Adenine ; analogs & derivatives ; Fanconi Syndrome ; Humans ; Organophosphonates

Background: Hepatitis B is a potentially serious form of liver inflammation due to infection by the hepatitis B virus (HBV). It occurs in both rapidly developing (acute) and long-lasting (chronic) forms, and is one of the most common chronic infectious diseases worldwide. HBV infection is very common in Thua Thien \ufffd?Hue. Objectives:. Our study is aimed to assess the efficacy and safety of Adefovir dipivoxil(ADV) in patients with HBeAg positive chronic hepatitis B .. Subjects and method: Design of study: Prospective; 36 patients with HbeAg (+) chronic B hepatitis were enrolled in this study, all patients were treated with Adefovir dipivoxil in 24 months at Hue University Hospital from October 2004 to September 2006 . Results: The rate of normalization of ALAT is 50 % after 6 months, 66.66% after 12 months and 69.44% after 24 months. The rate of HbeAg seroconversion is 11.11 % after 12 months and 30.55% after 24 months. This rate is Significantly higher in group of patients having the activity of SePT between 5 - 10 normal (58.33%). The rate of phenotypic resistance is only 2.77% after 12 months and 8.33% after 24 months. The tolerance is generally good\r\n', u'even in long - term treatment and no complication of renal\r\n', u'insufficiency was found. Conclusion: ADV appears an effective and safe in patients with HBeAg(+) chronic hepatitis. \r\n', u'
Hepatitis B ; Chronic/ pathology ; therapy ; Adenine/ analogs & ; derivatives

Adenine ; analogs & derivatives ; Hepatitis B, Chronic ; Humans ; Organophosphonates ; Tenofovir ; Treatment Failure

Adenine ; analogs & derivatives ; pharmacology ; Drug Resistance, Viral ; Hepatitis B virus ; drug effects ; Humans ; Organophosphonates ; pharmacology

OBJECTIVETo determine the mutational profile and clinical implications of the viral reverse-transcriptase (rt)A 181T mutation in hepatitis B virus (HBV) through population-based analysis of clinical samples.

METHODSSerum samples from 3, 013 patients who visited The 302 Hospital (Beijing, China) were investigated.HBV DNA was extracted and HBV mutations and genotypes were determined by direct sequencing.Recombinant plasmids harboring the rtA181T/sW172* mutant or wild type sequence were constructed and transfected into the HepG2 cell line. The levels of HBsAg in culture supernatants were compared and statistically analyzed.

RESULTSThe incidence of rtA181T across the study population was 4.1% (165/3, 013), and most of the rtAl 81T-positive patients had received adefovir and/or lamivudine.Forty percent (66/165) of the rtA 181T cases were single mutants and treatment responsive, 46.1% (76/165) included the adefovir-resistant mutation rtA 181 V/N236T, 12.1% (20/165) included the lamivudine-resistant mutation rtM204V/rtM2041, and 1.8% (3/165) included multidrug-resistant mutations.Interestingly, 73.9% (122/165) of the rtA181T-positive samples were detected with co-existing wild-type nucleotides at the site. The rates of HBV/C to HBV/B were 92.1% to 7.9% in the rtA181T-positive patients, but 82.1% to 17.9% in the rtA181T-negative paticnts (P less than 0.01).Almost all (98.2%; 129/165) of the rtA181T led to sW172*, while only 1.8% of the rtA181T (3/165) led to sW172L or sW172S.HBsAg secretion in vitro was reduced from the rtA181T/ sW172* strain, but there was no significant difference observed in the average serum HBsAg and HBV DNA levels of patients who carried or did not carry the mutant.

CONCLUSIONThe HBV rtA181T mutation is closely associated with adefovir and lamivudine exposure.rtA181T may led to sW172*, culminating in suppression of HBsAg secretion.However, co-existence of the mutant with wild-type sequences was common among our patient population, suggesting that the mutation had little impact on serum HBsAg and HBV DNA levels across the clinical study population.

Adenine ; analogs & derivatives ; Antiviral Agents ; China ; Genotype ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Lamivudine ; Mutation ; Organophosphonates

OBJECTIVETo determine whether or not enterovirus 71 (enteroviurs 71, EV71) may induce autophagy and affect the production and release of EV71 after the treatment of autophagy inhibitor.

METHODSWestern blots were performed to examine the conversion of LC3-I to LC3- II and the degradation of P62 after the RD-A cells were infected with EV71. CCID50 was determined by checking the virus titer in the supernatant of cells that treated with autophagy inhibitor 3-MA.

RESULTSEV71 infection enhances the type conversion of LC3 and degradation of P62. The infectious virus particles were decreased after the treatment of 3-MA.

CONCLUSIONEV71 infection could induce cell autophagy and the autophagy might contribute to the production and release of infectious EV71 particles.

Adenine ; analogs & derivatives ; pharmacology ; Antiviral Agents ; pharmacology ; Autophagy ; drug effects ; Cell Line, Tumor ; Enterovirus ; drug effects ; Humans

Adenine ; analogs & derivatives ; pharmacokinetics ; therapeutic use ; toxicity ; Antiviral Agents ; therapeutic use ; Clinical Trials as Topic ; Hepatitis B ; drug therapy ; Humans ; Organophosphonates

OBJECTIVETo investigate the effects of adefovir dipivoxil (ADV) on blood phosphorus metabolism in patients with chronic hepatitis B (CHB).

METHODSPatients with hepatitis B surface antigen (HBsAg)-positive CHB were treated with ADV alone, ADV combined with interferon (IFN), or ADV combined with lamivudine (LAM). Changes in levels of calcium, phosphate, urea, and creatinine were assessed at treatment weeks 4, 12, 24, 48, 72 and 96. Statistical analysis was carried out with SPSS 16 software; influential factors were analyzed by ANOVA and non-conditional logistic regression analysis.

RESULTSDuring the course of treatments, 32 (42.6%) of the patients presented with low phosphorus. The highest incidence of low phosphorus was found to have occurred at treatment week 24 (25.0%, 27.5% and 36.4% respectively, with no statistical difference between three groups, x2=0.225, P>0.225). Patients with hypophosphatemia did not show a significant difference in serum phosphorus levels from the other patients (F=1.853, P=0.169). Logistic regression showed a correlation between low phosphorus and sex (x2=7.876, P<0.05), age (t=2.479, P<0.05), and serum creatinine (t =-2.256, P<0.05), but not with blood urea nitrogen or blood calcium (P>0.05).

CONCLUSIONADV antiviral treatment can decrease the blood phosphorous levels of CHB patients, particularly over extended time of treatment, and the occurrence of low phosphorus is more common than of mild phosphorus decrease.Male and elderly patients may be at greater risk of this complication. The incidence and severity of low phosphorus is not significantly different for the different ADV-based treatment regimens.

Adenine ; analogs & derivatives ; Aged ; Antiviral Agents ; Creatinine ; Drug Therapy, Combination ; Hepatitis B, Chronic ; Humans ; Interferons ; Lamivudine ; Male ; Organophosphonates ; Phosphorus

AIMTo develop a sensitive and specific liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for the determination of adefovir in monkey plasma.

METHODSAdefovir and internal standard 9-(3-phosphonylmethoxypropyl) adenine were isolated from plasma by protein precipitation with methanol, then chromatographed by using a Diamonsil C18 column. The mobile phase consisted of methanol-water-formic acid (20:80:1). Electrospray ionization (ESI) source was applied and operated in the positive ion mode. Selected reaction monitoring (SRM) mode with the transitions of m/z 274-->m/z 162 and m/z 288-->m/z 176 were used to quantify adefovir and the internal standard, respectively.

RESULTSThe linear calibration curve was obtained in the concentration range of 0.02-4.00 mg.L-1. The lower limit of quantitation was 20 micrograms.L-1. The inter- and intra-day precision (RSD) was less than 5.8%, and the accuracy (relative error) was within +/- 4.5%. The method was successfully used in a pharmacokinetic study of adefovir dipivoxil in monkeys.

CONCLUSIONThe method is proved to be suitable for pre-clinical investigation of adefovir dipivoxil pharmacokinetics, which offers advantages of specificity and simple sample preparation compared with the previously reported methods.

Adenine ; analogs & derivatives ; blood ; pharmacokinetics ; Animals ; Antiviral Agents ; blood ; pharmacokinetics ; Biotransformation ; Chromatography, Liquid ; Macaca mulatta ; Organophosphonates ; Spectrometry, Mass, Electrospray Ionization

Adenine ; analogs & derivatives ; therapeutic use ; Guanine ; analogs & derivatives ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; Humans ; Lamivudine ; therapeutic use ; Nucleosides ; therapeutic use ; Organophosphonates ; therapeutic use