To explore mechanism and protective effect of rosiglitazone on myocardial ischemia reperfusion(I/R) injury.Methods:A total of 48 male Japanese white big-ear rabbits were randomly divided into control group(A),I/R grou...To explore mechanism and protective effect of rosiglitazone on myocardial ischemia reperfusion(I/R) injury.Methods:A total of 48 male Japanese white big-ear rabbits were randomly divided into control group(A),I/R group(B),low dose of rosiglitazone group(C),high dose of rosiglitazone group(D).Plasma concentration of and also reduced the concentration of plasma serum creatine kinase(CK),CK-MB.high-sensitivity C-reactive protein(hsCRP).ultrasuperoxide dismutase(SOD),malondialdehyde(MD.A).lactic acid glutathione skin peroxidase (C-SH-PX).nitric oxide(NO)and endothelin(ET) were measured 1 h later after I/R.Twenty-four hours after I/R the hearts were harvested for pathological and ultrastructural analysis.Area of myocardial infarction were tested.Results:Plasma concentration of CK,Ck-MB.hsCRP,NO. MDA and ET were decreased in C,D group compared with group B.Plasma concentration of T-SOD and GSH-Px were increased significantly in C.D group compared with group B.Compared with group B.pathological and ullraslructural changes in C and D group were slightly.There was significant difference in myocardial infarction area between group C.D and group B(P【0.05). Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B. Rosiglitazone may protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,and improve endothelial function.展开更多
Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-γ in the spinal cord. Meth...Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-γ in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally injected with methylprednisolone(30 mg/kg) and rosiglitazone(2 mg/kg) at 1 hour after injury, and methylprednisolone(15 mg/kg) at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better promoted recovery of neurological function after injury.展开更多
Rosiglitazone is a synthetic agonist of peroxisome proliferator-activated receptor γ which is used to improve insulin resistance in patients with typeⅡdiabetes.Rosiglitazone exerts its glucose-lowering effects by im...Rosiglitazone is a synthetic agonist of peroxisome proliferator-activated receptor γ which is used to improve insulin resistance in patients with typeⅡdiabetes.Rosiglitazone exerts its glucose-lowering effects by improving insulin sensitivity.Data from various studies in the past decade suggest that the therapeutic effects of rosiglitazone reach far beyond its use as an insulin sensitizer since it also has other benefits on the cardiovascular system such as improvement of contractile dysfunction,inhibition of the inflammatory response by reducing neutrophil and macrophage accumulation,and the protection of myocardial injury during ischemic/reperfusion in different animal models.Previous clinical studies in typeⅡdiabetes patients demonstrated that rosiglitazone played an important role in protectingagainst arteriosclerosis by normalizing the metabolic disorders and reducing chronic inflammation of the vascular system.Despite these benefits,inconsistent findings have been reported,and growing evidence has demonstrated adverse effects of rosiglitazone on the cardiovascular system,including increased risk of acute myocardial infarction,heart failure and chronic heart failure.As a result,rosiglitazone has been recently withdrawn from EU countries.Nevertheless,the effect of rosiglitazone on ischemic heart disease has not yet been firmly established.Future prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone would be the best way to resolve the uncertainties regarding the safety of rosiglitazone in patients with heart disease.展开更多
In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were inves...In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5, 2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion, respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and inter- leukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swell- ing (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflam- matory response after ischemia-reperfusion in this model.展开更多
Objective To study the preventive effect of rosiglitazone glial activation,oxidative/nitrative stress and spatial memory deficits induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)in rats.Methods ...Objective To study the preventive effect of rosiglitazone glial activation,oxidative/nitrative stress and spatial memory deficits induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)in rats.Methods 24 male Wistar rats were randomly divided into sham operated group,model group and rosiglitazone group.The model of Alzheimer's was induced by injection with ICV 10% STZ bilaterally,on day 1 and 3(3 mg·kg-1).The rats were treated with rosiglitazone(2 mg·kg-1,p.o.)for a consecutive 21 days,once a day,beginning 7 days prior to STZ injection.The learning and memory behavior was assessed using Morris water maze task and Y-maze 21 d after ICV STZ injection.Malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)levels and nitrotyrosine immunoreactivity in brain were estimated as parameters of oxidative/nitrative stress.Brain acetyl cholinesterase(AchE)activity was measured by EllMann's method and activated microglia and astrocytes were detected by immunohistochemistry.Results ICV STZ injection resulted in a severe deficit in spatial learning and memory associated with increased MDA level(+69.5%)and nitrotyrosine immunoreactivity(+23.7%),decreased SOD activity(-29.2%)and GSH(-25.1%)in brain.It also showed the activated microglia and astrocytes in the cortex and hippocampal CA1 region and a significant decrease in acetylcholinesterase activity(-40.2%).Compared with model group,chronic administration of rosiglitazone significantly shorten the escape latency time from the third day in place navigation test,increase the number of passing through primary flat place in spatial probe test in Morris water maze test,and decrease the error times in Y-maze test(P<0.05 or P<0.01).In addition,it also prevented the glial changes,decreased the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity in cortex(P<0.05),but had no effect on SOD activity in cortex.Conclusions Rosiglitazone has a neuroprotective role against streptozotocin-induced cognitive impairment and associated oxidative/nitrative stress.展开更多
This study investigated the anti-hypertensive mechanismof rosiglitazone in renovascular hypertensive rats,and examined its relationship to oxidative stress and lipid metabolism. The renovascular hypertension was induc...This study investigated the anti-hypertensive mechanismof rosiglitazone in renovascular hypertensive rats,and examined its relationship to oxidative stress and lipid metabolism. The renovascular hypertension was induced by stenosis of the left renal artery. Four groups of rats were selected: control,induced untreated,rosiglitazone( 20 mg / kg) and captopril( 10 mg / kg). After 14 d of administration,compared with induced untreated group,rosiglitazone group reduced the renovascular hypertensive rats ' systolic blood pressure and diastolic blood pressure,and decreased total cholesterol(TCH),triglyceride(TG),angiotensin II( Ang II) and angiotensin receptor( AT1) levels( P < 0. 05). Meanwhile,rosiglitazone remarkably decreased the levels of malondialdehyde( MDA) and hydrogen peroxide( H2O2) while improved the levels of supperoxide dismutase( SOD) and reduced glutathione( GSH). These results suggested that rosiglitazone could effectively decreased the blood pressure in renovascular hypertensive rats,and this might be performed by regulating the activity of angiotensin and the lipid metabolismand improving the oxidative stress.展开更多
The goal of this study was to track the influence of a highly publicized report on discussions between doctors and their patients and prescribing decisions made in response to concerns about potential medication adver...The goal of this study was to track the influence of a highly publicized report on discussions between doctors and their patients and prescribing decisions made in response to concerns about potential medication adverse side effects. This was a retrospective analysis of a primary care network’s electronic medical record database. From a diabetes registry of 12, 246 patients, 329 were identified as taking rosiglitazone prior to the June 14, 2007 release of an article in the New England Journal of Medicine;the article suggesting an increased risk of myocardial events. The entire content of all office visits, telephone messages, and medication lists for each patient were reviewed over a 2-year period subsequent to the article’s publication. Doctor/patient discussions regarding concerns for rosiglitazone were catalogued including the physician’s treatment recommendations. There were documented discussions on rosiglitazone’s potential adverse side effects for 64 patients;19.5 percent of this population. All of the discussions occurred between June 15 and October 30, 2007. Of the entire group, 59.3 percent (N = 195) remained on rosiglitazone. For those advised to continue rosiglitazone, the provider indicated that he/she wanted more data before determining if the drug was not safe or discounted the validity of the safety concerns. For those advised to discontinue rosiglitazone, 112 (83.6 percent) were placed on pioglitazone. An article suggesting potential adverse effects of rosiglitazone resulted in a documented discussion in 19.5 percent of patients on this medication. These findings suggest an awareness of this publication by patients, presumably derived from media reports. However, an awareness of this concern did not result in a substantial change in practice.The majority of patients remained on rosiglitazone. The content of these discussions suggest that most physicians’ recommended waiting for more published data before considering a change. While many factors influence physician’s prescribing behavior, this study demonstrates how a highly publicized report influences the doctor/ patient dialogue.展开更多
ix metalloproteinase(MMPs) plays a key role in the pathogenesis of chronic inflammatory disease,such as atherosclerosis.Among MMPs,MMP-2 is regarded as a major proteinase in atherosclerotic plaque lesions.Peroxisome p...ix metalloproteinase(MMPs) plays a key role in the pathogenesis of chronic inflammatory disease,such as atherosclerosis.Among MMPs,MMP-2 is regarded as a major proteinase in atherosclerotic plaque lesions.Peroxisome proliferator activated receptor-gamma(PPARg) ameliorates oxidative stress and the inflammatory response.The aim of the present study was to evaluate the effect of Rosiglitazone on Lipopolysaccharide(LPS)-induced MMP-2 activation as well as its possible mechanism.LPS-induced MMP-2 activity was inhibited by Rosiglitazone(PPARg agonist) in the rat aortic endothelial cells(RAEC).LPS-induced MMP-2 activation was diminished no matter exposure to NF-kB Activation Inhibitor II(JSH-23)or Ras inhibitor,farnesylthiosalicylic acid(FTS). Further study shows that LPS-induced activation of Phospho-Rho A and Phospho-MEKl/2 were significantly inhibited by Rosiglitazone.The activation of NF-kB p65 in the nuclear extract of cells was also significantly suppressed by Rosiglitazone, moreover,the expression of NF-κB p65 was partly activated by GW9662(PPARg antagonist).NF-kB DNA binding activity was also demolished by Rosiglitazone.In summary,our data showed that PPARg agonist,Rosiglitazone suppresses LPS-activated MMP-2 secretion via Ras-MEK1/2 signaling pathways and NF-kB activation.PPARg agonist and Ras-MEK1/2 pathway may be another potential therapeutic target for the disease induced by chronic inflammation.展开更多
The aim of this study was to formulate drug-loaded bio-lipstrips using novel bioexcipients isolated from the fruit pulp of Litchi chinesis(biomaterial L)and to explore the potentiality of lip skin as a novel translabi...The aim of this study was to formulate drug-loaded bio-lipstrips using novel bioexcipients isolated from the fruit pulp of Litchi chinesis(biomaterial L)and to explore the potentiality of lip skin as a novel translabial drug delivery system.The biomaterial,prepared by a simplified economical process and purified by hot dialysis,was subjected to various physicochemical evaluations along with spectral analysis including UV,FT-IR,Mass and ^(1)H NMR.The lipstrip formulated with the novel bioexcipients was screened for its functional properties,including filmability using a film-casting method,and bio/mucoadhesitivity using a shear-stress method,the Park and Robinson method and a rotating cylinder method.Rosiglitazone-loaded bio-lipstrips were formulated by using biomaterial L as a strip former and dextrose as a flexicizer.The formulated strips were subjected to various evaluations,including thickness,folding endurance,in-vitro release and in-vivo release.The release of rosiglitazone maleate was maintained over 24 h,which was confirmed in in-vitro and in-vivo release experiments.Our results reveal that this biopolymer possesses promising stripability as well as bio-adhesitivity.The formulated bio-lipstrips are feasible for delivering rosiglitazone maleate by translabial administration.展开更多
Objective:To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury.Methods:A total of 48 male SD rats were randomly divided into control group(A),I/R group(B),high dose of rosiglitazone(...Objective:To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury.Methods:A total of 48 male SD rats were randomly divided into control group(A),I/R group(B),high dose of rosiglitazone(C),low dose of rosiglitazone(D).Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,Superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),nitric oxide(NO)and endothelin(ET)were measured 1 h later after I/R.24 h after I/R hearts were harvested to observe pathological and ultrastructural changes.Immunohistochemistry and western blotting was used to test CD40 expression in myocardial tissue.Area of myocardial infarction were tested,arrhythmia rate during I/R was recorded.Results:Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,NO,MDA and ET were decreased in group C,D compared with group B.Plasm concentration of T-SOD and GSHPx was increased significantly in group C,D compared with group B.Compared with group B,pathological and ultrastructural changes in group C,D were slightly.Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B.Conclusions:Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,improve endothelial function,reduce oxidative stress and calcium overload.展开更多
基金supported by Planning Program of Department of Science and Technology of Liaoning Province(Grant No.2011225015)
文摘To explore mechanism and protective effect of rosiglitazone on myocardial ischemia reperfusion(I/R) injury.Methods:A total of 48 male Japanese white big-ear rabbits were randomly divided into control group(A),I/R group(B),low dose of rosiglitazone group(C),high dose of rosiglitazone group(D).Plasma concentration of and also reduced the concentration of plasma serum creatine kinase(CK),CK-MB.high-sensitivity C-reactive protein(hsCRP).ultrasuperoxide dismutase(SOD),malondialdehyde(MD.A).lactic acid glutathione skin peroxidase (C-SH-PX).nitric oxide(NO)and endothelin(ET) were measured 1 h later after I/R.Twenty-four hours after I/R the hearts were harvested for pathological and ultrastructural analysis.Area of myocardial infarction were tested.Results:Plasma concentration of CK,Ck-MB.hsCRP,NO. MDA and ET were decreased in C,D group compared with group B.Plasma concentration of T-SOD and GSH-Px were increased significantly in C.D group compared with group B.Compared with group B.pathological and ullraslructural changes in C and D group were slightly.There was significant difference in myocardial infarction area between group C.D and group B(P【0.05). Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B. Rosiglitazone may protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,and improve endothelial function.
文摘Methylprednisolone exhibits anti-inflammatory antioxidant properties, and rosiglitazone acts as an anti-inflammatory and antioxidant by activating peroxisome proliferator-activated receptor-γ in the spinal cord. Methylprednisolone and rosiglitazone have been clinically used during the early stages of secondary spinal cord injury. Because of the complexity and diversity of the inflammatory process after spinal cord injury, a single drug cannot completely inhibit inflammation. Therefore, we assumed that a combination of methylprednisolone and rosiglitazone might promote recovery of neurological function after secondary spinal cord injury. In this study, rats were intraperitoneally injected with methylprednisolone(30 mg/kg) and rosiglitazone(2 mg/kg) at 1 hour after injury, and methylprednisolone(15 mg/kg) at 24 and 48 hours after injury. Rosiglitazone was then administered once every 12 hours for 7 consecutive days. Our results demonstrated that a combined treatment with methylprednisolone and rosiglitazone had a more pronounced effect on attenuation of inflammation and cell apoptosis, as well as increased functional recovery, compared with either single treatment alone, indicating that a combination better promoted recovery of neurological function after injury.
基金Supported by Grants from the Thailand Research Fund RTA5280006(NC),BRG(SC),MRG5280169(AP)and the Commission of Higher Education Thailand(SP,NC)
文摘Rosiglitazone is a synthetic agonist of peroxisome proliferator-activated receptor γ which is used to improve insulin resistance in patients with typeⅡdiabetes.Rosiglitazone exerts its glucose-lowering effects by improving insulin sensitivity.Data from various studies in the past decade suggest that the therapeutic effects of rosiglitazone reach far beyond its use as an insulin sensitizer since it also has other benefits on the cardiovascular system such as improvement of contractile dysfunction,inhibition of the inflammatory response by reducing neutrophil and macrophage accumulation,and the protection of myocardial injury during ischemic/reperfusion in different animal models.Previous clinical studies in typeⅡdiabetes patients demonstrated that rosiglitazone played an important role in protectingagainst arteriosclerosis by normalizing the metabolic disorders and reducing chronic inflammation of the vascular system.Despite these benefits,inconsistent findings have been reported,and growing evidence has demonstrated adverse effects of rosiglitazone on the cardiovascular system,including increased risk of acute myocardial infarction,heart failure and chronic heart failure.As a result,rosiglitazone has been recently withdrawn from EU countries.Nevertheless,the effect of rosiglitazone on ischemic heart disease has not yet been firmly established.Future prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone would be the best way to resolve the uncertainties regarding the safety of rosiglitazone in patients with heart disease.
文摘In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5, 2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion, respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and inter- leukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swell- ing (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflam- matory response after ischemia-reperfusion in this model.
文摘Objective To study the preventive effect of rosiglitazone glial activation,oxidative/nitrative stress and spatial memory deficits induced by intracerebroventricular(ICV)injection of streptozotocin(STZ)in rats.Methods 24 male Wistar rats were randomly divided into sham operated group,model group and rosiglitazone group.The model of Alzheimer's was induced by injection with ICV 10% STZ bilaterally,on day 1 and 3(3 mg·kg-1).The rats were treated with rosiglitazone(2 mg·kg-1,p.o.)for a consecutive 21 days,once a day,beginning 7 days prior to STZ injection.The learning and memory behavior was assessed using Morris water maze task and Y-maze 21 d after ICV STZ injection.Malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)levels and nitrotyrosine immunoreactivity in brain were estimated as parameters of oxidative/nitrative stress.Brain acetyl cholinesterase(AchE)activity was measured by EllMann's method and activated microglia and astrocytes were detected by immunohistochemistry.Results ICV STZ injection resulted in a severe deficit in spatial learning and memory associated with increased MDA level(+69.5%)and nitrotyrosine immunoreactivity(+23.7%),decreased SOD activity(-29.2%)and GSH(-25.1%)in brain.It also showed the activated microglia and astrocytes in the cortex and hippocampal CA1 region and a significant decrease in acetylcholinesterase activity(-40.2%).Compared with model group,chronic administration of rosiglitazone significantly shorten the escape latency time from the third day in place navigation test,increase the number of passing through primary flat place in spatial probe test in Morris water maze test,and decrease the error times in Y-maze test(P<0.05 or P<0.01).In addition,it also prevented the glial changes,decreased the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity in cortex(P<0.05),but had no effect on SOD activity in cortex.Conclusions Rosiglitazone has a neuroprotective role against streptozotocin-induced cognitive impairment and associated oxidative/nitrative stress.
文摘This study investigated the anti-hypertensive mechanismof rosiglitazone in renovascular hypertensive rats,and examined its relationship to oxidative stress and lipid metabolism. The renovascular hypertension was induced by stenosis of the left renal artery. Four groups of rats were selected: control,induced untreated,rosiglitazone( 20 mg / kg) and captopril( 10 mg / kg). After 14 d of administration,compared with induced untreated group,rosiglitazone group reduced the renovascular hypertensive rats ' systolic blood pressure and diastolic blood pressure,and decreased total cholesterol(TCH),triglyceride(TG),angiotensin II( Ang II) and angiotensin receptor( AT1) levels( P < 0. 05). Meanwhile,rosiglitazone remarkably decreased the levels of malondialdehyde( MDA) and hydrogen peroxide( H2O2) while improved the levels of supperoxide dismutase( SOD) and reduced glutathione( GSH). These results suggested that rosiglitazone could effectively decreased the blood pressure in renovascular hypertensive rats,and this might be performed by regulating the activity of angiotensin and the lipid metabolismand improving the oxidative stress.
文摘The goal of this study was to track the influence of a highly publicized report on discussions between doctors and their patients and prescribing decisions made in response to concerns about potential medication adverse side effects. This was a retrospective analysis of a primary care network’s electronic medical record database. From a diabetes registry of 12, 246 patients, 329 were identified as taking rosiglitazone prior to the June 14, 2007 release of an article in the New England Journal of Medicine;the article suggesting an increased risk of myocardial events. The entire content of all office visits, telephone messages, and medication lists for each patient were reviewed over a 2-year period subsequent to the article’s publication. Doctor/patient discussions regarding concerns for rosiglitazone were catalogued including the physician’s treatment recommendations. There were documented discussions on rosiglitazone’s potential adverse side effects for 64 patients;19.5 percent of this population. All of the discussions occurred between June 15 and October 30, 2007. Of the entire group, 59.3 percent (N = 195) remained on rosiglitazone. For those advised to continue rosiglitazone, the provider indicated that he/she wanted more data before determining if the drug was not safe or discounted the validity of the safety concerns. For those advised to discontinue rosiglitazone, 112 (83.6 percent) were placed on pioglitazone. An article suggesting potential adverse effects of rosiglitazone resulted in a documented discussion in 19.5 percent of patients on this medication. These findings suggest an awareness of this publication by patients, presumably derived from media reports. However, an awareness of this concern did not result in a substantial change in practice.The majority of patients remained on rosiglitazone. The content of these discussions suggest that most physicians’ recommended waiting for more published data before considering a change. While many factors influence physician’s prescribing behavior, this study demonstrates how a highly publicized report influences the doctor/ patient dialogue.
文摘ix metalloproteinase(MMPs) plays a key role in the pathogenesis of chronic inflammatory disease,such as atherosclerosis.Among MMPs,MMP-2 is regarded as a major proteinase in atherosclerotic plaque lesions.Peroxisome proliferator activated receptor-gamma(PPARg) ameliorates oxidative stress and the inflammatory response.The aim of the present study was to evaluate the effect of Rosiglitazone on Lipopolysaccharide(LPS)-induced MMP-2 activation as well as its possible mechanism.LPS-induced MMP-2 activity was inhibited by Rosiglitazone(PPARg agonist) in the rat aortic endothelial cells(RAEC).LPS-induced MMP-2 activation was diminished no matter exposure to NF-kB Activation Inhibitor II(JSH-23)or Ras inhibitor,farnesylthiosalicylic acid(FTS). Further study shows that LPS-induced activation of Phospho-Rho A and Phospho-MEKl/2 were significantly inhibited by Rosiglitazone.The activation of NF-kB p65 in the nuclear extract of cells was also significantly suppressed by Rosiglitazone, moreover,the expression of NF-κB p65 was partly activated by GW9662(PPARg antagonist).NF-kB DNA binding activity was also demolished by Rosiglitazone.In summary,our data showed that PPARg agonist,Rosiglitazone suppresses LPS-activated MMP-2 secretion via Ras-MEK1/2 signaling pathways and NF-kB activation.PPARg agonist and Ras-MEK1/2 pathway may be another potential therapeutic target for the disease induced by chronic inflammation.
文摘The aim of this study was to formulate drug-loaded bio-lipstrips using novel bioexcipients isolated from the fruit pulp of Litchi chinesis(biomaterial L)and to explore the potentiality of lip skin as a novel translabial drug delivery system.The biomaterial,prepared by a simplified economical process and purified by hot dialysis,was subjected to various physicochemical evaluations along with spectral analysis including UV,FT-IR,Mass and ^(1)H NMR.The lipstrip formulated with the novel bioexcipients was screened for its functional properties,including filmability using a film-casting method,and bio/mucoadhesitivity using a shear-stress method,the Park and Robinson method and a rotating cylinder method.Rosiglitazone-loaded bio-lipstrips were formulated by using biomaterial L as a strip former and dextrose as a flexicizer.The formulated strips were subjected to various evaluations,including thickness,folding endurance,in-vitro release and in-vivo release.The release of rosiglitazone maleate was maintained over 24 h,which was confirmed in in-vitro and in-vivo release experiments.Our results reveal that this biopolymer possesses promising stripability as well as bio-adhesitivity.The formulated bio-lipstrips are feasible for delivering rosiglitazone maleate by translabial administration.
基金supported by Henan Province Natural Science Foundation(283v2110)
文摘Objective:To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury.Methods:A total of 48 male SD rats were randomly divided into control group(A),I/R group(B),high dose of rosiglitazone(C),low dose of rosiglitazone(D).Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,Superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px),nitric oxide(NO)and endothelin(ET)were measured 1 h later after I/R.24 h after I/R hearts were harvested to observe pathological and ultrastructural changes.Immunohistochemistry and western blotting was used to test CD40 expression in myocardial tissue.Area of myocardial infarction were tested,arrhythmia rate during I/R was recorded.Results:Plasm concentration of creatine kinase(CK),CK-MB,hsCRP,NO,MDA and ET were decreased in group C,D compared with group B.Plasm concentration of T-SOD and GSHPx was increased significantly in group C,D compared with group B.Compared with group B,pathological and ultrastructural changes in group C,D were slightly.Myocardial infarction area and arrhythmia rate were lower in group C,D compare with group B.Conclusions:Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration,inhibit inflammatory reaction,improve endothelial function,reduce oxidative stress and calcium overload.
