AIM:Stress induces gastric ulceration in human and experimental animals. People tend to smoke more cigarettes when under stress. Nitric oxide (NO) and nicotine have opposing effects on gastric integrity. The present s...AIM:Stress induces gastric ulceration in human and experimental animals. People tend to smoke more cigarettes when under stress. Nitric oxide (NO) and nicotine have opposing effects on gastric integrity. The present study examined the possible therapeutic benefit of NO in nicotine-treated rats with stress-induced gastric ulceration.METHODS:Rats drank a nicotine solution while control rats drank tap water for 20 days. The alkoloid was then replaced by water with or without supplementation of isosorbide dinitrate (NO donor) for an additional 10 days. Isosorbide dinitrate was given twice shortly before experiments (acute) or three times daily by oral gavages for 10 days after the rats stopped drinking nicotine solution. At the end of experiments,ulcer index, gastric adhesion mucus content and MPO activity were measured and analysed.RESULTS:Nicotine treatment decreased gastric mucus content and intensified stress-induced gastric ulcer. A higher ulcer index persisted even after the rats stopped drinking nicotine solution for 10 days. Acute NO donor showed no benefit on both mucus and ulcer index in nicotine treatment or/and stress condition.Chronic NO donor treatment reversed the worsening action of nicotine in stomach. Stress increased gastric mucosal myeloperoxidase (MPO) activity, which was antagonized by chronic NO treatment. However, nicotine was unlikely to change mucosal MPO activity.CONCLUSION:The intensifying action of nicotine on stressinduced gastric ulceration persists for 10 days after cessation.Nicotine treatment significantly decreases gastric mucus content that can be restored by chronic NO donor treatment.The present study suggests that NO antagonizes the ulcerogenic action of nicotine through a cytoprotective way.展开更多
AIM: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. We have found inducible nitric oxide synthase (iNOS) can be induced in hepatocytes of cirrhotic liver. This study further investigated...AIM: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. We have found inducible nitric oxide synthase (iNOS) can be induced in hepatocytes of cirrhotic liver. This study further investigated the temporal expression and activity of hepatic iNOS in cirrhosis development. METHODS: Cirrhosis was induced in rats by chronic bile duet ligatjon (BDL). At different time points after the operation, samples were collected to examine NO concentration, liver function, and morphological changes. Hepatocytes were isolated for determination of iNOS mRNA, protein and enzymatic activity. RESULTS: Histological examination showed early cirrhosis 1-2 wk after BDL, with advanced cirrhosis at 3-4 wk. Bilirubin increased dramatically 3 d after BDL, but decreased by 47% on d 14. Three weeks after BDL, it elevated again. Systemic NO concentration did not increase significantly until 4 wk after BDL, when ascites developed. Hepatocyte iNOS mRNA expression was identified 3 d after BDL, and enhanced with time to 3 wk, but reduced thereafter. iNOS protein showed a similar pattern to mRNA expression. iNOS activity decreased from d 3 to d 7, but increased again thereafter till d 21. CONCLUSION: Hepatic iNOS can be induced in the early stage, which increases with time as cirrhosis develops. lts enzymatic activity is significantly correlated with protein expression and histological alterations of the liver, but not with systemic NO levels, nor with absolute values of liver function markers.展开更多
AIM Macrophaga migration inhibitory factor (MIF) plays a pivotal role in inflammatory/immune diseases. This study aimed to determine MIF expression in H. pylori- induced gastritis, and the effect of H. pylori on MIF e...AIM Macrophaga migration inhibitory factor (MIF) plays a pivotal role in inflammatory/immune diseases. This study aimed to determine MIF expression in H. pylori- induced gastritis, and the effect of H. pylori on MIF expression in moncoytes in vitro. METHODS Seventy- nine patients (M/F,39/40,mean age,52 yrs) referred for upper endoscopy were selected;19 with gastric ulcer, 1.5 with duodenal ulcer and 4.5 with non - ulcer dyspepsia (NUD). Gastric antral and body biopsies were obtained for histological examinations,deuble immunostaining for MIF/T- cells (CD45RO) and MIF/macrophaga (KP1) ,and in situ hybridization for the expression of MIF mRNA.THp-1,a monocyte cell line,was co- incubated with different concentrations of the whole cell proteins prepared from H. pylori strain ATCC26695 or its isogenic type with cagA gene deleted. The expression of MIF protein was determined by using enzyme linked immunosorbent assay and the MIF rnRNA by retrospective transcription - polymerase chain reaction techniques. RESULTS H. pylori was detected in .50 patients (10 with gastric ulcer, /5 with duodenal ulcer and 25 with NUD). Overall,the numbers of total T - cells,MIF+T - cells,total macrophages,MIF + macrophages and MIF mRNA + cells were greater in the gastric antrum than in the body. There was a significant increase in the numbers of total T - cells, MIF+T-cells,total macrophages,MIF+ macrophages and MIF mRNA+ cells in H. pylori positive,compared with H. pylori negative patients, in both the antral and body mucosa. Moreover, the cell numbers increased with more severe chronic gastritis in both the antrum and body, The numbers were also significantly higher in ulcer patients than in NUD patients, particularly in H. pylori positive patients. In vitro,the expression of MIF protein and mRNA in monocytes was significantly increased by incubation with H. pylori whole cell proteins, in a time and dose dependent manner.CONCLUSIONS H. pylori infection stimulates the expression of MIF in the gastric inflammatory cells,which may play a significance role in gastric inflammation and ulceration.展开更多
Lung cancer is the leading cause of cancer-related death in the world as well as in China. It is estimated that approximately 429 000 Chinese individuals may die from lung cancer in 2005, and the mortality rate for l...Lung cancer is the leading cause of cancer-related death in the world as well as in China. It is estimated that approximately 429 000 Chinese individuals may die from lung cancer in 2005, and the mortality rate for lung cancer will double in the next century. 1 Currently, chemotherapy is the a main treatment of advanced and recurrent lung cancer. However, the recent development of tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib may change the therapeutic approaches for this disease. Gefitinib, for example, induces clinical responses in approximately 10% of patients with non-small cell lung cancer (NSCLC) in the USA and Europe, and 26% in Japan. 2,3 A study of gefitinib in 31 patients from Beijing showed an objective tumor response rate of 36%. 4展开更多
文摘AIM:Stress induces gastric ulceration in human and experimental animals. People tend to smoke more cigarettes when under stress. Nitric oxide (NO) and nicotine have opposing effects on gastric integrity. The present study examined the possible therapeutic benefit of NO in nicotine-treated rats with stress-induced gastric ulceration.METHODS:Rats drank a nicotine solution while control rats drank tap water for 20 days. The alkoloid was then replaced by water with or without supplementation of isosorbide dinitrate (NO donor) for an additional 10 days. Isosorbide dinitrate was given twice shortly before experiments (acute) or three times daily by oral gavages for 10 days after the rats stopped drinking nicotine solution. At the end of experiments,ulcer index, gastric adhesion mucus content and MPO activity were measured and analysed.RESULTS:Nicotine treatment decreased gastric mucus content and intensified stress-induced gastric ulcer. A higher ulcer index persisted even after the rats stopped drinking nicotine solution for 10 days. Acute NO donor showed no benefit on both mucus and ulcer index in nicotine treatment or/and stress condition.Chronic NO donor treatment reversed the worsening action of nicotine in stomach. Stress increased gastric mucosal myeloperoxidase (MPO) activity, which was antagonized by chronic NO treatment. However, nicotine was unlikely to change mucosal MPO activity.CONCLUSION:The intensifying action of nicotine on stressinduced gastric ulceration persists for 10 days after cessation.Nicotine treatment significantly decreases gastric mucus content that can be restored by chronic NO donor treatment.The present study suggests that NO antagonizes the ulcerogenic action of nicotine through a cytoprotective way.
文摘AIM: Nitric oxide (NO) has been implicated in the pathogenesis of liver cirrhosis. We have found inducible nitric oxide synthase (iNOS) can be induced in hepatocytes of cirrhotic liver. This study further investigated the temporal expression and activity of hepatic iNOS in cirrhosis development. METHODS: Cirrhosis was induced in rats by chronic bile duet ligatjon (BDL). At different time points after the operation, samples were collected to examine NO concentration, liver function, and morphological changes. Hepatocytes were isolated for determination of iNOS mRNA, protein and enzymatic activity. RESULTS: Histological examination showed early cirrhosis 1-2 wk after BDL, with advanced cirrhosis at 3-4 wk. Bilirubin increased dramatically 3 d after BDL, but decreased by 47% on d 14. Three weeks after BDL, it elevated again. Systemic NO concentration did not increase significantly until 4 wk after BDL, when ascites developed. Hepatocyte iNOS mRNA expression was identified 3 d after BDL, and enhanced with time to 3 wk, but reduced thereafter. iNOS protein showed a similar pattern to mRNA expression. iNOS activity decreased from d 3 to d 7, but increased again thereafter till d 21. CONCLUSION: Hepatic iNOS can be induced in the early stage, which increases with time as cirrhosis develops. lts enzymatic activity is significantly correlated with protein expression and histological alterations of the liver, but not with systemic NO levels, nor with absolute values of liver function markers.
文摘AIM Macrophaga migration inhibitory factor (MIF) plays a pivotal role in inflammatory/immune diseases. This study aimed to determine MIF expression in H. pylori- induced gastritis, and the effect of H. pylori on MIF expression in moncoytes in vitro. METHODS Seventy- nine patients (M/F,39/40,mean age,52 yrs) referred for upper endoscopy were selected;19 with gastric ulcer, 1.5 with duodenal ulcer and 4.5 with non - ulcer dyspepsia (NUD). Gastric antral and body biopsies were obtained for histological examinations,deuble immunostaining for MIF/T- cells (CD45RO) and MIF/macrophaga (KP1) ,and in situ hybridization for the expression of MIF mRNA.THp-1,a monocyte cell line,was co- incubated with different concentrations of the whole cell proteins prepared from H. pylori strain ATCC26695 or its isogenic type with cagA gene deleted. The expression of MIF protein was determined by using enzyme linked immunosorbent assay and the MIF rnRNA by retrospective transcription - polymerase chain reaction techniques. RESULTS H. pylori was detected in .50 patients (10 with gastric ulcer, /5 with duodenal ulcer and 25 with NUD). Overall,the numbers of total T - cells,MIF+T - cells,total macrophages,MIF + macrophages and MIF mRNA + cells were greater in the gastric antrum than in the body. There was a significant increase in the numbers of total T - cells, MIF+T-cells,total macrophages,MIF+ macrophages and MIF mRNA+ cells in H. pylori positive,compared with H. pylori negative patients, in both the antral and body mucosa. Moreover, the cell numbers increased with more severe chronic gastritis in both the antrum and body, The numbers were also significantly higher in ulcer patients than in NUD patients, particularly in H. pylori positive patients. In vitro,the expression of MIF protein and mRNA in monocytes was significantly increased by incubation with H. pylori whole cell proteins, in a time and dose dependent manner.CONCLUSIONS H. pylori infection stimulates the expression of MIF in the gastric inflammatory cells,which may play a significance role in gastric inflammation and ulceration.
文摘Lung cancer is the leading cause of cancer-related death in the world as well as in China. It is estimated that approximately 429 000 Chinese individuals may die from lung cancer in 2005, and the mortality rate for lung cancer will double in the next century. 1 Currently, chemotherapy is the a main treatment of advanced and recurrent lung cancer. However, the recent development of tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib may change the therapeutic approaches for this disease. Gefitinib, for example, induces clinical responses in approximately 10% of patients with non-small cell lung cancer (NSCLC) in the USA and Europe, and 26% in Japan. 2,3 A study of gefitinib in 31 patients from Beijing showed an objective tumor response rate of 36%. 4
