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11.
Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration‐dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B‐containing lipoproteins into plasma. Avasimibe induced cholesterol 7α‐hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol‐fed as well as in non‐cholesterol‐fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non‐HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50–500 mg/day, significantly reduced plasma total triglyceride and VLDL‐cholesterol. Although total cholesterol, LDL‐cholesterol, and HDL‐cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol‐lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol. 相似文献
12.
Antonio Amoroso Pierluigi Garzia Marta Vadacca Sara Galluzzo Flavia Del Porto Anna P Mitterhofer Antonella Afeltra 《The Journal of adolescent health》2003,32(1):94-97
We report on a 26-year-old female affected by Noonan syndrome (NS), a congenital disorder characterized by various phenotypic features and congenital anomalies) associated with a variety of autoimmune diseases, including systemic lupus erythematosus, celiac disease, and Hashimoto thyroiditis. Autoimmunity is seldom described in NS and the association between this congenital disease and three autoimmune disorders has not been previously reported. Should the occurrence of autoimmune disorders in NS be confirmed, a relevant clinical and laboratory evaluation of NS patients should be performed in order to clarify whether the immune system involvement represents only an occasional event or is a feature of the disease. 相似文献
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Carlos Calderón Rafael Rotaeche Arritxu Etxebarria Mercé Marzo Rosa Rico Marta Barandiaran 《BMC health services research》2006,6(1):138-11
Background
The GRADE method represents a new approach to grading the quality of evidence and strength of recommendations in the preparation of Clinical Practice Guidelines (CPG). In the context of a pilot study to assess the implementability of the system in Spain, we considered it relevant to gain an insight into the significance of the perceptions and attitudes expressed by the actual experts participating in the system try-out. 相似文献17.
Marta Padilla Castillo Yaiza Machado RyderManuel Cazorla Betancor Rocío Acebes TostiMargarita Medina Castellano Rosa Rodríguez-Mano 《Progresos de Obstetricia y Ginecología》2006
Heterotopic pregnancy is the combination of intrauterine and ectopic pregnancy. This potentially fatal condition rarely occurs in spontaneous conception cycles and consequently its diagnosis requires a high index of suspicion. We report a case of heterotopic pregnancy in a 30-year old primipara with no known risk factors who presented with acute abdominal pain due to a spontaneous heterotopic pregnancy. The ectopic pregnancy was resected via laparoscopy. After surgery, the intrauterine pregnancy was uneventful. 相似文献
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Marta Feldmesser 《Medical mycology》2005,43(7):571-587
Invasive aspergillosis is a disease of immunocompromised hosts and the pathogenesis of this disorder is heavily dependent upon the defect within a given host. Consequently, vaccine development is limited by our understanding of effective host responses and by limitations in our knowledge of fungal molecules that elicit protective immunity. Nonetheless, the past few years have witnessed advances in our understanding both of the immune response to this organism and in the relationship between antigenicity and the ability to confer protection. Manipulations that promote the development of T(H)1-associated responses correlate with increased resistance to disease, at least partly because of consequent enhancement of innate cellular effector function. Two areas of investigation most actively being pursued include the search for adjuvants that will allow products of Aspergillus fumigatus to become effective vaccine candidates, regardless of the form of immunity they ordinarily induce, and the identification of the specific antigens that will most effectively elicit beneficial responses. Strategies using antigen-exposed dendritic cells as adjuvants appear to be particularly promising. Though we currently are far away from a candidate that is applicable for human trials, recent progress is encouraging. 相似文献
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