Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance a...Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pat展开更多
OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine i...OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia,and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine.METHODS: In total,168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study,and randomly divided into two groups by simple randomization. Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily,while patients in the control group received pioglitazone hydrochloride alone. The treatment course was for12 weeks. Mini-mental state examinations(Chinese version) and Montreal Cognitive Assessments(Beijing version) were performed,and fasting plasma glucose,fasting insulin,hemoglobin A1 c,homeostasis model assessment of insulin resistance,plasma nitric oxide and endothelin-1 levels were measured before and after the treatment.RESULTS: The post-treatment levels for all measurements in both groups were better than pre-treatment levels(P < 0.05). The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group(P < 0.05).CONCLUSION: Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction. Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1. Therefore,the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine.展开更多
AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship ...AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.展开更多
Insulin resistance is associated with subclinical vascular disease that is not justified by conventional cardiovascular risk factors,such as smoking or hypercholesterolemia.Vascular injury associated to insulin resist...Insulin resistance is associated with subclinical vascular disease that is not justified by conventional cardiovascular risk factors,such as smoking or hypercholesterolemia.Vascular injury associated to insulin resistance involves functional and structural damage to the arterial wall that includes impaired vasodilation in response to chemical mediators,reduced distensibility of the arterial wall(arterial stiffness),vascular calcification,and increased thickness of the arterial wall.Vascular dysfunction associated to insulin resistance is present in asymptomatic subjects and predisposes to cardiovascular diseases,such as heart failure,ischemic heart disease,stroke,and peripheral vascular disease.Structural and functional vascular disease associated to insulin resistance is highly predictive of cardiovascular morbidity and mortality.Its pathogenic mechanisms remain undefined.Prospective studies have demonstrated that animal protein consumption increases the risk of developing cardiovascular disease and predisposes to type 2 diabetes(T2D)whereas vegetable protein intake has the opposite effect.Vascular disease linked to insulin resistance begins to occur early in life.Children and adolescents with insulin resistance show an injured arterial system compared with youth free of insulin resistance,suggesting that insulin resistance plays a crucial role in the development of initial vascular damage.Prevention of the vascular dysfunction related to insulin resistance should begin early in life.Before the clinical onset of T2D,asymptomatic subjects endure a long period of time characterized by insulin resistance.Latent vascular dysfunction begins to develop during this phase,so that patients with T2D are at increased cardiovascular risk long before the diagnosis of the disease.展开更多
Renal dysfunction is common in liver diseases,either as part of multiorgan involvement in acute illness or secondary to advanced liver disease.The presence of renal impairment in both groups is a poor prognostic indic...Renal dysfunction is common in liver diseases,either as part of multiorgan involvement in acute illness or secondary to advanced liver disease.The presence of renal impairment in both groups is a poor prognostic indicator.Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction.Obstructive or post renal dysfunction only rarely complicates liver disease.Hepatorenal syndrome(HRS)is a unique form of renal failure associated with advanced liver disease or cirrhosis,and is characterized by functional renal impairment without significant changes in renal histology.Irrespective of the type of renal failure,renal hypoperfusion is the central pathogenetic mechanism,due either to reduced perfusion pressure or increased renal vascular resistance.Volume expansion,avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment.Splanchnic vasoconstrictor agents,such as terlipressin,along with volume expansion,and early placement of transjugular intrahepatic portosystemic shunt(TIPS)may be effective in improving renal function in HRS.Continuous renal replacement therapy(CRRT)and molecular absorbent recirculating system(MARS)in selected patients may be life saving while awaiting liver transplantation.展开更多
基金Supported by National Health and Medical Research Council (NHMRC) of Australia Project Grants,No. APP1124125。
文摘Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pat
基金Supported by Research Project for Practice Development of National Traditional Chinese Medicine Clinical Research Bases(No.JDZX2012128)
文摘OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia,and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine.METHODS: In total,168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study,and randomly divided into two groups by simple randomization. Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily,while patients in the control group received pioglitazone hydrochloride alone. The treatment course was for12 weeks. Mini-mental state examinations(Chinese version) and Montreal Cognitive Assessments(Beijing version) were performed,and fasting plasma glucose,fasting insulin,hemoglobin A1 c,homeostasis model assessment of insulin resistance,plasma nitric oxide and endothelin-1 levels were measured before and after the treatment.RESULTS: The post-treatment levels for all measurements in both groups were better than pre-treatment levels(P < 0.05). The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group(P < 0.05).CONCLUSION: Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction. Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1. Therefore,the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine.
基金Supported by Shanghai Education Committee Foundation, No.024119114
文摘AIM: To investigate the difference in activation of STAT3 signaling between two human stomach adenocarcinoma cell lines: 5-fluorouracil resistant cell line and its parental cell line, and to evaluate its relationship with the expression of vascular endothelial growth factor (VEGF). METHODS: Western blot and electrophoretic mobility shift assay (EMSA) were used to detect the expression of phospho-STAT3 protein and constitutive activation of STAT3 in two human stomach adenocarcinoma cell lines, 5-fluorouracil resistant cell line SGC7901/R and its parental cell line SGC7901, respectively. The mRNA expression of VEGF was analysed by semi-quantitative RT-PCR. The expressive intensity of VEGF protein was measured by immunocytochemistry. RESULTS: The expressions of phospho-STATS protein and constitutive activation of STAT3 between two human stomach adenocarcinoma cell lines were different. Compared with the parental cell line SGC7901, the STAT3DNA binding activity and the expressive intensity of phospho-STAT3 protein were lower in the drug-resistant cell line SGC7901/R. The expression levels of VEGF mRNA and its encoded protein were also decreased in drugresistant cell line. CONCLUSION: Over-expression of VEGF may be correlated with elevated STAT3 activation in parental cell line. Lower VEGF expression may be correlated with decreased STAT3 activation in resistant cell line, which may have resulted from negative feedback regulation of STAT signaling.
文摘Insulin resistance is associated with subclinical vascular disease that is not justified by conventional cardiovascular risk factors,such as smoking or hypercholesterolemia.Vascular injury associated to insulin resistance involves functional and structural damage to the arterial wall that includes impaired vasodilation in response to chemical mediators,reduced distensibility of the arterial wall(arterial stiffness),vascular calcification,and increased thickness of the arterial wall.Vascular dysfunction associated to insulin resistance is present in asymptomatic subjects and predisposes to cardiovascular diseases,such as heart failure,ischemic heart disease,stroke,and peripheral vascular disease.Structural and functional vascular disease associated to insulin resistance is highly predictive of cardiovascular morbidity and mortality.Its pathogenic mechanisms remain undefined.Prospective studies have demonstrated that animal protein consumption increases the risk of developing cardiovascular disease and predisposes to type 2 diabetes(T2D)whereas vegetable protein intake has the opposite effect.Vascular disease linked to insulin resistance begins to occur early in life.Children and adolescents with insulin resistance show an injured arterial system compared with youth free of insulin resistance,suggesting that insulin resistance plays a crucial role in the development of initial vascular damage.Prevention of the vascular dysfunction related to insulin resistance should begin early in life.Before the clinical onset of T2D,asymptomatic subjects endure a long period of time characterized by insulin resistance.Latent vascular dysfunction begins to develop during this phase,so that patients with T2D are at increased cardiovascular risk long before the diagnosis of the disease.
文摘Renal dysfunction is common in liver diseases,either as part of multiorgan involvement in acute illness or secondary to advanced liver disease.The presence of renal impairment in both groups is a poor prognostic indicator.Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction.Obstructive or post renal dysfunction only rarely complicates liver disease.Hepatorenal syndrome(HRS)is a unique form of renal failure associated with advanced liver disease or cirrhosis,and is characterized by functional renal impairment without significant changes in renal histology.Irrespective of the type of renal failure,renal hypoperfusion is the central pathogenetic mechanism,due either to reduced perfusion pressure or increased renal vascular resistance.Volume expansion,avoidance of precipitating factors and treatment of underlying liver disease constitute the mainstay of therapy to prevent and reverse renal impairment.Splanchnic vasoconstrictor agents,such as terlipressin,along with volume expansion,and early placement of transjugular intrahepatic portosystemic shunt(TIPS)may be effective in improving renal function in HRS.Continuous renal replacement therapy(CRRT)and molecular absorbent recirculating system(MARS)in selected patients may be life saving while awaiting liver transplantation.
