A Comparative Study of Dihydroartemisin in Compounds in Treatment of Uncomplicated Falciparum Malaria in Kampong of Cambodia

Objective: To compare the safety and efficacy of two compounds of dihydroartemisinin(DHA) -Artekin and Artekin (T) in the treatment of uncomplicated falciparum malaria. Methods:The regimen of 8-tablet for 2 days of Artekin and Artekin (T) were applied to 100 patients with uncomplicated falciparum malaria, who were randomly divided into two groups. Each group contained 50 cases. The cure rate, the mean parasites clearance time, the mean fever clearance and side-effects were observed to assess the safety and efficacy of the compounds used. Results: The mean parasites clearance time was 31. 7±9.0 hours in the Artekin group and 32. 8±8. 8 hours in Artekin (T) group respectively; the mean fever clearance time was 12. 7±7. 2 hours in Artekin group and 16. 5±7. 9 hours in Artekin (T) group; there were no recrudescence case in both groups within the 28 days of follow-up, the cure rates in Artekin group and Artekin (T) groups were 100%. It indicated that the tolerability of both compounds were very good, the     

Evidence against stabilization of the transition state oxyanion by a pKa-perturbed RNA base in the peptidyl transferase center

The crystal structure of the ribosomal 50S subunit from Haloarcula marismortui in complex with the transition state analog CCdA-phosphate-puromycin (CCdApPmn) led to a mechanistic proposal wherein the universally conversed A2451 in the ribosomal active site acts as an "oxyanion hole" to promote the peptidyl transferase reaction [Nissen, P., Hansen, J., Ban, N., Moore, P.B., and Steitz, T.A. (2000) Science 289, 920-929]. In the model, close proximity (3 A) between the A2451 N3 and the nonbridging phosphoramidate oxygen of CCdApPmn suggested that the carbonyl oxyanion formed during the tetrahedral transition state is stabilized by hydrogen bonding to the protonated A2451 N3, the pKa of which must be perturbed substantially. We characterize the contribution of the putative hydrogen bond between the N3 of A2451 and the nonbridging phosphoramidate oxygen by using chemical protection and peptidyl transfer inhibition assays. If this putative hydrogen bond makes a significant thermodynamic contribution, then CCdApPmn-binding affinity to the 50S ribosomal subunit should be strongly pH-dependent, with affinity increasing as the pH is lowered. We report that CCdApPmn binds 50S ribosomes with essentially equal affinity at all pH values between 5.0 and 8.5. These data argue against a mechanism for peptidyl transfer in which a residue with near neutral pKa stabilizes the transition-state oxyanion, at least to the extent that CCdApPmn accurately mimics the transition state.     

高度疟疾流行区快速控制疟疾试验

[目的]探索在高度疟疾流行区快速控制疟疾的策略与方法.[方法]2004-2005两年期间,选择柬埔寨石居省疟疾高度流行区及其周边地带作为灭源灭疟试验区,共62个自然村21 343人口.在对当地疟疾流行情况进行了细致调查的基础上,采取三项主要灭源措施:①疟疾现症病人采用复方青蒿素(Artequick,ATQ)方案治疗,发热病人亦以此作假定性治疗;②儿童带虫率≥20%的17个村采用ATQ方案进行一次全民治疗;③儿童带虫率≥6%的27个村采用低剂量伯氨喹全民服药,每10d 1次,连续6个月.组织村抗疟员执行以上灭源措施.监测17个疫源村的人群带虫率,每6个月监测1次.[结果]采取灭源措施2年后,儿童带虫率从55.8%下降为5.3%:其中恶性疟带虫率由37.0%下降为2.3%;间日疟加三日疟带虫率由18.9%下降为3.0%;儿童恶性疟配子体带虫率由13.1%下降为1.2%.有8个村儿童恶性疟带虫率由采取措施前的平均46.5%下降至0.成人带虫率的改变与儿童带虫率改变相似,由46.5%降为6.3%;恶性疟带虫率由采取措施前的平均34.2%下降为2.5%,间日疟加三日疟带虫率由12.3%降为3.8%.[结论]灭源灭疟法有别于以控制蚊媒为主的传统方法,是一种又快又省钱的新方法和新策略,可在较短时间内扭转疟疾的高度流行,直至彻底消灭疟疾,值得在广大高疟区推广应用.     

RNA sequence analysis defines Dicer's role in mouse embryonic stem cells

Short RNA expression was analyzed from Dicer-positive and Dicer-knockout mouse embryonic [corrected] stem (ES) cells, using high-throughput pyrosequencing. A correlation of miRNA quantification with sequencing frequency estimates that there are 110,000 miRNAs per ES cell, the majority of which can be accounted for by six distinct miRNA loci. Four of these miRNA loci or their human homologues have demonstrated roles in cell cycle regulation or oncogenesis, suggesting that a major function of the miRNA pathway in ES cells may be to shape their distinct cell cycle. Forty-six previously uncharacterized miRNAs were identified, most of which are expressed at low levels and are less conserved than the set of known miRNAs. Low-abundance short RNAs matching all classes of repetitive elements were present in cells lacking Dicer, although the production of some SINE- and simple repeat-associated short RNAs appeared to be Dicer-dependent. These and other Dicer-dependent sequences resembled miRNAs. At a depth of sequencing that approaches the total number of 5' phosphorylated short RNAs per cell, miRNAs appeared to be Dicer's only substrate. The results presented suggest a model in which repeat-associated miRNAs serve as host defenses against repetitive elements, a function canonically ascribed to other classes of short RNA.     

青蒿素哌喹片治疗间日疟62例临床报道

[目的]观察青蒿素哌喹片(Aaequick)治疗间日疟的有效性、安全性及临床剂量.[方法]对62例间日疟患者采用成人总量4片Artequick 2 d疗程的给药方案治疗,观察近期治愈率、近期复发率以及平均原虫复燃天数等有效性指标,并评价其安全性.[结果]62例患者经治疗后临床症状较快缓解,平均原虫转阴时间为(60.7±23.9)h,平均退热时间为(14.1±7.8)h,其中54例完成28 d观察,近期治愈率为94.4%(51/54例),近期复发率为5.6%(3/54例).本组病例对Artequick的耐受性良好,仅有少数病人出现恶心、呕吐;且为自限性;比较服药前与服药后第7天的血液、生化、心电图等指标,未发现Artequick片有明显的毒性.[结论]青蒿素哌喹片治疗间日疟,具有高效、速效、副反应少等优点,值得,临床推广应用.     

青蒿素哌喹片治疗无并发症恶性疟的剂量探索试验

目的探索青蒿素哌喹片治疗无并发症恶性疟的安全有效的适宜剂量。方法收治7～65岁男性和女性病人共100例,按区组随机化方案分成2组,成人总量1400 mg组年龄(22±s12)岁,1750 mg组年龄(21±12)岁。分别于0h和24h给药一次,比较2组的平均原虫转阴和退热时间、28d治愈率及原虫复燃率。结果2组的平均原虫转阴时间分别是(61±19)h和(57±21)h,平均退热时间为(20±15)h和(18±10)h,P>0.05;28 d治愈率是80%和96%,原虫复燃率为20%和4%,总量1750 mg组显著优于1400 mg组(P<0.05)。2组耐受性均良好,未发现明显的不良反应。结论推荐青蒿素哌喹片的临床治疗剂量为总量1750 mg,每日1次,分2d服完为1个疗程。     

Identification of a novel piscine Cryptosporidium genotype and Cryptosporidium parvum in cultured rainbow trout (Oncorhynchus mykiss)

This study reports for the first time the presence and molecular characterization of Cryptosporidium in farmed rainbow trout (Oncorhynchus mykiss Walbaum, 1792). A total of 360 fish, with no apparent clinical signs of disease, were collected and classified into groups according to their size. Cryptosporidium oocysts were detected by immunofluorescence microscopy in 33 specimens (9.2%), which were located in pyloric caeca samples (42.4%), intestinal scrapings (39.4%), or at both locations (18.2%). In the smallest (youngest) fish group, a higher percentage of positive samples were detected in the pyloric caeca relative to the intestinal location (58.8 vs. 17.6%; P = 0.01), including a cluster with more than 10 oocysts observed in the pyloric caeca of one specimen. PCR amplification and sequencing of fragments of SSU-rDNA and hsp70 genes identified a novel Cryptosporidium piscine genotype (genotype 9) in two specimens and Cryptosporidium parvum in seven fish, including the specimen in which the oocyst cluster was observed. Moreover, Cryptosporidium oocysts were detected in farm water samples (41.7 and 16.7% from influent and effluent, respectively). Although Giardia was not found in gastrointestinal samples, Giardia cysts were observed in 50.0 and 33.3% of the influent and effluent water samples, respectively. The results support the existence of natural infections by C. parvum in freshwater cultured fish, suggesting that the rainbow trout could shed infectious oocysts in aquatic environments and it may be a potential source of human infection when this edible fish is handled.

     

Surveillance of the efficacy of artesunate and mefloquine combination for the treatment of uncomplicated falciparum malaria in Cambodia

Artesunate and mefloquine combination treatment has been used since 2000 in Cambodia as the first-line drug for the treatment of uncomplicated falciparum malaria. In order to assess its efficacy and safety, the national malaria control programme conducted 14 therapeutic efficacy studies with the drug combination between 2001 and 2004 at nine sites. In 2001 and 2002, co-blister packs of artesunate and mefloquine were used, whereas in 2003 and 2004, drugs were given individually from a bulk pack at a total dose of 12 mg/kg of artesunate and 25 mg/kg of mefloquine over 3 days. A total of 1025 patients were enrolled over the 4 years and 977 were follow-up during the period of 28 days. The PCR-corrected cure rates ranged from 85.7% to 100% with an overall cure rate of 95.8% (920/960). The studies in 2002 showed also that co-blister packs used on the basis of age and not on the basis of weight could lead to underdosed regimens but without any detectable effect on the treatment outcome. The follow-up period was extended from 28 to 42 days in three sites in 2004. A total of 219 among 255 were follow-up until day 42. The cure rate decreased but not significantly from 90.1% (73/81) with 28 days follow-up to 79.3% (46/58) with 42 days follow-up in Pailin, whereas the cure rate remained at 100% in the two other sites. Side effects were common, especially dizziness, but were mild and transient and patients recovered without any medical intervention.