RESUMO
OBJECTIVE: To explore the strategy for the treatment of chronic hepatitis B with YMDD mutation. METHODS: A total of 120 chronic hepatitis B patients with YMDD mutation were randomly assigned into four groups. In group A, patients received adefovir dipivoxil for 48 weeks. In group B, patients received adefovir dipivoxil in combination with lamivudine during the first 12 weeks and adefovir dipivoxil only for the following 36 weeks. In group C, patients received adefovir dipivoxil in combination with lamivudine for 48 weeks. In group D, patients received entecavir for 48 weeks. RESULTS: The rate of rebound of alanine aminotransferase (ALT) was 30.0% (9/30), 10.0% (3/30), 6.7% (2/30), 10.0% (3/30) (P < 0.05) during the first 12 weeks, and one patient with severe hepatitis was found in group A. The positive rate of YMDD mutation was 17.9%, 0, 0, 0 at week 12. There was no significant difference in the level of ALT and the rate of HBeAg seroconversion after 48-week treatment (P > 0.05). At week 48, there was significant difference in the ALT normalization rate and undetectable HBV DNA rate between group C and group A, and also between group D and group A, and the rate of drug resistant genotype was 6.9%, 6.7%, 0, 0. Two patients had rtN236T mutation in group A, and one patient had rtN236T mutation and another one had rtA181V mutation in group B. CONCLUSION: Adefovir dipivoxil in combination with lamivudine or entecavir are safe and effective therapies for chronic hepatitis B patients with YMDD mutation.
Assuntos
Antivirais/uso terapêutico , DNA Viral/sangue , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Adenina/administração & dosagem , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Alanina Transaminase/sangue , Antivirais/administração & dosagem , Farmacorresistência Viral , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Guanina/administração & dosagem , Guanina/análogos & derivados , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Humanos , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mutação , Organofosfonatos/administração & dosagem , Organofosfonatos/uso terapêutico , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: To explore the influence of beta-elemene on the proliferation, migration and RhoA expression of hepatic stellate cells (HSC) induced by angiotensin II (ANG II). METHODS: HSC were incubated in vitro. Proliferation and migration of the HSC were induced by ANG II. The effect on the proliferation of HSC was determined by MTT colorimetry. The migration ability was detected by transwell chamber cultures. Total RNA was extracted by TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Protein levels were determined by Western blot. RESULTS: Different concentrations (from 1 to 10 micromol/L) of ANG II markedly promoted the growth of the HSC in a concentration dependent way (0 micromol/L ANG II, F = 112.640, P less than 0.01). 10, 8, 4 micromol/L ANGII significantly induced HSC migration, F = 117.496, P less than 0.01. Compared with the 4 micromol/L ANG II group, 10 mg/L, 5 mg/L, 2.5 mg/L beta-elemene markedly inhibited HSC proliferation and migration induced by 4 micromol/L ANG II (F values were 95.706 and 55.600 and P less than 0.01). 4 micromol/L ANG II markedly promoted the protein and mRNA expressions of RhoA in HSC. 10 mg/L, 5 mg/L and 2.5 mg/L beta-elemene notably inhibited the expressions of RhoA protein and mRNA (F values were 217.119 and 18.010). CONCLUSION: ANG II can significantly induce the proliferation and migration of HSC. Beta-elemene can inhibit the proliferation and migration of HSC induced by ANG II. The effects of beta-elemene are mediated through inhibiting the RhoA signal transduction pathway and are associated with RhoA.
Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Sesquiterpenos/farmacologia , Proteína rhoA de Ligação ao GTP/metabolismo , Angiotensina II/farmacologia , Células Cultivadas , Células Estreladas do Fígado/citologia , HumanosRESUMO
OBJECTIVE: To investigate the relationship between carotid artery intima media thickness (IMT) and apolipoprotein (Apo) E gene polymorphisms in type 2 diabetes mellitus (DM2). METHODS: Two hundred and fifty-five DM2 patients without angiopathy and 107 healthy individuals were selected. PCR/allele-specific oligonucleotide probe was used to determine their apoE genotypes. RESULTS: The prevalence distribution of apoE genotypes and alleles in DM2 patients and that in controls were similar. The TC, LDL-C and Lp(a) concentrations in e4/4, e4/3 subgroups were significantly higher than those in e3/2, e2/2 subgroups (P<0.05). The average value of IMT in e4/4 e4/3 carriers (0.89 mm) was significantly greater than that in e3/2 e2/2 carriers (0.62 mm) (P<0.05). After adjustment for TC, LDL-C, TG, Lp(a), FBG, HbA1c, age, BMI, and smoking, ANCOVA showed that the average value of carotid IMT was significantly greater in subjects with e4/4 e4/3, compared with that in subjects with e3/2 e2/2(P=0.033). CONCLUSION: Apo e4 allele increases the risk for carotid artery atherosclerosis in the early stage of diabetic population.