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[交流] 求助翻译：药物化学方面的文献翻译1，有重赏

6．    L3 ANSWER 411 OF 1146  CAPLUS  COPYRIGHT 2004 ACS on STN
AN 2001:706911  CAPLUS  Full-text>
DN 136:14928
TI Current pharmacotherapy for hepatitis B infection
AU Galan, Mark V.; Boyce, Douglas; Gordon, Stuart C.
CS Division of Gastroenterology Hepatology, William Beaumont Hospital, Royal
   Oak, MI, USA
SO Expert Opinion on Pharmacotherapy (2001), 2(8), 1289-1298
   CODEN: EOPHF7; ISSN: 1465-6566
PB Ashley Publications Ltd.
DT Journal; General Review
LA English
AB A review.  Chronic infection with the hepatitis B virus (HBV) affects 350 million people worldwide, or approx. 5% of the global population, and commonly results in cirrhosis and hepatocellular carcinoma.  Until recently, the only available treatment was injectable interferon alpha and response rates were suboptimal.  Moreover, this expensive and toxic therapy had little applicability in the endemic regions of the world, i.e., Asia and Africa.  The realization that orally available nucleoside and nucleotide agents may effectively control this infection opened a new era in the management of chronic hepatitis B.  Oral lamivudine recently became approved for treatment of hepatitis B worldwide.  It is free of significant toxicity, improves liver histol. and rapidly diminishes HBV DNA levels; lamivudine is expected to become the first-line therapy of choice.  Nevertheless, the consistent emergence of lamivudine-resistant variants mandates the need to develop addnl. therapeutic agents.  Adefovir dipivoxil, a nucleotide, and entecavir, a nucleoside agent, are promising new drugs that might eventually be used in combination with lamivudine and therefore reduce the incidence of drug resistance.  There is a critical need to advance the research of hepatitis B antiviral agents so that effective combination therapies can become widely available.
RE.CNT  76 THERE ARE 76 CITED REFERENCES AVAILABLE FOR THIS RECORD
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7．    L3 ANSWER 412 OF 1146  CAPLUS  COPYRIGHT 2004 ACS on STN
AN 2001:682397  CAPLUS  Full-text>
DN 135:366361
TI Adefovir and tenofovir susceptibilities of HIV-1 after 24 to 48 weeks of
   adefovir dipivoxil therapy: Genotypic and phenotypic analyses of study
   GS-96-408
AU Miller, Michael D.; Margot, Nicolas A.; Lamy, Patrick D.; Fuller, Michael
   D.; Anton, Kristin E.; Mulato, Andrew S.; Cherrington, Julie M.
CS Gilead Sciences, Inc., Foster City, CA, 94404, USA
SO JAIDS, Journal of Acquired Immune Deficiency Syndromes (2001), 27(5),
   450-458
   CODEN: JJASFJ
PB Lippincott Williams & Wilkins
DT Journal
LA English
AB Aim of this study was to determine whether genotypic changes in HIV-1 (HIV) reverse transcriptase (RT) occur during adefovir dipivoxil (ADV) therapy that may alter the susceptibility of HIV to adefovir or the related nucleotide inhibitor, tenofovir.  GS-96-408 was a 1:1 randomized, double-blind, phase III clin. trial assessing the safety and efficacy of 120-mg daily ADV compared with placebo for the treatment of HIV when added to stable background antiretroviral therapy (ART).  Of 442 patients enrolled, 142 were prospectively selected for a virol. substudy.  Baseline and posttreatment (weeks 24-48) plasma samples were genotypically analyzed in HIV RT.  HIV from ADV-treated patients who developed RT mutations at week 24 were also phenotypically analyzed.  Nucleoside-associated RT mutations arose with similar frequency among the ADV- and placebo-treated patients, 32% (n = 23) and 28% (n = 20), resp., during the 24-wk blinded treatment phase.  RT mutations previously selected by adefovir in vitro (K70E or K65R) did not develop in any patient.  Most mutations were typical zidovudine (ZDV)-resistance mutations (e.g., M41L, D67N, K70R, T215Y) in patients taking ZDV or stavudine (d4T) concomitantly, demonstrating directly in the placebo arm that d4T is able to select for these mutations.  There appeared to be more patients developing D67N and K70R mutations in the ADV arm vs. more T215Y mutations in the placebo arm. Between weeks 24 and 48, 19 of 50 patients (38%) in the ADV arm developed similar RT mutations.  The mean HIV RNA responses at weeks 24 and 48 among the ADV-treated patients developing RT mutations were -0.68 log10 copies/mL (n = 23) and -0.52 log10 copies/mL (n = 19), resp., similar to the overall week-24 and week-48 responses (-0.53 and 0.48 log10 copies/mL, resp.).  Patient-derived HIV expressing the observed RT mutations showed insignificant decreases in adefovir susceptibility compared with wild-type in 12 of 16 cases (  HIV from 1 patient showed significantly reduced susceptibility to tenofovir, which was in association with a double insertion mutation after codon 69 that was also present at baseline.  HIV RT changes that arose during ADV therapy appear attributable to the patient's background ART.  ADV therapy may have influenced the pattern of ZDV-associated resistance mutations that developed, but this did not result in an observed loss of viral load suppression.  There was a trend toward decreased phenotypic susceptibility to adefovir in ADV-treated patients, with 4 of 16 analyzed patients showing mild, but significantly decreased susceptibility associated with the addnl. ZDV-associated mutations.  Decreased susceptibility to the related nucleotide analog, tenofovir, was not observed to develop in ADV-treated patients.
RE.CNT  33 THERE ARE 33 CITED REFERENCES AVAILABLE FOR THIS RECORD
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8．    L3 ANSWER 413 OF 1146  CAPLUS  COPYRIGHT 2004 ACS on STN
AN 2001:667540  CAPLUS  Full-text>
DN 136:379492
TI Safety and efficacy of adefovir dipivoxil in patients co-infected with
   HIV-1 and lamivudine-resistant hepatitis B virus: an open-label pilot
   study
AU Benhamou, Y.; Bochet, M.; Thibault, V.; Calvez, V.; Fievet, M. H.; Vig,
   P.; Gibbs, C. S.; Brosgart, C.; Fry, J.; Namini, H.; Katlama, C.; Poynard,
   T.
CS Service d'Hepato-Gastroenterologie, Groupe Hospitalier Pitie-Salpetriere,
   Paris, Fr.
SO Lancet (2001), 358(9283), 718-723
   CODEN: LANCAO; ISSN: 0140-6736
PB Lancet Ltd.
DT Journal
LA English
AB Background Lamivudine-resistant hepatitis B virus (HBV) is found in about 15-32% of infected patients with or without co-infection with HIV-1 after 1 yr of lamivudine therapy.  Adefovir dipivoxil is active in vivo and in vitro against wild-type and lamivudine-resistant HBV.  We assessed the safety and efficacy of a once daily dose of adefovir dipivoxil in an open-label trial for the treatment of lamivudine-resistant HBV infection in HIV-1-infected patients.  Methods 35 HIV-1/HBV co-infected patients receiving lamivudine therapy (150 mg twice daily) as part of their current HIV-1 antiretroviral regimen were enrolled.  Patients received a 10 mg once-daily dose of adefovir dipivoxil for 48 wk while maintaining their existing anti-HIV-1 therapy, including lamivudine.  Patients were assessed every 4 wk for safety and efficacy.  Findings Four patients withdrew from the study (two because of adverse events), leaving 31 patients who received adefovir dipivoxil for a median of 48 wk (range 44-48).  Mean decreases in serum HBV DNA concns. from baseline (log 8(64 copies/mL [SE log 0(08]) were -log 3(40 copies/mL [log 0(12] at week 24 (n=31) and -log 4(01 copies/mL [log 0(17] at week 48 (n=29; p  Two patients underwent hepatitis B e antigen seroconversion, one at week 32 and one at week 36. Adefovir dipivoxil was generally well tolerated, but was associated with a transient increase in serum alanine aminotransferase concns. in 15 patients.  We found no significant changes in either HIV-1 RNA or CD4 cell count.  Interpretation These results indicate that 48 wk of 10 mg daily adefovir dipivoxil is well tolerated and active against lamivudine-resistant HBV in HIV-1/HBV co-infected patients.
RE.CNT  30 THERE ARE 30 CITED REFERENCES AVAILABLE FOR THIS RECORD
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9．    L3 ANSWER 414 OF 1146  CAPLUS  COPYRIGHT 2004 ACS on STN
AN 2001:491941  CAPLUS  Full-text>
DN 136:295011
TI Synthesis of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and its oral
   prodrug adefovir dipivoxil
AU Zhang, Yong; Li, Xin; Gong, Ping; Wang, Yumei
CS Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang,
   110016, Peop. Rep. China
SO Shenyang Yaoke Daxue Xuebao (2001), 18(2), 95-97
   CODEN: SYDXFF; ISSN: 1006-2858
PB Shenyang Yaoke Daxue Xuebao Bianjibu
DT Journal
LA Chinese
OS CASREACT 136:295011
GI

AB The synthesis of PMEA (I) and its oral prodrug adefovir dipivoxil were reported.  Triisopropyl phosphite, diisopropyl 2- chloroethoxymethylphosphinate, 9-[2-(diisopropyloxyphosphonomethoxy)ethyl] adenine, 9-[2-(phosphonomethoxy)ethyl]adenine and adefovir dipivoxil were synthesized sep.  Some modifications were made so the synthetic method was more convenient than that in literature.
10．       L3 ANSWER 415 OF 1146  CAPLUS  COPYRIGHT 2004 ACS on STN
AN 2001:48900  CAPLUS  Full-text>
DN 135:86509
TI The intracellular activation of lamivudine (3TC) and determination of
   2'-deoxycytidine-5'-triphosphate (dCTP) pools in the presence and absence
   of various drugs in HepG2 cells
AU Kewn, Stephen; Hoggard, Patrick G.; Sales, Sean D.; Johnson, Mark A.;
   Back, David J.
CS Department of Pharmacology and Therapeutics, University of Liverpool,
   Liverpool, L69 3GE, UK
SO British Journal of Clinical Pharmacology (2000), 50(6), 597-604
   CODEN: BCPHBM; ISSN: 0306-5251
PB Blackwell Science Ltd.
DT Journal
LA English
AB Aims: Lamivudine (3TC, 2'-deoxy-3'-thiacytidine) requires intracellular metabolism to its active 5'-triphosphate, 3TC-5'-triphosphate (3TCTP), to inhibit the replication of hepatitis B virus (HBV).  We have investigated the activation of 3TC, in the presence and absence of a range of compds., in HepG2 cells.  The intracellular levels of the endogenous competitor of 3TCTP, 2'-deoxycytidine-5'-triphosphate (dCTP), were also determined and 3TCTP/dCTP ratios calculated  The effects of a number of compds. on 3TC (3H; 1 mM) phosphorylation were investigated by radiometric h.p.l.c. dCTP levels were determined using a template primer extension assay.  3TCTP/dCTP ratios were calculated from these results.  The phosphorylation of 3TC was significantly increased in the presence of either hydroxyurea (HU), methotrexate (MTX), or fludarabine (FLU).  For example, at 100 mM HU, control 3TCTP levels were increased to 361% of control, whereas at 100 mM FLU, control 3TCTP levels were increased to 155%.  DCTP pools were significantly reduced in the presence of HU and FLU, at 100 mM concns. only.  However, for all the above three compds. investigated, the ratio of 3TCTP/dCTP was favorably enhanced (e.g. at 1 mM MTX, 255% of control). Neither ganciclovir (GCV), lobucavir (LCV), penciclovir (PCV), adefovir dipivoxil (ADV), nor foscarnet (FOS) had any significant effects on 3TC phosphorylation or dCTP pools.  These results suggest that the activity of 3TC may be potentiated when combined with one of the modulators studied. The lack of an interaction between 3TC and the other anti-HBV agents is reassuring.  These in vitro studies can be used as an initial screen to examine potential interactions at the phosphorylation level.
RE.CNT  43 THERE ARE 43 CITED REFERENCES AVAILABLE FOR THIS RECORD
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