AIM: To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901.METHODS: Cell counts and MYT assay were used to quantify the influ...AIM: To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901.METHODS: Cell counts and MYT assay were used to quantify the influence of Nimesulide in the proliferation of SGC7901cells. Transmission electron microscopy and flow cytometry were used to observe the induction of Nimesulide the apoptosis of SGC7901 cells and influence in the distribution of cell cycle. The expression of P27kipl protein was observed by immunocytochemical staining.RESULTS: SGC-7901 Cells treated with Nimesulide at various concentrations exhibited a profound dose- and timedependent reduction in the proliferation rate over the 72 h test period. The highest survival rate of the cells was 78.7 %,but the lowest being 22.7 %. Nimesulide induced apoptosis of the cells in a dose-dependent and non-linear manner and increased the proportion of cells in the G0/G1 phase and decreased the proportion in the S and G2/M phase of the cell cycle. Meanwhile, Nimesulide could up-regulate the expression of P27kipl protein.CONCLUSION: The induction of apoptosis and cell cycle arrest are both anti-proliferative responses that likely contribute to the antineoplastic action of nimesulide on SGC7901 cells. The up-regulation of P27kipl gene may contribute to the accumulation of these cells in the G0/G1 phase following treatment with Nimesulide. Selective COX-2 inhibitor may be a new channel of the chemoprevention and chemotherapy for gastric carcinoma.展开更多
According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs （NSAID） independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent, d...According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs （NSAID） independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent, demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately, no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use, as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAID induced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2 （COX-2） expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer. Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users. However, some recommendations can be drawn from the results of clinical trails.展开更多
AIM： To clarify clinical features of the NSAID-induced sma bowel lesions using a new method of endoscopy. METHODS： This is a retrospective study and we analyzed seven patients with small bowel lesions while taking N...AIM： To clarify clinical features of the NSAID-induced sma bowel lesions using a new method of endoscopy. METHODS： This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone doubleballoon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at .lichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient. RESULTS： Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively. The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug. CONCLUSION： NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon.展开更多
AIM： To investigate the role of cryofibrinogen （CF） in active inflammatory bowel disease （IBD）. METHODS： CF was assayed in 284 subjects： 61 with active and 63 with inactive ulcerative colitis （UC）, 45 who had...AIM： To investigate the role of cryofibrinogen （CF） in active inflammatory bowel disease （IBD）. METHODS： CF was assayed in 284 subjects： 61 with active and 63 with inactive ulcerative colitis （UC）, 45 who had proctocolectomy, 35 with active and 20 with inactive Crohn＇s disease （CD）, 40 with other diseases and 20 healthy controls. Trypsin inhibitor （TI） and TI antibody （TI-Ab） were measured in plasma and CF complex by ELISA. RESULTS： CF in active UC was strikingly high compared with all other groups （x^2〈0.001）. Similarly, CF was significantly higher in active CD than in inactive CD or in controls （x^2〈0.01）. In UC, high CF and TI-Ab were associated with the need for operations. Further, high CF, CF/fibrinogen ratio, low TI and high TI-Ab in plasma were associated with disease activity or refractoriness to medication. Elevated CF was not associated with acute reactants like C-reactive protein and white blood cell counts except for erythrocyte sedimentation rate, suggesting that elevated CF was not a consequence of acute inflammation. CONCLUSION： Elevated CF in active IBD appears to be morbigenous. CF promotes IBD via two main mechanisms, quenching of TI （an anti-inflammatory substance） and impairing microvascular perfusion by forming protein aggregates. CF may also serve as a biomarker of chronic IBD. Additional studies are warranted to fully evaluate the role of CF in IBD and the outcome should contribute to a better understanding of the pathogenesis of IBD.展开更多
Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated ...Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated hyponatremia is observed mainly in patients with certain risk factors such as those receiving large doses of thiazides, having much comorbidity, such as heart failure, liver disease or malignancy, and taking several medications, such as non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors or tricyclic antide- pressants. Sodium concentration should be monitored in patients with risk factors for developing thiazide-associated hyponatremia and clini- cians should measure promptly serum sodium levels in patients with neurologic signs indicating reduced sodium levels. The clinical and biochemical profile of patients with thiazide-associated hyponatremia may be that of extracellular volume depletion or the syndrome of inap- propriate antidiuretic hormone secretion （SIADH）. The investigation of possible thiazide-associated hyponatremia includes the exclusion of other causes of decreased sodium levels and the identification of the characteristics of hyponatremia due to thiazides （extracellular volume depletion-related or SIADH-like）. Treatment should be carefully monitored to avoid serious neurologic complications due to overcorrection. Clinicians should discourage prescribing thiazides in patients with a history of diuretic-associated hyponatremia and should prefer low doses of thiazides in patients with risk factors for developing thiazide-associated hyponatremia.展开更多
Anti-tumor necrosis factor(TNF) drugs are widely prescribed for inflammatory disease. A loss of response to adalimumab is frequent and the pharmacokinetics of anti-TNF therapy have important implications for patient m...Anti-tumor necrosis factor(TNF) drugs are widely prescribed for inflammatory disease. A loss of response to adalimumab is frequent and the pharmacokinetics of anti-TNF therapy have important implications for patient management. Individual factors such as albumin, body weight, and disease severity based on the C-reactive protein level influence drug metabolism. Adalimumab trough levels are associated with clinical remission. On the other hand, the detection of antibodies is associated with clinical relapse. Immunosuppressive therapy could reduce antibody formation although the clinical impact is not proven. New algorithms are available to provide personalized treatment and adapt the dosage. More data are needed on dose de-escalation.展开更多
Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate th...Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell （TLSH） and soft tissue （TLST） samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 （PGE2） and cyclic adenosine monophosphate （cAMP）], inflammatory mediators [tumor necrosis factor （TNFα）, interleukin-1β （IL-1）, interleukin-2 （IL-2） and interleukin-6 （IL-6）] and ion （Na^＋ and Ca^2＋） were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats （P 〈 0.05）, and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats （P 〈 0.05）; and markedly reduced levels of PGE2, cAMP, TNFα, IL-1β, IL-2, IL-6, and Na^＋/Ca^2＋. In fever model, TLST could significantly reduce the levels of PGE2 （P 〈 0.01） in rats＇ homogenate and TNF a （P 〈 0.05）, IL-113 （P 〈 0.01） in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 （P 〈 0.01） and IL-6 （P 〈 0.01） in plasma and increase the content of Ca2＋ （P 〈 0.01） in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretie and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, cAMP, Na^＋/Ca^2＋ , TNF a, IL-1β, IL-2, and IL-6.展开更多
文摘AIM: To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901.METHODS: Cell counts and MYT assay were used to quantify the influence of Nimesulide in the proliferation of SGC7901cells. Transmission electron microscopy and flow cytometry were used to observe the induction of Nimesulide the apoptosis of SGC7901 cells and influence in the distribution of cell cycle. The expression of P27kipl protein was observed by immunocytochemical staining.RESULTS: SGC-7901 Cells treated with Nimesulide at various concentrations exhibited a profound dose- and timedependent reduction in the proliferation rate over the 72 h test period. The highest survival rate of the cells was 78.7 %,but the lowest being 22.7 %. Nimesulide induced apoptosis of the cells in a dose-dependent and non-linear manner and increased the proportion of cells in the G0/G1 phase and decreased the proportion in the S and G2/M phase of the cell cycle. Meanwhile, Nimesulide could up-regulate the expression of P27kipl protein.CONCLUSION: The induction of apoptosis and cell cycle arrest are both anti-proliferative responses that likely contribute to the antineoplastic action of nimesulide on SGC7901 cells. The up-regulation of P27kipl gene may contribute to the accumulation of these cells in the G0/G1 phase following treatment with Nimesulide. Selective COX-2 inhibitor may be a new channel of the chemoprevention and chemotherapy for gastric carcinoma.
文摘According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs （NSAID） independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent, demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately, no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use, as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAID induced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2 （COX-2） expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer. Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users. However, some recommendations can be drawn from the results of clinical trails.
文摘AIM： To clarify clinical features of the NSAID-induced sma bowel lesions using a new method of endoscopy. METHODS： This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone doubleballoon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at .lichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient. RESULTS： Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively. The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug. CONCLUSION： NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon.
文摘AIM： To investigate the role of cryofibrinogen （CF） in active inflammatory bowel disease （IBD）. METHODS： CF was assayed in 284 subjects： 61 with active and 63 with inactive ulcerative colitis （UC）, 45 who had proctocolectomy, 35 with active and 20 with inactive Crohn＇s disease （CD）, 40 with other diseases and 20 healthy controls. Trypsin inhibitor （TI） and TI antibody （TI-Ab） were measured in plasma and CF complex by ELISA. RESULTS： CF in active UC was strikingly high compared with all other groups （x^2〈0.001）. Similarly, CF was significantly higher in active CD than in inactive CD or in controls （x^2〈0.01）. In UC, high CF and TI-Ab were associated with the need for operations. Further, high CF, CF/fibrinogen ratio, low TI and high TI-Ab in plasma were associated with disease activity or refractoriness to medication. Elevated CF was not associated with acute reactants like C-reactive protein and white blood cell counts except for erythrocyte sedimentation rate, suggesting that elevated CF was not a consequence of acute inflammation. CONCLUSION： Elevated CF in active IBD appears to be morbigenous. CF promotes IBD via two main mechanisms, quenching of TI （an anti-inflammatory substance） and impairing microvascular perfusion by forming protein aggregates. CF may also serve as a biomarker of chronic IBD. Additional studies are warranted to fully evaluate the role of CF in IBD and the outcome should contribute to a better understanding of the pathogenesis of IBD.
文摘Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated hyponatremia is observed mainly in patients with certain risk factors such as those receiving large doses of thiazides, having much comorbidity, such as heart failure, liver disease or malignancy, and taking several medications, such as non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors or tricyclic antide- pressants. Sodium concentration should be monitored in patients with risk factors for developing thiazide-associated hyponatremia and clini- cians should measure promptly serum sodium levels in patients with neurologic signs indicating reduced sodium levels. The clinical and biochemical profile of patients with thiazide-associated hyponatremia may be that of extracellular volume depletion or the syndrome of inap- propriate antidiuretic hormone secretion （SIADH）. The investigation of possible thiazide-associated hyponatremia includes the exclusion of other causes of decreased sodium levels and the identification of the characteristics of hyponatremia due to thiazides （extracellular volume depletion-related or SIADH-like）. Treatment should be carefully monitored to avoid serious neurologic complications due to overcorrection. Clinicians should discourage prescribing thiazides in patients with a history of diuretic-associated hyponatremia and should prefer low doses of thiazides in patients with risk factors for developing thiazide-associated hyponatremia.
文摘Anti-tumor necrosis factor(TNF) drugs are widely prescribed for inflammatory disease. A loss of response to adalimumab is frequent and the pharmacokinetics of anti-TNF therapy have important implications for patient management. Individual factors such as albumin, body weight, and disease severity based on the C-reactive protein level influence drug metabolism. Adalimumab trough levels are associated with clinical remission. On the other hand, the detection of antibodies is associated with clinical relapse. Immunosuppressive therapy could reduce antibody formation although the clinical impact is not proven. New algorithms are available to provide personalized treatment and adapt the dosage. More data are needed on dose de-escalation.
基金supported by Marine Industry Research Special Funds for Public Welfare Projects(201205024–1)The Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(ysxk-2010)
文摘Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell （TLSH） and soft tissue （TLST） samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 （PGE2） and cyclic adenosine monophosphate （cAMP）], inflammatory mediators [tumor necrosis factor （TNFα）, interleukin-1β （IL-1）, interleukin-2 （IL-2） and interleukin-6 （IL-6）] and ion （Na^＋ and Ca^2＋） were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats （P 〈 0.05）, and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats （P 〈 0.05）; and markedly reduced levels of PGE2, cAMP, TNFα, IL-1β, IL-2, IL-6, and Na^＋/Ca^2＋. In fever model, TLST could significantly reduce the levels of PGE2 （P 〈 0.01） in rats＇ homogenate and TNF a （P 〈 0.05）, IL-113 （P 〈 0.01） in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 （P 〈 0.01） and IL-6 （P 〈 0.01） in plasma and increase the content of Ca2＋ （P 〈 0.01） in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretie and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, cAMP, Na^＋/Ca^2＋ , TNF a, IL-1β, IL-2, and IL-6.
