ABSTRACT
Chronic ethanol consumption can produce learning and memory deficits. Brain-derived neurotrophic factor (BDNF) and its receptors affect the pathogenesis of alcoholism. In this study, we examined the expression of BDNF, tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) in the hippocampus of a dog model of chronic alcoholism and abstinence. Twenty domestic dogs (9-10 months old, 15-20 kg; 10 males and 10 females) were obtained from Harbin Medical University. A stable alcoholism model was established through ad libitum feeding, and anti-alcohol drug treatment (Zhong Yao Jie Jiu Ling, the main ingredient was the stems of watermelon; developed in our laboratory), at low- and high-doses, was carried out. The Zhong Yao Jie Jiu Ling was effective for the alcoholism in dogs. The morphology of hippocampal neurons was evaluated using hematoxylin-eosin staining. The number and morphological features of BDNF, TrkB and p75NTR-positive neurons in the dentate gyrus (DG), and the CA1, CA3 and CA4 regions of the hippocampus were observed using immunohistochemistry. One-way ANOVA was used to determine differences in BDNF, TrkB and p75NTR expression. BDNF, TrkB and p75NTR-positive cells were mainly localized in the granular cell layer of the DG and in the pyramidal cell layer of the CA1, CA3 and CA4 regions (DG>CA1>CA3>CA4). Expression levels of both BDNF and TrkB were decreased in chronic alcoholism, and increased after abstinence. The CA4 region appeared to show the greatest differences. Changes in p75NTR expression were the opposite of those of BDNF and TrkB, with the greatest differences observed in the DG and CA4 regions.
Subject(s)
Animals , Male , Female , Dogs , Alcohol Abstinence , Alcoholism/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Hippocampus/chemistry , Receptor, Nerve Growth Factor/metabolism , Receptor, trkB/metabolism , Brain-Derived Neurotrophic Factor/genetics , Chronic Disease , Disease Models, Animal , Gene Expression Regulation , Hippocampus/metabolism , Immunohistochemistry , Receptor, Nerve Growth Factor/genetics , Receptor, trkB/geneticsABSTRACT
Neuroblastoma is a solid tumor that occurs mainly in children. Malignant neuroblastomas have a poor prognosis because conventional chemotherapeutic agents are not very effective. Survivin, a member of the inhibitor of the apoptosis protein family, plays a significant role in cell division, inhibition of apoptosis, and promotion of cell proliferation and invasion. Previous studies found that survivin is highly expressed in some malignant neuroblastomas and is correlated with poor prognosis. The aim of this study was to investigate whether survivin could serve as a potential therapeutic target of human neuroblastoma. We employed RNA interference to reduce survivin expression in the human neuroblastoma SH-SY5Y cell line and analyzed the effect of RNA interference on cell proliferation and invasion in vitro and in vivo. RNA interference of survivin led to a significant decrease in invasiveness and proliferation and increased apoptosis in SH-SY5Y cells in vitro. RNA interference of survivin inhibited tumor growth in vivo by 68±13% (P=0.002) and increased the number of apoptotic cells by 9.8±1.2% (P=0.001) compared with negative small interfering RNA (siRNA) treatment controls. Moreover, RNA interference of survivin inhibited the formation of lung metastases by 92% (P=0.002) and reduced microvascular density by 60% (P=0.0003). Survivin siRNA resulted in significant downregulation of survivin mRNA and protein expression both in vitro and in vivo compared with negative siRNA treatment controls. RNA interference of survivin was found to be a potent inhibitor of SH-SY5Y tumor growth and metastasis formation. These results support further clinical development of RNA interference of survivin as a treatment of neuroblastoma and other cancer types.
Subject(s)
Animals , Humans , Apoptosis/drug effects , Cysteine Proteinase Inhibitors/pharmacology , Inhibitor of Apoptosis Proteins/drug effects , Lung Neoplasms/secondary , Neuroblastoma/pathology , RNA, Small Interfering/pharmacology , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Down-Regulation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Immunohistochemistry , In Situ Nick-End Labeling , Inhibitor of Apoptosis Proteins/genetics , Inhibitor of Apoptosis Proteins/metabolism , Mice, Nude , Neoplasm Invasiveness , Neuroblastoma/secondary , Reverse Transcriptase Polymerase Chain Reaction , RNA, Neoplasm/drug effects , RNA, Neoplasm/metabolism , Xenograft Model Antitumor AssaysABSTRACT
A double-blind clinical trial with praziquantel was carried out. A total of 400 cases was treated with four different dosages, namely, 60, 50, 40 and 30 mg/kg body weight of praziquantel. The drug was given in one day divided into two doses. Identical placebo tablets were used to make up a total of 60 mg/kg. Tolerance was good in all with the exception of one case suffering from asthmatic attack with papule rashes over large area of the body surface. 394 patients were able to be followed up parasitologically six months post-treatment. 79.8%, 71.7%, 78.8% and 70.1% of the patients were negative in the groups with the total dose of 60, 50, 40 and 30 mg/kg respectively. The cure rates as well as the side effects were similar for the four groups. The efficacy was lower than that reported by other authors and the possibility of reinfection was incriminated. In villages with few snails the negative hatching rates in aforementioned four groups were 89.1%, 91.1%, 88.9% and 81.8%, while in villages with abundant snails the rates were 68.2%, 46.5%, 66.7% and 54.8%. The difference between the two areas was statistically significant. Higher efficacy was observed in adults with an average cure rate of 80.0% than in children under 15 years of age, the average cure rate being 57.1%.(ABSTRACT TRUNCATED AT 250 WORDS)