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Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.  相似文献   
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W. Moalla  F. Costes  R. Gauthier  Y. Maingourd  S. Ahmaidi   《ITBM》2004,25(4):199-204
Objective. – The purpose of this work is to study the muscular responses in children with congenital heart disease using near infrared spectroscopy during isometric exercise.Materials and methods. – Twelve healthy children and eight children with congenital heart disease (class II and III NYHA) performed an isometric knee extension on Cybex Norm. For every subject, maximal voluntary contraction (MVC) and endurance time (TE) at 50% of MVC was assessed. The near infrared spectroscopy (NIRS) has been used to assess muscular oxygenation (SmO2) and of blood volume (VS) during exercise and recovery. Half time recovery of the SmO2 (1/2 Trec) has been also measured.Results. – Cardiac subjects developed MVC and TE weaker than healthy subjects (MVC: 96.1 ±5.0 vs 125.1 ±6.7 N·m; P <0.01) and (TE: 60.88 ±5.7 vs 116.5 ±8.7 secondes; P <0.001). No significant difference of the SmO2 and the VS has been noted at rest. The SmO2 decrease rapidly to reach a plateau at 25% of TE in the healthy subjects, whereas the cardiac subjects reach this plateau at 50% of TE. During recovery, 1/2 Trec is significantly higher in cardiac subjects compared to healthy subjects (26.6 ±1.8 secondes vs 18.9 ±1.9 secondes; respectively, P <0.05).Conclusion. – A decreased muscular performance accompanied with oxygenation and blood volume abnormalities has been found in children with congenital heart diseases. The NIRS is a valuable non-invasive technique for assessment of oxygenation and blood volume during exercise.  相似文献   
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Spontaneous histopathological regression of cancer has been reported. The involvement of the immune system in such regression has been advocated, leading to the theory of immunological surveillance against cancer. A prediction of this theory is that common tumour antigens can be recognized upon repeated exposure by cell-mediated immunity, which leads to tumour regression and the subsequent appearance of tumour antigen-loss variants. However, no direct evidence has been provided in non-viral-induced experimental animal models of primary malignancy or in human primary cancer. This study examined two groups of melanoma patients where histopathological regression of the primary tumour was observed. Many of the 23 patients with multiple (> or =3) primary melanomas showed significant regression of their last melanoma (median 33%, mean 40) compared with matched melanomas from patients with a single primary melanoma (median 0%, mean 12) (p=0.0080), or compared with their first primary melanoma (p=0.0013). Regression was consistent with an 'immunization effect' seen in murine tumour transplantation studies, where inoculation with > or =3 asynchronous tumours induces transplantation rejection on subsequent challenge. A significant decrease in the expression of the melanoma common tumour antigen MART-1 in the last primary tumour from multiple melanoma patients (median 8%, mean 24) versus matched single melanoma patients (median 79%, mean 68) (p=0.0041) and in the last versus first tumour in multiple primary patients was found (p=0.0083). Metastases from 17 patients whose primary skin melanomas had completely regressed (occult primary melanoma) also showed significant MART-1 loss (median 0%, mean 11) compared with matched metastases from patients with non-regressing primary melanoma (median 51%, mean 50) (p=0.0013). MART-1 antigen-loss variants observed in the multiple primary and occult primary patients correlated with the presence of peripheral blood MART-1-specific cytotoxic T lymphocytes (CTLs) (p=0.03). No similar effects were observed with two other melanoma antigens, gp100 and CD63. Thus, in two groups of human melanoma patients, evidence is provided for histopathological tumour regression associated with cancer immune surveillance.  相似文献   
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AIM: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate. METHODS: This study was a prospective randomized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney. The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate. Consecutive cases of total colonoscopy over a 1-year period were recruited. Randomization into either standard colonoscopy (SC) or cap-assist...  相似文献   
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  • Baseline risk scores for TAVI patients, including STS and EuroSCORE, might not predict long‐term outcomes.
  • Including postprocedural data might improve risk stratification.
  • The ACEF‐7 risk score includes the lowest creatinine clearance in the first 7 postprocedural days and appears to be a good predictor of worse long‐term outcomes.
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