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Plasma levels of high-density lipoprotein cholesterol (HDL-C) show an inverse association with coronary heart disease (CHD). As a biological trait, HDL-C is strongly genetically determined, with a heritability index ranging from 40 % to 60 %. HDL represents an appealing therapeutic target due to its beneficial pleiotropic effects in preventing CHD. This review focuses on the genetic basis of cellular cholesterol efflux, the rate-limiting step in HDL biogenesis. There are several monogenic disorders (e.g., Tangier disease, caused by mutations within ABCA1) affecting HDL biogenesis. Importantly, many disorders of cellular cholesterol homeostasis cause a reduced HDL-C. We integrate information from family studies and linkage analyses with that derived from genome-wide association studies (GWAS) and review the recent identification of micro-RNAs (miRNA) involved in cellular cholesterol metabolism. The identification of genomic pathways related to HDL may help pave the way for novel therapeutic approaches to promote cellular cholesterol efflux as a therapeutic modality to prevent atherosclerosis. 相似文献
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Stéphanie Tellier Karine Brochard Arnaud Garnier Flavio Bandin Brigitte Llanas Vincent Guigonis Mathilde Cailliez Christine Pietrement Olivier Dunand Sylvie Nathanson Aurélia Bertholet-Thomas Lydia Ichay Stéphane Decramer 《Pediatric nephrology (Berlin, Germany)》2013,28(6):911-918
Background
Rituximab (RTX) has recently showed promising results in the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS).Methods
This was a retrospective multicenter study of 18 children treated with RTX for SDNS, with a mean follow-up of 3.2 years. RTX was introduced because of side effects or relapses during therapy with immunosuppressive agents. The children received one to four infusions of RTX during the first course of treatment, and subsequent infusions were given due to CD19-cell recovery (CD19?>1 %; 54 % of children) or relapse (41 %), as well as systematically (5 %).Results
Treatment with RTX maintained sustained remission without relapse in 22 % of patients and increased the duration of remission in all other patients. The time between two successive relapses was 9 months in the absence of re-treatment and 24.5 months when infusions were performed at the time of CD19-cell recovery. At the last follow-up, 44.5 % of patients were free of oral drug therapy. Of those still receiving oral drugs, all doses had been decreased. No serious adverse events occurred.Conclusion
The results of this retrospective study confirm the efficacy and very good safety of RTX in the treatment of SDNS. The optimal therapeutic protocol seems to be a repeated single infusion at the time of CD19-cell recovery. 相似文献76.
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Bruno Manfredini Baroni MSc Jeam Marcel Geremia MSc Rodrigo Rodrigues PE Rodrigo De Azevedo Franke PE Kiros Karamanidis PhD Marco Aurélio Vaz PhD 《Muscle & nerve》2013,48(4):498-506
Introduction: Changes in muscle architecture induced by eccentric knee extensor training remain unclear, as well the adaptive responses of synergistic knee extensor muscles with different geometrical designs. Methods: Ultrasonography images were taken from rectus femoris (RF) and vastus lateralis (VL) of 20 male volunteers before and after a non‐training control period of 4 weeks, and additional evaluations were performed after 4, 8, and 12 weeks of isokinetic eccentric training. Results: RF and VL had significant changes in muscle architecture within the first 4 training weeks, and the adaptive response throughout the intervention was similar. Muscle thickness increased by around 7–10%, fascicle length increased 17–19%, and pennation angle was unchanged. Conclusions: Increased muscle thickness due to eccentric training was related to increased fascicle length and not to pennation angle changes. Although RF and VL have a different fascicular geometry, they had similar morphological adaptations to eccentric training. Muscle Nerve 48 : 498–506, 2013 相似文献
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Maria Aparecida Camargos Bicalho Fausto Aloísio Pimenta Luciana Bastos‐Rodrigues Érika de Oliveira Hansen Samara Canguçu Neves Marina Melo Daniela Valadão Rosa Renan Pedra de Souza Débora Marques de Miranda Edgar Nunes de Moraes Marco Aurélio Romano‐Silva Luiz De Marco 《International journal of geriatric psychiatry》2013,28(6):640-646