Because of limited viral replication and lack of cytopathic effect in cell culture, a new PCR-bas... more Because of limited viral replication and lack of cytopathic effect in cell culture, a new PCR-based rapid seroneutralization assay for detection of GII.4 norovirus neutralized antibodies was developed with serum samples from acute-phase patients, convalescent-phase patients and healthy controls. According to this study, neutralizing antibodies were detected in 100% of convalescent-phase sera, and in 2.5% of healthy controls sera. However, all of the acute-phase serum samples could not neutralize virus efficiently. Compared to the results from ELISA (96.2% at sensitivity and 80% at specificity), the present in vitro neutralization assay is more specific and more sensitive.
The Journal of pharmacology and experimental therapeutics, 2006
Urotensin-II (U-II) is a cyclic peptide that acts through a specific G-protein-coupled receptor, ... more Urotensin-II (U-II) is a cyclic peptide that acts through a specific G-protein-coupled receptor, UT receptor. Urotensin-II and UT receptors have been described in pancreas and kidney, but their function is not well understood. We studied the effects of chronic treatment of diabetic rats with the orally active selective U-II receptor antagonist palosuran. Streptozotocin treatment causes pancreatic beta-cell destruction and leads to the development of hyperglycemia, dyslipidemia, and renal dysfunction. Long-term treatment of streptozotocin-induced diabetic rats with palosuran improved survival, increased insulin, and slowed the increase in glycemia, glycosylated hemoglobin, and serum lipids. Furthermore, palosuran increased renal blood flow and delayed the development of proteinuria and renal damage. The U-II system is unique in that it plays a role both in insulin secretion and in the renal complications of diabetes. Urotensin receptor antagonism might be a new therapeutic approach f...
Diabetic nephropathy is associated with enhanced renal synthesis of endothelin (ET)-1. The goal o... more Diabetic nephropathy is associated with enhanced renal synthesis of endothelin (ET)-1. The goal of this study was to investigate the effects of dual ET receptor antagonism in the early phase (2 months) and in the late phase (5 months) of diabetic nephropathy in rats, and to compare this approach to angiotensin-converting enzyme inhibition. Four groups of uninephrectomized streptozotocin-induced diabetic rats were assigned to receive orally vehicle, bosentan, enalapril, or their combination. A fifth group consisted of nondiabetic, uninephrectomized rats. At 2 weeks, untreated diabetic rats exhibited increased glomerular filtration rate and renal plasma flow. Bosentan, enalapril, and the combination all prevented hyperfiltration and hyperperfusion. By 5 months, diabetic rats developed marked increases in mean arterial pressure and renal vascular resistance, progressive proteinuria, and renal structural damage with glomerular sclerosis and hypertrophy. Bosentan completely prevented the...
Importance of endothelin in mediating the chronic renal alterations of chronic heart failure was ... more Importance of endothelin in mediating the chronic renal alterations of chronic heart failure was studied in rats chronically treated with bosentan after myocardial infarction. Rats were subjected to coronary artery ligation and were treated for 8 weeks with placebo or bosentan, a dual ET(A) and ET(B) receptor antagonist, (approximately 100 mg/kg/day) as food admix. Sham-operated rats served as normal controls. Cardiac and renal functions were measured at the end of 8-week treatment. Bosentan significantly reduced the elevated left ventricular end-diastolic pressure (from 26.6+/-3.3 to 11.4+/-2.2 mmHg, P<0.001) and the increased heart-to-body-weight ratio seen in untreated rats with myocardial infarction. Bosentan prevented the marked increase in renal vascular resistance (bosentan, 7.7+/-0.6; untreated, 15.6+/-2.5 mmHg/ml/min; P<0.001). This led to a significant increase in renal plasma flow resulting in a decrease in filtration fraction. Bosentan furthermore increased urinary...
Congestive heart failure (CHF) is commonly associated with renal dysfunction. The goal of the cur... more Congestive heart failure (CHF) is commonly associated with renal dysfunction. The goal of the current study was to evaluate the role of endothelin in the renal dysfunction of experimental CHF by using tezosentan, a potent dual endothelin receptor antagonist. Rats were subjected to coronary artery ligation. Cardiac and renal hemodynamics were assessed after 3-5 weeks, when CHF had developed. Compared with control rats, CHF rats had significantly higher left ventricular end-diastolic pressure (LVEDP), lower mean arterial pressure, and reduced dP/dt(max). CHF rats had severe renal vasoconstriction, as assessed by increased renal vascular resistance (RVR, p &lt; 0.001), decreased renal plasma flow (RPF, p &lt; 0.001), and glomerular filtration rate (GFR, p &lt; 0.001). Filtration fraction rose (p &lt; 0.001). Urine flow rate and sodium excretion were markedly lower. Acute administration of tezosentan induced a marked decrease in LVEDP without change of dP/dt(max) and heart rate. Tezosentan decreased RVR (-43%, p &lt; 0.001) and increased RPF and GFR. Filtration fraction decreased slightly. Tezosentan also increased urine flow rate and sodium excretion. These findings demonstrate that endothelin at least partly mediates the altered renal hemodynamics associated with experimental CHF. Dual endothelin receptor blockade could be useful for the improvement of both cardiac and renal function in CHF.
Because of limited viral replication and lack of cytopathic effect in cell culture, a new PCR-bas... more Because of limited viral replication and lack of cytopathic effect in cell culture, a new PCR-based rapid seroneutralization assay for detection of GII.4 norovirus neutralized antibodies was developed with serum samples from acute-phase patients, convalescent-phase patients and healthy controls. According to this study, neutralizing antibodies were detected in 100% of convalescent-phase sera, and in 2.5% of healthy controls sera. However, all of the acute-phase serum samples could not neutralize virus efficiently. Compared to the results from ELISA (96.2% at sensitivity and 80% at specificity), the present in vitro neutralization assay is more specific and more sensitive.
The Journal of pharmacology and experimental therapeutics, 2006
Urotensin-II (U-II) is a cyclic peptide that acts through a specific G-protein-coupled receptor, ... more Urotensin-II (U-II) is a cyclic peptide that acts through a specific G-protein-coupled receptor, UT receptor. Urotensin-II and UT receptors have been described in pancreas and kidney, but their function is not well understood. We studied the effects of chronic treatment of diabetic rats with the orally active selective U-II receptor antagonist palosuran. Streptozotocin treatment causes pancreatic beta-cell destruction and leads to the development of hyperglycemia, dyslipidemia, and renal dysfunction. Long-term treatment of streptozotocin-induced diabetic rats with palosuran improved survival, increased insulin, and slowed the increase in glycemia, glycosylated hemoglobin, and serum lipids. Furthermore, palosuran increased renal blood flow and delayed the development of proteinuria and renal damage. The U-II system is unique in that it plays a role both in insulin secretion and in the renal complications of diabetes. Urotensin receptor antagonism might be a new therapeutic approach f...
Diabetic nephropathy is associated with enhanced renal synthesis of endothelin (ET)-1. The goal o... more Diabetic nephropathy is associated with enhanced renal synthesis of endothelin (ET)-1. The goal of this study was to investigate the effects of dual ET receptor antagonism in the early phase (2 months) and in the late phase (5 months) of diabetic nephropathy in rats, and to compare this approach to angiotensin-converting enzyme inhibition. Four groups of uninephrectomized streptozotocin-induced diabetic rats were assigned to receive orally vehicle, bosentan, enalapril, or their combination. A fifth group consisted of nondiabetic, uninephrectomized rats. At 2 weeks, untreated diabetic rats exhibited increased glomerular filtration rate and renal plasma flow. Bosentan, enalapril, and the combination all prevented hyperfiltration and hyperperfusion. By 5 months, diabetic rats developed marked increases in mean arterial pressure and renal vascular resistance, progressive proteinuria, and renal structural damage with glomerular sclerosis and hypertrophy. Bosentan completely prevented the...
Importance of endothelin in mediating the chronic renal alterations of chronic heart failure was ... more Importance of endothelin in mediating the chronic renal alterations of chronic heart failure was studied in rats chronically treated with bosentan after myocardial infarction. Rats were subjected to coronary artery ligation and were treated for 8 weeks with placebo or bosentan, a dual ET(A) and ET(B) receptor antagonist, (approximately 100 mg/kg/day) as food admix. Sham-operated rats served as normal controls. Cardiac and renal functions were measured at the end of 8-week treatment. Bosentan significantly reduced the elevated left ventricular end-diastolic pressure (from 26.6+/-3.3 to 11.4+/-2.2 mmHg, P<0.001) and the increased heart-to-body-weight ratio seen in untreated rats with myocardial infarction. Bosentan prevented the marked increase in renal vascular resistance (bosentan, 7.7+/-0.6; untreated, 15.6+/-2.5 mmHg/ml/min; P<0.001). This led to a significant increase in renal plasma flow resulting in a decrease in filtration fraction. Bosentan furthermore increased urinary...
Congestive heart failure (CHF) is commonly associated with renal dysfunction. The goal of the cur... more Congestive heart failure (CHF) is commonly associated with renal dysfunction. The goal of the current study was to evaluate the role of endothelin in the renal dysfunction of experimental CHF by using tezosentan, a potent dual endothelin receptor antagonist. Rats were subjected to coronary artery ligation. Cardiac and renal hemodynamics were assessed after 3-5 weeks, when CHF had developed. Compared with control rats, CHF rats had significantly higher left ventricular end-diastolic pressure (LVEDP), lower mean arterial pressure, and reduced dP/dt(max). CHF rats had severe renal vasoconstriction, as assessed by increased renal vascular resistance (RVR, p &lt; 0.001), decreased renal plasma flow (RPF, p &lt; 0.001), and glomerular filtration rate (GFR, p &lt; 0.001). Filtration fraction rose (p &lt; 0.001). Urine flow rate and sodium excretion were markedly lower. Acute administration of tezosentan induced a marked decrease in LVEDP without change of dP/dt(max) and heart rate. Tezosentan decreased RVR (-43%, p &lt; 0.001) and increased RPF and GFR. Filtration fraction decreased slightly. Tezosentan also increased urine flow rate and sodium excretion. These findings demonstrate that endothelin at least partly mediates the altered renal hemodynamics associated with experimental CHF. Dual endothelin receptor blockade could be useful for the improvement of both cardiac and renal function in CHF.
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