In the present study, the effects of Pleurotus nebrodensis polysaccharide (PN-S) on the immune functions of immunosuppressed mice were determined. The immunosuppressed mouse model was established by treating the mice with cyclophosphamide (40 mg/kg/2d, CY) through intraperitoneal injection. The results showed that PN-S administration significantly reversed the CY-induced weight loss, increased the thymic and splenic indices, and promoted proliferation of T lymphocyte, B lymphocyte, and macrophages. PN-S also enhanced the activity of natural killer cells and increased the immunoglobulin M (IgM) and immunoglobulin G (IgG) levels in the serum. In addition, PN-S treatment significantly increased the phagocytic activity of mouse peritoneal macrophages. PN-S also increased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and nitric oxide (NOS) in splenocytes. qRT-PCR results also indicated that PN-S increased the mRNA expression of IL-6, TNF-α, INF-γ, and nitric oxide synthase (iNOS) in the splenocytes. These results suggest that PN-S treatment enhances the immune function of immunosuppressed mice. This study may provide a basis for the application of this fungus in adjacent immunopotentiating therapy against cancer and in the treatment of chemotherapy-induced immunosuppression.
Animals ; Antineoplastic Agents, Alkylating ; Biological Products ; pharmacology ; therapeutic use ; Cell Line ; Cyclophosphamide ; Immunity ; drug effects ; Immunologic Factors ; pharmacology ; therapeutic use ; Immunosuppression ; Interferon-gamma ; metabolism ; Interleukin-6 ; metabolism ; Macrophages ; drug effects ; metabolism ; Male ; Mice, Inbred BALB C ; Neoplasms ; drug therapy ; immunology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Phagocytosis ; drug effects ; Pleurotus ; chemistry ; Polysaccharides ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUND/AIMS: Lipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment. METHODS: In total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of beta cells (HOMA-beta) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx). RESULTS: A sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0+/-11.2 years, mean+/-SD; non-SVR, 56.6+/-9.9 years; P<0.01), there were no significant differences in the baseline characteristics between the SVR and non-SVR groups. In the SVR group, low density lipoprotein-cholesterol (LDL-C) had significantly changed at DTx and ATx compared to BTx. In addition, HOMA-IR and HOMA-beta were significantly changed at DTx in the SVR group. Among those with a high baseline insulin resistance (HOMA-IR >2.5), HOMA-IR was significantly changed at DTx in the SVR group. CONCLUSIONS: LDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).
Adult ; Aged ; Antiviral Agents/pharmacology/*therapeutic use ; Cholesterol/blood ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/*drug therapy ; Humans ; *Insulin Resistance ; Interferon-alpha/pharmacology/*therapeutic use ; Lipid Metabolism/drug effects ; Male ; Middle Aged ; Polyethylene Glycols/pharmacology/*therapeutic use ; Recombinant Proteins/pharmacology/therapeutic use ; Ribavirin/*therapeutic use ; Treatment Outcome ; Triglycerides/blood

OBJECTIVETo compare the effects of Bushen Jiedu Recipe (BJR) and Jianpi Jiedu Recipe (JJR) containing plasma on dendritic cells (DCs) of chronic hepatitis B virus (HBV) infection patients under different immune states.

METHODSRecruited were 36 chronic HBV infection outpatients from First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from April 2010 to January 2011. They were assigned to the immune tolerance group (18 cases) and the immune clearance group (18 cases).Another 10 healthy subjects were recruited as the healthy control group. Their anticoagulated peripheral venous blood was respectively collected. The peripheral blood mononuclear cells (PBMCs) were isolated and further extracted for incubating DCs. The DCs were intervened by BJR and JJR containing plasma. The morphology of DCs was identified. The expressions of CD1alpha, CD80, CD86, and HLA-DR were detected. The level of interferon-alpha (IFN-alpha) in the supernatant was observed by ELISA.

RESULTSThe CD80 expression level was lower in the immune clear group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, CD86, and HLA-DR were lower in the immune tolerance group than in the healthy control group before intervention (P < 0.05).The IFN-alpha expression level was lower in the immune tolerance group and the immune clearance group than in the healthy control group before intervention (P < 0.05). The expression levels of CD80, HLA-DR, and IFN-alpha were lower in the immune tolerance group than in the immune clearance group before intervention (P < 0.05). Compared with the same group before intervention, the CD80 expression significantly increased in each treatment group (P < 0.05). After intervention the expression levels of CD80 and HLA-DR were higher in the immune tolerance group than in the immune clearance group in the same time phase, and the CD86 expression level was higher in the BJR group than in the immune clearance group in the same time phase, showing statistical difference (P < 0.05).

CONCLUSIONSThe middle dose BJR and the small dose JJR both could promote the recovery of DCs in chronic HBV infection patients. Besides, BJR showed more prominent effects on the function of DCs in chronic HBV infection patients in the immune tolerance stage.

Adult ; B7-1 Antigen ; metabolism ; B7-2 Antigen ; metabolism ; Case-Control Studies ; Dendritic Cells ; drug effects ; immunology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; HLA-DR Antigens ; metabolism ; Hepatitis B, Chronic ; blood ; drug therapy ; immunology ; Humans ; Immune Tolerance ; drug effects ; Interferon-alpha ; metabolism ; Male ; Phytotherapy ; Plasma ; Young Adult

BACKGROUND/AIMS: When combined with pegylated interferon alpha-2b (Peg-IFN alpha-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV. METHODS: We retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg-IFN alpha-2b and RBV combination therapy. We divided the patients into groups A (> or =15 mg/kg/day, n=23) and B (<15 mg/kg/day, n=26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion. RESULTS: The early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, P=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, P=0.01). CONCLUSIONS: RBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients.
Antiviral Agents/pharmacology/*therapeutic use ; Body Mass Index ; Body Weight ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/drug effects ; Hepatitis C, Chronic/*drug therapy/virology ; Humans ; Interferon-alpha/pharmacology/*therapeutic use ; Male ; Polyethylene Glycols/pharmacology/*therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/pharmacology/therapeutic use ; Retrospective Studies ; Ribavirin/pharmacology/*therapeutic use ; Sex Factors ; Treatment Outcome

OBJECTIVETo investigate the prevalence and distribution of HCV genotypes and the clinical effect of interferon-alpha combined with ribavirin treatment in chronic hepatitis C patients in Kunming.

METHODS60 patients were divided into two groups based on drug therapies: PEG-interferon-a plus ribavirin treatment group for HCV 1b and interferon-a plus ribavirin treatment group for non-HCV-1b. Serum ALT levels and HCV RNA quantitations of the patients were detected during treatment and follow-up.

RESULTSThe HCV genotypes of 60 patients were determined by type specific probe assay, and five different types were found. Their overall prevalence were 21.7% for type 1b, 5% for type 2a, 16.7% for type 3a, 48.3% for type 3b, and 8.3% for type 6a. Sustained viral response rates for PEG-interferon treatment group were 46.1%, for interferon treatment group were 74.4%. The abnormal rate of serum ALT after the treatment had no significant difference between HCV-1b and non-HCV-1b patients (P>0.05). All patients with early viral responses got sustained viral response.

CONCLUSIONHCV-3b is the most dominant genotype in Kunming. The effect of PEG-interferon-a plus ribavirin treatment for genotype 1b is unsatisfactory. The early viral response is a good predictor for the responses to antiviral therapy in chronic hepatitis C patients.

Adult ; Aged ; Antiviral Agents ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Genotype ; Hepacivirus ; genetics ; Hepatitis C, Chronic ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; RNA, Viral ; Ribavirin ; therapeutic use ; Young Adult

OBJECTIVETo observe the effects of Bushenhuoxue Yin (BSHXY), a compound traditional Chinese herbal medicine, on nitric oxide (NO), tumor necrosis factor-&alpha; (TNF-&alpha;) and interferon-γ (IFN-γ) levels in the brain of a mouse model of Parkinson disease (PD).

METHODSForty-five C57BL/6 mice were randomized into MPTP-induced PD model group, BSHXY treatment group and normal control group. The contents of NO and the two cytokines in the brain tissue of the mice were determined by spectroscopy and enzyme-linked immunosorbent assay, respectively.

RESULTSThe concentration of NO in the brain tissue of the PD model group was 5.93 ∓ 0.79 µmol/g.protein, significantly higher than that in BSHXY group (P<0.01) and normal control group (P<0.01). The levels of TNF-&alpha; and IFN-γ in the PD model group were 0.36 ∓ 0.11 ng/L and 0.83 ∓ 0.25 ng/L, respectively, also higher than those in the other two groups (P<0.01 or 0.001). But BSHXY group and the normal control group showed no significant differences in the levels of NO, TNF-&alpha; and IFN-γ (P>0.05).

CONCLUSIONThe therapeutic effect of BSHXY on PD is partially attributed to decreased content of NO, TNF-&alpha; and IFN-γ in the brain.

Animals ; Brain ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Interferon-gamma ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide ; metabolism ; Parkinson Disease ; drug therapy ; metabolism ; Phytotherapy ; Random Allocation ; Tumor Necrosis Factor-alpha ; metabolism

Antiviral Agents ; pharmacology ; therapeutic use ; DNA, Viral ; blood ; Hepatitis B ; blood ; drug therapy ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; physiology ; Humans ; Interferon-alpha ; pharmacology ; therapeutic use ; Kinetics ; Lamivudine ; pharmacology ; therapeutic use ; Models, Statistical ; Viral Load

OBJECTIVETo investigate the effect of bortezomib on prophylaxis of acute graft-versus-host disease (aGVHD) after mouse allogeneic-bone marrow transplantation (allo-BMT) and its mechanism.

METHODSC57BL/6 (H-2(b)) mice were used as donors and BALB/c (H-2d+) mice as recipients. After allo-BMT, the BALB/c mice were divided into 3 groups, ie. group A:BMT control, group B: BMT + early infusion of bortezomib (1 mg kg(-1) d(-1), day 0-3), group C: BMT + late infusion of bortezomib (1 mg kg(-1) d(-1), day 5-7). Clinical manifestations of aGVHD, pathohistological changes, survival rate and levels of recipients H-2(b) cells detected by flow cytometry in the recipient mice were observed. Monodirectional mixed lymphocyte culture (MLC) system was established ex vivo and different concentrations of bortezomib (0, 2, 4, 8 nmol/L) were added to the system. The viability of the cells was detected by CCK-8 assay and cells apoptosis by flow cytometry. The concentrations of IL-2, IFN-gamma, TNF-alpha in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA).

RESULTSThe mice in group A developed typical aGVHD and all died of aGVHD within 3 weeks after transplantation, with a median survival time of (16.1 +/- 2.5) d. The symptoms of aGVHD was milder in group B than in group A, and the median survival time was significantly longer. The 60-day survival rate in group B was 70%, being significantly higher than that in other two groups(P<0.05). The mean value of donor-derived cell (H-2(b) cells) in group B was (98.1 +/- 1.1)% at 60 days. The symptoms of aGVHD was significantly severer in group C than in group A, and the median survival time was shorter. Bortezomib inhibited the cells viability in MLC system in a dose-dependent manner. After treated with 8 nmol/L bortezomib for 24 h, the inhibition ratio of cells viability was (41.4 +/- 6.0)%. The cell apoptosis rate increased gradually with bortezomib treatment for 12 h, 24 h and 36 h. After treated with 8 nmol/L bortezomib for 36 h, the apoptosis rate was (62.8 +/- 7.0)%. After treated for 24 h, the levels of IL-2, IFN-gamma and TNF-alpha in the supernatant were decreased.

CONCLUSIONSBortezomib administered immediately after allogeneic BMT can prevent aGVHD, improve the survival rate and have no influence of engraftment in the recipient mice. Delayed administration of bortezomib results in acceleration of aGVHD-induced mortality. Its mechanism maybe inhibition of the lymphocyte viability, increase of the cells apoptosis rate, and inhibition of secretion of IL-2, IFN-gamma, and TNF-alpha.

Animals ; Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; therapeutic use ; Bortezomib ; Cell Survival ; drug effects ; Cells, Cultured ; Disease Models, Animal ; Female ; Graft vs Host Disease ; prevention & control ; Interferon-gamma ; metabolism ; Interleukin-2 ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Pyrazines ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo evaluate the effects of antiviral agents on intrahepatic HBV covalently closed circular DNA (cccDNA) in HBeAg-positive chronic hepatitis B patients.

METHODSSeventy-one HBeAg positive chronic hepatitis B patients were enrolled in this study. Lamivudine was administered to 35 patients for 48 weeks, sequential therapy with lamivudine-IFN alpha-2b to 24 of the 71 patients for 48 weeks, and interferon alpha (IFN alpha-2b) was administered to 12 for 24 weeks. All subjects were followed-up for 24 weeks. Serum HBV DNA, intrahepatic HBV DNA and cccDNA were measured quantitatively by PCR. HBV genotypes were analyzed by PCR-RFLP.

RESULTSForty-eight weeks of sequential lamivudine-IFN alpha-therapy and lamivudine monotherapy and 24 weeks of IFN alpha monotherapy reduced the intrahepatic HBV DNA to (4.7+/-1.1) log10, (4.6+/-1.5) log10 and (5.6+/-1.5) log10, and cccDNA to (3.4+/-1.3) log10, (3.8+/-1.1) log10 and (5.0+/-1.5) log10, significantly lower than therapy (P < 0.05). Seventeen of the 71 patients developed HBeAg seroconversion, and the reduction of cccDNA in the HBeAg seroconverted patients was significantly more than that of the HBeAg positive patients (P < 0.05). After 24 weeks of antiviral therapy withdrawal, 18 patients achieved sustained virological response, and the baseline intrahepatic cccDNA in the patients with sustained virological response was significantly lower than that of patients with virological rebound (P < 0.05). The change in intrahepatic cccDNA correlated positively with the reduction in intrahepatic HBV DNA (P < 0.05). The cccDNA levels correlated with the serum HBeAg titers at the end of the treatment (P < 0.01). Of the total 71 cases, HBV genotype C accounted for 85.9% (n = 61), and genotype B for 14.1% (n = 10). There was no significant difference in the changes of intrahepatic HBV DNA and cccDNA levels between HBV genotypes C and B (P >0.05).

CONCLUSIONSBoth 48 weeks of sequential lamivudine-IFN alpha and lamivudine monotherapy strongly reduced intrahepatic HBV DNA and cccDNA more than 24 weeks of IFN alpha monotherapy. Low baseline intrahepatic cccDNA levels might predict a good long-term efficacy of antiviral treatment. The reduction of intrahepatic cccDNA correlated positively with the changes of intrahepatic HBV DNA, and intrahepatic cccDNA levels correlated with serum HBeAg titers. HBV genotypes had no obvious influence on intrahepatic HBV DNA load or cccDNA load.

Adult ; Antiviral Agents ; pharmacology ; therapeutic use ; DNA, Circular ; DNA, Viral ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; genetics ; Hepatitis B, Chronic ; drug therapy ; virology ; Humans ; Interferon-alpha ; pharmacology ; therapeutic use ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Middle Aged ; Recombinant Proteins ; Young Adult

OBJECTIVETo evaluate the effect of antiviral agents on intrahepatic HBV DNA and histology in HBeAg-positive chronic hepatitis B patients.

METHODSThirty-five patients were treated with lamivudine, 16 with interferon alfa (INF-alpha), 24 with sequential Lamivudine and INF-alpha. The total duration of therapy was 12 months. Intrahepatic HBV DNA was measured quantitatively by real-time polymerase chain reaction.

RESULTSThere was significant change in all parameters of the groups of patients at the end of treatment (P < 0.05). The patients treated with sequential treatment had slightly higher HBeAg seroconversion rate (38.1%) than that of the other patients (P=0.1352). The baseline levels of intrahepatic HBV DNA in the patients with HBeAg seroconversion or undetectable serum HBV DNA were significantly lower than that of the other patients (P < 0.05).

CONCLUSIONAntiviral agents could effectively inhibit intrahepatic HBV DNA and improve hepatic histology. The patients with low baseline intrahepatic HBV DNA level may achieve better antiviral efficacy. Sequential treatment might produce high HBeAg seroconversion rate.

Adolescent ; Adult ; Antiviral Agents ; pharmacology ; therapeutic use ; DNA, Viral ; blood ; metabolism ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens ; immunology ; metabolism ; Hepatitis B, Chronic ; drug therapy ; immunology ; pathology ; virology ; Humans ; Interferon-alpha ; pharmacology ; therapeutic use ; Lamivudine ; pharmacology ; therapeutic use ; Liver ; drug effects ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Time Factors