AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.
This study is to explore the actions of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) on endotoxin (lipopolysaccharide, LPS) induced rat acute lung injury (ALI) and effect of Rhubarb on them. LPS wa... This study is to explore the actions of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) on endotoxin (lipopolysaccharide, LPS) induced rat acute lung injury (ALI) and effect of Rhubarb on them. LPS was injected into the sublingual vein of male Wistar rats to prepare ALI animal models. The rats were divided into 4 groups: LPS, control, Rhubarb, and dexamethasone. Macroscopic and histopathological examinations of the lung specimens were performed and the biological indexes of lung, including wet weight/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability were observed. In the mean time, the contents of serum NO and the activities of lung tissue homogenate iNOS were measured. The results showed that in the LPS group, the injury and celluar infiltration in the pulmonary stroma and alveoli were more prominent than that in the control group. Lung wet weight/dry weight, the rate of neutrophils, protein content, pulmonary alveolar permeability, pulmonary vascular permeability were significantly increased (P<0.01); NO and iNOS were also markedly elevated (P<0.01). In the groups of dexamethasone and Rhubarb, the histopathological changes were significantly milder, and all the above biological indexes of lung injury and the contents of NO and the activities of iNOS were correspondingly decreased (P<0.05). The above data demonstrate that NO and the activities of iNOS play an important role in the onset of ALI; dexamethasone and Rhubarb interfering treatment can ameliorate lung injury and decrease the concentrations of NO and iNOS, showing that through inhibiting the levels of NO and the activities of iNOS, these 2 agents exert protective effect on ALI induced LPS. 展开更多
The Pharmacokinetics informations of aminoglycosides, their monograph and clinical Pharmacokinetics parameters are reported in this review. The Aminoglycosides are highly polarity and in reserve for serious infections...The Pharmacokinetics informations of aminoglycosides, their monograph and clinical Pharmacokinetics parameters are reported in this review. The Aminoglycosides are highly polarity and in reserve for serious infections caused by aerobic gram negative bacteria and some gram positive bacteria but their toxicity are major limitations in clinical use.展开更多
Background The benefit of statin use after acute ST-segment elevation myocardial infarction （STEMI） has been well established, however, the influence of the timing of statin administration has not been elucidated. T...Background The benefit of statin use after acute ST-segment elevation myocardial infarction （STEMI） has been well established, however, the influence of the timing of statin administration has not been elucidated. The objective of this study focused on early clinical outcomes after percutaneous coronary intervention （PCI）. Methods This analysis of the Korea Working Group on Myocardial Infarction registry （KorMI） study included 3,584 STEMI patients （mean age, 63 ±13 years;male, 2,684, 74.9%） undergoing PCI from January 2008 to June 2009. Rates of major adverse cardiac events （MACE：all-cause death, recurrent MI, and target lesion revascularization） were compared among patients grouped according to statin therapy timing：I, both during and after hospitalization （n=2,653, 74%）;II, only during hospita-lization （n=309, 8.6%）;III, only after discharge （n=157, 4.4%）;and IV, no statin therapy （n=465, 13%）. Mean follow-up duration was 234 ± 113 days. Results Multivariate factors of statin use during hospitalization included prior statin use, multiple diseased vessels, final thrombolysis in myocardial infarction flow grade III, and low-density lipoprotein cholesterol level. At 6-month follow-up, groups Ⅲ and Ⅳ had the highest MACE rates （2.3%, 3.9%, 5.1%, and 4.9%for groups I-IV, respectively, P=0.004）. After adjusting for confounders, groups Ⅱ-Ⅳ had a higher MACE risk than group Ⅰ [hazard ratio （HR）：3.20, 95%confidence interval （95%CI）：1.31-7.86, P=0.011;HR：3.84, 95%CI：1.47-10.02, P=0.006;and HR：3.17, 95%CI：1.59-6.40, P=0.001;respectively]. Conclusions This study, based on the national registry database, shows early and continuous statin therapy improvs early outcomes of STEMI patients after PCI in real-world clinical prac-tice.展开更多
Background Coronary heart disease （CHD） risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients 〉 65 years. The objective was to evaluate the safety and efficacy of lipid-...Background Coronary heart disease （CHD） risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients 〉 65 years. The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 nag ＋ ezetimibe 10 mg （EZ/Atorva） vs. increasing the atorvastatin dose to 40 mg, Methods Patients 〉 65 years with atherosclerotic vascular disease （LDL-C ≥1.81 mmol/L） or at high risk for coronary heart disease （LDL-C 〉 2.59 mmol/L） were randomized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 nag for 6 wk followed by atorvastatin 40 nag for 6 wk. The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk. Results EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients 〉 75 years （n = 228）, generally consistent with patients 65-74 years （n = 812）. More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients 〉 75 years at 12 wk. At 12 wk, more patients 〉 75 years achieved LDL-C targets with monotherapy vs. combination therapy. EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients 〉 75 years, generally consistent with the findings in patients 65-74 years. Conclusions Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and 〉 75 years of age.展开更多
Dyshpidemia is a well-established risk factor for atherosclerosis. Treating dyslipidemia in elderly patients requires specific knowledge and understanding of common dyslipidemias and the relative safety of various pha...Dyshpidemia is a well-established risk factor for atherosclerosis. Treating dyslipidemia in elderly patients requires specific knowledge and understanding of common dyslipidemias and the relative safety of various pharmacologic agents in the presence of possible multiple comorbidities. Lifestyle modification remains the first step in the treatment of dyslipidemia; however, it can be difficult to sustain and achieve acceptable compliance in the elderly and it is best used in combination with drug therapy. Statins are widely accepted as the first-line therapy. Several recent studies have demonstrated that statins are safe and effective in the elderly. However, it is important to note that there is very limited data regarding the effects of dyslipidemia treatment on morbidity and mortality in patients over 85 years of age. In summary, the clinicians must recognize that the presence of dyslipidemia in the elderly poses substantial risk of coronary events and stroke. The available evidence has demonstrated that in most elderly patients who are at increased risk for cardiovascular morbidity and mortality, treatment of dyslipidemia with appropriate therapy reduces the risk, and when used carefully with close monitoring for safety, the treatment is generally well tolerated. With increasing life expectancy, it is critical for physicians to recognize the importance of detection and treatment of dyslipidemia in the elderly.展开更多
Novel tricyclic sulfones as γ-secretase inhibitors have been reported by this laboratory for the treatment of Alzheimer's disease. Compounds in this series have comparable or better in vitro activities and in viv...Novel tricyclic sulfones as γ-secretase inhibitors have been reported by this laboratory for the treatment of Alzheimer's disease. Compounds in this series have comparable or better in vitro activities and in vivo efficacies than sulfonamide analogues re- ported previously by this laboratory. Based on the previously reported tricyclic sulfone scaffold, additional SAR studies of C ring were carried out. Various C-ring structures including cyclohexane, pyran, and piperidine were tolerated. Additionally, the 7- and 8- positions of the C-ring were identified as the best sites to introduce substituent for modulating the pharmacokinetic properties of compounds from this series.展开更多
文摘AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.
文摘 This study is to explore the actions of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) on endotoxin (lipopolysaccharide, LPS) induced rat acute lung injury (ALI) and effect of Rhubarb on them. LPS was injected into the sublingual vein of male Wistar rats to prepare ALI animal models. The rats were divided into 4 groups: LPS, control, Rhubarb, and dexamethasone. Macroscopic and histopathological examinations of the lung specimens were performed and the biological indexes of lung, including wet weight/dry weight, the rate of neutrophils and protein content in the pulmonary alveolar lavage fluid, pulmonary vascular permeability and pulmonary alveolar permeability were observed. In the mean time, the contents of serum NO and the activities of lung tissue homogenate iNOS were measured. The results showed that in the LPS group, the injury and celluar infiltration in the pulmonary stroma and alveoli were more prominent than that in the control group. Lung wet weight/dry weight, the rate of neutrophils, protein content, pulmonary alveolar permeability, pulmonary vascular permeability were significantly increased (P<0.01); NO and iNOS were also markedly elevated (P<0.01). In the groups of dexamethasone and Rhubarb, the histopathological changes were significantly milder, and all the above biological indexes of lung injury and the contents of NO and the activities of iNOS were correspondingly decreased (P<0.05). The above data demonstrate that NO and the activities of iNOS play an important role in the onset of ALI; dexamethasone and Rhubarb interfering treatment can ameliorate lung injury and decrease the concentrations of NO and iNOS, showing that through inhibiting the levels of NO and the activities of iNOS, these 2 agents exert protective effect on ALI induced LPS.
文摘The Pharmacokinetics informations of aminoglycosides, their monograph and clinical Pharmacokinetics parameters are reported in this review. The Aminoglycosides are highly polarity and in reserve for serious infections caused by aerobic gram negative bacteria and some gram positive bacteria but their toxicity are major limitations in clinical use.
文摘Background The benefit of statin use after acute ST-segment elevation myocardial infarction （STEMI） has been well established, however, the influence of the timing of statin administration has not been elucidated. The objective of this study focused on early clinical outcomes after percutaneous coronary intervention （PCI）. Methods This analysis of the Korea Working Group on Myocardial Infarction registry （KorMI） study included 3,584 STEMI patients （mean age, 63 ±13 years;male, 2,684, 74.9%） undergoing PCI from January 2008 to June 2009. Rates of major adverse cardiac events （MACE：all-cause death, recurrent MI, and target lesion revascularization） were compared among patients grouped according to statin therapy timing：I, both during and after hospitalization （n=2,653, 74%）;II, only during hospita-lization （n=309, 8.6%）;III, only after discharge （n=157, 4.4%）;and IV, no statin therapy （n=465, 13%）. Mean follow-up duration was 234 ± 113 days. Results Multivariate factors of statin use during hospitalization included prior statin use, multiple diseased vessels, final thrombolysis in myocardial infarction flow grade III, and low-density lipoprotein cholesterol level. At 6-month follow-up, groups Ⅲ and Ⅳ had the highest MACE rates （2.3%, 3.9%, 5.1%, and 4.9%for groups I-IV, respectively, P=0.004）. After adjusting for confounders, groups Ⅱ-Ⅳ had a higher MACE risk than group Ⅰ [hazard ratio （HR）：3.20, 95%confidence interval （95%CI）：1.31-7.86, P=0.011;HR：3.84, 95%CI：1.47-10.02, P=0.006;and HR：3.17, 95%CI：1.59-6.40, P=0.001;respectively]. Conclusions This study, based on the national registry database, shows early and continuous statin therapy improvs early outcomes of STEMI patients after PCI in real-world clinical prac-tice.
文摘Background Coronary heart disease （CHD） risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients 〉 65 years. The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 nag ＋ ezetimibe 10 mg （EZ/Atorva） vs. increasing the atorvastatin dose to 40 mg, Methods Patients 〉 65 years with atherosclerotic vascular disease （LDL-C ≥1.81 mmol/L） or at high risk for coronary heart disease （LDL-C 〉 2.59 mmol/L） were randomized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 nag for 6 wk followed by atorvastatin 40 nag for 6 wk. The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk. Results EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients 〉 75 years （n = 228）, generally consistent with patients 65-74 years （n = 812）. More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients 〉 75 years at 12 wk. At 12 wk, more patients 〉 75 years achieved LDL-C targets with monotherapy vs. combination therapy. EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients 〉 75 years, generally consistent with the findings in patients 65-74 years. Conclusions Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and 〉 75 years of age.
文摘Dyshpidemia is a well-established risk factor for atherosclerosis. Treating dyslipidemia in elderly patients requires specific knowledge and understanding of common dyslipidemias and the relative safety of various pharmacologic agents in the presence of possible multiple comorbidities. Lifestyle modification remains the first step in the treatment of dyslipidemia; however, it can be difficult to sustain and achieve acceptable compliance in the elderly and it is best used in combination with drug therapy. Statins are widely accepted as the first-line therapy. Several recent studies have demonstrated that statins are safe and effective in the elderly. However, it is important to note that there is very limited data regarding the effects of dyslipidemia treatment on morbidity and mortality in patients over 85 years of age. In summary, the clinicians must recognize that the presence of dyslipidemia in the elderly poses substantial risk of coronary events and stroke. The available evidence has demonstrated that in most elderly patients who are at increased risk for cardiovascular morbidity and mortality, treatment of dyslipidemia with appropriate therapy reduces the risk, and when used carefully with close monitoring for safety, the treatment is generally well tolerated. With increasing life expectancy, it is critical for physicians to recognize the importance of detection and treatment of dyslipidemia in the elderly.
文摘Novel tricyclic sulfones as γ-secretase inhibitors have been reported by this laboratory for the treatment of Alzheimer's disease. Compounds in this series have comparable or better in vitro activities and in vivo efficacies than sulfonamide analogues re- ported previously by this laboratory. Based on the previously reported tricyclic sulfone scaffold, additional SAR studies of C ring were carried out. Various C-ring structures including cyclohexane, pyran, and piperidine were tolerated. Additionally, the 7- and 8- positions of the C-ring were identified as the best sites to introduce substituent for modulating the pharmacokinetic properties of compounds from this series.
