treatment required more hospitalisation. This suggests that additional chemotherapy, Ara-C in particular, is not required.

  20. 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-

  1. Treatment of newly diagnosed acute promyelocytic leukemia (APL) : a comparison of French-Belgian-Swiss and PETHEMA results

    NARCIS (Netherlands)

    Ades, Lionel; Sanz, Miguel A.; Chevret, Sylvie; Montesinos, Pau; Chevallier, Patrice; Raffoux, Emmanuel; Vellenga, Edo; Guerci, Agnbs; Pigneux, Arnaud; Huguet, Francoise; Rayon, Consuelo; Stoppa, Anne Marie; de la Serna, Javier; Cahn, Jean-Yves; Meyer-Monard, Sandrine; Pabst, Thomas; Thomas, Xavier; de Botton, Stephane; Parody, Ricardo; Bergua, Juan; Lamy, Thierry; Vekhoff, Anne; Negri, Silvia; Ifrah, Norbert; Dombret, Herve; Ferrant, Augustin; Bron, Dominique; Degos, Laurent; Fenaux, Pierre

    2008-01-01

    All-trans retinoic acid (ATRA) plus anthracycline chemotherapy is the reference treatment of newly diagnosed acute promyelocytic leukemia (APL), whereas the role of cytosine arabinoside (AraC) remains disputed. We performed a joint analysis of patients younger than 65 years included in Programa para

  2. 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...

  3. 甲基转移酶在恶性骨肉瘤体外诱导分化过程中的作用%Role of Methyltransferase in Differentiation Induction in vitro of Malignant Osteosarcoma Cells

    Institute of Scientific and Technical Information of China (English)

    张岩; 夏仁云; 陈安民; 冯尔宥; 俞孟

    2006-01-01

    Objective: To observe the change of DNA methyltransferase (Dnmt) in osteosarcoma cell linesdifferentiation induction in vitro, so as to explore the function and relativity of Dnmt in malignant os teosarcoma cell during differentiation induction in vitro. Methods: After in vitro differentiation induction by all trans-retinoic acid (ATRA), morphological and functional changes of the cells were observed. The expression levels of Dnmt and PCNA mRNA were detected by semi-quantitative RT-PCR. Changes of cell cycle were determined by flow cytometry (FCM). Results: After treatment with ATRA, the growth of MG-63 cell was inhibited. The cells underwent morphological and functional differentiation. Alkaline phosphatase activity of the cells was increased. The relative expression levels of Dnmt and PCNA mRNA were decreased remarkably in osteosarcoma cells with the time delayed. Osteosarcoma cells were arrested in G1 phase. Conclusion: ATRA could inhibit cell growth and induce differentiation of MG-63 cells in morphologic and function. The Dnmt regulation directly links to cell cycle and PCNA mRNA levels. Inhibition of the Dnmt mRNA expression in MG-63 cells may be one of the important mechanisms of ATRA inducing differentiation of osteosarcoma cells.

  4. 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...

  5. Polymeric nanoparticles based on chitooligosaccharide as drug carriers for co-delivery of all-trans-retinoic acid and paclitaxel.

    Science.gov (United States)

    Zhang, Jing; Han, Jian; Zhang, Xiuli; Jiang, Jing; Xu, Maolei; Zhang, Daolai; Han, Jingtian

    2015-09-20

    An amphiphilic all-trans-retinoic acid (ATRA)-chitooligosaccharide (RCOS) conjugate was synthesized to form self-assembled polymeric nanoparticles to facilitate the co-delivery of ATRA and paclitaxel (PTX). The blank RCOS nanoparticles possessed low hemolytic activity and cytotoxicity, and could efficiently load PTX with a drug loading of 22.2% and a high encapsulation efficiency of 71.3%. PTX-loaded RCOS nanoparticles displayed a higher cytotoxicity to HepG2 cells compared to PTX plus ATRA solution when corrected by the accumulated drug release. Cellular uptake profiles of RCOS nanoparticles were evaluated via confocal laser scanning microscope and flow cytometry with FITC as a fluorescent mark. The RCOS nanoparticles could be rapidly and continuously taken up by HepG2 cells via endocytosis and transported into the nucleus, and the uptake rates increased with particle concentration. These results revealed the promising potential of RCOS nanoparticles as drug carriers for co-delivery of ATRA and PTX or other hydrophobic therapeutic agents.

  6. 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.

  7. All-trans-retinoic acid-induced pseudotumor cerebri in acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    T. M. Anoop

    2014-01-01

    Full Text Available All-trans-retinoic acid is an integral part in the treatment strategy of acute promyelocytic leukemia (APL. Here we describe a case of pseudotumor cerebri associated with all-trans-retinoic acid (ATRA during the induction therapy in an adult with acute promyelocytic leukemia (APL.

  8. Ultrastructural examination of the pycnidia and conidia of the genus Opegrapha (Arthoniales, Ascomycota

    Directory of Open Access Journals (Sweden)

    Anetta Wieczorek

    2013-12-01

    Full Text Available The paper presents a summary of examinations on the variation of pycnidia and conidia of the following Opegrapha species occurring in Poland: O. atra, O. calcarea, O. dolomitica, O. gyrocarpa, O. niveoatra, O. rupestris, O. varia, O. vermicellifera, O. viridis and O. vulgata.

  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. 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

  11. Molecular mechanisms of the antileukemia activities of retinoid and arsenic.

    Science.gov (United States)

    Nitto, Takeaki; Sawaki, Kohei

    2014-01-01

    Acute promyelocytic leukemia (APL) is characterized by the occurrence of translocations between chromosomes 15 and 17, resulting in generation of a fusion protein of promyelocytic leukemia (PML) and retinoid A receptor (RAR) α. APL cells are unable to differentiate into mature granulocytes since PML-RARα functions as a strong transcriptional repressor for a gene involved in granulocyte differentiation. All-trans retinoic acid (ATRA) is the first agent that has been developed to target specific disease-causing molecules, i.e., ATRA suppresses abnormal functions of oncogenic proteins. Moreover, ATRA facilitates the differentiation of APL cells toward mature granulocytes by changing epigenetic modifiers from corepressor complexes to co-activator complexes on target genes after binding to the ligand-binding domain at the RARα moiety of the PML-RARα oncoprotein. On the other hand, arsenic trioxide (ATO), another promising agent used to treat APL, directly binds to the PML moiety of the PML-RARα protein, causing oxidation and multimerization. ATO enhances the conjugation of small ubiquitin-like modifiers to PML-RARα, followed by ubiquitination and degradation, relieving the genes associated with granulocytic differentiation from suppressive restraint by the oncoprotein. Recent clinical studies have demonstrated that combination therapy with both ATRA and ATO is useful to achieve remission.

  12. Retinoic acid exerts dual regulatory actions on the expression and nuclear localization of interferon regulatory factor-1.

    Science.gov (United States)

    Luo, Xin M; Ross, A Catharine

    2006-05-01

    Interferon regulatory factor-1 (IRF-1), a transcription factor and tumor suppressor involved in cell growth regulation and immune responses, has been shown to be induced by all-trans retinoic acid (ATRA). However, the factors controlling the cellular location and activity of IRF-1 are not well understood. In this study, we examined the expression of IRF-1 and its nuclear localization, DNA-binding activity, and target gene expression in human mammary epithelial MCF10A cells, a model of breast epithelial cell differentiation and carcinogenesis. Following initial treatment with ATRA, IRF-1 mRNA and protein were induced within 2 hrs, reached a peak (>30-fold induction) at 8 hrs, and declined afterwards. IRF-1 protein was predominantly cytoplasmic during this treatment. Although a second dose of ATRA or Am580 (a related retinoid selective for retinoic acid receptor-alpha [RARalpha]), given 16 hrs after the first dose, restimulated IRF-1 mRNA and protein levels to a similar level to that obtained by the first dose, IRF-1 was predominantly concentrated in the nucleus after restimulation. ATRA and Am580 also increased nuclear RARalpha, whereas retinoid X receptor-alpha (RXRalpha)--a dimerization partner for RARalpha, was localized to the nucleus upon second exposure to ATRA. However, ATRA and Am580 did not regulate the expression or activation of signal transducer and activator of transcription-1 (STAT-1), a transcription factor capable of inducing the expression of IRF-1, indicating an STAT-1-independent mechanism of regulation by ATRA and Am580. The increase in nuclear IRF-1 after retinoid restimulation was accompanied by enhanced binding to an IRF-E DNA response element, and elevated expression of an IRF-1 target gene, 2',5'-oligoadenylate synthetase-2. The dual effect of retinoids in increasing IRF-1 mRNA and protein and in augmenting the nuclear localization of IRF-1 protein may be essential for maximizing the tumor suppressor activity and the immunosurveillance

  13. Effects of all-trans-retinoic acid and resveratrol on the gene expression of lysine-specific histone demethylase 1 in human melanoma cells A375%白藜芦醇和全反式维A酸对人黑素瘤细胞株A375 LSD-1表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐观辉; 李建军; 张建青; 彭友华; 郑锦芬

    2011-01-01

    Objective: To investigate the effects of all-trans- retinoic acid (ATRA) and resveratrol (Res) on the expression of lysine- specific histone demethylase 1 (LSD- 1 ) in human melanoma cells A375. Methods: The inhibitive effects of ATRA and RES on human melanoma cells A375 were measured using MTT colorimetric assay. The morphology of A375 cells was observed by inverted microscope. The expression of LSD- 1 mRNA was detected by RT - PCR. Results: Both ATRA and Res inhibited proliferation of A375 cells. The mRNA of LSD - 1 was significantly decreased in A375 cells treated with 100 μmol/L Res and 25.0 μmol/L ATRA when compared to the control cells (P<0.05). However, there was no significant difference in down-regulation of LSD- 1 between 100 μmol/L Res and 25.0μmol/L ATRA ( P > 0.05). Conclusion: ATRA and Res can inhibit the expression of LSD1, which may play a role against tumors.%目的: 确定白藜芦醇(resveratrol,Res)和全反式维A酸(all-trans-retinoic acid,ATRA)对人黑素瘤细胞株A375赖氨酸特异性组蛋白去甲基化酶 1(LSD-1)基因表达的影响.方法: MTT比色法检测Res和ATRA对A375细胞增殖的抑制;倒置显微镜观察A375细胞形态的变化;RT-PCR方法检测LSD-1的mRNA的表达.结果: Res和ATRA均能抑制A375细胞的增殖.100 μmol/L Res及25.0 μmol/L ATRA均能显著减少人恶性黑素瘤细胞株A375中LSD-1的mRNA的表达, 与对照组比较差异均有统计学意义(P<0.05),但对LSD-1的下调作用无显著差异(P>0.05).结论: 抑制黑色素瘤细胞LSD-1的表达,可能是Res和ATRA抗肿瘤的途径之一.

  14. 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

  15. Effects of the three TrKB-BDNF downstream signal pathways on the chemoresistance of neuroblastoma cells%TrkB-BDNF的三条下游信号传导通路对神经母细胞瘤细胞耐药的影响

    Institute of Scientific and Technical Information of China (English)

    刘建英

    2013-01-01

    目的 本研究探讨阻断TrkB-BDNF信号传导通路的三条下游信号传导通路后,NB细胞对化疗药物敏感性的影响.方法 常规培养SH-SY5Y NB细胞,用纳摩尔浓度全反式维甲酸(ATRA)诱导酪氨酸激酶受体B(TrkB)高表达,加入脑源性神经营养因子(BDNF)、化疗药顺铂(CDDP)和PI3K抑制剂LY294002、PLC抑制剂U73122、MAPK抑制剂U0126处理.四甲基偶氮蓝比色(MTT)实验方法检测应用三种抑制剂前后细胞的存活率的变化;流式细胞仪(FCM)检测应用三种抑制剂前后细胞凋亡率的变化.结果 ATRA+BDNF+CDDP组NB细胞的存活率及凋亡率与对照组相比,差异无显著性(P>0.05).ATRA +BDNF+LY294002+CDDP组细胞对顺铂的敏感性增加,细胞的存活率明显降低,凋亡率明显升高,与ATRA+BDNF+CDDP组相比,差异有显著性(P<0.05),而ATRA +BDNF+U73122+CDDP组、ATRA +BDNF+U0126+CDDP组细胞对顺铂的敏感性降低,细胞的存活率明显升高,凋亡率明显降低,与ATRA+BDNF+CDDP组相比,差异无显著性(P>0.05).结论 激活TrkB-BDNF信号传导通路可增强NB细胞耐药.TrkB–BDNF信号传导通路可能通过进一步激活其下游PI3K/Akt通路逆转耐药.

  16. Susceptibility of Pseudomonas aeruginosa biofilm to alpha-helical peptides: D-enantiomer of LL-37

    Directory of Open Access Journals (Sweden)

    Scott N. Dean

    2011-07-01

    Full Text Available Pseudomonas aeruginosa is a highly versatile opportunistic pathogen and its ability to produce biofilms is a direct impediment to the healing of wounds and recovery from infection. Interest in anti-microbial peptides has grown due to their potential therapeutic applications and their possible use against antibiotic resistant bacteria. LL-37 is the only cathelicidin expressed by humans. In this study, we tested LL-37 and the effect of a protease-resistant LL-37 peptide mimetic, the peptide enantiomer D-LL-37, for anti-microbial and anti-biofilm activity against P. aeruginosa. Both forms of the peptide were equally effective as anti-microbial peptides with similar killing kinetics. CD spectra were obtained to demonstrate the chirality of D- and L-LL-37, and the trypsin resistance of D-LL-37 was confirmed. The helical cathelicidin from the cobra Naja atra (NA-CATH, and synthetic peptide variations (ATRA-1, ATRA-2, NA-CATH:ATRA1-ATRA1 were also tested. Although the cobra cathelicidin and related peptides had strong anti-microbial activity, those tested did not inhibit Pseudomonas biofilm formation, neither did control peptides. Both D- and L-LL-37 inhibited the attachment of Pseudomonas to a 96-well plate and decreased the amount of pre-formed (established biofilm. D-LL-37 is able to promote Pseudomonas motility and decrease biofilm formation by altering the rate of twitching as well as by downregulating the expression of the biofilm-related genes, rhlA and rhlB, similar to L-LL-37. Both L- and D-LL-37 protected Galleria mellonella in vivo against Pseudomonas infection, while NA-CATH:ATRA1-ATRA1 peptide did not. This study demonstrates the ability and equivalence of D-LL-37 compared to L-LL-37 to promote bacterial twitching motility and inhibit biofilm formation, and protect against in vivo infection, and suggests that this peptide could be a critical advancement in the development of new treatments for P. aeruginosa infection.

  17. A novel all-trans retinoic acid derivative 4-amino‑2‑trifluoromethyl-phenyl retinate inhibits the proliferation of human hepatocellular carcinoma HepG2 cells by inducing G0/G1 cell cycle arrest and apoptosis via upregulation of p53 and ASPP1 and downregulation of iASPP.

    Science.gov (United States)

    Liu, Hui; Chen, Feihu; Zhang, Ling; Zhou, Qing; Gui, Shuyu; Wang, Yuan

    2016-07-01

    4-Amino-2-trifluoromethyl-phenyl retinate (ATPR), a novel all-trans retinoic acid (ATRA) derivative, was reported to function as a tumor inhibitor in various types of cancer cells in vitro. However, little is known concerning its antitumor effect on human hepatocellular carcinoma (HCC) HepG2 cells. The aims of the present study were to investigate the effects of ATPR on the proliferation of HepG2 cells and to explore the probable mechanisms. A series of experiments were performed following the treatment of HepG2 cells with ATRA and ATPR. MTT and plate colony formation assays were used to measure the cell viability. To confirm the influence on proliferation, flow cytometry was used to detect the distribution of the cell cycle. Apoptosis was observed by Hoechst staining and flow cytometry. In addition, to characterize the underlying molecular mechanisms, immunofluorescence was applied to observe the distribution of p53. The transcription and translation levels of p53 were analyzed by real-time quantitative RT-PCR (qRT-PCR) and western blotting. The expression levels of murine double minute 2 (MDM2), apoptosis stimulating proteins of p53 (ASPP), cell cycle- and apoptosis-associated proteins were detected by western blotting. After HepG2 cells were incubated with ATRA and ATPR, the viability of the HepG2 cells was inhibited in a dose- and time-dependent manner. As well, ATPR significantly suppressed HepG2 cell colony formation and arrested cells at the G0/G1 phase, while ATRA had no obvious effects. Both Hoechst staining and flow cytometry unveiled the apoptosis of HepG2 cells. Moreover, the fluorescent density of p53 was higher in the nuclei after exposure to ATPR than that in the ATRA group. HepG2 cells treated with ATPR showed elevated mRNA and protein levels of p53 when compared with these levels in the ATRA-treated cells. Western blotting showed that ATPR increased ASPP1, p21 and Bax expression and decreased MDM2, iASPP, cyclin D and E, cyclin

  18. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab.

    Science.gov (United States)

    Abaza, Yasmin; Kantarjian, Hagop; Garcia-Manero, Guillermo; Estey, Elihu; Borthakur, Gautam; Jabbour, Elias; Faderl, Stefan; O'Brien, Susan; Wierda, William; Pierce, Sherry; Brandt, Mark; McCue, Deborah; Luthra, Rajyalakshmi; Patel, Keyur; Kornblau, Steven; Kadia, Tapan; Daver, Naval; DiNardo, Courtney; Jain, Nitin; Verstovsek, Srdan; Ferrajoli, Alessandra; Andreeff, Michael; Konopleva, Marina; Estrov, Zeev; Foudray, Maria; McCue, David; Cortes, Jorge; Ravandi, Farhad

    2017-03-09

    The combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of standard-risk patients with newly diagnosed acute promyelocytic leukemia (APL). A recent study demonstrated the efficacy of this regimen with added gemtuzumab ozogamicin (GO) in high-risk patients. We examined the long-term outcome of patients with newly diagnosed APL treated at our institution on 3 consecutive prospective clinical trials, using the combination of ATRA and ATO, with or without GO. For induction, all patients received ATRA (45 mg/m(2) daily) and ATO (0.15 mg/kg daily) with a dose of GO (9 mg/m(2) on day 1) added to high-risk patients (white blood cell count, >10 × 10(9)/L), as well as low-risk patients who experienced leukocytosis during induction. Once in complete remission, patients received 4 cycles of ATRA plus ATO consolidation. One hundred eighty-seven patients, including 54 with high-risk and 133 with low-risk disease, have been treated. The complete remission rate was 96% (52 of 54 in high-risk and 127 of 133 in low-risk patients). Induction mortality was 4%, with only 7 relapses. Among low-risk patients, 60 patients (45%) required either GO or idarubicin for leukocytosis. Median duration of follow-up was 47.6 months. The 5-year event-free, disease-free, and overall survival rates are 85%, 96%, and 88%, respectively. Late hematological relapses beyond 1 year occurred in 3 patients. Fourteen deaths occurred beyond 1 year; 12 were related to other causes. This study confirms the durability of responses with this regimen.

  19. 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.

  20. 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.

  1. All-Trans Retinoic Acid Modulates TLR4/NF-κB Signaling Pathway Targeting TNF-α and Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative Colitis and Colitis Associated Cancer

    Science.gov (United States)

    Rafa, Hayet; Benkhelifa, Sarra; AitYounes, Sonia; Saoula, Houria; Belhadef, Said; Belkhelfa, Mourad; Boukercha, Aziza; Toumi, Ryma; Soufli, Imene; de Launoit, Yvan; Mahfouf, Hassen; Nakmouche, M'hamed

    2017-01-01

    Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is associated with bowel disease such as ulcerative colitis (UC). The data on role of NF-κB signaling in development and progression of CAC were derived from preclinical studies, whereas data from human are rare. The aim of this work was to study the contribution of NF-κB pathway during UC and CAC, as well as the immunomodulatory effect of all-trans retinoic acid (AtRA). We analyzed the expression of NOS2, TNF-α, TLR4, and NF-κB, in colonic mucosa. We also studied NO/TNF-α modulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF-κB, TNF-α, and NOS2 expression was reported in colonic mucosa. The relationship between LPS/TLR4 and TNF-α/NO production, as well as the role of NF-κB signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF-α induction through NF-κB pathway was suggested. AtRA downregulates NOS2 and TNF-α expression. Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF-κB signaling pathway targeting NOS2 and TNF-α expression. Therefore, we suggest that AtRA has a potential value in new strategies to improve the current therapy, as well as in the clinical prevention of CAC development and progression.

  2. 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)

    Aleksandra eMarchwicka

    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.

  3. PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells.

    Science.gov (United States)

    Fang, Yi; Garnier, Delphine; Lee, Tae Hoon; D'Asti, Esterina; Montermini, Laura; Meehan, Brian; Rak, Janusz

    2016-01-01

    Oncogenic transformation is believed to impact the vascular phenotype and microenvironment in cancer, at least in part, through mechanisms involving extracellular vesicles (EVs). We explored these questions in the context of acute promyelocytic leukemia cells (NB4) expressing oncogenic fusion protein, PML-RARa and exquisitely sensitive to its clinically used antagonist, the all-trans retinoic acid (ATRA). We report that NB4 cells produce considerable numbers of EVs, which are readily taken up by cultured endothelial cells triggering their increased survival. NB4 EVs contain PML-RARa transcript, but no detectable protein, which is also absent in endothelial cells upon the vesicle uptake, thereby precluding an active intercellular trafficking of this oncogene in this setting. ATRA treatment changes the emission profile of NB4-related EVs resulting in preponderance of smaller vesicles, an effect that occurs in parallel with the onset of cellular differentiation. ATRA also increases IL-8 mRNA and protein content in NB4 cells and their EVs, while decreasing the levels of VEGF and tissue factor (TF). Endothelial cell uptake of NB4-derived EVs renders these cells more TF-positive and procoagulant, and this effect is diminished by pre-treatment of EV donor cells with ATRA. Profiling angiogenesis-related transcripts in intact and ATRA-treated APL cells and their EVs reveals multiple differences attributable to cellular responses and EV molecular packaging. These observations point to the potential significance of changes in the angiogenic signature and activity associated with EVs released from tumor cells subjected to targeted therapy.

  4. PML/RARα-Regulated miR-181a/b Cluster Targets the Tumor Suppressor RASSF1A in Acute Promyelocytic Leukemia.

    Science.gov (United States)

    Bräuer-Hartmann, Daniela; Hartmann, Jens-Uwe; Wurm, Alexander Arthur; Gerloff, Dennis; Katzerke, Christiane; Verga Falzacappa, Maria Vittoria; Pelicci, Pier Giuseppe; Müller-Tidow, Carsten; Tenen, Daniel G; Niederwieser, Dietger; Behre, Gerhard

    2015-08-15

    In acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA) treatment induces granulocytic maturation and complete remission of leukemia. microRNAs are known to be critical players in the formation of the leukemic phenotype. In this study, we report downregulation of the miR-181a/b gene cluster in APL blasts and NB4 leukemia cells upon ATRA treatment as a key event in the drug response. We found that miR-181a/b expression was activated by the PML/RARα oncogene in cells and transgenic knock-in mice, an observation confirmed and extended by evidence of enhanced expression of miR-181a/b in APL patient specimens. RNA interference (RNAi)-mediated attenuation of miR-181a/b expression in NB4 cells was sufficient to reduce colony-forming capacity, proliferation, and survival. Mechanistic investigations revealed that miR-181a/b targets the ATRA-regulated tumor suppressor gene RASSF1A by direct binding to its 3'-untranslated region. Enforced expression of miR-181a/b or RNAi-mediated attenuation of RASSF1A inhibited ATRA-induced granulocytic differentiation via regulation of the cell-cycle regulator cyclin D1. Conversely, RASSF1A overexpression enhanced apoptosis. Finally, RASSF1A levels were reduced in PML/RARα knock-in mice and APL patient samples. Taken together, our results define miR-181a and miR-181b as oncomiRs in PML/RARα-associated APL, and they reveal RASSF1A as a pivotal element in the granulocytic differentiation program induced by ATRA in APL.

  5. Vitamin D and vitamin A receptor expression and the proliferative effects of ligand activation of these receptors on the development of pancreatic progenitor cells derived from human fetal pancreas.

    Science.gov (United States)

    Ng, Ka Yan; Ma, Man Ting; Leung, Kwan Keung; Leung, Po Sing

    2011-03-01

    The growth and development of pancreatic islet cells are regulated by various morphogens. Vitamin A modulates in vitro differentiation of islet cells and vitamin D affects beta-cell insulin secretion, while both vitamin ligands act through heterodimerization with the retinoid X receptor (RXR). However, their effects in modulating pancreatic development have not been determined. In this study, cultured human pancreatic progenitor cells (PPCs) isolated from human fetal pancreas were stimulated to differentiate into islet-like cell clusters (ICCs). RT-PCR, Western blotting and immunocytochemistry were used to examine the expression and localization of vitamin D receptor (VDR), retinoic acid receptor (RAR), and RXR in PPCs. The effects of added all-trans retinoic acid (atRA, a form of vitamin A), calcitriol (activated vitamin D) and of these ligands together on PPC cell viability, proliferation and apoptosis were assessed by MTT, BrdU and ELISA assays, respectively. Post-treatment neurogenin-3 (NGN3) expression, necessary for islet-cell lineage development, was examined by real-time RT-PCR. Results showed that RAR, RXR and VDR were expressed in PPCs. RAR and RXR were localized in nuclei, and the VDR in nuclei, cytoplasm and plasma membrane. atRA and calcitriol each increased PPC viability and proliferation; atRA additionally decreased PPC apoptosis. Co-addition of atRA and calcitriol had no additive effects on cell viability but did increase ngn3 responses. In conclusion, RAR, RXR and VDR are expressed in human fetal PPCs and PPC proliferation can be promoted by calcitriol, atRA or both together, data valuable for elucidating mechanisms underlying islet development and for developing clinical islet transplantation.

  6. TrkB受体的激活在神经母细胞瘤化疗耐药机制中作用的探讨%The Effects of Activation of TrkB on the Chemotherapy Resistance in Neuroblastoma

    Institute of Scientific and Technical Information of China (English)

    李爱敏; 张锦华; 张继红; 藤绍春

    2005-01-01

    目的:探讨TrKB受体在神经母细胞瘤(NB)化疗耐药机制中的作用.方法:选择缺乏TrkB及BDNF表达的人类NB细胞株SH-SY5Y,应用全反式维甲酸(ATRA)诱导TrkB表达,用脑源性神经生长因子(BDNF)激活TrkB受体通路,通过四甲基偶氮蓝比色(MTT)法及流式细胞仪(FCM)检测TrkB受体激活后顺铂对SY5Y生长及凋亡的影响.结果:BDNF+顺铂组、ATRA+顺铂组细胞存活率同单用顺铂组比较均无显著差异(P>0.05);ATRA+BDNF+顺铂组(浓度2.5~20μg/ml)NB细胞存活率明显高于顺铂组(P<0.01);ATRA+BDNF+顺铂组(5μg/ml)凋亡率明显低于ATRA+顺铂组(5μg/ml)(P<0.01).结论:T^B受体激活可阻断顺铂对SY5Y细胞的杀伤作用,其阻断作用是通过抑制细胞凋亡而实现的.TrkB激活在NB的化疗耐药机制中可能起重要作用.

  7. CX3CL1(+ Microparticles Mediate the Chemoattraction of Alveolar Macrophages toward Apoptotic Acute Promyelocytic Leukemic Cells

    Directory of Open Access Journals (Sweden)

    Wen-Hui Tsai

    2014-02-01

    Full Text Available Background/Aims: During the resolution phase of inflammation, release of “find-me” signals by apoptotic cells is crucial in the chemoattraction of macrophages toward apoptotic cells for subsequent phagocytosis, in which microparticles derived from apoptotic cells (apo-MPs are involved. A recent study reports that CX3CL1 is released from apoptotic cells to stimulate macrophages chemotaxis. In this study, we investigated the role of CX3CL1 in the apo-MPs in the cell-cell interaction between alveolar macrophage NR8383 cells and apoptotic all-trans retinoic acid-treated NB4 (ATRA-NB4 cells. Methods/Results: Apoptotic ATRA-NB4 cells and their conditioning medium (CM enhanced the chemoattraction of NR8383 cells as well as their phagocytosis activity in engulfing apoptotic ATRA-NB4 cells. The levels of CX3CL1(+ apo-MPs and CX3CL1 were rapidly elevated in the CM of ATRA-NB4 cell culture after induction of apoptosis. Both exogenous CX3CL1 and apo-MPs enhanced the transmigration of NR8383 cells toward apoptotic ATRA-NB4 cells. This pro-transmigratory activity was able to be partially inhibited either by blocking the CX3CR1 (CX3CL1 receptor of NR8383 cells with its specific antibody or by blocking the surface CX3CL1 of apo-MPs with its specific antibody before incubating these apo-MPs with NR8383 cells. Conclusion: CX3CL1(+ apo-MPs released by apoptotic cells mediate the chemotactic transmigration of alveolar macrophages.

  8. Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells.

    Science.gov (United States)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

    2016-09-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100μM) and doxorubicin (0.2µM) decreased the cell survival rate, but olanzapine (1-100µM) did not. Under granulocytic differentiation for 5days, clozapine, even at a concentration of 25μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation.

  9. All-trans retinoic acid effectively inhibits breast cancer stem cells growth in vitro%全反式维甲酸对乳腺癌干细胞的抑制作用

    Institute of Scientific and Technical Information of China (English)

    曾维根; 胡攀; 王佳妮; 刘仁斌

    2013-01-01

    目的 研究全反式维甲酸(ATRA)对乳腺癌干细胞的抑制作用.方法 采用CCK-8法检测ATRA对MCF-7和SK-BR-3细胞及其干细胞的抑制作用,并检测ATRA处理前后干细胞表型CD44+ CD24-的比例变化.利用球囊形成实验,研究ATRA对乳腺癌干细胞的自我更新能力的影响;将球囊贴壁培养,观察ATRA对干细胞分化的影响.结果 ATRA能够有效的抑制MCF-7和SK-BR-3细胞及其干细胞,但干细胞对ATRA更加敏感.10-6 mol/L ATRA对MCF-7细胞和干细胞的抑制率分别为(8.66±1.06)%和(21.09±3.25)% (P =0.004),对SK-BR-3细胞和干细胞的抑制率分别为(39.19 ±1.47)%和(51.22±2.80)% (P =0.005).ATRA能有效地抑制干细胞的成球能力,破坏其自我更新能力.10-6 mol/L ATRA处理后,MCF-7和SK-BR-3干细胞成球率分别为5.2% (5/96)和13.5% (13/96),而对照组分别为86.5%(83/96)和93.8%(90/96,均P<0.001).ATRA能促进CD44+ CD24-表型分化.10-6mol/L ATRA处理SK-BR-3干细胞后,CD44+ CD24-比例下降为(48.10±2.50)%,而对照组为(86.60±2.50)% (P <0.001).结论 ATRA能有效地抑制乳腺癌细胞和干细胞,但是对干细胞更敏感;ATRA能破坏乳腺癌干细胞的自我更新能力,并促进其分化.%Objective To detect the inhibitory effect of all-trans retinoic acid (ATRA) on breast cancer stem cells (CSCs).Methods The inhibitory effect of ATRA on MCF-7 and SK-BR-3 cell lines was analyzed using a Cell Counting Kit-8 (CCK-8).The proportion of CD44 + CD24-tumor cells of the two cell lines were measured before and after the ATRA treatment,and the role of ATRA in the regulation of CSC self-renewing ability was evaluated with a tumor sphere assay.The tumor spheres were grown in an adherent culture to evaluate the ATRA-induced differentiation of breast cancer stem cells.Results ATRA effectively inhibited the unsorted cells and stem cells,but the CSCs were more sensitive to ATRA.At a concentration of 10-6 mol/L,the inhibitory rate of MCF-7

  10. AM580, a stable benzoic derivative of retinoic acid, has powerful and selective cyto-differentiating effects on acute promyelocytic leukemia cells.

    Science.gov (United States)

    Gianní, M; Li Calzi, M; Terao, M; Guiso, G; Caccia, S; Barbui, T; Rambaldi, A; Garattini, E

    1996-02-15

    All-trans retinoic acid (ATRA) is successfully used in the cyto-differentiating treatment of acute promyelocytic leukemia (APL). Paradoxically, APL cells express PML-RAR, an aberrant form of the retinoic acid receptor type alpha (RAR alpha) derived from the leukemia-specific t(15;17) chromosomal translocation. We show here that AM580, a stable retinobenzoic derivative originally synthesized as a RAR alpha agonist, is a powerful inducer of granulocytic maturation in NB4, an APL-derived cell line, and in freshly isolated APL blasts. After treatment of APL cells with AM580 either alone or in combination with granulocyte colony-stimulating factor (G-CSF), the compound induces granulocytic maturation, as assessed by determination of the levels of leukocyte alkaline phosphatase, CD11b, CD33, and G-CSF receptor mRNA, at concentrations that are 10- to 100-fold lower than those of ATRA necessary to produce similar effects. By contrast, AM580 is not effective as ATRA in modulating the expression of these differentiation markers in the HL-60 cell line and in freshly isolated granulocytes obtained from the peripheral blood of chronic myelogenous leukemia patients during the stable phase of the disease. In NB4 cells, two other synthetic nonselective RAR ligands are capable of inducing LAP as much as AM580, whereas RAR beta- or RAR gamma-specific ligands are totally ineffective. These results show that AM580 is more powerful than ATRA in modulating the expression of differentiation antigens only in cells in which PML-RAR is present. Binding experiments, using COS-7 cells transiently transfected with PML-RAR and the normal RAR alpha, show that AM580 has a lower affinity than ATRA for both receptors. However, in the presence of PML-RAR, the synthetic retinoid is a much better transactivator of retinoic acid-responsive element-containing promoters than the natural retinoid, whereas, in the presence of RAR alpha, AM580 and ATRA have similar activity. This may explain the strong cyto

  11. 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

  12. Low-dose decitabine plus all-trans retinoic acid in patients with myeloid neoplasms ineligible for intensive chemotherapy.

    Science.gov (United States)

    Wu, Wei; Lin, Yan; Xiang, Lili; Dong, Weimin; Hua, Xiaoying; Ling, Yun; Li, Haiqian; Yan, Feng; Xie, Xiaobao; Gu, Weiying

    2016-06-01

    In our previous in vitro trials, decitabine and all-trans retinoic acid (ATRA) demonstrated synergistic effects on growth inhibition, differentiation, and apoptosis in SHI-1 cells; in K562 cells, ATRA enhanced the effect of decitabine on p16 demethylation, and the combination of the two drugs was found to activate RAR-β expression (p16 and RAR-β are two tumor suppressor genes). On the rationale of our in vitro trials, we used low-dose decitabine and ATRA to treat 31 myeloid neoplasms deemed ineligible for intensive chemotherapy. The regimen consisted of decitabine at the dose of 15 mg/m(2) intravenously over 1 h daily for consecutive 5 days and ATRA at the dose of 20 mg/m(2) orally from day 1 to 28 except day 4 to 28 in the first cycle, and the regimen was repeated every 28 days. After 6 cycles, decitabine treatment was stopped, and ATRA treatment was continued for maintenance treatment. Treated with a median of 2 cycles (range 1-6), 7 patients (22.6 %) achieved complete remission (CR), 7 (22.6 %) marrow CR (mCR), and 4 (12.9 %) partial remission (PR). The overall remission (CR, mCR, and PR) rate was 58.1 %, and the best response (CR and mCR) rate was 45.2 %. The median overall survival (OS) was 11.0 months, the 1-year OS rate was 41.9 %, and the 2-year OS rate was 26.6 %. In univariate analyses, age, performance status, comorbidities, white blood cell counts and platelets at diagnosis, percentage of bone marrow blasts, karyotype, and treatment efficacy demonstrated no impacts on OS (P > 0.05, each). Main side effects were tolerable hematologic toxicities. In conclusion, low-dose decitabine plus ATRA is a promising treatment for patients with myeloid neoplasms judged ineligible for intensive chemotherapy.

  13. [Successful treatment of acute promyelocytic leukemia in a pregnant woman by using all-trans retinoic acid].

    Science.gov (United States)

    Tsuda, H; Doi, H; Inada, T; Shirono, K

    1994-07-01

    A 34-year-old woman was admitted because of pancytopenia with DIC in the 28th week of pregnancy. Bone marrow aspirate demonstrated 81.2% abnormal cells which showed Auer bodies and faggot formation. Chromosomal analysis demonstrated an abnormality, t (15; 17). The patient was diagnosed as having acute promyelocytic leukemia (APL) and started to receive treatment with all-trans retinoic acid (ATRA) 70 mg/body/day per os. She had a cesarean section and gave birth to a female infant in the 29th week of pregnancy. An increase of WBC counts was observed on the 9th hospital day, then chemotherapy with anti-cancer agents was performed additionally. Complete remission was achieved on the 27th hospital day. Management of pregnant patients with APL could be improved by using ATRA instead of conventional combinations of cytotoxic agents.

  14. 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.

  15. 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.

  16. Acute promyelocytic leukemia: what is the new standard of care?

    Science.gov (United States)

    Watts, Justin M; Tallman, Martin S

    2014-09-01

    Acute promyelocytic leukemia (APL) is one of the most exciting stories of modern medicine. Once a disease that was highly lethal, the majority of patients are now cured with the advent of molecularly targeted therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). In many patients, chemotherapy can be omitted completely, particularly in patients with low- or intermediate-risk disease (white blood cell count ≤ 10,000/μl). Recent data show overall survival exceeding 90% with ATRA and ATO-based induction and consolidation strategies. In the uncommon patient in whom relapse does occur, most can still be cured with ATO and autologous hematopoietic cell transplantation. Remaining challenges in APL management include the rapid identification and treatment of newly diagnosed patients to decrease the early death rate, optimizing treatment strategies in high-risk patients (white blood cell count>10,000/μl), and the role of maintenance therapy in lower risk patients.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  18. Differentiation of stem cells upon deprivation of exogenous FGF2

    DEFF Research Database (Denmark)

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

    2012-01-01

    Establishing a model for in vitro differentiation of human embryonic stem cells (hESCs) towards the germ cell lineage could be used to identify molecular mechanisms behind germ cell differentiation that may help in understanding human infertility. Here, we evaluate whether a lack of exogenous...... 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...... impression on effects of removal of FGF2 and stimulation with ATRA, we combined the results of three cell lines for each experimental setting. When combining gene expression profiles of three cell lines for 96 genes, only 6 genes showed a significant up-regulation in all cell lines, when no FGF2 was added...

  19. Inorganic carbon turnover caused by digestion of carbonate sands and metabolic activity of holothurians

    Science.gov (United States)

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

    2013-11-01

    Recent measurements have shown that holothurians (sea cucumbers) may play an important role in the cycling of CaCO3 in tropical coral reef systems through ingestion and processing of carbonate sediment. In this report, we present estimates of inorganic carbon turnover rates determined from laboratory incubations of Holothuria atra, Holothuria leucospilota and Stichopus herrmanni. The pH values of the gut lumen ranged from 7.0 to 7.6 when digestive tracts were filled with sediment compared with 6.1-6.7 in animals with empty digestive tracts. Empty gut volume estimates for H. atra and S. herrmanni were 36 ± 4 mL and 151 ± 14 mL, respectively. Based on these measurements and the density and porosity of carbonate sediments of coral reefs, it is estimated that these species process 19 ± 2 kg and 80 ± 7 kg CaCO3 sand yr-1 per individual, respectively. The annual CaCO3 dissolution rates per H. atra and S. herrmanni individual are estimated to be 6.5 ± 1.9 g and 9.6 ± 1.4 g, respectively, suggesting that 0.05 ± 0.02% and 0.1 ± 0.02% of the CaCO3 processed through their gut annually is dissolved. During incubations the CaCO3 dissolution of the fecal casts was 0.07 ± 0.01%, 0.04 ± 0.01% and 0.21 ± 0.05% for H. atra, H. leucospilota and S. herrmanni, respectively. The CaCO3 saturation state in the incubation seawater 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.

  20. 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.

  1. 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.

  2. Effects of retinoic acid on growth hormone-releasing hormone receptor, growth hormone secretagogue receptor gene expression and growth hormone secretion in rat anterior pituitary cells.

    Science.gov (United States)

    Maliza, Rita; Fujiwara, Ken; Tsukada, Takehiro; Azuma, Morio; Kikuchi, Motoshi; Yashiro, Takashi

    2016-06-30

    Retinoic acid (RA) is an important signaling molecule in embryonic development and adult tissue. The actions of RA are mediated by the nuclear receptors retinoic acid receptor (RAR) and retinoid X receptor (RXR), which regulate gene expression. RAR and RXR are widely expressed in the anterior pituitary gland. RA was reported to stimulate growth hormone (GH) gene expression in the anterior pituitary cells. However, current evidence is unclear on the role of RA in gene expression of growth hormone-releasing hormone receptor (Ghrh-r), growth hormone secretagogue receptor (Ghs-r) and somatostatin receptors (Sst-rs). Using isolated anterior pituitary cells of rats, we examined the effects of RA on gene expression of these receptors and GH release. Quantitative real-time PCR revealed that treatment with all-trans retinoic acid (ATRA; 10(-6) M) for 24 h increased gene expression levels of Ghrh-r and Ghs-r; however, expressions of Sst-r2 and Sst-r5 were unchanged. Combination treatment with the RAR-agonist Am80 and RXR-agonist PA024 mimicked the effects of ATRA on Ghrh-r and Ghs-r gene expressions. Exposure of isolated pituitary cells to ATRA had no effect on basal GH release. In contrast, ATRA increased growth hormone-releasing hormone (GHRH)- and ghrelin-stimulated GH release from cultured anterior pituitary cells. Our results suggest that expressions of Ghrh-r and Ghs-r are regulated by RA through the RAR-RXR receptor complex and that RA enhances the effects of GHRH and ghrelin on GH release from the anterior pituitary gland.

  3. 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.

    Science.gov (United States)

    Peng, Jing-Bo; Luo, Chen-Hui; Wang, Yi-Cheng; Huang, Wei-Hua; Chen, Yao; Zhou, Hong-Hao; Tan, Zhi-Rong

    2014-01-17

    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.

  4. Liver-specific cytochrome P450 CYP2C22 is a direct target of retinoic acid and a retinoic acid-metabolizing enzyme in rat liver.

    Science.gov (United States)

    Qian, Linxi; Zolfaghari, Reza; Ross, A Catharine

    2010-07-01

    Several cytochrome P450 (CYP) enzymes catalyze the C4-hydroxylation of retinoic acid (RA), a potent inducer of cell differentiation and an agent in the treatment of several diseases. Here, we have characterized CYP2C22, a member of the rat CYP2C family with homology to human CYP2C8 and CYP2C9. CYP2C22 was expressed nearly exclusively in hepatocytes, where it was one of the more abundant mRNAs transcripts. In H-4-II-E rat hepatoma cells, CYP2C22 mRNA was upregulated by all-trans (at)-RA, and Am580, a nonmetabolizable analog of at-RA. In comparison, in primary human hepatocytes, at-RA increased CYP2C9 but not CYP2C8 mRNA. Analysis of the CYP2C22 promoter region revealed a RA response element (5'-GGTTCA-(n)5-AGGTCA-3') in the distal flanking region, which bound the nuclear hormone receptors RAR and RXR and which was required for transcriptional activation response of this promoter to RA in CYP2C22-luciferase-transfected RA-treated HepG2 cells. The cDNA-expressed CYP2C22 protein metabolized [3H]at-RA to more polar metabolites. While long-chain polyunsaturated fatty acids competed, 9-cis-RA was a stronger competitor. Our studies demonstrate that CYP2C22 is a high-abundance, retinoid-inducible, hepatic P450 with the potential to metabolize at-RA, providing additional insight into the role of the CYP2C gene family in retinoid homeostasis.

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

    Science.gov (United States)

    Perri, Mariarita; Yap, Jeremy L; Yu, Jianshi; Cione, Erika; Fletcher, Steven; Kane, Maureen A

    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 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.

  6. PPARγ agonists promote oligodendrocyte differentiation of neural stem cells by modulating stemness and differentiation genes.

    Directory of Open Access Journals (Sweden)

    Saravanan Kanakasabai

    Full Text Available Neural stem cells (NSCs are a small population of resident cells that can grow, migrate and differentiate into neuro-glial cells in the central nervous system (CNS. Peroxisome proliferator-activated receptor gamma (PPARγ is a nuclear receptor transcription factor that regulates cell growth and differentiation. In this study we analyzed the influence of PPARγ agonists on neural stem cell growth and differentiation in culture. We found that in vitro culture of mouse NSCs in neurobasal medium with B27 in the presence of epidermal growth factor (EGF and basic fibroblast growth factor (bFGF induced their growth and expansion as neurospheres. Addition of all-trans retinoic acid (ATRA and PPARγ agonist ciglitazone or 15-Deoxy-Δ(12,14-Prostaglandin J(2 (15d-PGJ2 resulted in a dose-dependent inhibition of cell viability and proliferation of NSCs in culture. Interestingly, NSCs cultured with PPARγ agonists, but not ATRA, showed significant increase in oligodendrocyte precursor-specific O4 and NG2 reactivity with a reduction in NSC marker nestin, in 3-7 days. In vitro treatment with PPARγ agonists and ATRA also induced modest increase in the expression of neuronal β-III tubulin and astrocyte-specific GFAP in NSCs in 3-7 days. Further analyses showed that PPARγ agonists and ATRA induced significant alterations in the expression of many stemness and differentiation genes associated with neuro-glial differentiation in NSCs. These findings highlight the influence of PPARγ agonists in promoting neuro-glial differentiation of NSCs and its significance in the treatment of neurodegenerative diseases.

  7. 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.

  8. Impacto ambiental da apicultura

    OpenAIRE

    1999-01-01

    A cultura da abelha doméstica Apis. mellifera L. ou apicultura é conhecida desde a antiguidade, sendo o mel uni alimento natural corrente entre os povos primitivos. Pinturas rupestres mostram que desde o neolítico o homem era atraído pelo mel, pois tentava recolher ninhos de abelhas selvagens e instalava-os em cavidades naturais das rochas, muito perto da sua habitação.

  9. 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.

  10. 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.

  11. 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

  12. Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

    Directory of Open Access Journals (Sweden)

    B.C. de-Medeiros

    1998-12-01

    Full Text Available Thirty-seven patients with acute promyelocytic leukemia (APL were treated with all-trans retinoic acid (ATRA. Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR was achieved, defined as: a presence of less than 5% blasts in the bone marrow, with b white blood cells >103/mm3, c platelets >105/mm3 and d hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7% patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days, was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS were observed in 7 (19%, 6 (16% and 4 (11% patients, respectively. Thirteen (35% patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3 and six of these presented with new signs of coagulopathy after chemotherapy. Four (11% patients died secondarily to intracerebral hemorrhage (IH and two (5.4% dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity. RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.

  13. 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.

  14. Crónica sobre Vargas Vila

    Directory of Open Access Journals (Sweden)

    Rafael Maya

    1965-05-01

    Full Text Available Hacia el año de 1924, siendo yo estudiante de la Facultad de Derecho de la Universidad Nacional, fui a pasar unas vacaciones a la ciudad de Barranquilla. Quería conocer el mar, y me atraía la idea de relacionarme con algunos escritores importantes de esa ciudad, que formaban parte del grupo literario llamado Voces, nombre de la revista que les servía de órgano de publicidad.

  15. Microbial modification of host long-distance dispersal capacity

    OpenAIRE

    Hutchings Linda; Bonte Dries; Martin Oliver Y; Goodacre Sara L; Woolley Chris; Ibrahim Kamal; George Thomas CF; Hewitt Godfrey M

    2009-01-01

    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 recoloni...

  16. 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.

  17. Retinoic acid represses CYP7A1 expression in human hepatocytes and HepG2 cells by FXR/RXR-dependent and independent mechanisms.

    Science.gov (United States)

    Cai, Shi-Ying; He, Hongwei; Nguyen, Trong; Mennone, Albert; Boyer, James L

    2010-08-01

    Cholesterol 7alpha-hydroxylase (CYP7A1) plays a key role in maintaining lipid and bile salt homeostasis as it is the rate-limiting enzyme converting cholesterol to bile acids. Deficiency of CYP7A1 leads to hyperlipidemia in man and mouse. Hyperlipidemia is often seen in patients when treated with high-dose retinoic acid (RA), but the molecular mechanisms remain elusive. Our present study revealed that CYP7A1 mRNA expression is greatly repressed by RA in both human hepatocytes and HepG2 cells where increased fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) expressions were also observed, suggesting farnesoid X receptor (FXR) and retinoid X receptor (RXR) were activated. Promoter reporter assays demonstrate that all-trans RA (atRA) specifically activated FXR/RXR. However, detailed molecular analyses indicate that this activation is through RXR, whose ligand is 9-cis RA. Knocking down of FXR or RXRalpha by small interference RNA (siRNA) in human hepatocytes increased CYP7A1 basal expression, but the repressive effect of atRA persisted, suggesting there are also FXR/RXR-independent mechanisms mediating atRA repression of CYP7A1 expression. Chromatin immunoprecipitation (ChIP) assay and cell transfection results indicate that PGC-1alpha plays a role in the FXR/RXR-independent mechanism. Our findings may provide a potential explanation for hyperlipidemic side effects observed in some patients treated with high-dose RA.

  18. THE DIFFERENTIATION SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: EXPERIENCE OF THE PETHEMA GROUP AND REVIEW OF THE LITERATURE.

    Directory of Open Access Journals (Sweden)

    Pau Montesinos

    2011-12-01

    Full Text Available Differentiation syndrome (DS, formerly known as retinoic acid syndrome, is the main life-threatening complication of therapy with differentiating agents (all-trans retinoic acid [ATRA] or arsenic trioxide [ATO] in patients with acute promyelocytic leukemia (APL. The differentiation of leukemic blasts and promyelocytes induced by ATRA and/or ATO may lead to cellular migration, endothelial activation, and release of interleukins and vascular factors responsible of tissue damage. Roughly one quarter of patients with APL undergoing induction therapy will develop the DS, characterized by unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, and/or a vascular capillary leak syndrome leading to acute renal failure. Although the development of the DS, particularly of the severe form, is still associated with a significant increase in morbidity and mortality during induction, the early administration of high-dose dexamethasone at the onset of the first symptoms seems likely to have dramatically reduced the mortality rate of this complication. In this article, we will review the clinical features, incidence, prognostic factors, management, and outcome of the DS reported in the scientific literature. We will make focus in the experience of the three consecutive Programa Español de Tratamientos en Hematología trials (PETHEMA LPA96, LPA99, and LPA2005, in which more than one thousand patients were treated with ATRA plus idarubicin for induction.

  19. THE DIFFERENTIATION SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: EXPERIENCE OF THE PETHEMA GROUP AND REVIEW OF THE LITERATURE.

    Directory of Open Access Journals (Sweden)

    Pau Montesinos

    2011-01-01

    Full Text Available

    Differentiation syndrome (DS, formerly known as retinoic acid syndrome, is the main life-threatening complication of therapy with differentiating agents (all-trans retinoic acid [ATRA] or arsenic trioxide [ATO] in patients with acute promyelocytic leukemia (APL. The differentiation of leukemic blasts and promyelocytes induced by ATRA and/or ATO may lead to cellular migration, endothelial activation, and release of interleukins and vascular factors responsible of tissue damage. Roughly one quarter of patients with APL undergoing induction therapy will develop the DS, characterized by unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, and/or a vascular capillary leak syndrome leading to acute renal failure. Although the development of the DS, particularly of the severe form, is still associated with a significant increase in morbidity and mortality during induction, the early administration of high-dose dexamethasone at the onset of the first symptoms seems likely to have dramatically reduced the mortality rate of this complication. In this article, we will review the clinical features, incidence, prognostic factors, management, and outcome of the DS reported in the scientific literature. We will make focus in the experience of the three consecutive Programa Español de Tratamientos en Hematología trials (PETHEMA LPA96, LPA99, and LPA2005, in which more than one thousand patients were treated with ATRA plus idarubicin for induction.

  20. Tn5-mutagenesis and identification of atr operon and trpE gene responsible for indole-3-acetic acid synthesis in Azospirillum brasilense Yu62

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To bring more information about synthesis of indole-3-acetic acid (IAA) from Azospirillum brasilense, a Tn5-insertion library of A. brasilense Yu62 was constructed and subjected to screening for IAA producing mutants. Two mutants with decreased IAA levels, named as A3 and A24, were isolated. The sequence analysis of loci tagged showed that the Tn5-1063a was located in the atrA gene encoding GntR family transcriptional regulator and trpE gene encoding component I of anthranilate synthase respectively. At the same time, atrB encoding phosphotransferase and atrC encoding aminotransferase were cloned downstream the atrA gene and atrA,atrB and atrC were clustered in an operon. Mutagenesis and complementation studies showed that atrA and atrC were involved in IAA synthesis. IAA levels of trpE mutant and wild-type strain could be improved by adding anthranilate into the medium.

  1. Clinical characteristics and outcomes in patients with acute promyelocytic leukaemia and hyperleucocytosis.

    Science.gov (United States)

    Daver, Naval; Kantarjian, Hagop; Marcucci, Guido; Pierce, Sherry; Brandt, Mark; Dinardo, Courtney; Pemmaraju, Naveen; Garcia-Manero, Guillermo; O'Brien, Susan; Ferrajoli, Alessandra; Verstovsek, Srdan; Popat, Uday; Hosing, Chitra; Anderlini, Paolo; Borthakur, Gautam; Kadia, Tapan; Cortes, Jorge; Ravandi, Farhad

    2015-03-01

    The clinical characteristics, treatment options and outcomes in patients with acute promyelocytic leukaemia (APL) and hyperleucocytosis remain poorly defined. This study reviewed 242 consecutive patients with APL; 29 patients (12%) had a white blood cell count (WBC) ≥ 50 × 10(9) /l at presentation (median WBC 85·5 × 10(9) /l). Patients with hyperleucocytosis had inferior complete remission (CR) rates (69% vs. 88%; P = 0·004) and higher 4-week mortality (24% vs. 9%; P = 0·018) compared to patients without hyperleucocytosis. We noted a trend towards inferior 3-year disease-free survival (DFS) (69% vs. 80%; P = 0·057) and inferior 3-year overall survival (OS) (74% vs. 92%; P = 0·2) for patients with hyperleucocytosis. Leukapheresis was performed in 11 (38%) of the 29 patients with hyperleucocytosis. CR rate and 3-year OS were not significantly improved in patients who received leukapheresis. CR rate and 3-year OS for the 15 patients with hyperleucocytosis treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) plus cytotoxic therapy (idarubicin or gemtuzumab ozogamicin) combinations were 100% and 100% vs. 57% and 35% for the 14 patients treated with non-ATRA/ATO combinations (P = 0·004 and P = 0·002). Leukapheresis does not improve the outcomes in patients with APL presenting with hyperleucocytosis. ATRA/ATO-based combinations are superior to other regimens in these patients.

  2. 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.

  3. Knockdown of lecithin retinol acyltransferase increases all-trans retinoic acid levels and restores retinoid sensitivity in malignant melanoma cells.

    Science.gov (United States)

    Amann, Philipp M; Czaja, Katharina; Bazhin, Alexandr V; Rühl, Ralph; Skazik, Claudia; Heise, Ruth; Marquardt, Yvonne; Eichmüller, Stefan B; Merk, Hans F; Baron, Jens M

    2014-11-01

    Retinoids such as all-trans retinoic acid (ATRA) influence cell growth, differentiation and apoptosis and may play decisive roles in tumor development and progression. An essential retinoid-metabolizing enzyme known as lecithin retinol acyltransferase (LRAT) is expressed in melanoma cells but not in melanocytes catalysing the esterification of all-trans retinol (ATRol). In this study, we show that a stable LRAT knockdown (KD) in the human melanoma cell line SkMel23 leads to significantly increased levels of the substrate ATRol and biologically active ATRA. LRAT KD restored cellular sensitivity to retinoids analysed in cell culture assays and melanoma 3D skin models. Furthermore, ATRA-induced gene regulatory mechanisms drive depletion of added ATRol in LRAT KD cells. PCR analysis revealed a significant upregulation of retinoid-regulated genes such as CYP26A1 and STRA6 in LRAT KD cells, suggesting their possible involvement in mediating retinoid resistance in melanoma cells. In conclusion, LRAT seems to be important for melanoma progression. We propose that reduction in ATRol levels in melanoma cells by LRAT leads to a disturbance in cellular retinoid level. Balanced LRAT expression and activity may provide protection against melanoma development and progression. Pharmacological inhibition of LRAT activity could be a promising strategy for overcoming retinoid insensitivity in human melanoma cells.

  4. RETINOID RECEPTORS IN BONE AND THEIR ROLE IN BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Petra eHenning

    2015-03-01

    Full Text Available Vitamin A (retinol is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA, which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RAR, RAR, RAR. RARs and closely related retinoid X receptors (RXR, RXR, RXR form heterodimers which bind to DNA and function as ligand activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver and processed to ATRA. ATRA’s effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented.

  5. STUDY ON EFFECTS OF QUERCETIN ON PML GENE AND PROTEIN IN LEUKEMIA CELL LINES

    Institute of Scientific and Technical Information of China (English)

    钟璐; 陈芳源; 韩洁英; 邵念贤; 欧阳仁荣

    2003-01-01

    Objective To investigate the effect of quercetin on PML gene and protein expression and localization in leukemia cell lines. MethodsCell morphology was assayed by Wright,s stain and fluorescence stain, and PML Mrna expression by RT-PCR, PML protein localization by immuno fluorescence.ResultsNB4 and HL-60 cells differentiated morphologically after treatment with all trans retinoic acid (ATRA) while K562 cells did not differentiate. Typical apoptosis was found in each cell line after treatment with quercetin. Immuno fluorescence analysis showed, after treatment with ATRA, the fusion protein disappeared in NB4 cells and PML protein relocated, while HL-60 and K562 cells had no difference from control cells. After treatment with quercetin, the fusion protein disappeared in NB4 cells, PML protein relocated, then degraded. In HL-60 cells and K562 cells, PML protein also located and then degraded. The expression of PML Mrna was not changed in all three cell lines after treatment with ATRA or quercetin. ConclusionPML plays the role of differentiation and apoptosis inducer in leukemia cells at the translational level. PML in POD plays the role of apoptosis inducer and the growth control of leukemia cells.

  6. Retinoid-dependent growth inhibition, differentiation and apoptosis in acute promyelocytic leukemia cells. Expression and activation of caspases.

    Science.gov (United States)

    Gianni, M; Ponzanelli, I; Mologni, L; Reichert, U; Rambaldi, A; Terao, M; Garattini, E

    2000-05-01

    In the NB4 model of acute promyelocytic leukemia (APL), ATRA, 9-cis retinoic acid (9-cis RA), the pan-RAR and RARalpha-selective agonists, TTNPB and AM580, induce growth inhibition, granulocytic differentiation and apoptosis. By contrast, two RXR agonists, a RARbeta agonist and an anti-AP1 retinoid have very limited activity, ATRA- and AM580-dependent effects are completely inhibited by RAR antagonistic blockade, while 9-cis RA-induced cell-growth-inhibition and apoptosis are equally inhibited by RAR and RXR antagonists. ATRA, 9-cis RA and AM580 cause upregulation of the mRNAs coding for pro-caspase-1, -7, -8, and -9, which, however, results in increased synthesis of only pro-caspase-1 and -7 proteins. These phenomena are associated with activation of pro-caspase-6, -7 and -8, cytochrome c release from the mitochondria, inversion of Bcl-2/Bax ratio and degradation of PML-RARalpha. Caspase activation is fundamental for retinoid-induced apoptosis, which is suppressed by the caspase-inhibitor z-VAD.

  7. 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.

  8. Effects of synthetic retinoids and retinoic acid isomers on the expression of alkaline phosphatase in F9 teratocarcinoma cells.

    Science.gov (United States)

    Gianni, M; Zanotta, S; Terao, M; Garattini, S; Garattini, E

    1993-10-15

    Expression of ALP in F9 teratocarcinoma cells is induced by all-trans retinoic acid (ATRA) (Gianni' et al., Biochem. J. 274: 673-678, 1991). The specific ligand for retinoic acid related receptors (RXRs), 9-cis retinoic acid (9-cis RA), and three synthetic analogs binding to the alpha, beta and gamma forms of the retinoic acid receptors (RARs), AM580, CD2019, and CD437, were used to study their effects on alkaline phosphatase (ALP) enzymatic activity and mRNA levels. At concentrations close to the Kd for their respective receptors, 9-cis RA, AM580 (the RAR alpha agonist) and CD437 (the RAR gamma agonist) clearly upregulate the expression of the ALP gene, whereas the effect of CD2019 (the RAR beta agonist) is very modest. A specific inhibitor of the RAR alpha, Ro 41-5253, completely blocks the induction of ALP triggered by AM580, while it has minor effects on the upregulation caused by ATRA, 9-cis RA, CD437 and CD2019. The induction of ALP observed with the various retinoids is inhibited by the contemporaneous treatment with dibutyryl cAMP. The levels of the RAR alpha and gamma transcripts are unaltered, while RAR beta mRNAs are induced by ATRA, AM580, CD437 and to a lower extent by 9-cis RA and CD2019.

  9. Role of retinoids in the prevention and treatment of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Catherine; C; Applegate; Michelle; A; Lane

    2015-01-01

    Vitamin A and its derivatives, retinoids, have been widely studied for their use as cancer chemotherapeutic agents. With respect to colorectal cancer(CRC), several critical mutations dysregulate pathways implicated in progression and metastasis, resulting in aberrant Wnt/β-catenin signaling, gain-of-function mutations in K-ras and phosphatidylinositol-3-kinase/Akt, cyclooxygenase-2 over-expression, reduction of peroxisome proliferatoractivated receptor γ activation, and loss of p53 function. Dysregulation leads to increased cellular proliferation and invasion and decreased cell-cell interaction and differentiation. Retinoids affect these pathways by various mechanisms, many involving retinoic acid receptors(RAR). RAR bind to all-trans-retinoic acid(ATRA) to induce the transcription of genes responsible for cellular differentiation. Although most research concerning the chemotherapeutic efficacy of retinoids focuses on the ability of ATRA to decrease cancer cell proliferation, increase differentiation, or promote apoptosis; as CRC progresses, RAR expression is often lost, rendering treatment of CRCs with ATRA ineffective. Our laboratory focuses on the ability of dietary vitamin A to decrease CRC cell proliferation and invasion via RAR-independent pathways. This review discusses our research and others concerning the ability of retinoids to ameliorate the defective signaling pathways listed above and decrease tumor cell proliferation and invasion through both RAR-dependent and RAR-independent mechanisms.

  10. Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo

    Science.gov (United States)

    Atashrazm, Farzaneh; Lowenthal, Ray M.; Dickinson, Joanne L.; Holloway, Adele F.; Woods, Gregory M.

    2016-01-01

    The morbidity and mortality associated with current therapies for acute promyelocytic leukemia (APL) remain a significant clinical concern, despite improvements in patient survival. Consequently, the development of adjuvant therapies that increase efficacy while reducing morbidities is important. Reducing the concentration of the toxic drugs in adjuvant therapy has the potential to reduce unwanted side effects. Therefore, this study aimed to determine the synergistic effects of fucoidan, an anti-tumor agent, with current APL therapies. When the human APL cell line, NB4, was treated in vitro with fucoidan plus ATO and ATRA at therapeutic and sub-therapeutic doses, there was an increase in sub-G0/G1 cells, annexin V/PI-positive-apoptotic cells and DNA fragmentation. This reduction in proliferation and increase in apoptosis was accompanied by enhanced myeloid differentiation as indicated by an increased expression of CD11b. This was not observed with the AML cell line Kasumi-1, suggesting specificity for APL. In vivo treatment of APL-bearing mice with fucoidan+ATRA or fucoidan+ATO delayed tumor growth, induced differentiation and increased tumor volume doubling time. The differentiated APL cells derived from the excised tumor mass exhibited decreased CD44 expression in fucoidan+ATRA treated mice. This could translate to decreased cell migration in APL patients. Our findings provide evidence supporting the use of fucoidan as an adjuvant therapeutic agent in the treatment of APL. PMID:27329592

  11. 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.

  12. 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.

  13. 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.

  14. Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo.

    Science.gov (United States)

    Atashrazm, Farzaneh; Lowenthal, Ray M; Dickinson, Joanne L; Holloway, Adele F; Woods, Gregory M

    2016-07-19

    The morbidity and mortality associated with current therapies for acute promyelocytic leukemia (APL) remain a significant clinical concern, despite improvements in patient survival. Consequently, the development of adjuvant therapies that increase efficacy while reducing morbidities is important. Reducing the concentration of the toxic drugs in adjuvant therapy has the potential to reduce unwanted side effects. Therefore, this study aimed to determine the synergistic effects of fucoidan, an anti-tumor agent, with current APL therapies.When the human APL cell line, NB4, was treated in vitro with fucoidan plus ATO and ATRA at therapeutic and sub-therapeutic doses, there was an increase in sub-G0/G1 cells, annexin V/PI-positive-apoptotic cells and DNA fragmentation. This reduction in proliferation and increase in apoptosis was accompanied by enhanced myeloid differentiation as indicated by an increased expression of CD11b. This was not observed with the AML cell line Kasumi-1, suggesting specificity for APL.In vivo treatment of APL-bearing mice with fucoidan+ATRA or fucoidan+ATO delayed tumor growth, induced differentiation and increased tumor volume doubling time. The differentiated APL cells derived from the excised tumor mass exhibited decreased CD44 expression in fucoidan+ATRA treated mice. This could translate to decreased cell migration in APL patients.Our findings provide evidence supporting the use of fucoidan as an adjuvant therapeutic agent in the treatment of APL.

  15. 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

  16. Hermit crab (Decapoda, Anomura attraction to dead gastropod baits in an infralittoral algae bank

    Directory of Open Access Journals (Sweden)

    Juarez C. B. Pezzuti

    2002-06-01

    Full Text Available Hermit crabs use gastropod shells as shelter and are adapted to follow chemical cues released from tissues of dead or injured gastropods as a way to find new and more adequate shells. The species composition, crab size, shell types adequacy and physical condition were compared between attracted individuals and crabs collected in previous samples. The previous sampling was carried out in five areas before each experiment. Then, five baits of crushed gastropods in nylon net bags were installed in these areas. Three samples were taken at 30min intervals, capturing all crabs within a circle of 60cm diameter. Attraction of hermit crabs was tested for four different gastropod baits to verify specificity of the chemical cues. Clibanarius antillensis, Pagurus brevidactylus and Paguristes tortugae were collected in the study area. Pagurus brevidactylus, the smallest species, turned out to be more attracted than the 2 other species. The results showed that attracted crabs utilized more gastropod shell types than that collected in previous samples, however shell utilization pattern did not differ between them. Attracted animals were slightly smaller (shield length than those collected in the previous samples but did not present significant differences in shell adequacy and condition. The four experimental baits attracted the crabs in similar ways not indicating a specific response from the crabs. The fact that attracted animals were smaller suggested that the attraction to dead gastropods might enable the acquisition of a new and larger shell and, consequently, chains of shell exchange between the attracted crabs.Ermitões utilizam conchas de gastrópodes para abrigo. Conchas novas e mais adequadas podem ser encontradas pelos ermitões pois estes são atraídos por substâncias químicas liberadas pelos tecidos de gastrópodes feridos ou mortos. A adequação, condição e tipo das conchas e a composição de espécies e o tamanho dos ermitões foram

  17. Effects of all-trans retinoic acid combined with gamma radiation on proliferation and apoptosis of esophageal carcinoma TE13 cells%全反式维甲酸联合射线对食管癌细胞TE13增殖及凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    邓秋媛; 董稚明

    2012-01-01

    Objective: To investigate the effects of ATRA (all-trans-retinoicacid) combined with gamma radiation on proliferation and apoptosis of human esophageal carcinoma TE1 3 cells, and to explore the possible mechanism. Methods: The effect of ATRA on the proliferation of TE13 cells was detected by MTT method. When the cell growth Rl (inhibitory rate) reached levels of 25%, 50% and 75%, the TE13 cells were treated with the corresponding inhibitory doses of ATRA combined with 4 Gy gamma radiation. The effects of this combination intervention on cell cycle distribution and apoptosis of TE13 cells were detected by FCM (flow cytometry). The colony-formation ability and cell viability were detected using colony-formation experiment. The expression of cyclinDl protein was detected by FCM. Results: The inhibitory effect of ATRA on the proliferation of TE1 3 cells was significant in a dose- and time-dependent manner. The cell growth Irs reached 22.0%, 55.1% and 71.1% at ATRA concentrations of 0.78, 6.25 and 12.5 μmol/L, respectively. The cell viability and colony-formation efficiency were significantly decreased in TE13 cells treated with ATRA in combination with 4 Gy gamma radiation, as compared with TE13 cells receiving administration of ATRA alone. The proliferative ability of TE1 3 cells was significantly reduced after ATRA treatment in combination with 4 Gy gamma radiation for 24 and 48 h; furthermore, the percentage of the cells arrested at phase Go/G, was increased accompanying with a significantly elevated apoptotic rate. Although the combination treatment (0.78 (imol/L ATRA and gamma radiation) had a weak influence on the expression of cyclinDl protein, which was significantly decreased in other groups (6.25 and 12.5 μmol/L ATRA). Conclusion: ATRA exerts an inhibitory influence on the proliferation of TE1 3 cells through down-regulating cyclinDl expression, arresting the cells at phase G0/G1 and inducing apoptosis. A higher-concentration of ATRA combined with gamma

  18. Effect of all-trans-retinoic acid on α-SMA, Collagen-Ⅰ and HSP47 expressions in TGF-β1-stimulated human lung fibroblasts%全反式维甲酸对HFL-Ⅰ细胞α-平滑肌肌动蛋白、Ⅰ型胶原、热休克蛋白47表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘巨源; 李佳鑫; 海广范; 陈永凤; 夏武; 贾岩龙

    2011-01-01

    目的 研究全反式维甲酸(ATRA)对转化生长因子-β1(TGF-β1)诱导的人胚肺成纤维细胞(HFL-Ⅰ)中α-平滑肌肌动蛋白(α-SMA),Ⅰ型胶原(Collagen-Ⅰ),热休克蛋白47(HSP47) mRNA和蛋白表达的影响.方法 体外培养HFL-Ⅰ细胞,MTT法检测不同浓度TGF-β1和ATRA分别作用3 d对HFL-Ⅰ细胞增殖能力的影响.随后分为6组:对照组、5 μg·L-1 TGF-β1组、10 μmol·L-1 ATRA组、5 μg·L-1 TGF-β1+0.1 μmol·L-1 ATRA组、5 μg·L-1 TGF-β1+1 μmol·L-1 ATRA组、5 μg·L-1 TGF-β1+10 μmol·L-1 ATRA组,RT-PCR和Western blot方法分别检测各实验组细胞中α-SMA,Collagen-Ⅰ,HSP47 mRNA和蛋白的表达.结果 ① MTT法检测结果显示不同浓度的TGF-β1可刺激HFL-Ⅰ细胞增殖,呈浓度依赖性(P<0.05);不同浓度的ATRA对HFL-Ⅰ细胞增殖能力均有明显抑制作用,并随药物浓度的增加而增强(P<0.05).② 5 μg·L-1 TGF-β1诱导后,HFL-Ⅰ细胞中α-SMA,Collagen-I,HSP47 mRNA和蛋白表达均明显上调(P<0.05).③ ATRA以浓度依赖性方式下调经TGF-β1诱导的HFL-Ⅰ细胞中α-SMA,Collagen-I,HSP47 mRNA和蛋白的表达(P<0.05).结论 ATRA能够抑制TGF-β1诱导的HFL-Ⅰ细胞的分化,其作用机制可能与降低Collagen-I、HSP47表达有关.%Aim To investigate the effects of all-transretinoic acid ( ATRA ) on the expression of α-smooth muscle actin( α-SMA ), Collagen-Ⅰ and heat shock protein 47 ( HSP47 ) in the TCF-β1-stimulated human lung fibroblasts ( HFL- Ⅰ ). Methods Firstly, cell proliferation of HFL- Ⅰ was detected by MTT after the cells were treated with different concentrations of TGF β1 and ATRA respectively for 3 days. HFL- Ⅰ cells in vitro were divided into six experimental groups: the control group; 5 μg · L-1 TGF-β1 group; 10 μmol · L-1 ATRA group; 5 μg · L-1 TGF-β1 +0. 1 μmol · L-1 ATRA group; 5 μg · L-1 TCF-β1 +1 μmol · L-1 ATRA group; 5 μg · L-1 TGF-β1 + lOμmol · L-1 ATRA group. Expressions of α-SMA, Collagen-

  19. Effects of all-trans retinoic acid on tumor recurrence and metastasis Efecto del ácido trans-retinoico sobre la recidiva tumoral y el desarrollo metastásico

    Directory of Open Access Journals (Sweden)

    I. García-Alonso

    2005-04-01

    Full Text Available Objective: all-trans-retinoic acid (ATRA promotes cell differentiation. We have studied its effect on the local recurrence and metastatic spreading of an experimental rhabdomyosarcoma in rats. Design: syngenic rhabdomyosarcoma cells (S4MH were inoculated s.c. in male WAG/RijCrl rats. After 25 days tumors were excised and a 40% hepatectomy was performed for all animals. Ten days later the rats were sacrificed and a thorough necropsy was performed. The animals were randomly allocated to receive daily doses of ATRA (5 mg/kg, i.p. or its solvent (Clinoleic®/ethanol 90/10, starting three days before surgery until the end of the experiment. Results: ATRA reduced the incidence of local recurrence from 70 to 33% (p Objetivo: el ácido trans-retinoico (ATRA, "all-trans retinoic acid" es un agente inductor de la diferenciación celular. Se estudia su efecto sobre la recidiva local y la diseminación metastásica de los tumores sólidos. Diseño experimental: mediante inoculación subcutánea de células de rabdomiosarcoma (S4MH se ha inducido un tumor en ratas WAG/RijCrl. Tras 25 días, se practicó una tumorectomía y simultáneamente hepatectomía del 40%. Los animales se sacrificaron el día 35, y fueron sometidos a estudio necrópsico. La mitad de los animales fueron tratados con ATRA (5 mg/kg, i.p. desde el día 22 al 35, mientras que los controles recibieron el excipiente (Clinoleico®/etanol 90/10. Resultados: el tratamiento redujo la tasa de recidiva local del 70 al 33% (p < 0,05, aunque no afectó a su tamaño (1,8 vs. 2,0 cc. El volumen medio de las metástasis inguinales se redujo a la sexta parte (0,2 vs. 1,2 cc; p < 0,05, si bien su frecuencia aumentó con el ATRA (86 vs. 29%; p < 0,05. La extensión retroperitoneal del rabdomisoarcoma también se redujo (0,7 vs. 5,1 cc; p < 0,05, aunque no hubo variación en la incidencia (71 vs. 67%. La incidencia de afectación pulmonar (100% en controles se redujo hasta el 33% (p < 0,05, a la vez que el

  20. Analysis a case of elderly newly diagnosed acute promyelocytic leukemia and a review of the literature%初发急性早幼粒细胞性白血病老年患者诊治全过程1例报告及文献复习

    Institute of Scientific and Technical Information of China (English)

    王传馥; 张洪娣; 潘祖玉; 俞卓伟

    2013-01-01

    Objective To observe the efficacy of all-trans retinoic acid (ATRA) and IV arsenic trioxide (ATO) plus chemotherapy regimens for a elderly patient with acute promyelocytic leukemia (APL). Methods a 71-year-old man with newly diagnosed APL, for induction, oral ATRA 60mg/d, and intravenous ATO 10mg/d, starting on day 1 and continuing until CR; idarubicin (IDA) and cytarabine (Ara-C) was added to induction treatment. Achieved hematologic and medullary complete remission( hCR and mCR), the patient treated with 3 consolidation courses. Course1: homoharringtonine 2mg/d, days1-5 combined with Ara-C 100mg/d, days1-5. Course2、 3: IDA10mg/d, daysl-3 combined with Ara-C 100mg/d, days1-3. The patients in molecular CR after 3 consolidation courses, bone marrow (BM) samples were assayed by quantitative RT-PCR for PML-RARA fusion transcripts is negative. Followed by nine courses maintenance therapy, each course of treatment for 3 months, a total of 27 months. Nine courses divided in two stages to carry on, the first stage include five courses (sequential regimen, m1: intravenous ATOl0mg/d, days1-10; m2: oralATRA 30mg/d, days1-30; m3: intravenous Methotrexate (MTX) 5mg, qw×4w) and the second stage include four courses (sequential regimen, ml: oral ATRA 30mg/d, days1-30; m2: oral MTX 15mg, qw×4w; m3: oral 6-mercaptopurine (6-MP) 50mg/d, days1-14). Results The 71-year-old patient with APL (moderate risk) administered ATRA, Ⅳ ATO and chemotherapy in combination was achieved molecular CR and continuing molecular CR more than 52 months. During the therapy, the patient suffered from the adverse events included pneumonia, hydrothorax, hepatic disfunction, herpes zoster, atrial premature beats and fibrillation atrial, etc. Treatment should be timely, and should pay more attention to support measures. For patients aged >70 years, the doses should be appropriately reduced. Conclusion Ederly patient with APL may be tolerant to ATRA combined with ATO plus chemotherapy, and obtain the

  1. 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.

  2. Inhibition of ALDH1A1 activity decreases expression of drug transporters and reduces chemotherapy resistance in ovarian cancer cell lines.

    Science.gov (United States)

    Januchowski, Radosław; Wojtowicz, Karolina; Sterzyńska, Karolina; Sosińska, Patrycja; Andrzejewska, Małgorzata; Zawierucha, Piotr; Nowicki, Michał; Zabel, Maciej

    2016-09-01

    The high mortality of ovarian cancer patients results from the failure of treatment caused by the inherent or acquired chemotherapy drug resistance. It was reported that overexpression of aldehyde dehydrogenase A1 (ALDH1A1) in cancer cells can be responsible for the development of drug resistance. To add the high expression of the drug transporter proteins the ALDHA1 is considered as a molecular target in cancer therapy. Therefore, we analysed drug-resistant ovarian cancer cell lines according to ALDHA1 expression and the association with drug resistance. The expression of ALDH1A1, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) was determined using a microarray and confirmed by Q-PCR, western blot and fluorescence analysis. ALDH1A1 activity was determined using an Aldefluor assay. The impact of all-trans retinoic acid (ATRA) and diethylaminobenzaldehyde (DEAB) on chemotherapy resistance was assessed by the MTT chemosensitivity assay. The most abundant expression of ALDH1A1 was noted in paclitaxel- and topotecan-resistant cell lines where two populations of ALDH-positive and ALDH-negative cells could be observed. Those cell lines also revealed the overexpression of P-gp and BCRP respectively, and were able to form spheres in non-adherent conditions. Pre-treatment with ATRA and DEAB reduced chemotherapy resistance in both cell lines. ATRA treatment led to downregulation of the ALDH1A1, P-gp and BCRP proteins. DEAB treatment led to downregulation of the P-gp protein and BCRP transcript and protein. Our results indicate that ALDH1A1-positive cancer cells can be responsible for drug resistance development in ovarian cancer. Developing more specific ALDH1A1 inhibitors can increase chemotherapy effectiveness in ovarian cancer.

  3. Escolha de ginecologia e obstetrícia por graduandos da Universidade de Brasília: um estudo de influências numa série histórica

    Directory of Open Access Journals (Sweden)

    Dejano T. Sobral

    Full Text Available Analisa-se a escolha de residência médica em Ginecologia e Obstetrícia (GO em função de características pessoais dos graduandos, eventos curriculares e contexto temporal da instituição. O estudo incluiu 792 egressos do curso de Medicina da Universidade de Brasília, formados no período 1994-2006. Os dados abrangeram descritores demográficos e de aprendizagem, preferência inicial por carreira, monitorias, rendimento acadêmico, estágio seletivo no internato e inscrição para residência médica ao término do curso. Análises de contingência e de regressão logística foram realizadas com os egressos agrupados segundo a escolha ou não de GO. No conjunto, 8% dos egressos escolheram GO, dentre os quais 33% manifestaram atração inicial pela área. Não houve tendência temporal consistente na escolha ou na atração inicial, mas no qüinqüênio 1997-2001 a proporção de escolha foi menor do que a de atração inicial, em correspondência a mudanças na ambiência do curso. A análise de regressão logística identificou seis fatores preditivos da escolha: estágio seletivo, monitoria e incremento de rendimento em GO, preferência inicial, sexo feminino e época de graduação. Em conclusão, fatores associados à escolha de GO numa série histórica de 13 anos incluíram características pessoais, eventos curriculares e fase da conjuntura institucional.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Keratins 2 and 4/13 in reconstituted human skin are reciprocally regulated by retinoids binding to nuclear receptor RARalpha.

    Science.gov (United States)

    Virtanen, Marie; Sirsjö, Allan; Vahlquist, Anders; Törmä, Hans

    2010-07-01

    Disorders of keratinization are often treated with vitamin A derivatives (retinoids) which affect keratinocyte differentiation, including keratin (KRT) gene expression. In vivo, suprabasal keratinocytes normally express only keratin (K) 1, K2 and K10, but after topical application of all-trans retinoic acid (ATRA), the granular cells will additionally express K4 and K13, i.e. keratins normally present in oral mucosa and in cultured epidermal keratinocytes. To learn more about the retinoid regulation of keratin expression under in vivo-like conditions, we cultured keratinocytes on de-epidermized dermis in only 0.5% serum. These cells produce a normal-looking epidermis that expresses high mRNA levels of KRT1, KRT2 and KRT10, but minimal amounts of KRT4 and KRT13. Addition of ATRA to the medium for 48 h caused a dose-dependent increase in KRT4/KRT13 and a down-regulation of KRT2 mRNA. An increase in K4 protein was also found. The response was greater than the up-regulation of another retinoid-regulated gene, CRABPII. By studying 10 retinoids with different affinities for the retinoic acid receptors (RAR) and retinoid X receptors (RXR) isoforms, the reciprocal expression of KRT2 and KRT4/KRT13 could be connected with agonists for RARalpha. Two of these agonists, CD336/Am580 and CD2081, altered the expression profile with similar potency as the pan-RAR agonists ATRA and CD367. Co-addition of a pan-RAR antagonist (CD3106/AGN193109) markedly inhibited the induction of KRT4/KRT13 expression, whereas the down-regulation of KRT2 was less affected. In conclusion, RARalpha agonists elicit a reciprocal modulation of KRT2 and KRT4/KRT13 expression in human epidermis, but whether or not the keratin genes also possess RARalpha-specific regulatory elements is still unclear.

  10. Critical role of the H6-H7 loop in the conformational adaptation of all-trans retinoic acid and synthetic retinoids within the ligand-binding site of RARalpha.

    Science.gov (United States)

    Mailfait, S; Thoreau, E; Belaiche, D; Formstecher And B Sablonniè, P

    2000-06-01

    The pleiotropic effects of the natural and synthetic retinoids are mediated by the activation of the two subfamilies of nuclear receptors, the retinoic acid receptors (RARs) and the retinoic X receptors (RXRs). At the molecular level, these events begin with the specific ligand recognition by a nuclear receptor subtype. The adaptation of ligands to the receptor binding site leads to an optimal number of interactions for binding and selectivity which justifies elucidation of the structural requirements of the ligand binding pocket. To explore the contribution of H6-H7 loop folding in the ligand-induced conformational changes explained by the mouse-trap model, four RARalpha mutants were constructed. Ligand binding and transactivation studies revealed that three residues from the H6-H7 loop (Gly(301), Phe(302) and Gly(303)) are critical for the conformational adaptation of both synthetic agonists and antagonists. Model building and analysis of both RARalpha-ATRA and RARalpha-CD367 complexes demonstrate that accommodation of CD367 results in a less tight contact of the saturated ring of this ligand with the amino acid side chains of the receptor ligand-binding pocket compared with that of ATRA. According to the flexibility of the agonists tested (ATRA>TTNPB=Am580> CD367), we observed a decrease in binding that was dependent on ligand structure rigidity. In contrast, the binding and transactivating activities of the L266A mutant confirmed the structural constraints imposed by synthetic ligands on binding affinity for the receptor and revealed that subtle local rearrangements induced by specific conformational adaptation changes result in different binding affinities. Our results illustrate the dynamic nature of the interaction between RARalpha and its ligands and demonstrate the critical role of the H6-H7 loop in the binding of both synthetic retinoid agonists and antagonists.

  11. Neuregulins are essential for spermatogonial proliferation and meiotic initiation in neonatal mouse testis.

    Science.gov (United States)

    Zhang, JiDong; Eto, Ko; Honmyou, Asuka; Nakao, Kazuki; Kiyonari, Hiroshi; Abé, Shin-ichi

    2011-08-01

    The transition from mitosis to meiosis is unique to germ cells. In murine embryonic ovaries and juvenile testes, retinoic acid (RA) induces meiosis via the stimulated by retinoic acid gene 8 (Stra8), but its molecular pathway requires elucidation. We present genetic evidence in vivo and in vitro that neuregulins (NRGs) are essential for the proliferation of spermatogonia and the initiation of meiosis. Tamoxifen (TAM) was injected into 14-day post-partum (dpp) Sertoli cell-specific conditional Nrg1(Ser-/-) mutant mice. TAM induced testis degeneration, suppressed BrdU incorporation into spermatogonia and pre-leptotene primary spermatocytes, and decreased and increased the number of STRA8-positive and TUNEL-positive cells, respectively. In testicular organ cultures from 5-6 dpp wild-type mice and cultures of their re-aggregated spermatogonia and Sertoli cells, FSH, RA [all-trans-retinoic acid (ATRA), AM580, 9-cis-RA] and NRG1 promoted spermatogonial proliferation and meiotic initiation. However, TAM treatment of testicular organ cultures from the Nrg1(Ser-/-) mutants suppressed spermatogonial proliferation and meiotic initiation that was promoted by FSH or AM580. In re-aggregated cultures of purified spermatogonia, NRG1, NRG3, ATRA and 9-cis-RA promoted their proliferation and meiotic initiation, but neither AM580 nor FSH did. In addition, FSH, RAs and NRG1 promoted Nrg1 and Nrg3 mRNA expression in Sertoli cells. These results indicate that in juvenile testes RA and FSH induced meiosis indirectly through Sertoli cells when NRG1 and NRG3 were upregulated, as NRG1 amplified itself and NRG3. The amplified NRG1 and NRG3 directly induced meiosis in spermatogonia. In addition, ATRA and 9-cis-RA activated spermatogonia directly and promoted their proliferation and eventually meiotic initiation.

  12. Moth sex pheromone receptors and deceitful parapheromones.

    Directory of Open Access Journals (Sweden)

    Pingxi Xu

    Full Text Available The insect's olfactory system is so selective that male moths, for example, can discriminate female-produced sex pheromones from compounds with minimal structural modifications. Yet, there is an exception for this "lock-and-key" tight selectivity. Formate analogs can be used as replacement for less chemically stable, long-chain aldehyde pheromones, because male moths respond physiologically and behaviorally to these parapheromones. However, it remained hitherto unknown how formate analogs interact with aldehyde-sensitive odorant receptors (ORs. Neuronal responses to semiochemicals were investigated with single sensillum recordings. Odorant receptors (ORs were cloned using degenerate primers, and tested with the Xenopus oocyte expression system. Quality, relative quantity, and purity of samples were evaluated by gas chromatography and gas chromatography-mass spectrometry. We identified olfactory receptor neurons (ORNs housed in trichoid sensilla on the antennae of male navel orangeworm that responded equally to the main constituent of the sex pheromone, (11Z,13Z-hexadecadienal (Z11Z13-16Ald, and its formate analog, (9Z,11Z-tetradecen-1-yl formate (Z9Z11-14OFor. We cloned an odorant receptor co-receptor (Orco and aldehyde-sensitive ORs from the navel orangeworm, one of which (AtraOR1 was expressed specifically in male antennae. AtraOR1•AtraOrco-expressing oocytes responded mainly to Z11Z13-16Ald, with moderate sensitivity to another component of the sex pheromone, (11Z,13Z-hexadecadien-1-ol. Surprisingly, this receptor was more sensitive to the related formate than to the natural sex pheromone. A pheromone receptor from Heliothis virescens, HR13 ( = HvirOR13 showed a similar profile, with stronger responses elicited by a formate analog than to the natural sex pheromone, (11Z-hexadecenal thus suggesting this might be a common feature of moth pheromone receptors.

  13. Heterodimeric BMP-2/7 antagonizes the inhibition of all-trans retinoic acid and promotes the osteoblastogenesis.

    Directory of Open Access Journals (Sweden)

    Wenjuan Bi

    Full Text Available OBJECTIVES: Hypervitaminosis A and alcoholism can result in a low mineral density and compromised regenerative capacity of bone, thus delaying implant osteointegration. The inhibitory effect of all-trans retinoic acid on osteoblastogenesis is considered to be one of the mechanisms. We hypothesized that heterodimeric bone morphogenetic protein-2/7 could antagonize all-trans retinoic acid and enhance osteoblastogenesis, with an aim to accelerate and enhance bone regeneration and implant osteointegration. MATERIALS AND METHODS: We applied 5 ng/ml or 50 ng/ml bone morphogenetic protein-2/7 to restore the osteoblastogenesis of pre-osteoblasts (MC3T3-E1 cell line that was inhibited by 1 µM all-trans retinoic acid. We evaluated the efficacy by assessing cell numbers (proliferation, alkaline phosphatase activity (a marker for early differentiation, osteocalcin (a marker for late differentiation, calcium deposition (a marker for final mineralization and the expression of osteoblastogenic genes (such as Runx2, Collagen Ia, alkaline phosphatase and osteocalcin at different time points. RESULTS: All-trans retinoic acid significantly inhibited the expression of all the tested osteoblastogenic genes and proteins except alkaline phosphatase activity. In the presence of ATRA, 50 ng/ml bone morphogenetic protein-2/7 not only completely restored but also significantly enhanced all the osteoblastogenic genes and proteins. On the 28(th day, mineralization was completely inhibited by all-trans retinoic acid. In contrast, 50 ng/ml BMP-2/7 could antagonize ATRA and significantly enhance the mineralization about 2.5 folds in comparison with the control treatment (no ATRA, no BMP2/7. CONCLUSIONS: Heterodimeric bone morphogenetic protein-2/7 bears a promising application potential to significantly promote bone regeneration and implant osteointegration for the patients with hypervitaminosis A and alcoholism.

  14. 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.

  15. 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

  16. 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.

  17. Virulence of mixed fungal infections in honey bee brood

    Directory of Open Access Journals (Sweden)

    Vojvodic Svjetlana

    2012-03-01

    Full Text Available Abstract Introduction Honey bees, Apis mellifera, have a diverse community of pathogens. Previous research has mostly focused on bacterial brood diseases of high virulence, but milder diseases caused by fungal pathogens have recently attracted more attention. This interest has been triggered by partial evidence that co-infection with multiple pathogens has the potential to accelerate honey bee mortality. In the present study we tested whether co-infection with closely related fungal brood-pathogen species that are either specialists or non-specialist results in higher host mortality than infections with a single specialist. We used a specially designed laboratory assay to expose honey bee larvae to controlled infections with spores of three Ascosphaera species: A. apis, the specialist pathogen that causes chalkbrood disease in honey bees, A. proliperda, a specialist pathogen that causes chalkbrood disease in solitary bees, and A. atra, a saprophytic fungus growing typically on pollen brood-provision masses of solitary bees. Results We show for the first time that single infection with a pollen fungus A. atra may induce some mortality and that co-infection with A. atra and A. apis resulted in higher mortality of honey bees compared to single infections with A. apis. However, similar single and mixed infections with A. proliperda did not increase brood mortality. Conclusion Our results show that co-infection with a closely related fungal species can either increase or have no effect on host mortality, depending on the identity of the second species. Together with other studies suggesting that multiple interacting pathogens may be contributing to worldwide honey bee health declines, our results highlight the importance of studying effects of multiple infections, even when all interacting species are not known to be specialist pathogens.

  18. Inhibition of mitotic kinase Aurora suppresses Akt-1 activation and induces apoptotic cell death in all-trans retinoid acid-resistant acute promyelocytic leukemia cells

    Directory of Open Access Journals (Sweden)

    Long Zi-Jie

    2011-05-01

    Full Text Available Abstract Background Aurora kinase ensures accurate chromosome segregation during cell cycle, maintaining genetic integrity in cell division. VX-680, a small-molecule Aurora kinase inhibitor, interferes with mitotic entry and formation of bipolar spindles. Here, we evaluated VX-680 as a potential agent for treatment of all-trans retinoid acid (ATRA-resistant acute promyelocytic leukemia (APL in vitro. Methods CD11b expression was utilized to assess cell differentiation by flow cytometry. Immunofluorescence staining was conducted to analyze formation of cell monopolar spindle. Cell proliferation was evaluated by MTT assay. Sub-G1 population and Annexin V/PI staining were used to measure cell apoptosis. Hoechst 33342 staining was applied for identifying morphological changes in nucleus of apoptotic cell. Aurora-A (Aur-A activation and the signaling pathways involved in apoptosis were detected by Western blot. JC-1 probe was employed to measure mitochondrial depolarization. Results VX-680 inhibited Aur-A by reducing autophosphorylation at the activation site, Thr288, accompanied by producing monopolar mitotic spindles in APL cell line NB4-R2 that was resistant to ATRA. In addition, we found that VX-680 inhibited cell proliferation as assessed by MTT assay. Flow cytometry showed that VX-680 led to apoptotic cell death in both dose- and time-dependent manners by either Sub-G1 or Annexin V/PI analysis. Hoechst 33342 staining represented typical apoptotic cells with nuclear fragmentation in VX-680 treated cells. Importantly, VX-680 inhibition of Aurora kinase suppressed Akt-1 activation and induced mitochondrial depolarization, which eventually resulted in apoptosis by activation of caspase pathway, as indicated by increasing proteolytic cleavage of procaspase-3 and poly ADP ribose polymerase (PARP in NB4-R2 cells. Conclusions Our study suggested potential clinical use of mitotic Aurora kinase inhibitor in targeting ATRA-resistant leukemic cells.

  19. Planeamento de Marketing Territorial e Implementação da Marca Ericeira

    OpenAIRE

    Pedro, Vera

    2014-01-01

    Num mundo em constante mudança é fundamental a criação de valor e primar pela diferença. As necessidades do consumidor devem então ser uma prioridade. É essencial conseguir elevar as pequenas cidades e garantir que todos os seus recursos são aproveitados. O presente projeto teve como base uma abordagem turística, tendo o seu início numa pesquisa geral do turismo em Portugal e de seguida restringindo a informação para o local eleito, a Ericeira. O projeto pressupõe a atração de turistas para a...

  20. Characterization of total retinoid-like activity of compounds produced by three common phytoplankton species.

    Science.gov (United States)

    Sychrová, Eliška; Priebojová, Jana; Smutná, Marie; Nováková, Kateřina; Kohoutek, Jiří; Hilscherová, Klára

    2016-12-01

    Phytoplankton can produce various bioactive metabolites, which may affect other organisms in the aquatic environment. This study provides the first information on the total retinoid-like activity associated with both intracellular and extracellular metabolites produced by selected phytoplankton species that could play a role in teratogenic effects and developmental disruption in exposed organisms. The studied species included a coccoid cyanobacteria (Microcystis aeruginosa), a filamentous cyanobacteria (Aphanizomenon gracile) and a green alga (Desmodesmus quadricauda), all of which commonly occur in freshwater bodies in Europe. Methanolic extracts from cellular material and extracellular exudates were prepared from cultures cultivated in two light-intensity variants with five replicates for each species. The retinoid-like activity was evaluated by in vitro assays along with chemical analyses of two potent retinoic acids (all-trans retinoic acid (ATRA) and 9cis-RA). The mean total retinoid-like activity of metabolites produced by the three studied species representing different phytoplankton taxonomic groups ranged from 705 to 5572ng ATRA equivalent/g dry matter corresponding to 0.064-0.234ng ATRA/10(6) cells. Retinoid-like activity was found in the cellular extracts of all species, while only the extracellular exudates of cyanobacteria exhibited detectable activity (41-1081ng ATRA/L). The greatest extracellular as well as total (extra- and intra- cellular together) retinoid-like activity was detected for Microcystis aeruginosa. The two potent retinoic acids studied were more frequently detected in cellular extracts than in extracellular exudates of all species. Their contribution to observed in vitro effects was relatively low for all tested samples (<10%), indicating a substantial contribution of other retinoid-like compounds to the overall activity. The results indicate possible influence of light intensity and cell density on the production of metabolites with

  1. Cultivo de microalgas com vinhaça digerida anaerobiamente

    OpenAIRE

    Serejo, Mayara Leite

    2012-01-01

    A busca por energias alternativas como os bicombustíveis cresce a cada ano e tem atraído atenção de muitas grupos de pesquisa, ganhando destaque a produção de microalgas para obtenção de biodiesel ou biogás. A utilização de resíduos para o cultivo de microalgas pode ser uma alternativa vantajosa, visto que alguns efluentes contêm quantidades de nutrientes necessários ao crescimento das microalgas. Nesta pesquisa foram estudadas as condições ideais de cultivo de microalgas utilizando a vinhaça...

  2. Producción de hidrógeno por oxidación parcial de metano sobre espinelas de aluminato de níquel

    OpenAIRE

    Astobiza Tamame, Amaia

    2016-01-01

    [ES] Durante las últimas décadas, el hidrógeno ha atraído la atención tanto de gobiernos como de empresas debido al rápido desarrollo que las pilas de combustible han mostrado, principalmente por sus posibles aplicaciones en el sector automovilístico, periodo durante el cual prácticamente todos los fabricantes de vehículos han mostrado sus prototipos empleando pilas de combustible. No obstante, la obtención de hidrógeno puro para la alimentación de las pilas de combustible presenta un proble...

  3. 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.

  4. Hacia un studio aspectual contrastive entre el Esloveno y el Español

    Directory of Open Access Journals (Sweden)

    Jasmina Markič

    1991-12-01

    Full Text Available El tema del aspecto verbal ha suscitado un sinfín de opiniones, reflexiones, teorías, definiciones y ha atraído a numerosos lingüistas detodas las corrientes. A pesar de que se hayan propuesto últimamente diversas soluciones al problema y se haya buscado una metodología para estudiar el aspecto, en la mayoría de los casos no se trata de investigaciones generales sobre el aspecto como categoría lingüística universal sino de estudios del aspecto en determinadas lenguas.

  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. Lectura intercultural de 'Los días del venado' de Liliana Bodoc

    OpenAIRE

    Difabio de Raimondo, Elbia Haydée

    2002-01-01

    La cultura clásica, en especial la griega, a menudo y sostenidamente ha atraído a escritores mendocinos de cuna o por adopción. En ese marco, el presente trabajo explora primero rasgos de la épica helénica y luego analiza elementos de la cultura americana precolombina, en el tratamiento de personajes, intervención divina, sucesos, espacio y tiempo en Los días del venado, obra reconocida con el primer premio de la Fundación "El Libro" a la mejor publicación juvenil de 2000. ...

  7. 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

    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 ...

  8. Efeito na sobrevivência, crescimento e reservas corporais de Episyrphus balteatus (De Geer) (Diptera: Syrphidae), de cinco espécies da família Asteraceae

    OpenAIRE

    2012-01-01

    A dependência dos sirfídeos adultos por pólen e néctar aumenta o potencial para o estabelecimento de flores no ecossistema olivícola e, desta forma, contribui para o incremento da luta biológica contra o algodão-da-oliveira, Euphyllura olivina Costa. A família das Asteraceae é uma das mais referenciadas em termos de preferências alimentares por parte dos sirfídeos, sendo a facilidade de acesso ao recurso floral e a sua fisionomia as principais responsáveis desta atração. Nes...

  9. Reflexiones preliminares sobre la responsabilidad por daños ambientales

    OpenAIRE

    Rodríguez, Gloria Amparo; Vargas-Chaves, Iván

    2015-01-01

    [ES]Aunque la problemática de los daños ambientales ha atraído el interés sustancial de profesionales y académicos de diversas disciplinas, los motivos que impulsan esas prácticas han recibido poca atención en la literatura jurídica colombiana. Especialmente desde la perspectiva de la responsabilidad. Este capítulo presenta unas reflexiones preliminares de la responsabilidad por daños ambientales, para introducir el estudio de diversos temas, hacia una construcción doctrinal enmarcada no sólo...

  10. Efeito do resfriamento sobre a textura post-mortem da carne do Matrinxã Brycon cephalus (Pisces: Characiforme)

    OpenAIRE

    Mahecha, Hector Suarez

    2002-01-01

    Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Agrárias. Programa de Pós-Graduação em Ciências dos Alimentos. O amolecimento da carne dos peixes, post-mortem, é um fator de qualidade diretamente influenciado pelas características dos tipos de colágenos presentes em cada espécie. A degradação do colágeno está relacionada com a armazenagem dos peixes sob resfriamento. Algumas pesquisas têm demonstrado, através de testes bioquímicos e, principalmente, atra...

  11. Despertando la curiosidad por las ciencias y la tecnología

    Directory of Open Access Journals (Sweden)

    E. García-Rubio

    2017-01-01

    Full Text Available Dado que la demanda de profesionales en el sector de las ciencias, tecnología, ingeniería y matemáticas aumenta, en este artículo expondremos la participación de los alumnos en concursos como una forma de hacer que se sientan más atraídos por la Ciencia y la Tecnología. Simultáneamente se cumple con el desarrollo de las competencias clave que por ley se deben desarrollar en la Educación Secundaria.

  12. Salud, salud mental y musicoterapia comunitaria en población revitalizada (reetnizada) indígena colombiana: el caso de la comunidad muisca de cota, 2012-2014

    OpenAIRE

    Morales Hernández, Leonardo A.

    2015-01-01

    El abordaje intercultural hacia las comunidades amerindias requiere el conocimiento específico del significado que tienen para ellos los conceptos, las prácticas comunitarias asociadas y las costumbres, particularmente en la salud y la salud mental. La comunidad muisca de Cota, Cundinamarca, es un grupo humano con características específicas dentro de su propia historia, que ha estado expuesto a diferentes circunstancias adversas y fenómenos de aculturación; esta comunidad actualmente atra...

  13. Eficácia de atrativos alimentares na captura de moscas-das-frutas em pomar de citros

    OpenAIRE

    Raga, Adalton; Machado,Rogério Amaro; Dinardo,Welci; Strikis,Pedro Carlos

    2006-01-01

    As moscas-das-frutas (Diptera: Tephritoidea) são importantes pragas de frutas cítricas no Estado de São Paulo, principalmente Anastrepha fraterculus (Wied.) e Ceratitis capitata (Wied.). O objetivo deste estudo foi medir a eficiência dos atrativos alimentares para monitoramento de moscas-das-frutas, em pomar de citros. O delineamento experimental adotado foi de blocos ao acaso com cinco tratamentos e cinco repetições. O ensaio foi instalado em 30/9/2003 e desenvolvidopor nove semanas. Os atra...

  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. CONTRIBUTIONS TO THE KNOWLEDGE OF THE SPECIES OF BEETLES (INSECTA: COLEOPTERA FROM WHEAT CROP

    Directory of Open Access Journals (Sweden)

    Mihai Tălmaciu

    2016-07-01

    Full Text Available This paper presents the species of beetles (Insecta: Coleoptera between in wheat crops from Tişiţa, in Vrancea county. The observations were made in a crop of wheat in 2013, who were placed the soil traps type Barber, during the two months, May and June. It was used three variants: • Variant 1 - consumption wheat untreated • Variant 2 - consumption wheat treaty • Variant 3 - treated wheat seed The gathering of samples from the traps was done periodically, every 12-15 days. The most species frequent gathered was: Pentodon idiota, Epicometis hirta, Opatrum sabulosum, Phyllotreta atra, Phyllotreta nemorum, Tanymecus dilaticollis.

  16. Nuestro único problema

    Directory of Open Access Journals (Sweden)

    Héctor Rojas Herazo

    1967-12-01

    Full Text Available Toda vida humana por ser, en profundidad y superficie, una batalla contra la muerte, es un fenómeno epopéyico. Más admirable cuanto más secreta y personal sea esa batalla. Pues no nos enfrentamos a este o aquel obstáculo ni somos atraídos por este o aquel señuelo. Nuestra íntima preocupación, nuestro único problema, nuestro máximo terror es sabernos materia de disolución, míseras astillas para alimentar el insaciable fuego de la muerte.

  17. [Sense organs on palps and fore tarsi of gamasid mites (Parasitiformes, Rhinonyssidae), parasites of the nasal cavity of the great tit, the rock dove, and the Eurasian coot].

    Science.gov (United States)

    Leonovich, S A; Dimov, I

    2012-01-01

    The main sensory organs (the palpal organ and the tarsal sensory complex) were examined by scanning electron microscopy method in parasites of the nasal cavity of the great tit Parus major (Ptilonyssus sairae, Ptilonyssus pari), the rock dove Columba livia (Mesonyssus melloi), and the Eurasian coot Fulica atra (Rallinyssus caudistigmus). It was shown that differences in the topography of sensilla within the tarsal complex correspond to the taxonomic relations between species and genera, whereas differences in the structure of the palpal organ are not associated with the taxonomy and, probably, reflect ecological peculiarities of parasitism.

  18. Ecos lorquianos en seis dramaturgas españolas contemporáneas: una mirada intertextual

    OpenAIRE

    Boo Tomás, Sara

    2016-01-01

    [spa] El presente estudio muestra de qué manera la tragedia simbolista de Federico García Lorca -nos referimos a Bodas de sangre, Yerma, La casa de Bernarda Alba y Doña Rosita la soltera- sigue presente en la dramaturgia femenina española contemporánea. Con el propósito de crear un diálogo intertextual que nos permita ver en qué medida estas obras influyen en seis textos teatrales pertenecientes a la escena española más reciente: El color de agosto, 1987, de Paloma Pedrero (1957); Atra bilis ...

  19. Iodinated (Perfluoro)alkyl Quinoxalines by Atom Transfer Radical Addition Using ortho-Diisocyanoarenes as Radical Acceptors.

    Science.gov (United States)

    Leifert, Dirk; Studer, Armido

    2016-09-12

    A simple method for the preparation of functionalized quinoxalines is reported. Starting from readily accessible ortho-diisocyanoarenes and (perfluoro)alkyl iodides, the quinoxaline core is constructed during (perfluoro)alkylation by atom transfer radical addition (ATRA), resulting in 2-iodo-3-(perfluoro)alkylquinoxalines. The radical cascades are readily initiated either with visible light or by using α,α'-azobisisobutyronitrile (AIBN). The heteroarene products are obtained in high yields (up to 94 %), and the method can be readily scaled up. Useful follow-up chemistry documents the value of the novel radical quinoxaline synthesis.

  20. 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.

  1. FORMULACIÓN, EVALUACIÓN ORGANOLÉPTICA Y FÍSICO-QUÍMICA DE UNA MERMELADA MIXTA A BASE DE LOCHE (Cucurbita maxima Dutch) Y MARACUYÁ (Passiflora edulis)

    OpenAIRE

    Barrientos Jiménez, Nora Elizabeth; Universidad Señor de Sipán

    2015-01-01

    En la actualidad, existen en el mercados muchas variedades y marcas de mermeladas, las cuales han incrementado su demanda, debido a la amplia variedad de sabores y a su vez el productor ofrece ahora una mermelada con mayor valor nutritivo; y cada vez el consumidor se ve atraído por su consumo de preferencia en épocas de invierno. El presente trabajo representa una alternativa agradable, útil y genera un valor agregado al loche que a la fecha sólo se conoce su aplicación en la gastronomía; al ...

  2. 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...

  3. Caracterização de terminadores e promotores para otimização do fluxo metabólico de xilose em Saccharomyces cerevisiae linhagem industrial PE-2 : Characterization of promoters and terminators to optimize the metabolic flux of xylose in Saccharomyces cerevisiae industrial strain PE-2

    OpenAIRE

    Gabriel Vieira Santello

    2016-01-01

    Avanços biotecnológicos introduziram recentemente mudanças em muitos setores da indústria a fim de promover o uso de recursos renováveis para produzir moléculas de relevância econômica, tais como o etanol. O uso de biomassa vegetal para a produção de combustíveis renováveis tem atraído muita atenção, mas a viabilidade de tal processo depende do desenvolvimento de organismos geneticamente modificados capazes de consumir eficientemente açúcares de 5 carbonos abundantes nesse material e tolerar ...

  4. Desarrollo de métodos numérico-interpretativos para la realización de ensayos de bombeo

    OpenAIRE

    López García, José María

    2016-01-01

    Los ensayos de bombeo son, sin lugar a dudas, una de las pruebas más fiables y de mayor interés que se hacen en el medio físico. No son pruebas estrictamente puntuales, dado que el bombeo atrae flujo desde distancias lejanas al pozo, la prueba tiene una excelente representatividad espacial. Los métodos de interpretación mediante ensayos de bombeo se empezaron a plantear en la primera mitad del pasado siglo. Con los ensayos de bombeo se puede calcular la transmisividad y coeficiente de almace...

  5. Applications of entropy on financial markets

    OpenAIRE

    STOSIC, Darko

    2016-01-01

    Nos últimos anos, mercados financeiros têm cada vez atraído mais atenção entre físicos, cientistas da computação e outros pesquisadores dedicados a estudos de sistemas complexos, devido ao seu comportamento fenomenológico que torna a previsão de causa-efeito extremamente difícil. Como resultado, uma área interdisciplinar de pesquisa, chamada "econofísica", surgiu para complementar métodos tradicionais da estatística e econometria, desenvolvendo técnicas com origem na física est...

  6. Study on the inhibitory effects and related toxicity of all-trans-retinoic acid combined with arsenic trioxide on transplanted tumor of human bladder neoplasms in nude mice%全反式维甲酸联合三氧化二砷抗膀胱癌作用及其毒副作用的实验研究

    Institute of Scientific and Technical Information of China (English)

    周振玉; 张永; 陈家存

    2011-01-01

    目的 观察全反式维甲酸(ATRA)联合三氧化二砷(As2 O3)对膀胱癌细胞株BIU-87裸鼠移植瘤生长的抑制作用,及其毒副作用。方法建立人膀胱癌裸鼠皮下移植瘤模型40只,随机等分为4组:对照组,ATRA组,As2 O3组,ATRA和As2O3联合用药组;裸鼠瘤体内连续注射用药14d。停药后48 h检测血常规和肝、肾功能;处死裸鼠,测量移植瘤体积、重量,计算抑瘤率;移植瘤及心、肝、肾等组织HE染色,观察其病理变化;瘤组织免疫组化S-P法检测血管内皮生长因子(VEGF)表达、CD43标记的微血管密度MVD的表达。结果与对照组比较,As2 O3组及ATRA组移植瘤生长明显受到抑制(质量抑瘤率分别为43.77%,41.82%),两者联合用药后,抑制作用显著增强(质量抑瘤率为68.55%),抑瘤率差异具有统计学意义(x2 =26.81,P<0.01);As2O3组、ATRA组、联合用药组均不同程度下调VEGF表达(OD值分别为27.33±2.17,20.72±2.01,19.23±2.32,17.16±1.59)及MVD的表达(OD值分别为141.12±8.38,43.39±7.41,44.77±8.25,30.56±7.71),联合用药组下调最显著;各用药组均出现轻度白细胞抑制(t =3.16,3.08,3.37,P<0.01),联合用药组抑制程度与单一用药组比较差异无统计学意义(P>0.05),肝、肾功能各指标比较差异均无统计学 意义(P>0.05)。结论ATRA联合As2 O3在体内能够协同抑制膀胱癌BIU-87细胞移植瘤的生长和血管生成,仅有白细胞轻度抑制,对肝肾功能无毒副作用。%Objective To investigate the inhibitory effects and related toxicity of all-trans-retinoic acid(ATRA) combined with arsenic trioxide(As2O3) on transplanted human bladder neoplasms in nude mice.Methods The subcutaneously transplanted tumor models of human bladder neoplasms in nude mice were established and then it was randomly divided into four teams: Saline group, ATRA group, As2 O3 group and the combination of ATRA and As2 O3 group.Each group

  7. Parasitoid wasps (Hymenoptera from puparia of sarcosaprophagous flies (Diptera: Calliphoridae; Sarcophagidae in Buenos Aires, Argentina

    Directory of Open Access Journals (Sweden)

    Adriana OLIVA

    2008-01-01

    Full Text Available Se registró la emergencia de parasitoides (Hymenoptera de crías experimentales de Diptera sarcosaprófagas (Calliphoridae, Sarcophagidae, atraídas a cebos de carne bovina, en Buenos Aires (Argentina durante 1998-2003. Se determinaron cuatro taxones: Tachinaephagus zealandicus Ashmead (Encyrtidae, Brachymeria podagrica (Fabricius (Chalcididae, Nasonia vitripennis (Walker (Pteromaliidae y Alysia sp. (Braconidae: Alysiinae. Sólo las dos primeras especies resultaron abundantes en todos los años. Se ha graficado el número total de emergencias de cada especie para cada mes, junto con las temperaturas promedio máxima y mínima.

  8. New records of Helophoridae, Hydrochidae, and Hydrophilidae (Coleoptera) from New Brunswick, Canada

    Science.gov (United States)

    Webster, Reginald P.; Sweeney, Jon D.

    2016-01-01

    Abstract The following three species of Helophoridae are newly recorded for New Brunswick, Canada: Helophorus (Kyphohelophorus) turberculatus Gyllenhal, Helophorus (Rhopaleloporus) oblongus LeConte, Helophorus (Rhopaleloporus) marginicollis Smetana. Hydrochus subcupreus Randall, family Hydrochidae, and the following 15 species of Hydrophilidae are newly reported for the province: Berosus fraternus LeConte, Berosus peregrinus (Herbst), Berosus sayi Hansen, Paracymus despectus (LeConte), Chaetarthria atra (LeConte), Cymbiodyta acuminata Fall, Cymbiodyta blanchardi Horn, Cymbiodyta minima Notman, Enochrus (Lumetus) hamiltoni Horn, Enochrus (Methydrus) consors (LeConte), Enochrus (Methydrus) consortus Green, Enochrus (Methydrus) pygmaeus nebulosus (Say), Cercyon (Cercyon) cinctus Smetana, Cercyon (Cercyon) herceus frigidus Smetana, Cercyon (Dicyrtocercyon) ustulatus (Preyssler). PMID:27110166

  9. Avances en el tratamiento de los pacientes con Leucemia Promielocítica Aguda en Recaída

    OpenAIRE

    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).

  10. Bacteriocinas: sustituto de preservantes tradicionales en la industria alimentaria

    OpenAIRE

    Carolina Rojas; Pedro Vargas

    2008-01-01

    Durante los últimos años, el consumidor se ha vuelto más exigente en cuanto a calidad y expectativas de un producto saludable y fresco. Para satisfacer al consumidor es necesario investigar y encontrar opciones que permitan obtener alimentos que ofrezcan características interesantes, como es el caso de alimentos donde la tendencia es eliminar el uso de preservantes y obtener productos más naturales. Las bacteriocinas han atraído la atención como sustituto potencial de compuestos preservantes ...

  11. Aspectos de la construcción del conocimiento sobre la sociedad

    OpenAIRE

    Delval, Juan

    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...

  12. 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...

  13. 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.

  14. Massive pulmonary embolism at the onset of acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Federica Sorà

    2016-07-01

    Full Text Available Life-threatening bleeding is a major and early complication of acute promyelocytic leukemia (APL, but in the last years there is a growing evidence of thromboses in  APL. We report the first case of a young woman with dyspnea as the first symptom of APL due to massive pulmonary embolism (PE successfully treated with thrombolysis for PE and heparin. APL has been processed with a combination of all-trans retinoic acid (ATRA and arsenic trioxide (ATO obtaining complete remission.

  15. A new efficient pose estimation and tracking method for personal devices : application to interaction in smart spaces

    OpenAIRE

    Li, Juan

    2016-01-01

    Esta tesis aborda la estimación y el seguimiento de posición y orientación de los dispositivos personales con seis grados de libertad (6-GdL) y las aplicaciones en espacios inteligentes. Este problema ha atraído la atención de industrias e investigadores de diversos campos, tales como los espacios inteligentes, la robótica, el seguimiento en interiores y la Realidad Aumentada. Además, se discute el problema relevante de la selección de la cámara en un sistema con múltiples cámaras, ya que es ...

  16. Paisajes migratorios en la Región de Murcia: territorio y ciudad en los flujos contrapuestos norte-sur (turismo residencial) y sur-norte (migración laboral)

    OpenAIRE

    2013-01-01

    El fenómeno de las migraciones contemporáneas asume en el área mediterránea unas características propias, pues al tiempo que se registra la afluencia de contingentes procedentes de África y América asociados a actividades productivas, también se producen importantes aportes de la Europa occidental que son atraídos por el turismo residencial. Estos flujos, de características socioeconómicas y culturales tan diferentes, coinciden en un mismo contexto territorial y provocan procesos urbanos y ar...

  17. Acute myocardial/cerebral infarction as first/relapse manifestation in one acute promyelocytic leukemia patient.

    Science.gov (United States)

    Li, Ying; Suo, Shanshan; Mao, Liping; Wang, Lei; Yang, Chunmei; Xu, Weilai; Lou, Yinjun; Mai, Wenyuan

    2015-01-01

    In the clinical setting, bleeding is a common manifestation of acute promyelocytic leukemia (APL), whereas thrombosis is relatively rare, especially as an initial symptom. Here, we report an unusual case of APL with acute myocardial infarction as the first manifestation and cerebral infarction as the relapse manifestation in a healthy young woman. This unique case emphasizes that a thrombotic event could be the first manifestation of an underlying hematological disorder such as APL and could also be a sign of relapse. Rapid detection of the underlying disorder and the timely use of anticoagulation therapy and ATRA are crucial for preventing further deterioration of the disease and saving the patient's life.

  18. 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...

  19. "¿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...

  20. INTRODUÇÃO À DIVISÃO 3-TRICOTÔMICA DE SIGNOS

    OpenAIRE

    Queiroz, João; FEEC/UNICAMP

    2011-01-01

    C.S.Peirce desenvolveu, por mais de 40 anos, entre 1865 e 1911, baseado em uma teoria lógica-fenomenológica de categorias, diversas “classificações de signos”. Estas classificações tem atraído e desafiado, por décadas, gerações de pesquisadores e muitas comunidades de linguistas e semioticistas. O propósito deste artigo é apresentar, introdutoriamente, uma de suas mais elaboradas classificações – as dez classes de signos.

  1. Inhibition of fat cell differentiation in 3T3-L1 pre-adipocytes by all-trans retinoic acid: Integrative analysis of transcriptomic and phenotypic data

    Directory of Open Access Journals (Sweden)

    Katharina Stoecker

    2017-03-01

    Full Text Available The process of adipogenesis is controlled in a highly orchestrated manner, including transcriptional and post-transcriptional events. In developing 3T3-L1 pre-adipocytes, this program can be interrupted by all-trans retinoic acid (ATRA. To examine this inhibiting impact by ATRA, we generated large-scale transcriptomic data on the microRNA and mRNA level. Non-coding RNAs such as microRNAs represent a field in RNA turnover, which is very important for understanding the regulation of mRNA gene expression. High throughput mRNA and microRNA expression profiling was performed using mRNA hybridisation microarray technology and multiplexed expression assay for microRNA quantification. After quantitative measurements we merged expression data sets, integrated the results and analysed the molecular regulation of in vitro adipogenesis. For this purpose, we applied local enrichment analysis on the integrative microRNA-mRNA network determined by a linear regression approach. This approach includes the target predictions of TargetScan Mouse 5.2 and 23 pre-selected, significantly regulated microRNAs as well as Affymetrix microarray mRNA data. We found that the cellular lipid metabolism is negatively affected by ATRA. Furthermore, we were able to show that microRNA 27a and/or microRNA 96 are important regulators of gap junction signalling, the rearrangement of the actin cytoskeleton as well as the citric acid cycle, which represent the most affected pathways with regard to inhibitory effects of ATRA in 3T3-L1 preadipocytes. In conclusion, the experimental workflow and the integrative microRNA–mRNA data analysis shown in this study represent a possibility for illustrating interactions in highly orchestrated biological processes. Further the applied global microRNA–mRNA interaction network may also be used for the pre-selection of potential new biomarkers with regard to obesity or for the identification of new pharmaceutical targets.

  2. Assessment of neuromuscular fatigue by frequency analysis of the electromyographic signal of the control subjects and patients suffering from temporomandibular disorders treated with occlusal splints resilient and rigid

    OpenAIRE

    2012-01-01

    A incapacidade de produzir repetidamente no tempo um determinado nível de força ou potência muscular designa-se por fadiga neuromuscular. A etiologia da fadiga muscular tem atraído o interesse de pesquisadores há mais de um século. Contudo, os seus agentes e locais definitivos permanecem ainda por serem identificados. Este trabalho teve por objetivo avaliar a fadiga neuromuscular por meio da análise de frequência do sinal eletromiográfico dos músculos masseter e temporal anterior de ambos os ...

  3. Comportamiento del mercado turístico extranjero en el Caribe Mexicano

    OpenAIRE

    Güemes-Ricalde, Dr. Francisco J.; Lic. Norman J. Correa-Ruiz,

    2009-01-01

    El Caribe mexicano atrae visitantes de regiones distintas en diferentes épocas del año. A los prestadores de servicios turísticos les resulta difícil conocer y separar las preferencias de actividades que realizan los visitantes de cada país. Arriban visitantes mexicanos y extranjeros, las preferencias de estos últimos en relación a la demanda de servicios son diferentes. Contrario a lo que se conocía, el estudio de mercado determinó que la demanda mexicana representa un mercado importante en ...

  4. ロペ・デ・アギーレの表象をめぐって

    OpenAIRE

    2012-01-01

    Parece que el tema de Lope de Aguirre les atrae tanto a los novelistas como a los cineastas, ya que hay varias obras con ese tema en ambos campos artísticos tales como La aventura equinoccial de Ramón José Sender, Lope de Aguirre, príncipe de la libertad de Miguel Otero Silva, Aguirre, Der Zorn Gottes de Werner Herzog, o El Dorado de Carlos Saura. Entre ellas la novela de Miguel Otero Silva se destaca por su estilo experimental similar al de la nueva novela histórica, aunque Seymour Menton no...

  5. Sistema de gestão e auditoria fiscal na nuvem

    OpenAIRE

    Rolo, Luís Carlos Pereira

    2016-01-01

    A evolução da computação na nuvem tem crescido nos últimos anos e por conseguinte, tem também atraído muitos utilizadores e empresas. De tal forma que, existem cada vez mais aplicações na nuvem e serviços disponibilizados por este tipo de infraestruturas, a custos razoáveis, sobretudo baseados no custo de utilização dos recursos elásticos da nuvem consoante a sua necessidade e quantidade. Isto advém devido estes serem aprovisionados mediante solicitação. A grande capacidade de armazenamento, ...

  6. 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...

  7. 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.

  8. Infraestructura pública y precios de vivienda: Una aplicación de regresión geográficamente ponderada en el contexto de precios hedónicos

    OpenAIRE

    Duque, Juan C.; Velasquez, E.; Agudelo, J.

    2012-01-01

    El análisis de las externalidades en el sector inmobiliario ha atraído desde hace varios años la atención de los investigadores suscitando una gran cantidad de estudios al respecto. En este artículo se utilizan modelos econométricos tradicionales, de la econometría espacial y de regresión ponderada geográficamente, para analizar y comparar a la luz de estos modelos la influencia que tiene en los precios de las viviendas la existencia de una estación del metro en San Javier ubicada en el centr...

  9. Arboviroses em primatas não humanos capturados em Mato Grosso do Sul

    OpenAIRE

    2011-01-01

    No período de fevereiro a setembro de 2010 foram realizados inquéritos soro- epidemiológico em primatas não humanos e captura de vetores transmissores, com o intuito de investigar a possível circulação de arboviroses nos municípios de Bonito, Campo Grande e Jardim, no estado do Mato Grosso do Sul, Brasil. Foram utilizados 65 primatas de vida livre e de cativeiro e potenciais vetores, utilizando capturados de Castro, atração humana e puçás. As amostras séricas foram testadas pel...

  10. USO DE ATRAYENTES Y SUPLEMENTOS ALIMENTICIOS PARA EL INCREMENTO DE DEPREDADORES DE ESCAMA BLANCA DEL MANGO, AULACASPIS TUBERCULARIS NEWSTEAD (HEMIPTERA: DIASPIDIDAE)

    OpenAIRE

    Luis Martín HERNÁNDEZ-FUENTES; Mario Alfonso URÍAS-LÓPEZ; José Isabel LÓPEZ ARROYO; Jaime Gustavo LÓPEZ ARRIAGA

    2012-01-01

    El mango es un cultivo importante en México, en años recientes se ha observado un incremento poblacional de Aulacaspos tubercularis en este frutal. Se evaluaron atrayentes y suplementos alimenticios para retener y/o atraer depredadores de A. tubercularis en dos ciclos de producción (2009- 2010). Se observó mayor efecto de tratamientos en la variable huevos de Ceraeochrysa con el uso de 0.25 mL de salicilato de metilo (SM) por árbol. Adultos de Pentilia fueron ligeramente atraídos con las dife...

  11. Trombose arterial em leucemia promielocítica aguda Arterial thrombosis in acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Sonia Regina Iantas

    2007-12-01

    Full Text Available Acute promyeloclocytic leukemia can present coagulopathies which are frequently very serious due to hemorrhagic conditions. Treatment using anthracyclines and retinoids provide a good response. The development of arterial thrombosis is uncommon. In this work a 56-year-old male patient with acute arterial insufficiency was evaluated. This patient was immediately submitted to thromboembolectomy with the removal of a white thrombus. Postoperative tests showed acute promyelocytic leukemia with transposition (15;17 Treatment with ATRA and Idarubicin chemotherapy was initiated with the patients's response being satisfactory. Currently, the patient is incomplete remission and a recent cytogenetics test does not show the t(15;17.

  12. PARACIUDADES. Rompiendo tabúes en búsqueda de una renovación urbana.

    OpenAIRE

    Carlos Medellín

    2015-01-01

    ¿Qué pasaría si los pensamientos y anhelos de los ciudadanos comenzaran a ser expresados libremente y, de este modo, permitir que todos seamos atraídos o convertidos en atracción, rompiendo los tabúes sobre la forma de abordar al extraño y al desconocido? ¿Qué pasaría si los ciudadanos tuviésemos acceso a una superficie reactiva al aire libre, pero que opera bajo nuestro propio control? El objetivo de esta iniciativa es utilizar y explorar la ciudad de otra manera al hacer evidente lo q...

  13. Un nuevo virus A/H1N1, una nueva pandemia: Influenza un riesgo permanente para una humanidad globalizada

    OpenAIRE

    2014-01-01

    La influenza es una enfermedad altamente infectocontagiosa de la cual se tienen registros históricos descriptivos desde la época griega y de certeza etiológica tan solo hace casi ocho décadas atras. Su agente causal es el virus del influenza de los que se conoce exiten tres grandes tipos: A B y C. El tipo A tiene la propiedad de circular por diversos reservorios biológicos, tales como el hombre, los cerdos y las aves, entre otros. Representa además una elevada variabilidad g...

  14. What's behind the word? Assay for nonconformity

    OpenAIRE

    Jaime Torres

    2008-01-01

    El valor, sentido, uso y significado que tiene la palabra pueden ser ubicados en un escenario multidireccional: en el plano de lo real o en el plano de lo simbólico; en el uso práctico o en la imaginación; en el hacer y en el desear. La palabra nos ha conducido en la historia por el misticismo (la magia), por la verdad de las cosas (la ciencia), por ello es que nos provoca inquietud y nos atrae; toda palabra genera sospecha, sorprende, domina, ilusiona, entristece y libera; sin ella no podemo...

  15. Uma aplicação das tecnicas de preferencia declarada ao setor hoteleiro de Florianopolis

    OpenAIRE

    May, Gabriela de Oliveira

    1996-01-01

    Dissertação (mestrado) - Universidade Federal de Santa Catarina. Centro Tecnologico As técnicas de preferência declarada têm sido utilizadas em diversas áreas como forma de avaliar as preferências dos indivíduos por produtos e serviços. Constituem-se em técnicas atuais empregadas para estudos de marketing e transporte. Conhecendo as preferências dos clientes, um hotel tem condições de elaborar estratégias de atração mais adequadas às aspirações do segmento atendido, investindo em atributos...

  16. A review of the genus Minthodes Brauer & Bergenstamm (Diptera: Tachinidae) in Iran, with the description of a new species.

    Science.gov (United States)

    Gilasian, Ebrahim; Ziegler, Joachim; Parchami-Araghi, Mehrdad

    2016-10-04

    Minthodes susae Gilasian & Ziegler sp. nov. (Diptera: Tachinidae), from southwestern Iran, is described and illustrated, and compared with M. brevipennis (Brauer & Bergenstamm) from Turkey. A lectotype is recognised for Pseudomintho brevipennis Brauer & Bergenstamm (currently a species of Minthodes) and its designation is attributed to Mesnil. Minthodes pictipennis Brauer & Bergenstamm is newly recorded from Iran and Turkey, and M. latifacies Herting is reported from Iran for the first time. An identification key to the four Minthodes Brauer & Bergenstamm species known to occur in Iran is provided. Finally, new data are given on the intraspecific variation of Minthodes atra (Kugler).

  17. La reputación en centros concertados de educación en la Región de Murcia

    OpenAIRE

    Zapata Conesa, Juan

    2011-01-01

    El objeto del presente trabajo es un estudio a nivel teórico y empírico sobre la reputación en centros concertados de educación en la Región de Murcia. Estudiaremos en primer lugar el concepto de activo intangible, cuyo valor no aparece en los registros contables de las empresas, para posteriormente definir qué es la reputación corporativa y sus principales características. La reputación empresarial pese a que está configurada por múltiples dimensiones ha atraído la atención...

  18. Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells.

    Science.gov (United States)

    Sun, Rong; Liu, Yang; Li, Shi-Yong; Shen, Song; Du, Xiao-Jiao; Xu, Cong-Fei; Cao, Zhi-Ting; Bao, Yan; Zhu, Yan-Hua; Li, Ya-Ping; Yang, Xian-Zhu; Wang, Jun

    2015-01-01

    Combination treatment through simultaneous delivery of two or more drugs with nanoparticles has been demonstrated to be an elegant and efficient approach for cancer therapy. Herein, we employ a combination therapy for eliminating both the bulk tumor cells and the rare cancer stem cells (CSCs) that have a high self-renewal capacity and play a critical role in cancer treatment failure. All-trans-retinoic acid (ATRA), a powerful differentiation agent of cancer stem cells and the clinically widely used chemotherapy agent doxorubicin (DOX) are simultaneously encapsulated in the same nanoparticle by a single emulsion method. It is demonstrated that ATRA and DOX simultaneous delivery-based therapy can efficiently deliver the drugs to both non-CSCs and CSCs to differentiate and kill the cancer cells. Differentiation of CSCs into non-CSCs can reduce their self-renewal capacity and increase their sensitivity to chemotherapy; with the combined therapy, a significantly improved anti-cancer effect is demonstrated. Administration of this combinational drug delivery system can markedly augment the enrichment of drugs both in tumor tissues and cancer stem cells, prodigiously enhancing the suppression of tumor growth while reduce the incidence of CSC in a synergistic manner.

  19. DIFFERENTIATION SYNDROME IN PROMYELOCYTIC LEUKEMIA : CLINICAL PRESENTATION, PATHOGENESIS AND TREATMENT

    Directory of Open Access Journals (Sweden)

    Eduardo Magalhães Rego

    2011-10-01

    Full Text Available Differentiation syndrome (DS represents a life-threatening complication in patients with acute promyelocytic leukemia (APL undergoing induction therapy with all-trans retinoic acid (ATRA or arsenic trioxide (ATO. It affects about 20-25% of all patients and there are no definitive diagnostic criteria. Clinically, DS is characterized by weight gain, fever not attributable to infection, respiratory distress, cardiac involvement, hypotension, and/or acute renal failure. At the histological point of view, there is an extensive interstitial and intra-alveolar pulmonary infiltration by maturing myeloid cells, endothelial cell damage, intra-alveolar edema, inter-alveolar hemorrhage, and fibrinous exsudates. DS pathogenesis is not completely understood, but it is believed that an excessive inflammatory response is the main phenomenon involved, which results in increased production of chemokines and expression of adhesion molecules on APL cells. Due to the high morbidity and mortality associated with DS, its recognition and the prompt initiation of the treatment is of utmost importance. Dexamethasone is considered the mainstay of treatment of DS, and the recommended dose is 10 mg twice daily by intravenous route until resolution of DS. In severe cases (respiratory or acute renal failure it is recommended the discontinuation of ATRA or ATO until recovery.

  20. Marketing vivencial: o caso de eventos musicais no shopping.

    Directory of Open Access Journals (Sweden)

    Ana Akemi Ikeda

    2005-12-01

    Full Text Available À medida que o mercado de shopping centers vem crescendo no Brasil e tornando-se cada vez mais competitivo, gerar fluxo de freqüentadores torna-se uma tarefa, cada vez mais, desafiadora. Diante deste cenário, o objetivo neste artigo é estudar a experiência proporcionada por eventos musicais em shopping. Para isso, além de pesquisa bibliográfica sobre o assunto, foi analisado um projeto de shows musicais realizado pelo Shopping Anália Franco, em São Paulo, que visava a melhorar a atração de visitantes, permanência do público no local e impacto nas vendas. O trabalho foi complementado com uma pesquisa de campo com os freqüentadores dos shows musicais. Os resultados mostraram que esse tipo de experiência pode beneficiar o estabelecimento em termos de maior simpatia e satisfação do público, melhoria de imagem, atração de novos consumidores, aumento do fluxo de visitantes e do volume de vendas.

  1. 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.

  2. 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.

  3. Retinoids and nuclear retinoid receptors in white and brown adipose tissues: physiopathologic aspects.

    Science.gov (United States)

    Flajollet, Sébastien; Staels, Bart; Lefebvre, Philippe

    2013-08-01

    Vitamin A, ingested either as retinol or β-carotene from animal- or plant-derived foods respectively, is a nutrient essential for many biological functions such as embryonic development, vision, immune response, tissue remodeling, and metabolism. Its main active metabolite is all trans-retinoic acid (atRA), which regulates gene expression through the activation of α, β, and γ isotypes of the nuclear atRA receptor (RAR). More recently, retinol derivatives were also shown to control the RAR activity, enlightening the interplay between vitamin A metabolism and RAR-mediated transcriptional control. The white and brown adipose tissues regulate the energy homeostasis by providing dynamic fatty acid storing and oxidizing capacities to the organism, in connection with the other fatty acid-consuming tissues. This concerted interorgan response to fatty acid fluxes is orchestrated, in part, by the endocrine activity of the adipose tissue depots. The adipose tissues are also sites for synthesizing and storing vitamin A derivatives, which will act as hormonal cues or intracellularly to regulate essential aspects of adipocyte biology. As agents that prevent adipocyte differentiation hence, expected to decrease fat mass, and inducers of uncoupling protein expression, thus, favoring energy expenditure, retinoids have prompted many investigations to decipher their roles in adipose tissue pathophysiology, which are summarized in this review.

  4. Treatment of acute promyelocytic leukemia during pregnancy.

    Science.gov (United States)

    Yang, Daisy; Hladnik, Lindsay

    2009-06-01

    Management of the pregnant patient with acute promyelocytic leukemia (APL) is a challenge. Immediate treatment of APL is critical, as it is an oncologic emergency, with a high risk of morbidity and mortality associated with disseminated intravascular coagulation. However, administration of chemotherapy and differentiating agents in pregnancy is controversial because of potential teratogenic effects. In addition, complications associated with APL, including retinoic acid syndrome, add to the complexity of management. To better understand how to manage this complex patient care situation, we searched the PubMed database (January 1972-May 2008) for English-language articles about maternal and fetal outcomes resulting from APL treatment during pregnancy. A total of 42 cases from 35 articles were identified: 12 first-trimester, 21 second-trimester, and 9 third-trimester cases. The most commonly administered agents were all-trans-retinoic acid (ATRA), anthracyclines, and antimetabolites. Complete remission was reported in 35 (83%) of 42 patients. Administration of ATRA or chemotherapy in the first trimester was associated with an increased risk of fetal malformations and spontaneous abortion, whereas administration in the second and third trimesters was associated with relatively favorable fetal outcomes. The overall treatment of the pregnant patient with APL should include a discussion about pregnancy termination, especially if APL is diagnosed in the first trimester. If the pregnancy is to continue, then the appropriate chemotherapy regimen needs to be determined. Frequent fetal monitoring, along with aggressive management of potential APL-related complications, is necessary to allow for optimal maternal and fetal outcomes.

  5. A designated centre for people with disabilities operated by Irish Society for Autism, Meath

    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.

  6. 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.

  7. 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.

  8. TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA WITH AIDA BASED REGIMEN

    Directory of Open Access Journals (Sweden)

    Ramzi Jeddi

    2011-09-01

    Full Text Available In Tunisia, the ATRA era began in 1998 with the use, consecutively, of two regimens combining ATRA and an anthracycline with cytarabine (APL93, and without cytarabine (LPA99. From 2004, 51 patients with confirmed APL either by t(15;17 or PML/RARA were treated according to the PETHEMA LPA 99 trial. Forty three patients achieved CR (86%. The remaining seven patients had early death (one died before treatment onset: four caused by differentiation syndrome (DS and three died from central nervous system hemorrhage. Multivariate analysis revealed that female gender (P=0.045, baseline WBC> 10 G/L ( P=0.041 and serum creatinine > 1.4mg/dl ( P=0.021 were predictive of mortality during induction. DS was observed in 16 patients (32% after a median onset time of 15 days from treatment onset (range, 2–29. Body mass index ≥ 30 (P=0.01 was the only independent predictor of DS. Occurrence of hypertensive peaks significantly predicted occurrence of DS (P=0.011 and was significantly associated with high BMI (p=0.003. With a median follow-up of 50 months, 5 year cumulative incidence of relapse, event free and overall survival were 4.7%, 74% and 78%, respectively.

  9. Iontophoretic delivery of lipophilic and hydrophilic drugs from lipid nanoparticles across human skin.

    Science.gov (United States)

    Charoenputtakun, Ponwanit; Li, S Kevin; Ngawhirunpat, Tanansait

    2015-11-10

    The combined effects of iontophoresis and lipid nanoparticles on drug delivery across human epidermal membrane (HEM) were investigated. The delivery of lipophilic and hydrophilic drugs, all trans-retinoic acid (ATRA), salicylate (SA), and acyclovir (ACV), across HEM from lipid nanoparticles, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), was compared in passive and iontophoresis experiments in vitro. Iontophoresis experiments were also performed with synthetic Nuclepore membrane for comparison. Drug distribution in the skin after iontophoretic delivery with the lipid nanoparticles was examined using a model probe rhodamine B base (RhoB). The drug-loaded lipid nanoparticles had average sizes of ∼ 118-169 nm and a negative zeta potential. Iontophoresis did not enhance the delivery of ATRA across HEM from SLN and NLC. However, HEM distribution study of RhoB suggested that lipophilic drugs could be delivered into the deeper layer of the skin following iontophoretic delivery of the drugs from the lipid nanoparticles. Iontophoresis enhanced the delivery of hydrophilic drug SA with the lipid nanoparticles. Similarly, iontophoresis enhanced the delivery of ACV when it was loaded in SLN. These results suggest that lipid nanoparticles are a promising drug delivery method that can be combined with iontophoresis to improve skin delivery of hydrophilic drugs.

  10. Pathogenesis of disseminated intravascular coagulation in patients with acute promyelocytic leukemia, and its treatment using recombinant human soluble thrombomodulin.

    Science.gov (United States)

    Ikezoe, Takayuki

    2014-07-01

    Acute promyelocytic leukemia (APL) is an uncommon subtype of acute myelogenous leukemia characterized by the proliferation of blasts with distinct morphology, a specific balanced reciprocal translocation t(15;17), and life-threatening hemorrhage caused mainly by enhanced fibrinolytic-type disseminated intravascular coagulation (DIC). The introduction of all-trans retinoic acid (ATRA) into anthracycline-based induction chemotherapy regimens has dramatically improved overall survival of individuals with APL, although hemorrhage-related death during the early phase of therapy remains a serious problem. Moreover, population-based studies have shown that the incidence of early death during induction chemotherapy is nearly 30 %, and the most common cause of death is associated with hemorrhage. Thus, development of a novel treatment strategy to alleviate abnormal coagulation in APL patients is urgently required. Recombinant human soluble thrombomodulin (rTM) comprises the active extracellular domain of TM, and has been used for treatment of DIC since 2008 in Japan. Use of rTM in combination with remission induction chemotherapy, including ATRA, produces potent resolution of DIC without exacerbation of bleeding tendency in individuals with APL. This review article discusses the pathogenesis and features of DIC caused by APL, as well as the possible anticoagulant and anti-leukemic action of rTM in APL patients.

  11. Regulation of sperm flagellar motility activation and chemotaxis caused by egg-derived substance(s) in sea cucumber.

    Science.gov (United States)

    Morita, Masaya; Kitamura, Makoto; Nakajima, Ayako; Sri Susilo, Endang; Takemura, Akihiro; Okuno, Makoto

    2009-04-01

    The sea cucumber Holothuria atra is a broadcast spawner. Among broadcast spawners, fertilization occurs by means of an egg-derived substance(s) that induces sperm flagellar motility activation and chemotaxis. Holothuria atra sperm were quiescent in seawater, but exhibited flagellar motility activation near eggs with chorion (intact eggs). In addition, they moved in a helical motion toward intact eggs as well as a capillary filled with the water layer of the egg extracts, suggesting that an egg-derived compound(s) causes motility activation and chemotaxis. Furthermore, demembranated sperm flagella were reactivated in high pH (> 7.8) solution without cAMP, and a phosphorylation assay using (gamma-32P)ATP showed that axonemal protein phosphorylation and dephosphorylation also occurred in a pH-dependent manner. These results suggest that the activation of sperm motility in holothurians is controlled by pH-sensitive changes in axonemal protein phosphorylation. Ca2+ concentration affected the swimming trajectory of demembranated sperm, indicating that Ca2+-binding proteins present at the flagella may be associated with regulation of flagellar waveform. Moreover, the phosphorylation states of several axonemal proteins were Ca2+-sensitive, indicating that Ca2+ impacts both kinase and phosphatase activities. In addition, in vivo sperm protein phosphorylation occurred after treatment with a water-soluble egg extract. Our results suggest that one or more egg-derived compounds activate motility and subsequent chemotactic behavior via Ca2+-sensitive flagellar protein phosphorylation.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 治疗急性早幼粒细胞白血病的几个问题%Problems in the treatment of acute promyelocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    林凤茹; 郭晓楠; 任金海

    2011-01-01

    Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia, is characterized by rapid progress, prone to developing DIC, and high mortality. Typical chromosome translocation with PMLRARα fusion gene occurs in more than 95% of APL cases. Since 1986, the outcome of APL has been significantly improved in our country by firstly using ATRA and ATO for treating APL, making APL of AML curable by chemotherapy only. Based on our limited experiences, we discussed the related problems in the treatment of APL.%急性早幼粒细胞白血病(APL)为急性髓系白血病的一个亚型,以进展快,易发生弥散性血管内凝血(DIC)和死亡率高为特征.95%以上APL患者有典型染色体易位t(15;17)形成PMLRARα融合基因.1986年以来,中国首创以全反式维甲酸(ATRA)和亚砷酸(ATO)治疗APL,使APL的转归大大改观,成为仅用药物可治愈的AML.结合作者经验讨论治疗APL中的有关问题.

  17. Acute promyelocytic leukemia with cryptic t(15;17) on isochromosome 17: a case report and review of literature.

    Science.gov (United States)

    Tang, Yuting; Wang, Ying; Hu, Liang; Meng, Fankai; Xu, Danmei; Wan, Kai; Huang, Lifang; Li, Chunrui; Zhou, Jianfeng

    2015-01-01

    Acute Promyelocytic Leukemia (APL) is one of the most curable leukemia which shows great sensitivity to all-trans retinoic acid (ATRA) although a small number of the patients present poor prognosis and short survival. Isochromosome 17 in APL which usually bears an additional copy of RARA/PML fusion gene is considered to be a negative factor on its prognosis. Cryptic t(15;17) on i(17q) leads to an extra copy of PML/RARA rather than RARA/PML which may confer a worse prognosis. We describe here a rare APL case with complex chromosomal abnormality including isochromosome 17 bearing cryptic t(15;17) showing poor outcome. The patient lacks a classic t(15;17) and fluorescence in situ hybridization (FISH) presents 2 PML/RARA fusion signals on both long arms of the isochromosome. The patient also acquired a secondary mutation at relapse when the initial karyotype was already a complex karyotype involving chromosome 13, 17 and 22 at the same time. The poor response of this patient to traditional chemotherapy like ATRA and novel therapy like arsenic trioxide (ATO) suggests that early auto-hematological stem cell transplantation may be the choice of APL with isochromosome 17 especially with cryptic t(15;17) on i(17q). We are the first to show a clear history and evidence of FISH of these kind of cases. A small summary of cases with cryptic t(15;17) on isochromosome 17 is also made.

  18. One Case of PML / Rara Fusion Gene-Negative Chromosomal Changes Associated With Complex Karyotypes of Acute Promyelocytic Leukemia%PML/RARa阴性伴复杂核型染色体改变的急性早幼粒细胞白血病(APL)一例

    Institute of Scientific and Technical Information of China (English)

    赵丽菲; 张小卿

    2012-01-01

    急性早幼粒细胞白血病( APL)是急性白血病的一种特殊类型.全反式维甲酸(ATRA)、三氧化二砷相继应用于APL的治疗,使其成为急性髓系白血病中治愈率最高的一个亚型;而PML/RARa阴性伴复杂核型染色体改变的急性髓系白血病M3型则属于高危预后.%Acute promyelocytic leukemia ( APL) is a special type of acute leukemia. All-trans retinoic acid ( ATRA ), arsenic trioxide have been used in the treatment of APL, to become acute myeloid leukemia, a subtype of the highest cure rate.But PML / RARa negative chromosomal changes associated with complex karyotypes of acute myeloid leukemia M3 type belong to high-risk prognostic.

  19. Induction of differentiation and apoptosis- a possible strategy in the treatment of adult acute myelogenous leukemia.

    Science.gov (United States)

    Bruserud, O; Gjertsen, B T; Huang, Ts

    2000-01-01

    A differentiation block with accumulation of immature myeloid cells characterizes acute myelogenous leukemia (AML). However, native AML cells often show some morphological signs of differentiation that allow a classification into different subsets, and further differentiation may be induced by exposure to various soluble mediators, e.g., all trans-retinoic acid (ATRA) and several cytokines. Combination therapy with ATRA and chemotherapy should now be regarded as the standard treatment for the acute promyelocytic leukemia variant of AML. Several agents can induce leukemic cell differentiation for other AML subtypes, although these effects differ between patients. Differentiation may then be associated with induction of apoptosis, and differentiation-inducing therapy may therefore become useful in combination with intensive chemotherapy to increase the susceptibility of AML blasts to drug-induced apoptosis. However, it should be emphasized that differentiation and apoptosis can occur as separate events with different regulation in AML cells, and future studies in AML should therefore focus on: A) the identification of new agents with more predictable effects on differentiation and apoptosis; B) the use of clinical and laboratory parameters to define new subsets of AML patients in which differentiation/apoptosis induction has a predictable and beneficial effect, and C) further characterization of how AML blast sensitivity to drug-induced apoptosis is modulated by differentiation induction.

  20. 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.

  1. [PML-RARα and p21 are key factors for maintaining acute promyelocytic leukemia stem cells survival].

    Science.gov (United States)

    Ding, Fei; Li, Jun-Min

    2011-10-01

    Tumor stem/progenitor cells are the cells with the characteristics of self-renewal, differentiating to all the other cell populations within tumor, which are also regarded as the source of tumor relapse, drug-resistance and metastasis. As a subtype of acute myeloid leukemia, acute promyelocytic leukemia (APL) represents the target of therapy due to the good response of the oncogenic protein PML-RARα to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). This review summarizes the latest research results of APL as follows: (1) there probably are two APL stem/progenitor cell populations within APL, and self-renewal and survival of APL stem/progenitor cells highly depend on PML-RARα expression, cell cycle inhibitor p21, self-renewal associated molecules and chemokines; and (2) ATRA and ATO eradicate APL stem/progenitor cells mainly by PML-RARα degradation, FOXO3A activation and the inhibition of self-renewal-associated signaling pathway of sonic hedgehog. These findings are helpful to improve other tumor therapy.

  2. Parasitism of Trombidium brevimanum larvae on agrobiont linyphiid spiders from Germany.

    Science.gov (United States)

    Tomić, Vladimir; Mąkol, Joanna; Stamenković, Srdjan; Büchs, Wolfgang; Prescher, Sabine; Sivčev, Ivan; Graora, Draga; Sivčev, Lazar; Gotlin-Čuljak, Tatjana; Dudić, Boris

    2015-08-01

    An experiment on three differently-managed agricultural fields in Ahlum, Germany, which aimed at establishing the impact of different management systems on the biodiversity of predators and decomposers, yielded a significant number of spiders parasitized by larvae of Trombidium brevimanum (Actinotrichida, Parasitengona, Trombidiidae). Spider data from the whole sampling period (September 2010-July 2012), indicated that ectoparasitic larvae were recorded only on spiders in pitfall traps in the period of June-July 2011. In this period, only eight species of Linyphiidae--out of 42 species assigned to nine spider families recorded from the study area--were parasitized by mites; considerable levels of parasitism were recorded on Erigone atra, E. dentipalpis, and Oedothorax apicatus. The highest prevalence of parasitism was recorded on the organic field for E. atra (29%), while on the integrated and conventional fields significantly fewer parasitized spiders were observed. The preferred attachment sites on the spider host were regions with softer cuticle, especially regions on the carapace and on the abdomen, adjacent to the pedicel.

  3. Improved Homology Model of the Human all-trans Retinoic Acid Metabolizing Enzyme CYP26A1

    Directory of Open Access Journals (Sweden)

    Mohamed K. A. Awadalla

    2016-03-01

    Full Text Available A new CYP26A1 homology model was built based on the crystal structure of cyanobacterial CYP120A1. The model quality was examined for stereochemical accuracy, folding reliability, and absolute quality using a variety of different bioinformatics tools. Furthermore, the docking capabilities of the model were assessed by docking of the natural substrate all-trans-retinoic acid (atRA, and a group of known azole- and tetralone-based CYP26A1 inhibitors. The preferred binding pose of atRA suggests the (4S-OH-atRA metabolite production, in agreement with recently available experimental data. The distances between the ligands and the heme group iron of the enzyme are in agreement with corresponding distances obtained for substrates and azole inhibitors for other cytochrome systems. The calculated theoretical binding energies agree with recently reported experimental data and show that the model is capable of discriminating between natural substrate, strong inhibitors (R116010 and R115866, and weak inhibitors (liarozole, fluconazole, tetralone derivatives.

  4. EFFECTS OF ALL-TRANS RETINOIC ACID ON BLOOD COAGULATION AND FIBRINOLYSIS IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA%全反式维甲酸对APL病人凝血和纤溶指标影响

    Institute of Scientific and Technical Information of China (English)

    刘静; 汪洪毅

    2011-01-01

    Objective To observe changes of blood coagulation and fibrinolysis in patients with acute promyelocytic leukemia (APL) during remission following treatment by all-trans retinoic acid (ATRA) and investigate the relation of white blood cell (WBC) count in peripheral blood with ATRCA therapy for APL.Methods Initial therapy was offered to 45 APL patients, of whom, 21 with peripheral WBC count of ≥ 10 × 109/L (high-WBC group); 22 with WBC< 10 × 109/L (low-WBC group) 22 cases).Oral ATRA 60 mg/d.was given.To those with WBC>4.0 × 109/L, low-dose chemotherapy-daonomycin 20 mg/d for 3 days plus cytarabine 100 mg/day, for 7 days-was offered; to those with platelet of <20 × 109/L accompanied by hemorrhagic tendency, platelet suspension was transfused; to those infected, antibiotics were given.WBC, fibrinogen (FIB), prothrombin time (PT), activated partial thromboplastin time (APTT), and changes in bone marrow cells were monitored before treatment and one,two, and four weeks after ATRA therapy.Results Before ATRA therapy, FIB in high-WBC group was lower than that in lowWBC group (t= -3.082, P<0.05), while PT was higher than that in low-WBC group (t=3.720,P<0.05).There was no significant difference between the two groups in terms of APTT (t=- 1.157, P>0.05).Complete remission was achieved in 36 patients, partial remission in three, and non-remission in one.Three died of brain hemorrhage.After the first week of therapy, WBC count elevated, and gradually returned to normal until the fourth week (F=9.041 ,q=2.825-6.786,P<0.05).With the application of ATRA, plasma FIB and PT recovered by degrees, and reached to normal levels as complete remission achieved (F= 1 5.346,37.147;q=4.012- 13.673;P<0.05).Symptoms of bleeding were improved quickly.Conclusion The number of peripheral leukocytes in APL patients is an important risk factor of whether there is disseminated intravascular coagulation or not.After ATRA therapy, the early mortality due to bleeding declines

  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. EFFECT OF 1,25-(OH)2D3 COMBINED WITH ALL-TRANS RETINOIC ACID ON FOXP3 EXPRESSION IN TREG CELLS IN MICE WITH ULCERATIVE COLITIS%1,25-(OH)2D3和全反式视黄酸联合应用对溃疡性结肠炎小鼠TREG细胞Foxp3表达的影响

    Institute of Scientific and Technical Information of China (English)

    张小艳; 杨雯; 张英; 李秀花; 邱服斌

    2016-01-01

    目的 探讨1,25-(OH)2D3和全反式视黄酸(all-trans retinoic acid,ATRA)联合应用对溃疡性结肠炎小鼠Treg细胞Foxp3蛋白及其相关细胞因子的表达和血钙、肌酐水平的影响.方法 6w龄雌性C57BL/6小鼠50只,随机分为正常对照组(CN),溃疡性结肠炎模型组(model,M),1,25-(OH)2D3干预,全反式视黄酸(ATRA)干预,1,25-(OH) 2D3+ATRA联合干预共5组,除CN组外,其余4组随意饮3%糖酐酯(DSS)溶液建立溃疡性结肠炎模型,从造模D3开始干预,干预剂1,25-(OH)2D3和ATRA分别用花生油溶解(后者需在暗光下进行),干预剂量1,25-(OH)2D3100ng(d/capita),ATRA 0.2 mg(d/capita),1,25-(OH) 2D3+ATRA(100ng/d+0.2mg/d)每天对应灌胃干预,9d后处死小鼠,取血清和结肠组织.按小鼠一般情况进行疾病活动指数(disease activity index,DAI)评分;测量结肠长度;观察结肠大体形态和病理学损伤情况,并对其进行组织病理学评分;生物化学方法检测小鼠结肠髓过氧化物酶(myeloperoxidase,MPO)活性和血清钙、肌酐水平;免疫组化法测结肠组织Foxp3、TGF-β、IL-10蛋白表达情况.结果 与M组比较,三个干预组小鼠溃疡性结肠炎大体形态改善,组织学损伤较轻,结肠长度缩短有所缓解,结肠组织MPO活性下降,Foxp3蛋白及其相关细胞因子TGF-β、IL-10表达水平上升,血钙和肌酐水平下降.且联合干预组相比单独干预组效果更明显,差异具有统计学意义(除血钙).结论 1,25-(OH)2D3和全反式视黄酸(ATRA)联合应用能够增强Treg细胞Foxp3的表达,使Treg细胞更好地发挥抑制免疫应答的作用,并可能缓解1,25-(OH)2D3引起的血钙升高,改善肾功能.

  7. NLS-RARα promotes proliferation and inhibits differentiation in HL-60 cells.

    Science.gov (United States)

    Hu, Xiu-Xiu; Zhong, Liang; Zhang, Xi; Gao, Yuan-Mei; Liu, Bei-Zhong

    2014-01-01

    A unique mRNA produced in leukemic cells from a t(15;17) acute promyelocytic leukemia (APL) patient encodes a fusion protein between the retinoic acid receptor α (RARα) and a myeloid gene product called PML. Studies have reported that neutrophil elastase (NE) cleaves bcr-1-derived PML-RARα in early myeloid cells, leaving only the nuclear localization signal (NLS) of PML attached to RARα. The resultant NLS-RARα fusion protein mainly localizes to, and functions within, the cell nucleus. It is speculated that NLS-RARα may act in different ways from the wild-type RARα, but its biological characteristics have not been reported. This study takes two approaches. Firstly, the NLS-RARα was silenced with pNLS-RARα-shRNA. The mRNA and protein expression of NLS-RARα were detected by RT-PCR and Western blot respectively. Cell proliferation in vitro was assessed by MTT assay. Flow cytometry (FCM) was used to detect the differentiation of cells. Secondly, the NLS-RARα was over-expressed by preparation of recombinant adenovirus HL-60/pAd-NLS-RARα. The assays of mRNA and protein expression of NLS-RARα, and cell proliferation, were as above. By contrast, cell differentiation was stimulated by all trans retinoic acid (ATRA) (2.5µmol/L) at 24h after virus infection of pAd-NLS-RARα, and then detected by CD11b labeling two days later. The transcription and translation of C-MYC was detected in HL-60/pAd-NLS-RARα cells which treated by ATRA. Our results showed that compared to the control groups, the expression of NLS-RARα was significantly reduced in the HL-60/pNLS-RARα-shRNA cells, and increased dramatically in the HL-60/pAd-NLS-RARα cells. The proliferation was remarkably inhibited in the HL-60/pNLS-RARα-shRNA cells in a time-dependent manner, but markedly promoted in the HL-60/pAd-NLS-RARα cells. FCM outcome revealed the differentiation increased in HL-60/pNLS-RARα-shRNA cells, and decreased in the HL-60/pAd-NLS-RARα cells treated with 2.5µmol/L ATRA. The

  8. Effect of all trans-retinoic acid combined with suberoylanilide hydroxamic acid on breast cancer cells MCF-7%全反式维A酸联合辛二酰苯胺异羟肟酸对乳腺癌MCF-7细胞的作用

    Institute of Scientific and Technical Information of China (English)

    薛文潮; 李光; 张妮娜; 何涛

    2016-01-01

    Objective Induction and differentiation of tumor cells is a new therapy of cancer. Nowadays, differentiation inducing agents were widely used in treatment of acute lymphoblastic leukemia, therefore it is imperative to develop the investigation in vitro of solid tumors. This study was to combine all trans-retinoic acid (ATRA) and suberoylanilide hydroxamic acid (SAHA) on the proliferation of MCF-7 to investigate whether the combination of the two drugs have synergistic effect.Methods Human breast cancer cell line MCF-7 was culturedin vitro. When the cells entered the logarithmic growth phase, a certain concentration of ATRA (or) SAHA were added into the petri dishes. Morphological changes of cells were observed under inverted microscope, the anti-proliferative effect was measured by MTT assay. Absorbance value and inhibition rate were compared by repeated measurement data, using LSD for multiple comparison.Results Inverted microscope observation showed that, morphological changes of cells in ATRA combined with SAHA group was obvious than ATRA or SAHA group, and with the extension of time the effect was more remarkable. The absorbance value of A1 and B1 group was not statistically significant compared with the control group at 24 h (P=0.092). Compared with the control group, the B1 group had no statistical significance at 48 h (P=1.243). The average absorbance of each experimental group was less than that of the control group at 72 h, 96 h, 120 h (groups:F=320.648, P=0.000; different time-point:F=219.245,P=0.000; interaction:F=117.962,P=0.000). The proliferation inhibition rate of single drug group was higher than that of the control group, and the ATRA combined with SAHA group was significantly higher than that in the single drug group (groups:F=462.792, P=0.000; different time-point:F=315.024,P=0.000; interaction:F=179.682,P=0.000); q values in A1+B1 group and A2+B1 group of combined effects of two drugs at 24 h and 48 h were greater than 1.15, performed as

  9. Differentiating effect of PPARγ ligand rosiglitazone and all trans-retinoic acid on myeloma cells and its possible mechanism%罗格列酮与全反式维甲酸对骨髓瘤细胞分化的影响及其可能机制

    Institute of Scientific and Technical Information of China (English)

    黄海雯; 陈广华; 常惠荣; Howard C.H.Chow; Anska Y.H.Leung; Raymond Liang; 吴德沛

    2009-01-01

    Objective To investigate the effects of PPARγ ligand(rosiglitazone,RGZ)as well as combined with all trans-retinoic acid(ATRA)on human myeloma cells and try to explore the possible mechanism.Methods Human myeloma cell lines U266 and RPMl.8226 cells were treated with RGZ in the presence or absence of ATRA.Cell proliferation was evaluated by [~3H] thymidine incorporation,cell cycle distribution and CD49e expression were analyzed by flow cytometry,morphology changes were evaluated by Wright-Giemsa staining.and p27~(Klpl)and p21~(Wafl)expression was detected by Western blotting.Results The exposure to RGZ induced proliferation inhibifion in both cell Iines in a dose-dependent manner.After cultured with 5 μmol/L RGZ,the proportion of U266 and RPMl-8226 cells in phase G_0/G_1 was(45.2±6.7)%and(40.3±7.3)%,respectively(P<0.05).The proportion of the cells in phase G_2/M and Swag(52.2±7.4)%and(57.4±9.5)%,respectively(P<0.05).These changes were more evident when the RGZ concentration was increased to 10 μmol/L.A combination of RGZ with ATRA enhanced the growth inhibition and eell cycle arrest effects of RGZ.The RGZ-treated myeloma cells displayed morphological characteristics of cell difierentiation.and more evident signs of differentiation were observed when RGZ wag combined with ATRA.These changes were confirmed by the detection of CD49e expression.The expression of p27~(Klpl)and p21~(Wafl)in myeloma cells was up-regulated by RGZ and this change Was more apparent when RGZ was used in combination with ATRA.Conclusion RGZ Can induce cell cycle arrest and cell differentiation in myeloma cells which maybe caused by up-regulation of p27~(Klpl)and p21~(Wafl)expression.ATRA can enhance these effects of RGZ on multiple myeloma cells and combined nile of thesetwo drugs may show a synergistic effect on myeloma cells.%目的 探讨过氧化物酶体增殖物活化受体γ(PPARγ)的配体罗格列酮(RGZ)与全反式维甲酸(ATRA)对骨髓瘤细胞分化的

  10. Protective effect of all-trans retinoic acid pretreatment against rat intestinal injury induced by hepatic inflow occlusion%全反式维甲酸预处理对肝血流阻断大鼠肠道的保护作用

    Institute of Scientific and Technical Information of China (English)

    王钟兴; 黄婵燕; 方佳峰; 陈图锋

    2013-01-01

    目的:探讨全反式维甲酸(ATRA)对肝血流阻断所致肠道损伤的影响和机制.方法:32只雄性SD大鼠,随机分为4组:假手术(sham)组、肝血流阻断(HIO)组、溶媒对照(DMSO+ HIO)组和ATRA预处理(ATRA+ HIO)组.ATRA预处理组以ATRA 15 mg·kg-1·d-1灌胃,溶媒对照组以等体积二甲基亚砜(DMSO)灌胃,共10 d.Pringl'e,s法建立肝血流阻断模型,持续30 min,解除阻断再灌注2h后,采集各组大鼠末端回肠和血清.光镜下观察回肠病理改变、行肠黏膜组织Chiu氏评分;比色法检测血清二胺氧化酶(DAO)水平、回肠组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性;ELISA法测定血清白细胞介素(IL)-1β及肿瘤坏死因子(TNF)-α水平;Western blotting检测组织中胞浆锰超氧化物歧化酶(MnSOD)和胞核NF-κB p65蛋白的表达量.结果:相对于HIO组和DMSO+ HIO组,ATRA能缓解肝血流阻断后肠黏膜组织病理损伤,降低Chiu氏评分和血清DAO水平(P<0.05),减少回肠组织中MDA含量(P<0.05),提高SOD活性(P<0.05),增加组织MnSOD的表达(P<0.05),减少胞核NF-κB p65蛋白含量(P<0.05),降低血清IL-1β和TNF-α水平(P<0.05).结论:ATRA通过增加组织抗氧化能力,抑制NF-κB通路的激活,减少促炎因子的产生,从而减轻大鼠肝血流阻断造成的肠道损伤.

  11. Effect of receptor-selective retinoids on growth and differentiation pathways in mouse melanoma cells.

    Science.gov (United States)

    Desai, S H; Boskovic, G; Eastham, L; Dawson, M; Niles, R M

    2000-05-15

    Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor beta (RARbeta) expression, an increase in protein kinase Calpha (PKCalpha) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARalpha and RARgamma and nuclear retinoid X receptors (RXR) alpha and beta constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8, 8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was most effective at inhibiting anchorage-dependent growth, whereas the RARgamma-selective ligand 6-[(5,6,7, 8-tetrahydro-5,5,8, 8-tetramethyl-2-naphthalenyl)(hydroxyimino)methyl]-2-naphthalen ecarbo xylic acid (SR11254) was most potent at inhibiting anchorage-independent growth. In contrast, 4-(5,6,7,8-tetrahydro-5,5, 8,8-tetramethyl-2-naphthalenecarboxamido)-benzoic acid (Am580), an RARalpha-selective ligand, was the most effective receptor-selective agonist for inducing RARbeta mRNA and increasing the amount of PKCalpha protein. All of the retinoids induced a concentration-dependent increase in AP-1 transcriptional activity, with little difference in effectiveness among the receptor-selective retinoids. A synergistic increase in the amount of PKCalpha was found when an RAR-selective agonist was combined with an RXR-selective agonist. One possible explanation for this result is that an RXR-RAR heterodimer in which both receptors are liganded is required for maximum expression of this critical component of the ATRA-induced differentiation pathway. Our data suggest that synthetic retinoids can activate different growth and

  12. Combination of arsenicum trioxide and all trans retinoic acid in the treatment of relapsed acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    A. N. Sokolov

    2015-01-01

    Full Text Available From 2001 to 2013 eleven patients with relapsed acute promyelocytic leukemia (APL (median age – 30 years received arsenicum trioxide (ATO. ATO was administered as a 2nd line relapse therapy in 9 patients, as 1st line relapse therapy in 2 patients. ATO was administered in a dose of 0.1 mg/kg in 7 patients, 0.15 mg/kg – in 4 patients. The induction duration was 14 days in 3 patients, 24–35 days in 2 patients, 60 days in 6 patients. From the 1st day of ATO patients received 45 mg/m2 all trans retinoic acid (ATRA (1 patient – from day 29 of ATO therapy. Maintenance therapy ATO + ATRA (10–14 days courses, every four weeks patients were receiving during 10–15 months. 2 from 3 patients with molecular relapses achieved remission lasting 57 and 89 months after the 14-day ATO courses. 1 from 2 patients with bone marrow relapse achieved remission lasting 27 months after the 24–35-day ATO courses. 60-day courses were effective in 5 of 6 patients: in 4 of which remission are retained during 16, 19, 27, 57 months; 1 patient was relapsed after 12 months; 1 patient did not achieve molecular remission. 3 patients received allogeneic hematopoietic stem cell transplantation (alloHSCT, 2 of which alive in remission. 1 patient received autologous hematopoietic stem cell transplantation in the 2nd molecular remission (alive in remission. 4 patients died: 1 – in the 3rd relapse (duration of 2nd remission – 9 months, 1 – in remission from complications after alloHSCT, 1 – from APL progression, 1 – sudden death in 2nd remission lasting 72 months. ATO + ATRA for 60 days with supportive therapy are more effective than chemotherapy in the treatment of APL relapse. Interferon α + ATRA are inappropriate treatment of APL molecular and cytogenetic relapse. Using autologous HSCT in 2nd molecular remission will improve the results of APL relapse treatment.

  13. Acute promyelocytic leukaemia with translocation of t(11;17(q23;q21: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Xiao-li CHANG

    2013-05-01

    Full Text Available Objective  To study the clinical attributes, treatment and prognosis of acute promyelocytic leukaemia (APL with translocation of t(11;17(q23;q21. Methods  A case of APL with t(11;17(q23;q21 was reported, and the cytomorphology, immunology, cytogenetics and molecular genetics of the patient were analyzed. The related literature published in recent 20 years domestically and abroad was reviewed. Results  The case herewith studied was a male patient aged 35 years with leucocyte count (WBC of 38.17×109 in peripheral blood, and 88.5% of promyelocytes in bone marrow. Marrow karyotype analysis showed 46, XY, t(11;17(q23;q21 and PLZF-RARA rearrangement was detected. The patient was definitely diagnosed as APL with t(11;17 (q23;q21. Complete morphological and genetic remission was achieved after a combined chemotherapy of As2O3 and ATRA, then a molecular biological remission was achieved after the treatment of 3 courses of large dose cytarabine. The patient was followed up to February 2013 with disease-free survival of nearly 10 months. Up to date, 20 cases of APL with t(11;17(q23;q21 have been reported domestically and abroad, and their clinical attributes were reviewed. For the 20 cases, the mean age was 48.9±16.3 years and the male/female ratio was 9:1. Among the patients, males aged over 45 years accounted for 55%, implying that the elderly males may be high-risk population. The incidence of DIC was 60%, most of which got poor curative effect of ATRA. Conclusion  APL with t(11;17(q23;q21 is a very rare illness with distinct morphological changes and clinical characteristics. Prolonged combined chemotherapy with As2O3 and ATRA with large dose cytarabine may be beneficial to attain a remission and prolong survival.

  14. Avaliação do Plano Operacional de Comercialização do Turismo: o caso de Bonito, município de Mato Grosso do Sul-Brasil

    Directory of Open Access Journals (Sweden)

    Milton Augusto Pasquotto Mariani

    2011-09-01

    Full Text Available

    O presente estudo tem como objetivo geral analisar as percepções do trade turístico de Bonito acerca do plano de comercialização desenvolvido para o município, buscando a compreensão da interface marketing-turismo. Tratando-se o marketing turístico como uma ferramenta para a conquista e manutenção de clientes, a fim de que a experiência vivenciada pelo turista seja única e inesquecível, o presente estudo justifica-se na busca de contribuições para a gestão pública do destino turístico analisado, com vistas a sua consolidação como pólo na atração de visitantes. Trata-se de um estudo qualitativo, de natureza exploratória, descritiva e explicativa, cujo procedimento de coleta, análise e interpretação dos dados resumiu-se em entrevistas com os atores locais. Os resultados apontam que aproximadamente 89% dos sujeitos consideram o plano importante para o desenvolvimento da atividade turística local, sendo que 44% o consideram importante para “vender” o destino como ícone brasileiro no ecoturismo; 33% o consideram importante por propiciar o direcionamento da região rumo à atração de turistas do mundo todo e 11% o consideram importante como ação estratégica para superar as dificuldades existentes e construir um novo posicionamento estratégico no mercado turístico. Sendo assim, referindo-se ao turismo como um dos principais setores empregatícios e gerador de renda para o município, o plano de comercialização se apresenta como uma ferramenta importante para a consolidação do destino como um verdadeiro pólo na atração de turistas.

  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. HDAC3 as a molecular chaperone for shuttling phosphorylated TR2 to PML: a novel deacetylase activity-independent function of HDAC3.

    Directory of Open Access Journals (Sweden)

    Pawan Gupta

    Full Text Available TR2 is an orphan nuclear receptor specifically expressed in early embryos (Wei and Hsu, 1994, and a transcription factor for transcriptional regulation of important genes in stem cells including the gate keeper Oct4 (Park et al. 2007. TR2 is known to function as an activator (Wei et al. 2000, or a repressor (Chinpaisal et al., 1998, Gupta et al. 2007. Due to the lack of specific ligands, mechanisms triggering its activator or repressor function have remained puzzling for decades. Recently, we found that all-trans retinoic acid (atRA triggers the activation of extracellular-signal-regulated kinase 2 (ERK2, which phosphorylates TR2 and stimulates its partitioning to promyelocytic leukemia (PML nuclear bodies, thereby converting the activator function of TR2 into repression (Gupta et al. 2008; Park et al. 2007. Recruitment of TR2 to PML is a crucial step in the conversion of TR2 from an activator to a repressor. However, it is unclear how phosphorylated TR2 is recruited to PML, an essential step in converting TR2 from an activator to a repressor. In the present study, we use both in vitro and in vivo systems to address the problem of recruiting TR2 to PML nuclear bodies. First, we identify histone deacetylase 3 (HDAC3 as an effector molecule. HDAC3 is known to interact with TR2 (Franco et al. 2001 and this interaction is enhanced by the atRA-stimulated phosphorylation of TR2 at Thr-210 (Gupta et al. 2008. Secondly, in this study, we also find that the carrier function of HDAC3 is independent of its deacetylase activity. Thirdly, we find another novel activity of atRA that stimulates nuclear enrichment of HDAC3 to form nuclear complex with PML, which is ERK2 independent. This is the first report identifying a deacetylase-independent function for HDAC3, which serves as a specific carrier molecule that targets a specifically phosphorylated protein to PML NBs. This is also the first study delineating how protein recruitment to PML nuclear bodies occurs

  17. {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

  18. 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

  19. 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»?

  20. Application of transfer function model to predict transport of Atrazine in soil%应用传递函数模型预报农药阿特拉津在土壤中的运移

    Institute of Scientific and Technical Information of China (English)

    任理; 毛萌

    2002-01-01

    本文首先对农药阿特拉津(Atrazine)在稳定流场饱和均质土壤中的运移进行了室内实验研究,采用易混合置换的方法,获得了示踪溶质Br-和Atrazine同步脉冲输入1h后的出流浓度动态;其次由批技术得到Atrazine的分配系数,进而获得阻滞因子,在此基础上应用传递函数模型,根据示踪溶质的迁移预报了吸附作用存在时Atrazine在土壤中的运移动态.

  1. Estudio de algunos géneros bacterianos asociados a la rizosfera de los cultivos de gerbera (Gerbera jamesonii y clavel (Dianthus barbatus, Dianthus caryophyllus

    Directory of Open Access Journals (Sweden)

    Annia Hernández

    2000-01-01

    Full Text Available En este trabajo se realizó la caracterización de algunos géneros bacterianos presentes en la rizosfera de los cultivos de gerbera (Gerbera jamesonii y clavel (Dianthus barbatus y Dianthus caryophyllus, en un suelo Ferralítico Rojo compactado de San José de las Lajas. También se estudió la quimioatracción de los exudados radicales de estos cultivos hacia diferentes rizobacterias (Pseudomonas (Burkholderia cepacia, P. fluorescens y Azospirillum brasilense. En ambos casos se utilizó el Modelo Espermosférico. Los resultados obtenidos demostraron que Pseudomonas constituye una población dominante en relación con Azospirillum, Bacillus y Streptomyces. Pseudomonas (Burkholderia cepacia fue la cepa más fuertemente atraída por los exudados radicales de gerbera y clavel, a los 14 días y 40 minutos de exposición

  2. Android lietotne "Velo novietnes"

    OpenAIRE

    Lipkovs, Emīls

    2015-01-01

    Velo novietnes ir lietotne Android platformai, kura ir domāta informācijas izplatīšanas atvieglošanai un informācijas apkopošanai par velo novietņu atrašanās vietām, velosipēdu servisa centriem un velo celiņiem Rīgā. Šobrīd pārvietojoties ar velosipēdu, nav parocīga veida kā atrast drošu vietu, kur novietot velosipēdu, kad to neizmanto, vai arī atrast informāciju par servisa centriem Rīgā, ja kaut kas ir atgadījies ar velosipēdu. Braucējam ir jāapmeklē dažādas interneta vietnes, lai iegūtu...

  3. Monocamadas sp2 corrugadas e suas aplicações

    OpenAIRE

    Luís Henrique de Lima

    2014-01-01

    Monocamadas sp2 de grafeno e nitreto de boro hexagonal (h-BN) têm atraído muita atenção devido ao descobrimento de importantes propriedades, por exemplo, alta resistência mecânica, boa condutividade térmica e excelente estabilidade química e térmica. Porém, enquanto o grafeno é um semicondutor de gap nulo com alta mobilidade dos portadores de carga; o h-BN é um isolante com um largo band gap. Além disso, quando estas monocamadas sp2 são obtidas na superfície de uma variedade de substratos, el...

  4. SANEAMENTO AMBIENTAL NA RIDE DF E A CONFIGURAÇÃO DOS TERRITÓRIOS DE TENSÃO

    OpenAIRE

    Araújo Sobrinho, Fernando Luiz; Frederico de Oliveira, Carlos; Weyl, Luana M; Fernandes Rufo, Tiago

    2012-01-01

    O presente trabalho aborda a questão do saneamento ambiental nos municípios integrantes da Região Integrada de Desenvolvimento do Entorno do Distrito Federal e a sua configuração espacial. O processo de ocupação territorial dessa região funda-se na implantação da cidade de Brasília que encontra-se sob processo de metropolização. Tal situação é agravada pela forte atração populacional exercida pela oferta de empregos  fez com que surgissem cidades dormitórios ao redor de Brasília. Mesmo que o ...

  5. Representaciones de la ciudad moderna en las obras de Roberto Arlt y Mário de Andrade

    OpenAIRE

    Volker Jaeckel

    2011-01-01

    Resumo: Buenos Aires e São Paulo são duas cidades que se transformaram em símbolos da modernidade da América latina. As duas cidades exercem uma atração especial sobre os autores dos movimentos de vanguarda do século XX. Nas décadas dos anos 1929 e 1930 as duas metrópoles atravessavam um profundo processo de transformação social, e ao mesmo tempo alcançaram a afirmação como principais centros de cultura e intelectualidade do continente sul-americano. No presente trabalho pretende-se estabelec...

  6. Nursing care of a case with acute promyelocytic leukemia undergoing RA treatment complicated with acute cellulites%1例全反式维甲酸治疗急性早幼粒细胞白血病诱发急性疏松结缔组织炎病人的护理

    Institute of Scientific and Technical Information of China (English)

    郑莉; 郭飞燕

    2005-01-01

    @@ 全反式维甲酸(ATRA)治疗急性早幼粒细胞白血病(APL),用药方法简单,无化疗药物的细胞毒副作用,可使85%以上的APL病人获完全缓解(CR),成为当今治疗APL的常规首选药[1].但也存在一些不良反应[2],如维甲酸综合征(RAR-S),皮肤、口唇干燥,头痛头晕,骨关节痛等.现将我院使用ATRA治疗APL过程中发生的1例疏松结缔级织炎报道如下.

  7. Logística Reversa Para Gestão de Resíduos e Coprodutos da Cadeia de Biodiesel – Estudo de Caso Em Usinas do Nordeste Brasileiro

    OpenAIRE

    ALMEIDA, Kelma Maria Vitorino

    2012-01-01

    A consciência ambiental sobre fontes alternativas de energia tem atraído o interesse mundial para pesquisas sobre biodiesel. No Brasil, o Programa Nacional para o Uso e Produção de Biodiesel (PNPB) foi criado em 2005. O aumento da produção de biodiesel, por sua vez, resulta numa maior geração de coprodutos e resíduos, como a torta proveniente da etapa de extração de óleo, e a glicerina do processo de produção de biodiesel, não existindo dados consolidados a respeito da gestão d...

  8. Nav2 is necessary for cranial nerve development and blood pressure regulation

    Directory of Open Access Journals (Sweden)

    Moechars Dieder

    2010-02-01

    Full Text Available Abstract Background All-trans retinoic acid (atRA is required for nervous system development, including the developing hindbrain region. Neuron navigator 2 (Nav2 was first identified as an atRA-responsive gene in human neuroblastoma cells (retinoic acid-induced in neuroblastoma 1, Rainb1, and is required for atRA-mediated neurite outgrowth. In this paper, we explore the importance of Nav2 in nervous system development and function in vivo. Results Nav2 hypomorphic homozygous mutants show decreased survival starting at birth. Nav2 mutant embryos show an overall reduction in nerve fiber density, as well as specific defects in cranial nerves IX (glossopharyngeal and X (vagus. Nav2 hypomorphic mutant adult mice also display a blunted baroreceptor response compared to wild-type controls. Conclusions Nav2 functions in mammalian nervous system development, and is required for normal cranial nerve development and blood pressure regulation in the adult.

  9. The study of the expression of the Cx43 in the oral squamous cell carcinoma and Tca8113%间隙连接蛋白43在口腔颌面部鳞癌组织及舌癌细胞株(Tca8113)中表达的研究

    Institute of Scientific and Technical Information of China (English)

    宋娟; 张汉东

    2012-01-01

    目的:探讨间隙连接蛋白43(Cx43)在口腔鳞癌组织(oscc)和舌鳞癌细胞株(Tca8113)中的表达及其生物学行为的关系:细胞分化诱导剂全反式维甲酸(ATRA)对人舌鳞癌细胞株(Tca8113)中Cx43表达的影响.方法:应用免疫组织、细胞化学、免疫荧光及结合免疫印迹技术,观察OSCC组织中以及ATRA对Tca8113细胞株进行培养及分化诱导后Cx43在蛋白水平的变化.结果:Cx43在正常口腔鳞状上皮主要表达于相邻细胞间相互接触的细胞膜上,而在OSCC组织中,Cx43细胞膜表达与组织的分化程度、转移之间有显著性差异(Cx43:x2=7.42、12.43,P<0.05、P<0.01).免疫细胞化学检测可见舌癌细胞中Cx43异常定位于细胞浆中和/或细胞膜不与邻近细胞接触的游离缘上.Tca8113经ATRA诱导后,Cx43蛋白表达增加.结论:Cx43表达的改变与OSCC的发生和发展有关.ATRA可以通过上调Cx43表达,实现对肿瘤生长的抑制%Objective: To investigate the expression of connexin 43 and its relationship with the biological behavior in oral squamous cell carcinoma (OSCC) and Tca8113;to investigate the effects of connexin 43 in tongue carcinoma cell line (Tca8113) by all-trans-retinoic acid (ATRA). Method: Immunohistochemical and immunofluorescence was used to detect the expressions of Cx43 in oral squamous carcinoma. Western blot was adopted to examine the expressions of Cx43 in tongue carcinoma cell line (Tca8113) by all-trans-retinoic acid (ATRA). Result: In normal oral squamous epithelium the expression of Cx43 was typically shown in the membrane at intercellular contact,but in OSCC they were aberrantly expressed in cytoplasm.The significant difference was observed between low Cx43 expression and differentiation,metastasis (Cx43:X2= 7.42,12.43,P <0.05,P <0.01).In Tca8113 cell line Cx43 was detected mainly either intracytoplas-mically or in plasma membrane free from contact with other cells by immunocytochemistry and immunofluorescence

  10. Apoptosis of human leukemic HL—60 cells induced to differentiate by treatment with RA or DMSO

    Institute of Scientific and Technical Information of China (English)

    SUNHONG; YONGCHAOWANG

    1995-01-01

    In present study,we studied the effect of all-trans retinoic acid(ATRA)and dimethylsulfoxide(DMSO)on the induction of apoptosis in HL-60 cell line.Based on morphological changes by Hochest 33342 staining and identification of internuclesomal NDA celeavage by gel electrophoresis,we observed aberrant nuclear chromatin condensation and ladder-like pattern of DNA degradation. Using Flow Cytometric method.We found sub-G1 peak in RA-treated HL-60 cells starting 5 to 6d after the initiation of the treatment However,Such an obvious apoptotic peak was not identified in DMSO-differentiated cells.Combining the research accomplished before.our study approves further that apoptosis could be a common mode of death of terminally differentiated HL-60 cells.

  11. Vitamin A and retinoid signaling: genomic and nongenomic effects.

    Science.gov (United States)

    Al Tanoury, Ziad; Piskunov, Aleksandr; Rochette-Egly, Cécile

    2013-07-01

    Vitamin A or retinol is arguably the most multifunctional vitamin in the human body, as it is essential from embryogenesis to adulthood. The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs, and PPARβ/δ), polymorphic retinoic acid (RA) response elements, and multiple coregulators. It also involves extranuclear and nontranscriptional effects, such as the activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of several actors of RA signaling. However, vitamin A itself proved recently to be active and RARs to be present in the cytosol to regulate translation and cell plasticity. These new concepts expand the scope of the biologic functions of vitamin A and RA.

  12. 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.

  13. The association of environmental changes and the replacement of mosquito fauna in the Colombo District, Sri Lanka

    Directory of Open Access Journals (Sweden)

    BAS Priyangika

    2014-06-01

    Full Text Available The mosquito survey was carried out for 8 months between October 2009 and May 2010. Investigations included 12 randomly selected urban (6 and semi-urban (6 areas in the Colombo District of Sri Lanka. Thirty eight mosquito species were found and Anopheles interruptus, An. pseudojamesii, Aedes stenovensoni, Ae. edwardsi, Ae. vittatus, Culex  barraudi, Cx. fatigans, Cx. univittatus, Cx. aculeatus, Cx. purplexus, Cx. spiculosus, Cx. quadripalpis, Cx. halifaxi, Uranotaenia atra, Ur. unguiculata were new findings that were not recorded  previously in the period 1981-1982 from the same locations although 11 different breeding habitats were examined. Rainfall had a direct relation (P=0.000 with the distribution and the density of mosquitoes. Unplanned urbanization, human activities and irregular or non-disposal of domestic waste products have led to a population replacement of the mosquito fauna in these locations.

  14. Los problemas del aprendizaje en la escuela. Perspectiva social

    Directory of Open Access Journals (Sweden)

    Sindo FROUFE QUINTAS

    2009-11-01

    Full Text Available Pocos temas han tenido tanta importancia y repercusión en la escuela como el problema de los trastornos de aprendizaje desde una perspectiva social/sociológica. Distintos tipos de profesionales como psicólogos, neurólogos, ópticos, fisioterapeutas, pedíatras, pedagogos y maestros han manifestado/mostrado un gran interés por conocer/descifrar en profundidad su etiología. Quedan aún muchas lagunas/misterios por aclarar. La mente humana es duramente compleja. La cultura es un bien que todo el mundo desea conquistar. Por ella se entra en el mundo de la civilización tecnológica y en la interpretación correcta de los distintos sistemas de comunicación que abren nuevos horizontes al hombre de la técnica.

  15. Acute promyelocytic leukemia during pregnancy: a systematic analysis of outcome.

    Science.gov (United States)

    Verma, Vivek; Giri, Smith; Manandhar, Samyak; Pathak, Ranjan; Bhatt, Vijaya Raj

    2016-01-01

    The outcomes of acute promyelocytic leukemia (APL) in pregnancy are largely unknown. The MEDLINE database was systematically searched to obtain 43 articles with 71 patients with new-onset APL during pregnancy. Induction therapy included various regimens of all-trans retinoic acid (ATRA), cytarabine, and anthracycline and resulted in a complete remission rate of 93%. Obstetric and fetal complications included pre-term deliveries (46%), spontaneous/therapeutic abortion/intrauterine death (33.3%) and other neonatal complications (25.9%). Mothers diagnosed in the first trimester were more likely to experience obstetric (p pregnancy. The vast majority of APL patients in pregnancy may achieve remission with initial induction therapy. APL or its therapy in pregnancy, however, is associated with a high risk of fetal and obstetrical complications. The results of our study may help in patient counseling and informed decision-making.

  16. Freqüência horária e sazonalidade de Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) na Ilha de São Luís, Maranhão, Brasil Hourly frequency and seasonality of Lutzomyia longipalpis (Diptera: Psychodidae: Phlebotominae) on São Luís Island, Maranhão, Brazil

    OpenAIRE

    José Manuel Macário Rebêlo

    2001-01-01

    A distribuição sazonal e horária de Lutzomyia longipalpis foi estudada nos ambientes peri e intradomiciliar de duas localidades da Ilha de São Luís, estado do Maranhão. Os 11.200 exemplares capturados foram atraídos por quatro armadilhas CDC nos anos de 1996 e 1997, mensalmente, das 18h às 6h. L. longipalpis comportou-se como uma espécie anual, tendo sido encontrada em alta freqüência em todos os meses do ano, tendendo a ser mais abundante no período chuvoso (57,2%) do que no seco (42,8%). As...

  17. 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.

  18. El México abismal de Roberto Bolaño

    Directory of Open Access Journals (Sweden)

    Felipe Adrián Ríos Baeza

    2016-07-01

    Full Text Available Este trabajo de análisis no solo resalta la presencia de México, en cuanto motivo literario y espacio refractado estéticamente, en la literatura de Roberto Bolaño, cuestión que ha atraído a la mayoría de la crítica especializada, sino analiza su comportamiento y su influjo en diversos personajes, con el propósito de demostrar la hipótesis de que dicho país deviene algo más que una referencia. En su obra, México resulta un acontecimiento, como se entiende en la crítica posestructuralista, capaz de alterar la percepción de quienes allí habitan o arriban, posibilitando la invención de un territorio altamente caótico y cambiante.

  19. The Management of religious Diversity in West Africa: the excepcionalism of the Wolof and Yoruba in the post-independence period

    OpenAIRE

    2014-01-01

    La prevalencia del pluralismo religioso entre los yoruba y wolof ha atraído la atención de los estudiosos, con énfasis en el sostenimiento de la convivencia pacífica en medio de la diversidad religiosa. En este trabajo se compara la gestión de la diversidad religiosa entre los wolof y Yoruba destacando los diferentes contextos sociales en que se gestiona. El wolof y Yoruba adoptó un enfoque sincretista de la religión de la época pre-colonial y la norma persiste a pesar de la introducción y la...

  20. Cariótipo em leucemia mielóide aguda: importância e tipo de alteração em 30 pacientes ao diagnóstico

    OpenAIRE

    Pelloso Luís Arthur Flores; Chauffaille Maria de Lourdes Lopes Ferrari; Ghaname Fabiana Sinnot; Yamamoto Mihoko; Bahia Daniella Márcia Maranhão; Kerbauy José

    2003-01-01

    OBJETIVO: Análise sob o ponto de vista citogenético e clínico de pacientes com LMA. MÉTODOS: Foram estudados 30 pacientes, sendo 16 homens e 14 mulheres. A idade variou de 19 a 84 anos. O diagnóstico baseou-se na classificação OMS, imunofenotipagem e citogenética clássica por banda G. Foram tratados com o protocolo daunorrubicina e citarabina (3+7), com adição de ATRA na Leucemia Promielocítica Aguda. RESULTADOS: A taxa de sucesso de cariótipo foi 84%. De acordo com o cariótipo, os pacientes ...

  1. Memoria y relato

    Directory of Open Access Journals (Sweden)

    Igoa, José Manuel

    2004-01-01

    Full Text Available En este artículo se hacen algunas reflexiones acerca de las relaciones entre la memoria y el relato partiendo de un intento de aclarar la semántica de estos dos términos, sobre todo del primero. En su primera parte, se examinan diversas maneras de entender y abordar estas relaciones desde una óptica predominantemente psicológica. La segunda parte del artículo se dedica a explorar el papel que desempeñan los diversos sistemas y mecanismos de la memoria humana, tal y como se conciben y estudian actualmente en la Psicología Cognitiva, en las tareas de comprender y recordar relatos. También se subrayan en ella algunos problemas relevantes que han atraído la atención de los investigadores y expertos en la materia.…

  2. Immunomodulatory effects of honey cannot be distinguished from endotoxin

    DEFF Research Database (Denmark)

    Timm, Michael; Bartelt, Stine; Hansen, Erik Wind

    2008-01-01

    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 resistant...... to boiling and its immunomodulatory activity could be abrogated by the addition of polymyxin B. We speculate that the observed in vitro immunomodulatory effects of honey might solely be explained by the endotoxin content in the natural honeys....

  3. 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.

  4. Do paradigma molecular ao impacto no prognóstico: uma visão da leucemia promielocítica aguda

    OpenAIRE

    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...

  5. Selección de conexiones de acero para zonas sísmicas con base en criterios de confiabilidad

    Directory of Open Access Journals (Sweden)

    David de León Escobedo

    2011-01-01

    Full Text Available Los hallazgos encontrados a raíz del terremoto de Northridge en 1994 han atraído actualmente la atención de los especialistas, sobre todo en cuanto a los problemas de diseño y seguridad de las conexiones soldadas para estructuras ubicadas en zonas sísmicas. Para equilibrar la seguridad requerida deben tomarse decisiones en relación con los costos para prevenir la posibilidad de excederse algún estado límite de servicio. Las técnicas de confiabilidad estructural proporcionan el marco adecuado para incluir las incertidumbres inherentes en el proceso de diseño. La formulación propuesta permite apoyar a diseñadores y a constructores para la selección del tipo de conexión más conveniente para las zonas sísmicas.

  6. Desenvolvimento de mix de sais com reduzido teor de sódio: otimização e caracterização sensorial temporal (TDS e TI)

    OpenAIRE

    Gonçalves, Carla Saraiva

    2013-01-01

    A redução de sódio em alimentos tem atraído muita atenção, uma vez que os estudos indicam uma correlação entre a ingestão de sal na dieta e algumas doenças. Métodos de otimização são úteis dentro da ciência sensorial como uma maneira de obter um resultado sob um conjunto específico de condições para que seja possível compreender questões que proporcione potenciais fórmulas. Neste estudo, avaliou-se a concentração ótima do cloreto de sódio na sopa de batata, usando a escala ideal, e a magnitud...

  7. DETECTION AND ITS CLINICAL VALUE OF MINIMAL RESIDUAL DISEASES IN ACUTE PROMYELOCYTIC LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    姜国胜; 唐天华; 毕可红; 张玉昆; 任海全; 赵良玉; 郭桂月; 刘秀兰; 任青华; 姜枫勤; 刘传芳; 彭军; 田志刚

    2002-01-01

    Objective: To detect the minimal residual diseases (MRD) in acute promyelocytic leukemia (APL) after complete remission (CR) and to analyze its clinical value in prognosis. Methods: Reverse transcription Polymerase chain reaction (RT/PCR) was used to detect MRD of patients with APL. Results: MRD positive rate in patients with APL was 92.8% (39/42) before treatment and 56.7 (21/37) immediately after the ATRA or chemotherapy- induced CR. Furthermore, MRD positive rate wasrelated to the relapse in APL patients and could be considered as a marker to predict the relapse of patients with APL after CR. The MRD detection could also be applied to direct the consolidation therapy to prevent relapses. Conclusion: RT-PCR is valuable to monitor MRD and can be used as a marker to predict relapses.

  8. Acute Promyelocytic Leukemia in Four Year Old Female Child - A Case Report

    Directory of Open Access Journals (Sweden)

    Anirudha V. Kushtagi

    2014-07-01

    Full Text Available Leukemia is the most common malignancy of childhood representing about 30 % of oncohematological diseases diagnosed in children less than 15 years of age. We report the case of a 4 year old girl with acute promyelocytic leukemia whose blasts showed the morphology characteristic of acute promyelocytic leukemia variant. The case is reported because in the paediatric population the acute promyelocytic leukemia is a rare occurrence moreover, it represent a true oncohematology emergency, in this case the laboratory has a significant role since the timing of diagnosis must be very short. It helps in therapeutic protocols compared to conventional therapeutic protocols in Acute Myeloid Leukemia (AML, the introduction of retinoid All-Trans-Retinoic Acid (ATRA, both in children and adults with Acute Promyelocytic Leukemia (APL, has significantly reduced the early mortality.

  9. 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.

  10. Característica higroscópica e termodinâmica do coentro desidratado Hygroscopic and thermodynamic features of dehydrated coriander

    OpenAIRE

    Adriano Sant'Ana Silva; Francisco de Assis Cardoso Almeida; Niédja Marizze Cezar Alves; Karla dos Santos Melo; Josivanda Palmeira Gomes

    2010-01-01

    A determinação das isotermas de adsorção de umidade constitui fator essencial nos projetos e estudos de sistemas de secagem, processamento, armazenagem, embalagem e predição tempo de prateleira de produtos alimentícios. A obtenção das isotermas dar-se por meio da variação do conteúdo de umidade de equilíbrio em função da atividade de água a uma dada temperatura constante. A predição das curvas das isotermas é realizada por meio da aplicação de modelos matemáticos aos dados experimentais. Atra...

  11. Característica higroscópica e termodinâmica do coentro desidratado

    OpenAIRE

    Silva,Adriano Sant'Ana; Almeida,Francisco de Assis Cardoso; Alves,Niédja Marizze Cezar; Melo,Karla dos Santos; Gomes,Josivanda Palmeira

    2010-01-01

    A determinação das isotermas de adsorção de umidade constitui fator essencial nos projetos e estudos de sistemas de secagem, processamento, armazenagem, embalagem e predição tempo de prateleira de produtos alimentícios. A obtenção das isotermas dar-se por meio da variação do conteúdo de umidade de equilíbrio em função da atividade de água a uma dada temperatura constante. A predição das curvas das isotermas é realizada por meio da aplicação de modelos matemáticos aos dados experimentais. Atra...

  12. Digitalização das promoções de vendas e email marketing

    OpenAIRE

    Tojal, Fábio Manuel da Silva Pereira

    2014-01-01

    Dissertação de Mestrado apresentado ao Instituto de Contabilidade e Administração do Porto para a obtenção do grau de Mestre em Marketing Digital, sob orientação de Professor Doutor António Correia de Barros As Promoções de Vendas são um mecanismo de atração dos clientes fidelizados e de novos clientes. Estas focam aspetos como a importância das Marcas e o Preço que influencia bastante a decisão de compra e requer estratégias especialmente de comunicação para criar uma envolvente em tor...

  13. Lichensphere: a protected natural microhabitat of the non-lichenised fungal communities living in extreme environments of Antarctica.

    Science.gov (United States)

    Santiago, Iara F; Soares, Marco Aurélio; Rosa, Carlos A; Rosa, Luiz H

    2015-11-01

    We surveyed the diversity, distribution and ecology of non-lichenised fungal communities associated with the Antarctic lichens Usnea antarctica and Usnea aurantiaco-atra across Antarctica. The phylogenetic study of the 438 fungi isolates identified 74 taxa from 21 genera of Ascomycota, Basidiomycota and Zygomycota. The most abundant taxa were Pseudogymnoascus sp., Thelebolus sp., Antarctomyces psychrotrophicus and Cryptococcus victoriae, which are considered endemic and/or highly adapted to Antarctica. Thirty-five fungi may represent new and/or endemic species. The fungal communities displayed high diversity, richness and dominance indices; however, the similarity among the communities was variable. After discovering rich and diverse fungal communities composed of symbionts, decomposers, parasites and endemic and cold-adapted cosmopolitan taxa, we introduced the term "lichensphere". We hypothesised that the lichensphere may represent a protected natural microhabitat with favourable conditions able to help non-lichenised fungi and other Antarctic life forms survive and disperse in the extreme environments of Antarctica.

  14. 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...

  15. Los comuneros olvidados : la insurrección de 1781 en los llanos del Casanare

    Directory of Open Access Journals (Sweden)

    Jane M. Rausch

    1996-01-01

    Full Text Available Posiblemente ningún acontecimiento en la historia de la Nueva Granada del siglo XVIII ha atraído más la atención que la Insurrección de los Comuneros de 1781. En el bicentenario del levantamiento armado más serio que haya tenido lugar en el virreinato antes·de las guerras de independencia, los historiadores continúan debatiendo su significación. Mientras algunos consideran a los rebeldes como reformistas que buscaban la disminución de los impuestos sin desafiar el derecho de España a gobernar, otros los consideran precursores de la independencia política; y otros afirman que la insurrección pudo constituirse en una revolución social desde abajo traicionada por los de arriba.

  16. DESIGN EM SITES DE ENCONTRO: PROMESSAS DE AMOR VERDADEIRO, RÁPIDO, ANÔNIMO E GRATUITO

    Directory of Open Access Journals (Sweden)

    Ana Beatriz Pereira de Andrade

    2011-10-01

    Full Text Available O presente ensaio parte de pesquisa em desenvolvimento sobre a atração amorosa na Internet. Os sites de namoro são considerados lugar de encontro na rede, oferecendo aos seus usuários inúmeros recursos interativos para facilitar o conhecimento de possíveis parceiros amorosos. O design das páginas principais e anúncios são fonte de rico material de análise, reforçando mensagens atrativas que podem contribuir para o sucesso destes sites junto à sua clientela. Pretende-se apontar aspectos relacionados às estratégias utilizadas pelos sites para atrair pessoas.

  17. A new three-way variant t(15;22;17)(q22;q11.2;q21) in acute promyelocytic leukemia.

    Science.gov (United States)

    Kato, Takayasu; Hangaishi, Akira; Ichikawa, Motoshi; Motokura, Toru; Takahashi, Tsuyoshi; Kurokawa, Mineo

    2009-03-01

    Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid alpha-receptor (RARA) at 17q21. We report the case of a 44-year-old man with APL carrying a new complex variant translocation (15;22;17). Karyotypic analysis with G-banding of bone marrow cells revealed t(15;22;17) (q22;q11.2;q21). Fluorescence in situ hybridization with a PML/RARA dual-color DNA probe showed the fusion signals. RT-PCR analysis showed long-form PML/RARA fusion transcripts. A complete remission was attained with a course of conventional chemotherapy with all-trans retinoic acid (ATRA). This is the first report of a new three-way translocation of 22q11 involvement with APL.

  18. 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.

  19. Control de la forma, tamaño y composición de nanoestructuras de semiconductores III-V: anillos y puntos cuánticos

    OpenAIRE

    González Taboada, Alfonso

    2010-01-01

    La epitaxia de haces moleculares (MBE) es una técnica de crecimiento extremadamente versátil que permite la obtención de películas delgadas cristalinas nanoestructuradas. En particular, los puntos cuánticos (QDs) de InAs en GaAs (001) han atraído la atención de numerosos grupos de investigación durante las dos últimas décadas.1 Los niveles discretos de energía característicos de esas nanoestructuras presentan una fuerte dependencia con el tamaño, composición y morfología de las mismas. ...

  20. História em quadrinhos e a função poética na publicidade

    Directory of Open Access Journals (Sweden)

    Roberto Elísio dos Santos

    2015-08-01

    Full Text Available A relação entre a publicidade e as histórias em quadrinhos remonta ao início do século XX, quando as tiras publicadas em jornais atraíam a atenção crescente dos leitores. Partindoda função poética da linguagem, conforme a classificação feita pelo linguista russo Roman Jakobson, e seuuso na publicidade, este texto pretende categorizar as principais formas em que os quadrinhos atendem às necessidades de campanhas publicitárias. Por meio de elementos característicos da função poética da linguagem, os anúncios podem trazer informações úteis e manterem-se interessantes e vendáveis.

  1. What's behind the word? Assay for nonconformity

    Directory of Open Access Journals (Sweden)

    Jaime Torres

    2008-06-01

    Full Text Available El valor, sentido, uso y significado que tiene la palabra pueden ser ubicados en un escenario multidireccional: en el plano de lo real o en el plano de lo simbólico; en el uso práctico o en la imaginación; en el hacer y en el desear. La palabra nos ha conducido en la historia por el misticismo (la magia, por la verdad de las cosas (la ciencia, por ello es que nos provoca inquietud y nos atrae; toda palabra genera sospecha, sorprende, domina, ilusiona, entristece y libera; sin ella no podemos existir en el mundo, ni tampoco dar cuenta que caminamos en él, y sin su presencia no podríamos transformarlo.

  2. O COMPUTADOR NO ENSINO DE QUÍMICA: Impressões versus Realidade. Em Foco as Escolas Públicas da Baixada Fluminense.

    Directory of Open Access Journals (Sweden)

    Anna Maria Canavarro Benite

    Full Text Available O uso de Tecnologias da Informação e Comunicação (TICs na educação tem atraído atenção generalizada. Esse panorama permite diferentes leituras sobre a utilização de computadores no processo de ensino-aprendizagem. Nesta perspectiva, este artigo relata uma reflexão em bases sócio-históricas e culturais, sobre a compreensão das potencialidades e limitações do uso do computador em Escolas do Ensino Médio da Rede Pública da Baixada Fluminense, para o Ensino de Química. Algumas considerações gerais, referentes às primeiras experiências desta utilização concluem nossa apresentação da investigação.

  3. El fútbol español como paradigma. Una miscelánea

    OpenAIRE

    Leguina, Joaquín

    2006-01-01

    Esta miscelánea aborda el fenómeno futbolístico en España, primero desde la óptica del espectáculo: ¿por qué este juego de pelota atrae a las masas?, ¿qué papel juegan los árbitros en la emoción del juego? son algunas de las preguntas que el autor pretende elucidar. A continuación, el autor aborda la relación entre los clubes de fútbol con sus connotaciones ideológicas y políticas y el consiguiente juego identitario de equipos como el Club de Fútbol Barcelona y el Atlethi...

  4. Analysis of the management of Twyfelfontein World Heritage Site, Namibia

    OpenAIRE

    Imalwa, Emma

    2016-01-01

    Tese de Doutoramento em Quaternário, Materias e Culturas Os sítios culturais designados como Património Mundial estão entre as principais atrações turísticas do mundo. O uso do Patrimônio Mundial pelos visitantes gera tensões às organizações do património, sobre as suas possibilidades de proteção e apresentação dos valores universais excecionais pelos quais um sítio foi inscrito na Lista do Património Mundial. O reconhecimento dos desafios locais do património mundial tem forçado uma avali...

  5. Relações de Produção no Garimpo de Poconé - MT

    Directory of Open Access Journals (Sweden)

    José Manuel Carvalho Marta

    2011-05-01

    Full Text Available Este artigo trata de atividades garimpeiras em Poconé, Mato Grosso, no período de 1985 a 1995, período no qual o garimpo respondeu mais fortemente pela geração de renda da população em emprego informal no Estado. Caracteriza-se o trabalho semi-mecanizado de aproveitamento dos rejeitos dos “rabos de bica” no processo industrial de recuperação com moinhos de martelo e de bola. Ademais, procura-se discutir o crescimento populacional decorrente da atração do garimpo e da população garimpeira ao longo do período.

  6. Biotecnologia para saúde humana: tecnologias, aplicações e inserção na indústria farmacêutica

    OpenAIRE

    Neto, Carla Reis de Souza; Capanema, Luciana Xavier de Lemos; Palmeira Filho, Pedro Lins; Pieroni, João Paulo; Souza, José Oswaldo Barros de; Silva, Leandro Gomes da

    2009-01-01

    As potencialidades de aplicação da biotecnologia no campo da saúde são muitas e têm atraído o interesse não apenas de cientistas, mas também da indústria, de investidores privados e dos gestores de políticas públicas em todo o mundo. No sentido de contribuir para a organização e o desenvolvimento do complexo industrial da saúde no Brasil, é necessário entender melhor as apostas que estão sendo feitas em nível mundial, tanto pela indústria, em termos de aplicações, quanto pelo meio científico,...

  7. Capturando colibríes a través de un lente

    Directory of Open Access Journals (Sweden)

    Yeisson Ricardo Cárdenas

    2017-01-01

    Full Text Available Mi gusto por las aves me ha llevado a vivir varias experiencias enriquecedoras, una de ellas ha sido a través de la fotografía. Cuando comencé a observar estos increíbles animales, quedé sorprendido por su gran diversidad de colores, formas y cantos. A medida que iba fotografiando diferentes tipos de aves, me empecé a sentir atraído por un grupo en especial: los colibríes, los cuales son difíciles de fotografiar debido a su particular tamaño y ágiles movimientos. Esto produjo en mí un interés por consultar y algunas veces investigar acerca de su evolución, diversidad e importancia ecológica

  8. Estudo químico-quântico do potencial carcinogênico de agrotóxicos

    OpenAIRE

    Anunciada Barros, Karina

    2010-01-01

    Neste trabalho verificamos o potencial carcinogênico de alguns agrotóxicos utilizados na agricultura. Para a previsão da carcinogenicidade foram realizados cálculos computacionais semi-empíricos RM1 de parâmetros eletrônicos como afinidade eletrônica (EA), energia de interação (∆EH-L), momento dipolo (μ), atração eletrostática (∆q) e calor de formação (Hf). Utilizamos o modelo proposto por Pavão e Leão para descrever a interação carcinógeno-DNA. Seguindo a teoria da ressonânc...

  9. HOXB6-mRNA and its gene expression in the differentiation process of human cytomegalovirus-infected hematopoietic stem progenitor cells into granulocyte and erythrocyte progenitor cells%经人巨细胞病毒感染人脐血造血干细胞向粒-巨噬系和红系祖细胞增殖过程中HOXB6-mRNA及其基因表达

    Institute of Scientific and Technical Information of China (English)

    刘文君; 陈艾; 陈红英; 冉伶; 郭渠莲

    2008-01-01

    BACKGROUND: Is the inhibition of the hematopoietic stem progenitor cell (HSPC) proliferation and differentiation after human cytomegalovirus (HCMV) infection associated with abnormal expression of infected cell proliferated gene?OBJECTIVE: To observe the HOXB6-mRNA expression in the process of proliferation and differentiation of HCMV-infected HSPC into colony-forming unit granulocyte-macrophage (CFU-GM) and colony-forming unit erythroid (CFU-E).DESIGN: A controlled observation.SETTING: Laboratory for Molecular Biology, Affiliated Hospital of Luzhou Medical College, Lanzhou, Gansu Province, China.MATERIALS: All cord blood (CB) specimens were provided by the Obstetrics Department of Affiliated Hospital of Luzhon Medical College. They were collected from the umbilical vein of normal term neonates delivered spontaneously. All neonate mothers were healthy and HBS-Ag-negative. HCMV-IgM antibody revealed by routine ELUSA and HCMV-DNA checked by PCR were undetectable. Written informed consent for the laboratory measurements was obtained from each neonate mother, and the protocol was approved by the hospital's Ethics Committee. HCMV-AD169 strains were obtained from the Institute of Virology, Chinese Academy of Preventive Medicine. All-trans retinoic acid (ATRA, lot No. 20010126) was provided by Chongqing Huapont Pharm. Co., Ltd., China.METHODS: This study was performed at the Laboratory of Molecular Biology (state-level), Affiliated Hospital of Luzhou Medical College of Luzhou Medical College from April 2006 to April 2007. Cord blood mononuclear cells were separated for HSPC culture. According to different interventions, the study consisted of 4 groups. Control group: no HCMV virus solution was added and equal volume of culture medium was added instead. HCMV group: 105 PFU/mL HCMV-AD169 virus solution was added to the culture system. ATRA group: ATRA was added into the cultivation system at the final concentration of 60 μ mol/L. HCMV+ATRA group: ATRA was added into the

  10. 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

  11. Molecular recognition of CYP26A1 binding pockets and structure-activity relationship studies for design of potent and selective retinoic acid metabolism blocking agents.

    Science.gov (United States)

    Sun, Bin; Song, Shuai; Hao, Chen-Zhou; Huang, Wan-Xu; Liu, Chun-Chi; Xie, Hong-Lei; Lin, Bin; Cheng, Mao-Sheng; Zhao, Dong-Mei

    2015-03-01

    All-trans-retinoic acid (ATRA), the biologically most active metabolite of vitamin A, plays a major role in the regulation of cellular differentiation and proliferation, and it is also an important pharmacological agent particularly used in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. However, ATRA is very easy to be metabolized into 4-hydroxyl-RA in vivo by CYP26A1, an inducible cytochrome P450 enzyme, eventually into more polar metabolites. Therefore, it is vital to develop specific retinoic acid metabolism blocking agents (RAMBAs) to inhibit the metabolic enzyme CYP26A1 in the treatment of relevant diseases aforementioned. In this study, CYP26A1 and its interactions with retinoic acid-competitive metabolism blocking agents were investigated by a combined ligand- and structure-based approach. First, since the crystal structure of CYP26A1 protein has not been determined, we constructed the 3D structure of CYP26A1 using homology modeling. In order to achieve a deeper insight into the mode of action of RAMBAs in the active site, the molecular superimposition model and the common feature pharmacophore model were constructed, and molecular docking was performed. The molecular superimposition model is composed of three features: the main chain groups, side chain groups, and azole groups. The common feature pharmacophore model consists of five chemical features: four hydrophobic groups and one hydrogen acceptor (HHHHA). The results of molecular docking show that the characteristic groups of RAMBAs were mapped into three different active pockets, respectively. A structure-activity relationship (SAR) was obtained by a combination of the molecular superimposition and docking results with the pharmacophore model. This study gives more insight into the interaction model inside the CYP26A1 active site and provides guidance for the design of more potent and possibly more selective RAMBAs.

  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. Retinoids in lung cancer chemoprevention and treatment.

    Science.gov (United States)

    Toma, S; Raffo, P; Isnardi, L; Palumbo, R

    1999-01-01

    In this review, we aim to synthesize the emerging picture of retinoids in lung cancer through a summary of ongoing investigations in biology, chemoprevention and therapy settings, in an attempt to clarify the possible role of these agents in such a disease. Early work in head and neck cancer has evidenced the capability of retinoids to interrupt field carcinogenesis by reversing premalignant lesions and decreasing the incidence of second primary tumors (SPTs). At this time, the completed randomized trials in lung cancer have failed to demonstrate an evident chemopreventive effect of the tested agents on different study end points, although both a marginally significant benefit of retinol palmitate in time-to-development rates for smoke-related SPTs and a potential preventive effect of retinol supplementation against mesothelioma in selected populations of asbestos-exposed workers have been recently reported. Concerning the role of retinoids in lung cancer treatment, a moderate activity of 13-cis-retinoic acid (13cRA) or all-transretinoic acid (ATRA) as single agents has been reported in small series of advanced, mostly pretreated lung cancer patients. More encouraging findings derive from combination studies, in which retinoids, especially ATRA, are added to either alpha-interferon or chemotherapy and radiotherapy. Major recent advances have been made towards the understanding of retinoids mechanisms of action; at this regard, the role of RAR-beta basal or treatment-induced levels seems to be of particular interest as intermediate end point and/or independent prognostic factor, besides their known importance in lung carcinogenesis. Future research for chemopreventive and therapeutic programs with retinoids in lung cancer should be focused on the investigation of new generation compounds with a specificity for individual retinoid nuclear receptors. Such selective molecules may have a greater activity against lung cancer, with a more favourable toxicity profile, as

  14. DNA-mediated adjuvant immunotherapy extends survival in two different mouse models of myeloid malignancies

    Science.gov (United States)

    Le Pogam, Carole; Patel, Satyananda; Gorombei, Petra; Guerenne, Laura; Krief, Patricia; Omidvar, Nader; Tekin, Nilgun; Bernasconi, Elena; Sicre, Flore; Schlageter, Marie-Helene; Chopin, Martine; Noguera, Maria-Elena; West, Robert; Abu, Ansu; Mathews, Vikram; Pla, Marika; Fenaux, Pierre; Chomienne, Christine; Padua, Rose Ann

    2015-01-01

    We have previously shown that a specific promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) DNA vaccine combined with all-trans retinoic acid (ATRA) increases the number of long term survivors with enhanced immune responses in a mouse model of acute promyelocytic leukemia (APL). This study reports the efficacy of a non-specific DNA vaccine, pVAX14Flipper (pVAX14), in both APL and high risk myelodysplastic syndrome (HR-MDS) models. PVAX14 is comprised of novel immunogenic DNA sequences inserted into the pVAX1 therapeutic plasmid. APL mice treated with pVAX14 combined with ATRA had increased survival comparable to that obtained with a specific PML-RARA vaccine. Moreover, the survival advantage correlated with decreased PML-RARA transcript levels and increase in anti-RARA antibody production. In HR-MDS mice, pVAX14 significantly improved survival and reduced biomarkers of leukemic transformation such as phosphorylated mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) 1. In both preclinical models, pVAX14 vaccine significantly increased interferon gamma (IFNγ) production, memory T-cells (memT), reduced the number of colony forming units (CFU) and increased expression of the adapter molecule signalling to NF-κB, MyD88. These results demonstrate the adjuvant properties of pVAX14 providing thus new approaches to improve clinical outcome in two different models of myeloid malignancies, which may have potential for a broader applicability in other cancers. PMID:26378812

  15. Influence of larval and pupal products on the oviposition behavior of Aedes Fluviatilis (Lutz (Diptera: Culicidae

    Directory of Open Access Journals (Sweden)

    Rotraut A. G. B. Consoli

    1988-06-01

    Full Text Available Several larval and pupal products of Aedes fluviatilis (Lutz were tested for their influence on the oviposition behaviour of females of the same species. Significant (alfa = 0,05 atractiveness was shown by: larval water, previously containing 5 to 15 larvae/1,5 ml; larval water, preserved up to 38 days; evaporate and reconstructed larval water extracts up to 2 years after production and water filtered through fresh or dried ground larvae. hexanic larval water extracts and water filtered through fresh or dired ground pupae did not influence oviposition.Estudou-se a influência sobre o comportamento de oviposição das fêmeas de Aedes fluviatilis (Lutz de produtos derivados das formas imaturas da mesma espécie. As fêmeas foram atraídas significativamente (x=0,05 por ocasião da ovoposição por: água destilada que contivera 5 ou 15 larvas/1,5 ml, a mesma água (5 larvas/1,5 mlapós sua preservação por 38 dias; extratos evaporados e reconstituídos de água que conteve larvas, por até dois anos a sua produção, e filtrados de macerados frescos e secos de larvas. Extratos hexânicos de água que conteve larvas e filtrados de macerados descos e secos de pupas não atraíram a ovoposição das fêmeas.

  16. 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.

  17. Transcriptional regulation of genes involved in retinoic acid metabolism in Senegalese sole larvae.

    Science.gov (United States)

    Boglino, Anaïs; Ponce, Marian; Cousin, Xavier; Gisbert, Enric; Manchado, Manuel

    2017-01-01

    The aim of this study was the characterization of transcriptional regulatory pathways mediated by retinoic acid (RA) in Senegalese sole larvae. For this purpose, pre-metamorphic larvae were treated with a low concentration of DEAB, an inhibitor of RALDH enzyme, until the end of metamorphosis. No differences in growth, eye migration or survival were observed. Nevertheless, gene expression analysis revealed a total of 20 transcripts differentially expressed during larval development and only six related with DEAB treatments directly involved in RA metabolism and actions (rdh10a, aldh1a2, crbp1, igf2r, rarg and cyp26a1) to adapt to a low-RA environment. In a second experiment, post-metamorphic larvae were exposed to the all-trans RA (atRA) observing an opposite regulation for those genes involved in RA synthesis and degradation (rdh10a, aldh1a2, crbp1 and cyp26a1) as well as other related with thyroid- (dio2) and IGF-axes (igfbp1, igf2r and igfbp5) to balance RA levels. In a third experiment, DEAB-pretreated post-metamorphic larvae were exposed to atRA and TTNPB (a specific RAR agonist). Both drugs down-regulated rdh10a and aldh1a2 and up-regulated cyp26a1 expression demonstrating their important role in RA homeostasis. Moreover, five retinoic receptors that mediate RA actions, the thyroid receptor thrb, and five IGF binding proteins changed differentially their expression. Overall, this study demonstrates that exogenous RA modulates the expression of some genes involved in the RA synthesis, degradation and cellular transport through RAR-mediated regulatory pathways establishing a negative feedback regulatory mechanism necessary to balance endogenous RA levels and gradients.

  18. Reduced retinoids and retinoid receptors' expression in pancreatic cancer: A link to patient survival.

    Science.gov (United States)

    Bleul, Tim; Rühl, Ralph; Bulashevska, Svetlana; Karakhanova, Svetlana; Werner, Jens; Bazhin, Alexandr V

    2015-09-01

    Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. All-trans retinoic acid (ATRA) is the major physiologically active form of vitamin A, regulating expression of many genes. Disturbances of vitamin A metabolism are prevalent in some cancer cells. The main aim of this work was to investigate deeply the components of retinoid signaling in PDAC compared to in the normal pancreas and to prove the clinical importance of retinoid receptor expression. For the study, human tumor tissues obtained from PDAC patients and murine tumors from the orthotopic Panc02 model were used for the analysis of retinoids, using high performance liquid chromatography mass spectrometry and real-time RT-PCR gene expression analysis. Survival probabilities in univariate analysis were estimated using the Kaplan-Meier method and the Cox proportional hazards model was used for the multivariate analysis. In this work, we showed for the first time that the ATRA and all-trans retinol concentration is reduced in PDAC tissue compared to their normal counterparts. The expression of RARα and β as well as RXRα and β are down-regulated in PDAC tissue. This reduced expression of retinoid receptors correlates with the expression of some markers of differentiation and epithelial-to-mesenchymal transition as well as of cancer stem cell markers. Importantly, the expression of RARα and RXRβ is associated with better overall survival of PDAC patients. Thus, reduction of retinoids and their receptors is an important feature of PDAC and is associated with worse patient survival outcomes.

  19. MIR125B1 represses the degradation of the PML-RARA oncoprotein by an autophagy-lysosomal pathway in acute promyelocytic leukemia.

    Science.gov (United States)

    Zeng, Cheng-Wu; Chen, Zhen-Hua; Zhang, Xing-Ju; Han, Bo-Wei; Lin, Kang-Yu; Li, Xiao-Juan; Wei, Pan-Pan; Zhang, Hua; Li, Yangqiu; Chen, Yue-Qin

    2014-10-01

    Acute promyelocytic leukemia (APL) is characterized by the t(15;17)-associated PML-RARA fusion gene. We have previously found that MIR125B1 is highly expressed in patients with APL and may be associated with disease pathogenesis; however, the mechanism by which MIR125B1 exerts its oncogenic potential has not been fully elucidated. Here, we demonstrated that MIR125B1 abundance correlates with the PML-RARA status. MIR125B1 overexpression enhanced PML-RARA expression and inhibited the ATRA-induced degradation of the PML-RARA oncoprotein. RNA-seq analysis revealed a direct link between the PML-RARA degradation pathway and MIR125B1-arrested differentiation. We further demonstrated that the MIR125B1-mediated blockade of PML-RARA proteolysis was regulated via an autophagy-lysosomal pathway, contributing to the inhibition of APL differentiation. Furthermore, we identified DRAM2 (DNA-damage regulated autophagy modulator 2), a critical regulator of autophagy, as a novel target that was at least partly responsible for the function of MIR125B1 involved in autophagy. Importantly, the knockdown phenotypes for DRAM2 are similar to the effects of overexpressing MIR125B1 as impairment of PML-RARA degradation, inhibition of autophagy, and myeloid cell differentiation arrest. These effects of MIR125B1 and its target DRAM2 were further confirmed in an APL mouse model. Thus, MIR125B1 dysregulation may interfere with the effectiveness of ATRA-mediated differentiation through an autophagy-dependent pathway, representing a novel potential APL therapeutic target.

  20. Experimental effect of retinoic acids on apoptosis during the development of diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Nami Nishikiori

    2008-03-01

    Full Text Available Nami Nishikiori1,2, Makoto Osanai2, Hideki Chiba2, Takashi Kojima2, Shuichiro Inatomi1,2, Hiroshi Ohguro1, Norimasa Sawada2Departments of 1Ophthalmology and 2Pathology, Sapporo Medical University School of MedicinePurpose: This study was conducted to investigate whether retinoic acids (RAs had any effect on apoptosis during the development of diabetic retinopathy.Methods: To investigate whether RAs had any effect on apoptosis during the development of diabetic retinopathy, we housed 32 C57BL/6 male mice and induced diabetes in 24 by intra peritoneal injections of streptozotocin (STZ; Sigma, St Louis, MO and treated 16 of the diabetic mice with the RAs, all-trans-retinoic acid (ATRA (seven mice and 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenylcarboxamido] benzoic acid (Am580 (nine mice. The other eight mice were used as diabetic controls. We then measured apoptosis in the retina by TdT-dUTP terminal nick-end labeling assay.Results: RAs inhibited the apoptosis of retinal cells in diabetic retinopathy. Many apoptotic cells were observed in retinas of the eight diabetic control mice (mean v