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     

Changes of hepatic vitronectin levels in patients with chronic hepatitis C treated with interferon alpha

Hepatic vitronectin expression was assessed in 27 patients with chronic hepatitis C before and after interferon alpha treatment and in 7 control patients. Before interferon therapy, vitronectin was localized in the hepatocytes and in the portal and central venous regions. A high correlation was found for the vitronectin expression level with the histological grading and staging scores in the hepatocytes as well as in the portal region. After interferon therapy, the hepatic vitronectin was significantly decreased in the sustained and transient responders, but it was not as markedly decreased in the nonresponders and the non-treated group. A good correlation was found for the vitronectin expression with the staging scores but not with the grading scores in the portal region. These findings suggest that hepatic vitronectin is influenced by interferon therapy and that it may play an important role as a hepatic adhesion molecule through the improvement of inflammation, necrosis and fibrogenesis.     

Severe exacerbation of hepatitis after short-term corticosteroid therapy in a patients with "latent" chronic hepatitis B

We present a case of severe exacerbation of hepatitis after short-term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with "latent" chronic hepatitis B showing no HBV-related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)-related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G-to-A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan.     

Severe exacerbation of hepatitis after short‐term corticosteroid therapy in a patient with “latent” chronic hepatitis B

Abstract: We present a case of severe exacerbation of hepatitis after short‐term corticosteroid therapy for chronic inflammatory demyelinating polyneuropathy (CIPD) with “latent” chronic hepatitis B showing no HBV‐related antigens and antibodies. After corticosteroid pulse therapy for CIPD, the patient had severe exacerbation of hepatitis twice. Although she did not show any hepatitis B virus (HBV)‐related antigens or antibodies, sequences of HBV were detected in serum and liver by a nested polymerase chain reaction. A sequence analysis of HBV at the second exacerbation showed that the G‐to‐A point mutation at nucleotide 1896 that converted codon 28 from tryptophan (TGG) to a stop codon (TAG) in the precore region resulted in amino acid change, which has been frequently observed in fulminant hepatitis and severe hepatitis in Japan.     

Spontaneous Rupture of the Spleen Secondary to Metastatic Hepatocellular Carcinoma: A Report of a Case and Review of the Literature

An extremely rare case of splenic rupture at the site of metastasis of hepatocellular carcinoma is reported. A 62-yr-old woman with hepatocellular carcinoma and its suspected metastasis to the spleen died of intraperitoneal hemorrhage. Autopsy disclosed a laceration of the spleen as the definitive cause of the hemorrhage. There were multiple nodules of metastatic hepatocellular carcinoma in the spleen, some of which were exposed at the lacerated portion of the splenic capsule. This may be the first report of a case of spontaneous rupture of the spleen secondary to metastatic hepatocellular carcinoma. Splenic rupture can he one of the causes of hemoperitoneum in patients with hepatocellular carcinoma.     

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.     

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.     

Elevated serum aminotransferase induced by isoniazid in relation to isoniazid acetylator phenotype

Of 143 patients with pulmonary tuberculosis receiving isoniazid therapy, 52 (36%) had a transient elevation in serum aminotransferases. Among 74 patients taking isoniazid, rifampicin and streptomycin, 35 (47%) had such an increase, while of 69 patients taking isoniazid, amino-salicylic acid and streptomycin, 17 (24%) did; this difference was significant. Isoniazid therapy could be continued in all patients with the abnormal test results. In 36 of the patients receiving isoniazid, rifampicin and streptomycin, isoniazid and its metabolites were studied in the serum and urine using high-performance liquid chromatography after the oral administration of 10 mg per kg of isoniazid. We had chosen for this test 18 patients with normal aminotransferase levels and 18 with abnormal levels. There were 14 rapid acetylators in the patients with abnormal aminotransferase levels and 7 rapid acetylators in the patients with normal levels; this difference was significant. These results indicate that liver dysfunction is more often caused by an isoniazid/rifampicin regimen, and patients who are rapid acetylators are more susceptible.     

Defective immunoregulation in primary biliary cirrhosis: CD4+, Leu-8+ T cells have abnormal activation and suppressor function in vitro

To determine whether abnormalities of lymphocyte function in primary biliary cirrhosis are due to altered function of immunoregulatory T cell subpopulations, phenotypic and functional characteristics of CD4+ T cells were examined. The proportion of CD4+ T cells expressing the Leu-8 and CD45R antigens was normal in patients with primary biliary cirrhosis. The capacity of CD4+, Leu-8- T cells to provide helper function for pokeweed mitogen-stimulated immunoglobulin synthesis by B cells in vitro was similar in patients and controls. However, in contrast to normal individuals and patients with other liver diseases, CD4+, Leu-8+ T cells from six of 10 patients with primary biliary cirrhosis did not suppress, but enhanced immunoglobulin synthesis. Whereas treatment of CD4+ T cells from normal individuals with anti-Leu-8 monoclonal antibody enhanced their suppressor function, similar treatment of CD4+ T cells from patients with primary biliary cirrhosis did not increase their suppressor function. To determine whether the abnormal regulatory function of CD4+, Leu-8+ T cells was due to a defect of cell activation, the proliferative response of CD4+ T cell subpopulations to mitogenic stimulation was examined. The proliferative responses of CD4+, Leu-8- T cells from patients with primary biliary cirrhosis and controls were similar, but the proliferative responses of CD4+, Leu-8+ T cells from patients with primary biliary cirrhosis were lower than those of control cells.(ABSTRACT TRUNCATED AT 250 WORDS)