Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear.It has been postulated that an increase in the intracell...Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear.It has been postulated that an increase in the intracellular concentration of fatty acid metabolites activates a serine kinase cascade,which leads to defects in insu-lin signaling downstream to the insulin receptor.In addition,the complex network of adipokines released from adipose tissue modulates the response of tissues to insulin.Among the many molecules involved in the intracellular processing of the signal provided by insulin,the insulin receptor substrate-2,the protein kinase B and the forkhead transcription factor Foxo 1a are of particular interest,as recent data has provided strong evidence that dysfunction of these proteins results in insulin resistance in vivo.Recently,studies have revealed that phosphoinositidedependent kinase 1-independent phosphorylation of protein kinase Cε causes a reduction in insulin receptor gene expression.Additionally,it has been suggested that mitochondrial dysfunction triggers activation of several serine kinases,and weakens insulin signal transduction.Thus,in this review,the current developments in understanding the pathophysiological processes of insulin resistance in type 2 diabetes have been summarized.In addition,this study provides potential new targets for the treatment and prevention of type 2 diabetes.展开更多
Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy o...Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy of a monoamine oxidase type B inhibitor (MAOBI) with levodopa or a catechol-O-methyl transferase inhibitor (COMTI) with levodopa provides benefits to PD patients. Direct comparison of efficacy and side effect profiles is complex. The aim of this study is to investigate the different AE profiles of MAOBI and COMTI combination therapies. Data used to analyze the AEs of different PD medications were retrieved from “The Boston University Medical Center’s Parkinson’s Disease and Movement Disorder Database”. Ten categories of AEs were compared between patients receiving MAOBI and COMTI combination treatment. In total, 87 subjects were included in the analysis. Out of ten AEs, the presence of dementia was signifi- cantly different between the MAOBI and COMTI groups with an OR of 6.9 (COMTI vs MAOBI, 95% CI 1.3 - 37.0). Motor fluctuations were also found to be differently distributed in the two medication groups with an OR of 3.1 (COMTI vs MAOBI, 95% CI 1.0 - 9.8). In this retrospective database analysis of patients treated with combination treatment for PD, combination therapy of a COMTI with levodopa was more likely to be associated with dementia and motor fluctuations than a MAOBI with levodopa.展开更多
目的了解A、B、AB型全血加入O型全血不同剂量后血型正反鉴定、抗-A、抗-B抗体效价、直接与间接抗人-IgG实验变化。方法完全随机抽取4℃保存24 h A、B、AB型全血分别60 m l,按不同比例加入O型抗-A、抗-B效价1∶64的全血9、12、15、18 m ...目的了解A、B、AB型全血加入O型全血不同剂量后血型正反鉴定、抗-A、抗-B抗体效价、直接与间接抗人-IgG实验变化。方法完全随机抽取4℃保存24 h A、B、AB型全血分别60 m l,按不同比例加入O型抗-A、抗-B效价1∶64的全血9、12、15、18 m l置入100 m l塑料血袋内混匀后,置37℃孵箱,间隔15 m in摇动1次。分别在1、2、4、8、12、24 h留取标本,做血型正反鉴定、抗-A、抗-B抗体效价、直接与间接抗人-IgG实验。结果不同型全血加入不同剂量O型全血,37℃不同时间血型正反鉴定相符;相对应抗-A、抗-B抗体效价逐渐下降到消失;直接与间接抗人-IgG实验的变化,以B型接受O型的反应最小,在接受600 m l直接与间接抗人-IgG均为阴性,800 m l同1 200 m l反应基本一致。A、AB型接受O型后直接与间接抗人-IgG反应基本一致,实验结果均为阳性。结论以B型接受O型的反应最小,在接受600 m l直接与间接抗人-IgG均为阴性。800 m l同1 200 m l反应基本一致,A、AB型直接与间接抗人-IgG均为阳性。原则上最好不输O型全血,从直接抗人-IgG实验分析,只要红细胞上存在不完全抗体,就一定会影响红细胞的寿命与质量。展开更多
文摘Free fatty acids are known to play a key role in promoting loss of insulin sensitivity in type 2 diabetes mellitus but the underlying mechanism is still unclear.It has been postulated that an increase in the intracellular concentration of fatty acid metabolites activates a serine kinase cascade,which leads to defects in insu-lin signaling downstream to the insulin receptor.In addition,the complex network of adipokines released from adipose tissue modulates the response of tissues to insulin.Among the many molecules involved in the intracellular processing of the signal provided by insulin,the insulin receptor substrate-2,the protein kinase B and the forkhead transcription factor Foxo 1a are of particular interest,as recent data has provided strong evidence that dysfunction of these proteins results in insulin resistance in vivo.Recently,studies have revealed that phosphoinositidedependent kinase 1-independent phosphorylation of protein kinase Cε causes a reduction in insulin receptor gene expression.Additionally,it has been suggested that mitochondrial dysfunction triggers activation of several serine kinases,and weakens insulin signal transduction.Thus,in this review,the current developments in understanding the pathophysiological processes of insulin resistance in type 2 diabetes have been summarized.In addition,this study provides potential new targets for the treatment and prevention of type 2 diabetes.
文摘Currently, levodopa is the most effective and commonly used medication to control motor symptoms in Parkinson’s disease (PD). However, its long-term use is associated with adverse effects (AEs). Combination therapy of a monoamine oxidase type B inhibitor (MAOBI) with levodopa or a catechol-O-methyl transferase inhibitor (COMTI) with levodopa provides benefits to PD patients. Direct comparison of efficacy and side effect profiles is complex. The aim of this study is to investigate the different AE profiles of MAOBI and COMTI combination therapies. Data used to analyze the AEs of different PD medications were retrieved from “The Boston University Medical Center’s Parkinson’s Disease and Movement Disorder Database”. Ten categories of AEs were compared between patients receiving MAOBI and COMTI combination treatment. In total, 87 subjects were included in the analysis. Out of ten AEs, the presence of dementia was signifi- cantly different between the MAOBI and COMTI groups with an OR of 6.9 (COMTI vs MAOBI, 95% CI 1.3 - 37.0). Motor fluctuations were also found to be differently distributed in the two medication groups with an OR of 3.1 (COMTI vs MAOBI, 95% CI 1.0 - 9.8). In this retrospective database analysis of patients treated with combination treatment for PD, combination therapy of a COMTI with levodopa was more likely to be associated with dementia and motor fluctuations than a MAOBI with levodopa.
文摘目的了解A、B、AB型全血加入O型全血不同剂量后血型正反鉴定、抗-A、抗-B抗体效价、直接与间接抗人-IgG实验变化。方法完全随机抽取4℃保存24 h A、B、AB型全血分别60 m l,按不同比例加入O型抗-A、抗-B效价1∶64的全血9、12、15、18 m l置入100 m l塑料血袋内混匀后,置37℃孵箱,间隔15 m in摇动1次。分别在1、2、4、8、12、24 h留取标本,做血型正反鉴定、抗-A、抗-B抗体效价、直接与间接抗人-IgG实验。结果不同型全血加入不同剂量O型全血,37℃不同时间血型正反鉴定相符;相对应抗-A、抗-B抗体效价逐渐下降到消失;直接与间接抗人-IgG实验的变化,以B型接受O型的反应最小,在接受600 m l直接与间接抗人-IgG均为阴性,800 m l同1 200 m l反应基本一致。A、AB型接受O型后直接与间接抗人-IgG反应基本一致,实验结果均为阳性。结论以B型接受O型的反应最小,在接受600 m l直接与间接抗人-IgG均为阴性。800 m l同1 200 m l反应基本一致,A、AB型直接与间接抗人-IgG均为阳性。原则上最好不输O型全血,从直接抗人-IgG实验分析,只要红细胞上存在不完全抗体,就一定会影响红细胞的寿命与质量。
