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191.
192.
Olivia Fletcher Lorna Gibson Nichola Johnson Dan R Altmann Jeffrey M P Holly Alan Ashworth Julian Peto Isabel Dos Santos Silva 《Cancer epidemiology, biomarkers & prevention》2005,14(1):2-19
We reviewed all English-language articles on associations among circulating levels of the insulin-like growth factors (IGF) and their binding proteins (IGFBP), polymorphisms in their genes, and breast cancer risk. In premenopausal women, five of eight IGF-I studies and four of six IGFBP-3 studies of circulating levels found that women in the highest quantile had more than twice the risk of developing breast cancer of those in the lowest, although in some this effect was only apparent at young ages. In postmenopausal women, however, there was no consistent effect. A simple sequence length polymorphism 1 kb 5' to IGF-I was examined in relation to circulating levels of IGF-I (12 studies) or breast cancer risk (4 studies), but there was no convincing evidence of any effect. For an A/C polymorphism 5' to IGFBP-3, all three studies were consistent with a modest effect on circulating levels, but no evidence of a direct effect on breast cancer risk was seen in the only relevant study. Variation within the reference range of IGF-I and IGFBP-3 may confer only modest increases in breast cancer risk, and any single polymorphism may only account for a small proportion of that variation. Nevertheless, population attributable fractions for high circulating levels of IGF-I and IGFBP-3 and for common genetic variants could be substantial. Further large studies, or combined analysis of data from existing studies, are needed to quantify these effects more precisely. 相似文献
193.
Anti-inflammatory effects of fructose-1,6-bisphosphate on carrageenan-induced pleurisy in rat. 总被引:3,自引:0,他引:3
José Carlos Farias Alves Filho Roberto Christ Vianna Santos Telmo Abelin Castaman Jarbas Rodrigues de Oliveira 《Pharmacological research》2004,49(3):245-248
In the present study, we evaluated the effect of fructose-1,6-bisphosphate (FBP), a high energy intermediate metabolite of glycolysis, in an acute model of lung injury. Injection of carrageenan into the pleural cavity of rats elicited an acute inflammation response characterized by a fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear neutrophils. FBP (500mg/kg) attenuated the inflammation parameters: exudate volume, total leukocytes and the number of polymorphonuclear leukocytes, but the protein concentration in the exudate was not significantly affected by treatment with FBP. The precise site and mechanism of the anti-inflammatory effect was not addressed, considering the diverse pharmacological actions of FBP. This drug has anti-inflammatory actions suggesting that it may represent a novel strategy for the modulation of inflammatory response. 相似文献
194.
The snake venom metalloproteinase-disintegrin jararhagin (JG) has no chemotactic activity but stimulates the migration of neutrophils in vivo through a mechanism still unclear. In this study we investigated the effects of jararhagin on epithelial cell adhesion and migration in vitro. F-actin arrangement and the distribution of laminin, fibronectin, several integrins and phosphorylated Focal Adhesion Kinase (FAK) were studied using rhodamine–phalloidin and immunofluorescence. Maximum stimulation of migration (about 100%) was obtained with 5 μg/ml JG, with about 38% inhibition of cellular adhesion. In migratory cells the toxin stimulated the formation of filopodia, lamellipodia and stress fibers. The pericellular fibronectin matrix was lost in migrating cells, while laminin was less affected. The toxin stimulated FAK phosphorylation and the recruitment of v-containing integrins to focal contacts, whereas integrins containing the 2 subunit were reduced in these junctions. Inactivation of the toxin with 1,10 phenanthroline showed that the catalytic activity is important for the effect of jararhagin on cell migration, FAK phosphorylation and for the recruitment of v, but not as much for the anti-adhesive effect. In conclusion, jararhagin stimulates the migration of epithelial cells in vitro through a mechanism that involves its proteolytic activity, qualitative changes in cellular adhesion and the formation of actin-rich cellular processes. 相似文献
195.
Significance of High Density Lipoprotein-Cholesterol in Cardiovascular Risk Prevention 总被引:2,自引:0,他引:2
Juan F. Ascaso Arturo Fernández-Cruz Pedro González Santos Antonio Hernández Mijares Alipio Mangas Rojas Prof. Jesus Millán Luis Felipe Pallardo Juan Pedro-Botet Francisco Pérez-Jiménez Gonzalo Pía Xavier Pintó Ignacio Plaza Juan Rubiés-Prat 《Am J Cardiovasc Drugs》2004,4(5):299-314
In the approach to lipid-related risk factors for cardiovascular diseases, serum high density lipoprotein-cholesterol (HDL-C) levels bear a particular significance as this lipoprotein is considered to be an antiatherogenic factor mainly, but not only, because of its influence and impact on reverse cholesterol transport. Hence the need and requirement to consider serum HDL-C levels for both primary and secondary prevention of cardiovascular disease. A particularly important aspect is the association of the 'low HDL syndrome' with the metabolic syndrome. These factors force us to consider serum HDL-C level as a therapeutic target by itself, or even in association with low density lipoprotein-cholesterol (LDL-C) levels when the latter are increased. This review stresses the aspects connecting serum HDL-C levels and cardiovascular risk, and looks at the populations that should be considered amenable to therapeutic management because of low serum HDL-C levels. We review therapeutic strategies, both pharmacological and nonpharmacological. The aim of this review is to present therapeutic management recommendations for correcting the proportion of cardiovascular risk that is attributable to changes in HDL-C. Serum HDL-C levels of >40 mg/dL must be a therapeutic target in primary and secondary prevention. This goal is particularly important in patients with low serum HDL-C levels and ischemic heart disease (IHD) or its equivalents, even if the therapeutic target for serum LDL-C levels (<100 mg/dL) has been achieved. The first choice for this clinical condition is fibric acid derivates. The same therapeutic option should be considered in patients without IHD with low serum HDL-C levels and high cardiovascular risk (>20%), hypertriglyceridemia, type 2 diabetes mellitus, or metabolic syndrome. 相似文献
196.
197.
Amber J. Hromi‐Fiedler Gabriela dos Santos Buccini Muriel Bauermann Gubert Katie Doucet Rafael Prez‐Escamilla 《Maternal & child nutrition》2019,15(1)
Scaling up breastfeeding programmes has not been highly prioritized despite overwhelming evidence that breastfeeding benefits the health of mothers and children. Lack of evidence‐based tools for scaling up may deter countries from prioritizing breastfeeding. To fill this gap, Becoming Breastfeeding Friendly (BBF) was developed to guide countries in effectively scaling up programmes to protect, promote, and support breastfeeding. BBF includes an evidence‐based toolbox that consists of a BBF Index, case studies, and a 5‐meeting process. These three interrelated components enable countries to assess their breastfeeding scaling up environment, identify gaps, propose policy recommendations, develop a scaling up plan, and track progress. The toolbox was developed based on current evidence and expert guidance from a Technical Advisory Group, which was composed of global breastfeeding and metric experts with experience in the scaling up of health and nutrition programmes in low‐, middle‐, and high‐income countries. The BBF toolbox required a step‐by‐step iterative approach to describe and systematize each component, thus an operational manual was developed. The BBF toolbox and BBF operational manual underwent intensive pretesting in two countries, Ghana and Mexico, resulting in the modification of each component plus the operational manual. Pretesting continues in six additional countries demonstrating that BBF is a robust and dynamic multi‐sectoral process that, with relatively minor adaptations, can be successfully implemented in countries across world regions. 相似文献
198.
The introduction of tyrosine kinase inhibitors (TKIs) has changed the landscape of therapy for chronic myelogenous leukemia
(CML). Once considered an incurable malignancy, CML now has become a manageable chronic condition. Despite the great advances
that imatinib has brought to the treatment of CML, some patients still develop resistance to imatinib and other TKIs, such
as dasatinib and nilotinib. Furthermore, none of the clinically available TKIs is capable of eradicating leukemia stem cells
and therefore curing CML. Several new compounds have been developed in recent years in an attempt to manage TKI-resistant
CML. These include third-generation TKIs (ponatinib, danusertib) and even old compounds such as omacetaxine, which were developed
before imatinib and now find a possible niche in the treatment of imatinib-resistant CML. We review the current preclinical
and clinical data on the most promising new compounds for the treatment of CML. 相似文献
199.
Jos V. dos Santos Patricia F. Freixo islan de C. Vivarini Jorge M. Medina Lucio A. Caldas Marcia Attias Karina L. Dias Teixeira Teresa Cristina C. Silva Ulisses G. Lopes 《Viruses》2022,14(9)
Viral coinfections can modulate the severity of parasitic diseases, such as human cutaneous leishmaniasis. Leishmania parasites infect thousands of people worldwide and cause from single cutaneous self-healing lesions to massive mucosal destructive lesions. The transmission to vertebrates requires the bite of Phlebotomine sandflies, which can also transmit Phlebovirus. We have demonstrated that Leishmania infection requires and triggers the Endoplasmic stress (ER stress) response in infected macrophages. In the present paper, we tested the hypothesis that ER stress is increased and required for the aggravation of Leishmania infection due to coinfection with Phlebovirus. We demonstrated that Phlebovirus Icoaraci induces the ER stress program in macrophages mediated by the branches IRE/XBP1 and PERK/ATF4. The coinfection with L. amazonensis potentiates and sustains the ER stress, and the inhibition of IRE1α or PERK results in poor viral replication and decreased parasite load in macrophages. Importantly, we observed an increase in viral replication during the coinfection with Leishmania. Our results demonstrated the role of ER stress branches IRE1/XBP1 and PERK/ATF4 in the synergic effect on the Leishmania increased load during Phlebovirus coinfection and suggests that Leishmania infection can also increase the replication of Phlebovirus in macrophages. 相似文献