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Spacecraft observations revealed that rocks on carbonaceous asteroids, which constitute the most numerous class by composition, can develop millimeter-to-meter-scale fractures due to thermal stresses. However, signatures of this process on the second-most populous group of asteroids, the S-complex, have been poorly constrained. Here, we report observations of boulders' fractures on Dimorphos, which is the moonlet of the S-complex asteroid (65803) Didymos, the target of NASA's Double Asteroid Redirection Test (DART) planetary defense mission. We show that the size-frequency distribution and orientation of the mapped fractures are consistent with formation through thermal fatigue. The fractures' preferential orientation supports that these have originated in situ on Dimorphos boulders and not on Didymos boulders later transferred to Dimorphos. Based on our model of the fracture propagation, we propose that thermal fatigue on rocks exposed on the surface of S-type asteroids can form shallow, horizontally propagating fractures in much shorter timescales (100 kyr) than in the direction normal to the boulder surface (order of Myrs). The presence of boulder fields affected by thermal fracturing on near-Earth asteroid surfaces may contribute to an enhancement in the ejected mass and momentum from kinetic impactors when deflecting asteroids.
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The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 ± 4 degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens of metres per second to about 500 metres per second.
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Occupational and environmental exposures in the agricultural industry have been associated with several illnesses and poor health outcomes. Information regarding the characteristics and health status of the labor force working in the agricultural sector in Puerto Rico is limited. The overall objective of this study was to increase the available information on agricultural workers health and needs by ascertaining the potential differences in characteristics and health status of farmworkers when compared to the general population in rural Puerto Rico This cross-sectional study used the collection and analysis of medical records of agricultural workers and non-agricultural workers in Hospital General Castañer, located in Lares, Puerto Rico. The research period was five years, from 2012 to 2016. This research described agricultural workers' demographic and socioeconomic profile and evaluated relationships between one or more demographic variables and farmer's health. Agricultural workers presented alower prevalence of hypertensive disease (69.4%) and ahigher prevalence of cerebrovascular disease (3.4%) when compared to non-agricultural workers. In other words, agricultural workers were 21% less likely to have hypertensive disease as compared to non-agricultural workers. Results for agricultural workers showed that 4.0% of the workers were diagnosed with arthritis, and 48.8% had suffered at least one type of dorsopathy. The results from this research provide useful information for developing an appropriate framework to address Puerto Rican agricultural worker's health while promoting the agricultural industry development on the island. Finally, this study provided insight into the prevalence and demographic characteristics of agriculture workers in acentral region of Puerto Rico. Further efforts are needed to better define the agricultural workers and farming communities in Puerto Rico that may be exposed to related hazards.
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Emprego , Fazendeiros , Doença Crônica , Estudos Transversais , Humanos , Porto Rico/epidemiologiaRESUMO
OBJECTIVE: The aim of this pilot study was to determine whether the low anti-müllerian hormone (AMH) serum level, due to severe endometriosis, was associated with diminished oocyte yield, poor oocyte/embryo quality and reduced in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) clinical outcomes in young patients (<37 years old). PATIENTS AND METHODS: A total of 50 IVF cycles of patients younger than 37 with severe endometriosis were retrospectively analyzed in a single center between November 2016 and July 2018. The clinical outcome was then compared to a control group of 84 patients with no story of endometriosis and normal AMH value. AMH value was evaluated within three months before the stimulation. In these two groups, number and maturation of retrieved oocytes, embryo quality, and pregnancy outcomes were evaluated and compared using Student's t-test and Fisher's test. RESULTS: The number of oocytes retrieved per cycle and the percentage of mature oocytes (MII) were significantly lower (p < 0.001) in IVF patients with severe endometriosis and AMH value ≤ 1.1 ng/ml (Group A; 3.8±2.6 retrieved oocytes, 70% MII) compared to patients without endometriosis and AMH levels > 1.1 ng/ml (Group B; 6.9±4.6 retrieved oocytes, 83% MII). On the other hand, embryo morphology, implantation rate (31% vs. 33%; p = 0.833) and pregnancy rate (50% vs. 49%; p = 1) were comparable in the two groups. CONCLUSIONS: This study shows that younger patients with an impairment of the ovarian reserve due to severe endometriosis, displayed a diminished oocyte yield but not a reduction in embryo quality and pregnancy outcomes. These results suggest that serum AMH levels should not be adopted as a criterion for discouraging these patients from undergoing IVF/ICSI treatments.
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Endometriose/patologia , Fertilização in vitro , Oócitos/patologia , Adulto , Hormônio Antimülleriano/metabolismo , Feminino , Humanos , Oócitos/metabolismo , Gravidez , Índice de Gravidade de DoençaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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The preparation of Fe-decorated sporopollenins was achieved using pollen grains and an ionic liquid as solvent and functionalizing agent. The integrity of the organic capsules was ascertained through scanning electron microscopy studies. The presence of Fe in the capsule was investigated using FT-IR, X-ray photoemission spectroscopy and energy-dispersive X-ray spectroscopy. Electron paramagnetic resonance and magnetization measurements allowed us to demonstrate the paramagnetic behavior of our Fe-functionalized sporopollenin. A few potential applications of pollen-based systems functionalized with magnetic metal ions via ionic liquids are discussed.
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Síndrome de Birt-Hogg-Dubé/diagnóstico , Neoplasias de Cabeça e Pescoço/diagnóstico , Adulto , Síndrome de Birt-Hogg-Dubé/genética , Síndrome de Birt-Hogg-Dubé/patologia , Dermoscopia , Testes Genéticos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Técnicas de Diagnóstico MolecularRESUMO
Von Willebrand disease is a commonly inherited bleeding disorder caused by defects of von Willebrand factor (vWF). In the most common valve diseases, aortic valve stenosis (AVS) and mitral valve regurgitation (MVR), a bleeding tendency has been described in a number of patients. This has been associated to a high turbulence of blood flow through the compromised valve, promoting degradation of vWF with loss of high-molecular-weight multimers of vWF (HMWM), leading to an acquired von Willebrand syndrome (AvWS). We analysed three groups of patients, one affected by AVS, treated with transcatheter aortic valve implantation (TAVI), the second group of patients affected by MVR, treated with Mitraclip® mitral valve repair. The third group was represented by patients also affected by AVS, but not eligible for TAVI and treated with standard surgery. A fourth group of patients that underwent percutaneous coronary intervention (PCI) with stenting was used as a control. Our results demonstrated that the level of vWF measured as antigen concentration (vWF:Ag) increases in all cohorts of patients after treatment, while in control PCI patients, no modification of vWF:Ag has been registered. Western blot analysis showed only a quantitative loss of vWF in the pre-treatment time, but without significant HMWM modification. The monitoring of the vWF:Ag concentration, but not the quality of HMWM, can indicate the status of blood flow in the treated patients, thus introducing the possibility of using the vWF antigen detection in monitoring the status of replaced or repaired valves.
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Estenose da Valva Aórtica/sangue , Insuficiência da Valva Mitral/sangue , Fator de von Willebrand/análise , Estenose da Valva Aórtica/diagnóstico , Humanos , Insuficiência da Valva Mitral/diagnóstico , Intervenção Coronária Percutânea , Plasma , Substituição da Valva Aórtica Transcateter , Doenças de von WillebrandRESUMO
The pathogenic molecular mechanisms underlying the insurgence of nasal polyps has not been completely defined. In some patients, these lesions can have a recurrence after surgery removal, and the difference between recurrent and not recurrent patients is still unclear. To molecularly characterize and distinguish between these two classes, a cohort of patients affected by nasal polyposis was analysed. In all patients we analysed the p63 isoform expression using fresh tissues taken after surgery. Moreover, confocal immunofluorescence analysis of fixed sections was performed. The results show high ΔNp63 expression in samples from the nasal polyps of patients compared to the normal epithelia. Analysis of the expression level of the TAp63 isoform shows differential expression between the patients with recurrence compared to those not recurring. The data, considered as the ΔN/TAp63 ratio, really discriminate the two groups. In fact, even though ΔNp63 is expressed in non-recurrent patients, the resulting ratio ΔN/TAp63 is significantly lower in these patients. This clearly indicates that the status of TAp63 expression, represented by the ΔN/TAp63 ratio, could be considered a prognostic marker of low recurrence probability. In these samples we also investigated the expression of OTX2 transcription factor, known to be a selective activator of TAp63, detecting a significant correlation. Database analysis of HNSCC patients showed increased survival for the patients presenting OTX2 amplification and/or overexpression. These results, together with the fact that TAp63 can be selectively upregulated by HDAC inhibitors, open the possibility to consider local treatment of recurrent nasal polyps with these molecules.
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Pólipos Nasais/metabolismo , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Humanos , Pólipos Nasais/genética , Fatores de Transcrição Otx/genética , Fatores de Transcrição Otx/metabolismo , Isoformas de Proteínas/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Melanoma is a dangerous form of skin cancer derived from the malignant transformation of melanocytes. The transcription factor SOX2 is not expressed in melanocytes, however, it has been shown to be differentially expressed between benign nevi and malignant melanomas and to be essential for melanoma stem cell maintenance and expansion in vitro and in xenograft models. By using a mouse model in which BRafV600E mutation cooperates with Pten loss to induce the development of metastatic melanoma, we investigated if Sox2 is required during the process of melanomagenesis, melanoma growth and metastasis and in the acquisition of resistance to BRAF inhibitors (BRAFi) treatments. We found that deletion of Sox2 specifically in Pten null and BRafV600E-expressing melanocytes did not prevent tumor formation and did not modify the temporal kinetics of melanoma occurrence compared to Sox2 wt mice. In addition, tumor growth was similar between Sox2 wt and Sox2 deleted (del) melanomas. By querying publicly available databases, we did not find statistically significant differences in SOX2 expression levels between benign nevi and melanomas, and analysis on two melanoma patient cohorts confirmed that Sox2 levels did not significantly change between primary and metastatic melanomas. Melanoma cell lines derived from both Sox2 genotypes showed a similar sensitivity to vemurafenib treatment and the same ability to develop vemurafenib resistance in long-term cultures. Development of vemurafenib resistance was not dependent on SOX2 expression also in human melanoma cell lines in vitro. Our findings exclude an oncogenic function for Sox2 during melanoma development and do not support a role for this transcription factor in the acquisition of resistance to BRAFi treatments.
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Melanoma/etiologia , Fatores de Transcrição SOXB1/fisiologia , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Humanos , Indóis/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/secundário , Camundongos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/fisiologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/fisiologia , Sulfonamidas/uso terapêutico , VemurafenibRESUMO
We assessed a method for the preparation of small, highly stable and unprotected Pd nanoparticles by picosecond laser ablation in 2-propanol. The nanoparticles can be extracted from 2-propanol by centrifugation and redispersed in water, where a strongly negative ζ-potential assures long term stability. The proposed procedure permits reduction of particle size down to 1.6nm and optimization of the Pd(0):Pd(II) ratio which, in the best cases, was of the order of 6:1. The increase of this ratio with ablation times has been correlated to the high temperature conversion of PdO to metallic Pd by a simple theoretical model. A study of the relationship between colloid absorption at 400nm and Pd concentration permitted the role of PdO in the determination of the UV-vis spectra to be clarified and the limits of the Mie theory for the evaluation of colloid concentration to be established. The absorption at 400nm can be used as a fast method to estimate the Pd content in the colloids, provided that a calibration of the ablation process is preliminarily performed.
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We propose energy-selective neutron imaging as a new and non-destructive method to investigate rare metallic meteorites. It is based on attenuation of a neutron beam of limited spectral distribution in a sample depending on the elemental composition and crystalline structure. Radiography and tomography allow obtaining the presence, morphology and orientation information in the bulk of mineral inclusions, oxide crust and crystalline structure. Its usage in classification and meteor formation studies would be of great value.
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A significant proportion of human cancers overexpress DNA polymerase beta (Pol beta), the major DNA polymerase involved in base excision repair. The underlying mechanism and biological consequences of overexpression of this protein are unknown. We examined whether Pol beta, expressed at levels found in tumor cells, is involved in the repair of DNA damage induced by oxaliplatin treatment and whether the expression status of this protein alters the sensitivity of cells to oxaliplatin. DNA damage induced by oxaliplatin treatment of HCT116 and HT29 colon cancer cells was observed to be associated with the stabilization of Pol beta protein on chromatin. In comparison with HCT116 colon cancer cells, isogenic oxaliplatin-resistant (HCT-OR) cells were found to have higher constitutive levels of Pol beta protein, faster in vitro repair of a DNA substrate containing a single nucleotide gap and faster repair of 1,2-GG oxaliplatin adduct levels in cells. In HCT-OR cells, small interfering RNA knockdown of Pol beta delayed the repair of oxaliplatin-induced DNA damage. In a different model system, Pol beta-deficient fibroblasts were less able to repair 1,2-GG oxaliplatin adducts and were hypersensitive to oxaliplatin treatment compared with isogenic Pol beta-expressing cells. Consistent with previous studies, Pol beta-deficient mouse fibroblasts were not hypersensitive to cisplatin treatment. These data provide the first link between oxaliplatin sensitivity and DNA repair involving Pol beta. They demonstrate that Pol beta modulates the sensitivity of cells to oxaliplatin treatment.
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DNA Polimerase beta/metabolismo , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos/farmacologia , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Dano ao DNA , DNA Polimerase beta/deficiência , DNA Polimerase beta/genética , Reparo do DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Células HCT116 , Células HT29 , Humanos , Camundongos , Camundongos Knockout , Oxaliplatina , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
Energy homeostasis is controlled by a complex regulatory system of molecules that affect food intake and that are critical for maintaining a stable body weight during life. Ghrelin is a peptide of 28 amino acid synthesized predominantly by the stomach and the gut, which activate the type 1a growth hormone (GH) secretagogue receptor (GHS-R1a), a G-protein coupled receptor. The acylated form of ghrelin potently stimulates GH secretion both in vitro and in vivo in several animal species, including humans. Beside the endocrine effect, ghrelin shows also extraendocrine activities, including stimulation of feeding behaviour. Several classes of small synthetic peptide and non-peptide ligands of the GHS-R1a have been described and are able to release GH and stimulate food intake. However, in time, it appeared that the stimulating effects on GH secretion could be divorced from those on food intake, suggesting that more than a single receptor might be involved. Several experimental data have even questioned the physiological role of ghrelin in the control of GH secretion and energy metabolism. By using novel agonists, partial agonists, and antagonists for the GHS-R1a receptor, we have studied whether the stimulation of this receptor could account for the purported physiological role of ghrelin. Our results demonstrate that the ability to bind in vitro the GHS-R1a is not predictive of the in vivo biological activity of the compounds and that the endocrine and extraendocrine effects could be mediated also by receptors different from the GHS-R1a.
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Comportamento Alimentar/fisiologia , Grelina/fisiologia , Hormônio do Crescimento/metabolismo , Hormônio do Crescimento Humano/metabolismo , Receptores de Grelina/fisiologia , Triazóis/efeitos adversos , Análise de Variância , Animais , Metabolismo Energético , Grelina/metabolismo , Homeostase , Humanos , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/fisiologia , Triazóis/administração & dosagemRESUMO
AIMS: To examine the expression of DNA mismatch repair (MMR) proteins and the presence of microsatellite instability (MSI) in seven primary mucosal melanomas of the head and neck (MMHN). METHODS AND RESULTS: Haematoxylin and eosin staining and immunohistochemical analysis for routine diagnostic markers and for MMR proteins were performed. Six cases were examined for MSI. Four cases were monomorphous and three cases were pleomorphic type MMHN. Melanocytic markers were positive in all cases. Immunoreactivity for MMR proteins was weak in normal epithelium. The neoplastic tissue in six cases showed positivity for all MMR proteins with different percentages. One case showed weak positivity for hMSH2 and hMSH6 and no immunoreactivity for hMLH1 or hPMS2. Staining intensity was higher in tumour cells than in matched normal mucosa in three cases for hMSH2 and hMLH1 and in two cases for hPMS2. None of the examined cases showed MSI. CONCLUSIONS: Expression of hMSH2 and hMLH1 proteins was up-regulated in three cases, whereas in two cases that of hPMS2 was increased. hMSH6 expression was comparable to that of normal cells in all cases. The percentage of positive neoplastic cells and the intensity of staining seemed to be greater in pleomorphic melanomas. Six cases were MMR-proficient and microsatellite stable.
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Reparo de Erro de Pareamento de DNA , DNA de Neoplasias/genética , Neoplasias de Cabeça e Pescoço/genética , Melanoma/genética , Instabilidade de Microssatélites , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Idoso , Idoso de 80 Anos ou mais , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/metabolismo , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Proteína 2 Homóloga a MutS/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regulação para CimaRESUMO
BACKGROUND: According to bilingual education, only through sign language will deaf children attain linguistic and cognitive development, enabling them to learn a second language--spoken or written. However, it is also necessary for families to learn sign language in order to have a more efficient communication. AIM: To analyze methodological aspects of the teaching-learning process of Sign Language to family groups. METHOD: Transcription and analysis of video recordings were made. RESULTS: The practice of teaching of the deaf teacher modifies itself during the research period and his attitude influences the way by which parents participate. CONCLUSION: The teaching methodology used by the deaf teacher interferes significantly in the motivation/participation of parents, followed by the acceptance of deafness and sign language.
Tema: a abordagem bilíngüe considera que através da língua de sinais, o surdo alcança um bom desenvolvimento lingüístico e cognitivo, favorecendo a aprendizagem da língua oral e ou escrita. Neste sentido, é necessário que os pais também aprendam a língua de sinais para uma comunicação eficaz. Objetivo: analisar aspectos metodológicos do processo ensino/aprendizagem no grupo de língua de sinais aos familiares de sujeitos surdos. Método: foram realizadas vídeo gravações do grupo, com posterior transcrição e análise dosepisódios. Resultados: a prática de ensino do instrutor surdo se modifica ao longo do período pesquisado e sua atitude influencia no modo de participação dos pais. Conclusão:a metodologia de ensino utilizada pelo instrutor surdo interfere significativamente na motivação/participação dos pais, na aceitação da surdez e da língua de sinais.
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Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Surdez , Aprendizagem , Relações Pais-Filho , Língua de Sinais , Ensino , ComunicaçãoRESUMO
Estrogens are direct mitogens for hormone-responsive human breast cancercells, where they promote cell cycle progression and induce transcriptional activation of "immediate early" and cyclin genes. Nongenomic signaling by estrogens, including rapid changes of mitogen-activated protein(MAP) kinase and other signal-transduction-cascades activity, has been proposed to be essential for the mitogenic actions of these hormones and their nuclear receptors. Because regulation of gene transcription is considered a key step in cell cycle control by mitogenic protein kinase cascades, here we investigated the possibility that estrogen might induce the activation of extracellular signal-regulated kinase (Erk) 1/2-, c-Jun NH(2)-terminal kinase-, p38- or protein kinase A-responsive transcription factors in the cell nucleus during stimulation of early G(1) progression, a timing coincident with the maximum effects of these hormones on such enzyme activity. No significant changes in protein kinase-mediated transcription factor activity could be detected here after estrogen stimulation of either MCF-7 or ZR-75.1 cells. Furthermore, these steroids were able to induce activation of the human CCND1 gene promoter, accumulation of cyclin D1 and pRb phosphorylation, all key events in cell cycle stimulation by mitogens, even in the presence of Erk1/2 activation blockade by a MAP kinase-activating kinase (Mek)1/2 inhibitor. Thus, estrogens do not appear to convey significant protein kinase-dependent signaling to the cell nucleus during the early phases of human breast cancer cell stimulation. Furthermore, hormonal regulation of G(1) gene transcription can occur even without additional activation of the Mek-Erk1/2 pathway by estrogen receptors.
Assuntos
Neoplasias da Mama/patologia , Estradiol/farmacologia , Fase G1/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno , MAP Quinase Quinase Quinase 1 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias da Mama/enzimologia , Núcleo Celular/enzimologia , Núcleo Celular/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ciclina D1/biossíntese , Ciclina D1/genética , Fase G1/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , MAP Quinase Quinase 4 , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteína do Retinoblastoma/metabolismo , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por MitógenoRESUMO
The intracellular concentration of cholesterol is regulated by the balance between endogenous synthesis and exogenous uptake. Oestrogens have been reported to be involved in the physiological regulation of cellular cholesterol content. Relevant reports have focused on long-term responses and there is a lack of information about the relationship between the timing of the oestrogen effect and the regulation of cholesterol homeostasis. The aim of this work has been to set up a systematic picture of the short-term effects induced by oestrogen on hepatic lipid metabolism in vivo and the involvement of some relevant signal transduction pathways. At intervals after oestrogen administration (30 min to 6 h), oestrogen receptor expression and changes in liver cAMP, IP(3) and protein kinase C-alpha (PKC-alpha) were followed. Changes in the expression of the low density lipoprotein receptor at mRNA and protein levels, and of hydroxy-methyl-glutaryl-CoA reductase activity have been verified. At the same time, the content of hepatic cholesterol, ubiquinone and dolichol and of plasma cholesterol have been determined. Changes of rab 5 and rab 8, small GTP-binding prenylated proteins involved in the transfer of neosynthesised proteins through the cell, have been also checked. In vivo treatment with oestradiol produced no change in cyclic AMP but a rapid increase in IP(3), increased PKC-alpha localisation on the membranes and enhanced expression of the low density lipoprotein receptor in the liver occurred. PKC inhibition completely prevented any increase in low density lipoprotein receptor mRNA in isolated and perfused rat liver. Early changes of ubiquinone and dolichol content and a later reduction in hepatic hydroxy-methyl-glutaryl-CoA reductase activity and plasma cholesterol content were also detectable. A functional role of the IP(3) -protein kinase C-alpha pathway in the induction of the low density lipoprotein receptor is suggested. Experimental Physiology (2001) 86.1, 39-45.
Assuntos
Estradiol/farmacologia , Inositol 1,4,5-Trifosfato/fisiologia , Isoenzimas/fisiologia , Metabolismo dos Lipídeos , Fígado/metabolismo , Proteína Quinase C/fisiologia , Transdução de Sinais/fisiologia , Animais , Colesterol/sangue , Dolicóis/metabolismo , Hidroximetilglutaril-CoA Redutases/metabolismo , Técnicas In Vitro , Masculino , Proteína Quinase C-alfa , Ratos , Ratos Sprague-Dawley , Receptores de LDL/metabolismo , Ubiquinona/metabolismoRESUMO
The role exerted by protein kinase C (PKC) on estrogen-induced DNA synthesis has been investigated in hepatic and mammary gland cells, HepG2 and MCF7. 17-beta-estradiol stimulated DNA synthesis in HepG2 and MCF7 cells, maximal effect occurring at 10 nM. DNA synthesis stimulation was prevented by anti-estrogen ICI 182,780 and by inhibitor of PKC, Ro 31-8220. The rapid estradiol effects in MCF7 cells were determined by following the inositol trisphosphate (IP(3)) production and PKC-alpha membrane translocation. After estradiol treatment the increase of IP(3) production, prevented by anti-estrogen or by phospholipase C (PLC) inhibitor (neomycin), was present in MCF7 cells. In MDA cells, devoid of estrogen receptor, no effect was observed. The PKC-alpha presence on the membranes appeared unchanged in MCF7 cells. The PLC inhibitors, neomycin and U73,122, and PKC-alpha down regulator, phorbol 12-myristate 13-acetate (PMA), were able to prevent estradiol-induced DNA synthesis in hepatoma cells, but ineffective in mammary cells; wortmannin, an inhibitor of phosphoinositide 3-kinases (PI3-K), blocked DNA synthesis in both cell lines. These data show that beta-estradiol, via an estrogen receptor-mediated mechanism, activates more signal transduction pathways, and consequently different PKC isoforms in two responsive cell lines. In both cell lines PI3-K/PKC pathway is functional to the estrogen regulation of DNA synthesis, whereas in HepG2 cells the parallel involvement of the PLC/PKC-alpha pathway is present. The reported results indicate that the DNA synthesis stimulation by beta-estradiol requires the estrogen receptor and utilises one or more activated pathways in dependence on the cell equipment.
Assuntos
Neoplasias da Mama , Carcinoma Hepatocelular , Replicação do DNA/efeitos dos fármacos , Estradiol/farmacologia , Isoenzimas/metabolismo , Neoplasias Hepáticas , Proteína Quinase C/metabolismo , Androstadienos/farmacologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Membrana Celular/enzimologia , Replicação do DNA/fisiologia , Inibidores Enzimáticos/farmacologia , Estrenos/farmacologia , Feminino , Humanos , Indóis/farmacologia , Isoenzimas/antagonistas & inibidores , Neomicina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C-alfa , Inibidores da Síntese de Proteínas/farmacologia , Pirrolidinonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Estimulação Química , Timidina/metabolismo , Timidina/farmacologia , Trítio , Células Tumorais Cultivadas , Fosfolipases Tipo C/metabolismo , WortmaninaRESUMO
To identify predictive factors for postoperative success and potential predictors for satisfactory outcome of endovascular grafting for abdominal aortic aneurysm (AAA), we collected data from our prospective database, which includes a series of consecutive patients undergoing endovascular repair at the Vascular Surgery Unit, Policlinico Monteluce, Perugia, Italy. From April 1997 to July 1998, 202 patients were referred to our Unit for elective AAA repair; 94 patients (47%) were selected for endografting. Placement of the graft using endovascular technique without conversion to open laparotomy, in addition to no mortality, major morbidity, or endoleak at 30-day follow-up, was defined as postoperative success. The influence of anatomical features on postoperative results was analyzed by univariate and multivariate analysis. Our experience shows that endoluminal repair of AAA is safe and effective in the short term and male patients with small aneurysms are optimal candidates for successful repair.