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1.
Christian Burri Patrick D. Yeramian James L. Allen Ada Merolle Kazadi Kyanza Serge Alain Mpanya Pascal Lutumba Victor Kande Betu Ku Mesu Constantin Miaka Mia Bilenge Jean-Pierre Fina Lubaki Alfred Mpoo Mpoto Mark Thompson Blaise Fungula Munungu Francisco Manuel Théophilo Josenando Sonja C. Bernhard Carol A. Olson Johannes Blum Richard R. Tidwell Gabriele Pohlig 《PLoS neglected tropical diseases》2016,10(2)
Background
Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.Methods
The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.Findings/Conclusion
Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. 相似文献2.
A new type of IRES within gag coding region recruits three initiation complexes on HIV-2 genomic RNA
Laure Weill Laurie James Nathalie Ulryck Nathalie Chamond Cecile H. Herbreteau Theophile Ohlmann Bruno Sargueil 《Nucleic acids research》2010,38(4):1367-1381
Genomic RNA of primate lentiviruses serves both as an mRNA that encodes Gag and Gag-Pol polyproteins and as a propagated genome. Translation of this RNA is initiated by standard cap dependant mechanism or by internal entry of the ribosome. Two regions of the genomic RNA are able to attract initiation complexes, the 5′ untranslated region and the gag coding region itself. Relying on probing data and a phylogenetic study, we have modelled the secondary structure of HIV-1, HIV-2 and SIVMac coding region. This approach brings to light conserved secondary-structure elements that were shown by mutations to be required for internal entry of the ribosome. No structural homologies with other described viral or cellular IRES can be identified and lentiviral IRESes show many peculiar properties. Most notably, the IRES present in HIV-2 gag coding region is endowed with the unique ability to recruit up to three initiation complexes on a single RNA molecule. The structural and functional properties of gag coding sequence define a new type of IRES. Although its precise role is unknown, the conservation of the IRES among fast evolving lentiviruses suggests an important physiological role. 相似文献
3.
Courtioux B Boda C Vatunga G Pervieux L Josenando T M'Eyi PM Bouteille B Jauberteau-Marchan MO Bisser S 《International journal for parasitology》2006,36(9):1057-1065
Trypanosoma brucei gambiense infection is an important public health challenge in sub-Saharan Africa. This parasitic disease is difficult to diagnose due to insidious clinical signs and transient parasitaemias. The clinical course is marked by two stages of increasing disease severity. An early systemic parasitic invasion is followed by the development of a progressive meningo-encephalitis. During this latter stage, a broad spectrum of neurological signs appears, which finally lead to a demyelinating and fatal stage if untreated. Treatment is toxic and difficult to administer when the CNS is invaded. Therefore, accurate diagnostic methods for stage determination are needed. The classically used criteria are not sufficiently specific and mechanisms of parasite invasion through the blood-brain barrier remain poorly understood. As cytokines/chemokines are involved in the early recruitment of leukocytes into the CNS, this study has focused on their potential value to define the onset of CNS involvement. Levels of monocyte chemoattractant protein-1/CCL-2, macrophage inflammatory protein-1α/CCL-3, IL-8/CXCL-8, regulated upon activation T cell expressed and secreted (RANTES)/CCL-5 and IL-1β were measured in paired sera and CSF from 57 patients and four controls. Patients were classified into three groups (stage 1, intermediate and stage 2) according to current field criteria for stage determination (CSF cell count, presence of trypanosomes in CSF and neurological signs). In sera, cytokine/chemokine levels were poorly related to disease stage. Only CXCL-8 was higher in stage 1 patients when compared with stage 2 and CCL-5 was higher in controls when compared with patients. In contrast, in CSF the expression of the selected cytokines, except CCL-5, was associated with the presence of neurological signs, demonstrating their diagnostic value. We observed a relationship between the presence of trypanosomes or trypanosome-related compounds in CSF and levels of IL-1β, CXCL-8, CCL-2 and CCL-3. These cytokines and chemokines may be triggered by the parasite and hence are potential markers of CNS invasion. 相似文献
4.
In situ mapping of nitrifiers and anammox bacteria in microbial aggregates by means of confocal resonance Raman microscopy 总被引:1,自引:0,他引:1
Pätzold R Keuntje M Theophile K Müller J Mielcarek E Ngezahayo A Anders-von Ahlften A 《Journal of microbiological methods》2008,72(3):241-248
In the present work the exploration of microbial communities by confocal resonance Raman microscopy (CRRM) is reported. Using the resonance Raman effect of cytochrome c (Cyt c) we were able to record the microbial distribution of nitrifiers and anammox bacteria directly in their natural environment without the need of sample preparation. For this new non-invasive investigation a reference database of bacteria assumed to be found in microbial aggregates obtained from biological wastewater treatment was created. Reference spectra of enriched cultures of the interesting bacteria were taken by means of optical tweezers. Significant spectra were achieved in less than 1 s (excitation wavelength 532 nm, laser power 9 mW) due to the resonance Raman effect. In addition, the impact of different parameters on the reference spectra, such as integration time and culture conditions, was analysed. We successfully demonstrate the grouping of bacteria down to strain level based on the heterogeneity of the resonance Raman spectra of the heme protein Cyt c. 相似文献
5.
The conformational change of the ribose ring in NH4GpG and cis-[Pt(NH3)2(GpG)]+ was confirmed by FT-IR spectroscopic evidence as being C2′-endo, C3′-endo, anti, gg sugar ring pucker in the solid state. These results were compared with 1H NMR spectral data in aqueous solution. The FT-IR spectrum of NH4GpG shows marker bands at 802 cm?1 and 797 cm?1 which are assigned to the C3′-endo, anti, gg sugar-phosphate vibrations of ribose (?pG) and ribose (Gp?), respectively. The FT-IR spectrum of cis-[Pt(NH3)2(GpG)]+ (with N7N7 chelation in the GpG sequence) shows a marker band at 800 cm?1 which is assigned to the C3′-endo, and a new shoulder band at 820 cm?1 related to a C2′-endo ring pucker. The ribose conformation of (?pG) moiety in NH4-GpG, C3′-endo, anti, gg changes into C2′-endo, anti, gg when a platinum atom is chelated to N7N7 in the GpG sequence. 相似文献
6.
Elias T. Ayuk Bahiru Duguma Steve Franzel Joseph Kengue Matthias Mollet Theophile Tiki-Manga Pauline Zekeng 《Economic botany》1999,53(3):292-301
Dacryodes edulis is one of the most preferred tree species by farmers in the humid lowlands of Cameroon. The fruit of the species figures prominently in cross-boundary trade between Cameroon, Nigeria and Gabon. Although there exist empirical data on the volume of trade of the fruit at this level, no data are available at the farm level. A field survey was undertaken to identify uses, management, and farmers’ improvement objectives and to quantify, at the farm-level, the economic potential of the species. The results of the survey indicate thatD. edulis is widely planted and found mainly in tree crop fields and in home gardens. The fruit is highly consumed and traded. The farm-level value of fruit production reaches $US161 a year per grower or collector. The dead branches of the species are used as firewood and its bark is used as medicine. Desired improvement objectives include increased fruit size, good tasting fruit, high yield and reduced time to bearing. 相似文献
7.
Caroline Boda Bertrand Courtioux Pierre Roques Lynda Pervieux Gédéon Vatunga Théophile Josenando Constant Roger Ayenengoye Bernard Bouteille Marie-Odile Jauberteau Sylvie Bisser 《PloS one》2009,4(7)
Human African trypanosomiasis (HAT) is a deadly vector-born disease caused by an extracellular parasite, the trypanosome. Little is known about the cellular immune responses elicited by this parasite in humans. We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in the blood and cerebrospinal fluid (CSF) of 33 HAT patients and 27 healthy controls identified during a screening campaign in Angola and Gabon. We evaluated the subsets and activation markers of B and T lymphocytes. Patients had a higher percentage of CD19+ B lymphocytes and activated B lymphocytes in the blood than did controls, but lacked activated CD4+ T lymphocytes (CD25+). Patients displayed no increase in the percentage of activated CD8+ T cells (HLA-DR+, CD69+ or CD25+), but memory CD8 T-cell levels (CD8+CD45RA−) were significantly lower in patients than in controls, as were effector CD8 T-cell levels (CD8+CD45RA+CD62L−). No relationship was found between these blood immunophenotypes and disease severity (stage 1 vs 2). However, CD19+ B-cell levels in the CSF increased with disease severity. The patterns of T and B cell activation in HAT patients suggest that immunomodulatory mechanisms may operate during infection. Determinations of CD19+ B-cell levels in the CSF could improve disease staging. 相似文献
8.
Jean C. Ndom Joseph T. Mbafor Luc M. Meva’a Zanestsie Kakam Arwa S. Phanuel Etienne Ndongo Laurence M. Harwood Theophile N. Mpondo 《Phytochemistry letters》2010,3(4):201-206
Fractionation of a MeOH/CH2Cl2 (1/1) extract of the aerial parts of Senecio erechtitoides led to the isolation of six compounds including the hitherto unknown N-phenethylamide derivative named N-(p-hydroxyphenethyl)pentacosanamide (1), and a kauranoid derivative named derivative named ent-7-oxo-16α,17-dihydroxykauran-19-oic acid (2), as well as four known compounds, ent-Kaur-16-en-19-oic acid (3), ent-7β-hydroxykaur-16-en-19-oic acid (4), ent-7-oxokaur-16-en-19-oic acid (5), steppogenin 4′-O-β-d-glucoside (6). Their structures and relative configurations were elucidated on the basis of spectroscopic methods, chemical reactions, and comparison with previously known analogs. All isolates were evaluated for their antimicrobial activity and only diterpenoids were found to possess a potent inhibitor effect against the range of microorganism. 相似文献
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10.
Sylvie Bisser Crispin Lumbala Etienne Nguertoum Victor Kande Laurence Flevaud Gedeao Vatunga Marleen Boelaert Philippe Büscher Theophile Josenando Paul R. Bessell Sylvain Biéler Joseph M. Ndung’u 《PLoS neglected tropical diseases》2016,10(4)