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.     

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)     

Occult hepatitis B virus infection in HBs antigen-negative hepatocellular carcinoma in a Japanese population: involvement of HBx and p53

Hepatitis B virus (HBV) genome was reported to be detected in serum or liver tissues in hepatocellular carcinoma (HCC) patients negative for hepatitis B surface antigen (HBsAg). Hepatitis B x (HBx) and p53 protein were reported to play an important role in HBV-related hepatocarcinogenesis. To clarify latent HBV infection in HBsAg- and anti-hepatitis C virus (anti-HCV)-negative HCC in a Japanese population and involvement of HBx and p53 protein in these patients, we performed the sensitive and specific nested polymerase chain reaction (PCR) and immunohistochemical analysis. Of 1,024 HCC patients we saw between 1974 and 1998, 66 (6.4%) were negative for HBsAg and anti-HCV. Serum DNA was amplified by nested PCR by using specific primers of surface (S), core (C) and X regions in 26 patients negative for HBsAg and anti-HCV. Eighteen (69%) patients were positive for either S, C, or X region and the results of PCR were confirmed by Southern blotting. Of 18 PCR-positive patients, 3 were positive for anti-HBs and 9 were positive for anti-HBc, however, one was negative for any HBV markers. In HBsAg-negative and PCR-positive patients, the positive rates of expression of HBx and p53 were 8/13 (62%) and 7/13 (54%), being comparable to those in HBsAg-positive HCC patients. The results of the present study suggest that high prevalence of HBV infection is observed in HBsAg-negative HCC in a Japanese population and expression of HBx and p53 is consistent with a role, in these patients, for the transforming ability of these proteins.