Involvement of hippocampal serotonin and neuropeptide Y in depression induced by chronic unpredicted mild stress.

Accumulated evidence indicates a role of the hippocampal 5-hydroxy-tryptamine (5-HT) and neuropeptide Y (NPY) in the response to stress and modulation of depression, but it is unclear whether and how the hippocampal 5-HT and NPY systems make contributions to chronic unpredicted mild stress (CUMS)-induced depression. Here we observed that rats receiving a variety of chronic unpredictable mild stressors for 3 weeks showed a variety of depression-like behavioral changes, including a significant reduction in body weight, sucrose preference, and locomotion, rearing and grooming in open field test, and a significant increase in immobility time in forced swimming test. These CUMS-induced behavioral changes were suppressed or blocked by intra-hippocampal injection of 5-HT (31.25 microg/microl) or NPY (10 microg/microl). These data suggest a critical role of reduced hippocampal 5-HT and NPY neurotransmission in CUMS-induced depression.

Effects of γ-interferon on hepatic fibrosis of schistosoma japonicum-infected mice.

AIM: To probe the effect of γ-IFN on hepatic fibrosis in schistosomiasis japonica. METHODS: The amount and distribution of γ-IFN and extracellular matrix in the liver of 60 S. japonicum infected mice and 30 healthy mice at different stages, and their dynamics in 20 infected mice after administration of recombinant γ-interferon were determined by immunohistochemical streptavidin biotin peroxidase complex method. RESULTS: The amount of γ-IFN in liver peaked at the 16(th) week after infection (3 mice respectively reached 2+, 3+ and 4+ grade), which was higher than the levels of infected mice at the 8(th)-12(th) week (P < 0.01), and γ-IFN was mostly distributed around egg granuloma. Fibronectin, laminin, type I and III collagens in liver of most infected mice reached 1+ grade and individual 2+ grade at the 8(th) week after infection, which were higher than those of healthy controls (P < 0.01), and were linearly distributed around egg granuloma . With chronicity and decrease of γ-interferon, however, the matrix proteins and collagens gradually increased, peaked respectively at the 20(th) and 24(th) week (over 70% infected mice with 3+ to 4+ grade), became wide and thick, and deposited in band like or retiform shape around and in egg granuloma. After administration of γ-IFN, only 3 infected mice had 2+ grade of fibronectin at the 20(th) week, and 2 mice had 3+ grade of type III collagen at the 24(th) week, and none of them reached 4+ grade, which were significantly less than the untreated group at the same stage (P < 0.01-0.05). CONCLUSION: γ-interferon may play an important role in opposing the inflammatory response of egg granuloma, decreasing secretion and deposition of extracellular matrix in the liver and suppressing hepatic fibrosis.

Detection of replicative form of HCV RNA in peripheral blood leukocytes and its clinical significance.

Nested RT-PCR, done by using degenerated primer pair, was used to detect hepatitis C virus RNA (HCV RNA) in serum, plasma, liver and peripheral blood mononuclear cells (PBMC) of 30 patients with acute and chronic posttransfusion hepatitis C and 7 asymptomatic anti-HCV positive subjects. The results showed that the percentages of both the plus and minus strands of HCV RNA in PBMC of the patients with chronic hepatitis C was significantly higher than that with acute hepatitis C and asymptomatic anti-HCV positive subjects (P < 0.05-0.001). In 17 patients who were subjected to biopsy, the positive rate of the both strands of HCV RNA in PBMC of the patients with AH was lower than that of CAH (P < 0.05). In serum and plasma of all 37 cases, the minus strand of HCV RNA was not detected. Both plus and minus strands in liver of one patient with AH were positive, but the minus strand in PBMC negative. In 6 patients with CAH whose both strands in liver were positive, both strands in PBMC in 5 patients were also found. The present data confirmed that PBMC of the patients with hepatitis C were infected by HCV and the longer the infection time, the bigger the possibility of PBMC infection by HCV. The patients with active liver disease (CAH) had higher positive rate of minus strands of HCV RNA in PBMC. The results suggested that HCV may not only infect PBMC but also replicate in PBMC, and that the occurrence of minus strand of HCV RNA is associated with activity of liver disease.

Changes of T cell subsets in peripheral blood of patients with Schistosomiasis japonica and their relation to interleukin-1.

T cell subsets in peripheral blood were phenotyped in 56 patients with different stages of Schistosomiasis japonica, including 17 with acute, 14 with chronic and 25 with advanced infection. The activity of interleukin-1 (IL-1) produced by peripheral blood mononuclear cells (PBMC) induced by lipopolysaccharide (LPS) in vitro was simultaneously detected in these three groups of patients. It was found that the percentages of CD3+ (total T cell), CD4+ (helper/inducer T cell) and CD8+ (suppressor/cytotoxic T cell) T cell and the level of IL-1 were significantly increased in the group of acute Schistosomiasis japonica. In the groups of chronic and advanced Schistosomiasis japonica, the proportion of CD3+ T cell, the ratio of CD3+/CD4+ and the level of IL-1 were remarkably reduced, and the percentage of CD8+ T cell was increased. The rate of CD4+ T cell was obviously decreased in cases patients with advanced Schistosomiasis japonica. The percentage of CD4+ T cell was positively correlated to the level of IL-1 in the three groups of patients. These results indicate that T cell subsets and IL-1 may play an important role in the immunoregulation of Schistosomiasis japonica.

[Study of cytopathogenic effect of epidemic hemorrhagic fever virus on normal human bone marrow cells].

The cytopathogenic effect of epidemic hemorrhagic fever virus (EHFV) on cultured human bone marrow cells (HBC) was studied. Specific viral antigen in HBC was detected at various times after EHFV infection with trypan-blue stain and electron microscopy. It was shown that the infection rate of HBC was over 80% at 3 weeks after infection. The death rate of HBC in the infection group was significantly higher than that in the control group on 1-4 weeks after infection. Injury of cell membrane organs after infection with EHFV were significantly earlier and more severe as it was shown by electron microscopy. It was demonstrated that EHFV could cause cytopathogenic effect on cells of nomal human bone marrow.

Changes in T cell subsets and T suppressor cell function and their relationship in human schistosomiasis japonica.

The function of spontaneous T suppressor cell (STs) of peripheral blood was examined in 56 patients with schistosomiasis japonica at various stages. The subsets of T cell were simultaneously phenotyped in 46 cases. The percentages of CD3+ (pan T cell), CD4+ (helper/inducer T cell) and CD8+ (suppressor/cytotoxic T cell) in patients with acute schistosomiasis japonica were significantly higher than those in the normal controls. In patients with chronic and advanced schistosomiasis japonica, the percentage of CD8+ T cell and the function of STs were greatly increased, but the percentage of CD3+ T cell and the ratio of CD4+/CD8+ were obviously reduced. All of these markers changed more significantly in patients with advanced schistosomiasis japonica. The percentage of CD8+ T cell in patients with acute schistosomiasis japonica was negatively correlated with the function of STs. In patients with chronic and advanced schistosomiasis japonica the percentage of CD8+ T cell was correlated positively and the ratio of CD4+/CD8+ negatively with the function of STs. The results indicated that the cellular immunity was significantly increased in cases of acute schistosomiasis japonica and decreased in those with chronic or advanced schistosomiasis japonica. The increased CD8+ T cell may be principally cytotoxic T cells in patients with acute schistosomiasis japonica, but suppressor T cells in patients with chronic and advanced schistosomiasis japonica. The subsets of T cells and the function of T suppressor cells may play an important role in the immunoregulation of schistosomiasis japonica.

Immunohistochemical detection of HBsAg and HBcAg in the liver of patients with schistosomiasis japonica complicated by hepatocellular carcinoma.

In liver biopsies from 21 patients with schistosomiasis japonica complicated by hepatocellular carcinoma (HCC), 69 patients with advanced schistosomiasis japonica, and 25 patients with HCC, HBsAg and HBcAg were investigated with peroxidase-antiperoxidase technique. The positive rate of HBAg (i.e. HBsAg and/or HBcAg) in the liver of patients with schistosomiasis japonica complicated by HCC was significantly higher than in the group of advanced schistosomiasis japonica, but similar to that in cases of HCC. The location of carcinoma cells in the liver was not related to the distribution of Schistosoma ova in patients with schistosomiasis japonica complicated by HCC. The results indicated that the complication with hepatitis B virus infection may be one of the major factors involved in the development of HCC in patients with schistosomiasis japonica.

Changes in the level of IL-2, T cell subsets and the function of T suppressor cells in patients with schistosomiasis japonica.

The level of interleukin-2 (IL-2) produced by peripheral blood mononuclear cells in vitro, T cell subsets and the function of T suppressor cells (Ts) in patients with schistosomiasis japonica were investigated. It was found that the level of IL-2 induced by schistosomal antigens was significantly high and positively related to the percentage of CD4+ cells. In the groups of chronic and advanced schistosomiasis japonica, the level of IL-2 induced by schistosomal antigens was markedly lower than that in the group of acute schistosomiasis japonica, but significantly higher than that in the group of normal controls. The IL-2 level was negatively related to the percentage of CD8+ T cells and the ratio of CD4+/CD8+. The level of IL-2 induced by PHA was greatly reduced in the group of advanced schistosomiasis japonica. The changes in the level of IL-2 and its relationship with T cell subsets and the function of Ts are also discussed.