Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only parti...Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only partially understood. However, evidence suggests that adenosine, released during the initial ischemic insult, activates a variety of G protein-coupled agonists, such as opioids, bradykinin, and catecholamines, resulting in the activation of protein kinases, especially protein kinase C(PKC). This leads to the translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates the opening of the ATP-sensitive K+ channel, which confers resistance to ischemia. It is known that a range of different hypoglycemic agents that activate the same signaling cascades at various cellular levels can interfere with protection from ischemic preconditioning. This review examines the effects of several hypoglycemic agents on myocardial ischemic preconditioning in animal studies and clinical trials.展开更多
Diabetes mellitus is the chronic disorder emerging as major world health problem which increases the rate of morbidity and mortality. The aim of the present study was to ascertain patterns of prescription of oral hypo...Diabetes mellitus is the chronic disorder emerging as major world health problem which increases the rate of morbidity and mortality. The aim of the present study was to ascertain patterns of prescription of oral hypoglycemic agents to type 2 diabetic patients attending a university hospital, and to assess patient compliance. A prospective, observational and non comparative study was conducted in 200 established diabetes mellitus type 2 patients attending outpatient department at Majeedia Hospital, New Delhi, India. Prescriptions from registered patients were included in the study. Once the consultation by the physician was over, the prescriptions were reviewed and the patients were interviewed. The information was collected in an inhouse designed documentation proforma. In a pool of 200 type 2 diabetics, more than half were female (n=106, 53%). The mean age of the patients were found to be 50.4 ± 11.7 years and mean body mass index, 25.8 ± 4.4 kg/m2. A total of 432 oral hypoglycemic agents were prescribed to the patients. Highly significant number of patients were prescribed combination therapy, (n=143, 71.5%) as compared to monotherapy (n=57, 28.5%),展开更多
肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞...肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞免疫逃逸途径,重新激活抗肿瘤免疫应答过程,成为晚期HCC治疗的新手段。然而,长期临床结果显示,采用PD-1/PD-L1抑制剂单药治疗晚期HCC的病人仍存在较高的复发率和转移率。免疫联合疗法是目前针对晚期HCC患者的新的治疗策略,其中PD-1/PD-L1抑制剂联合抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物在晚期HCC治疗中显示出了良好的疗效和安全性。PD-1/PD-L1抑制剂联合抗VEGF药物可通过参与癌症免疫循环途径抑制肝癌细胞的生长。该文就PD-1/PD-L1抑制剂联合抗VEGF药物在晚期HCC治疗中的临床研究作一综述。展开更多
The hypoglycemic activity of an ethanol extract of Hibiscus rosa-sinsnsis was studied in glucose located rats. Afer a single dose of the extract, a slight but insignificant hypoglycemic effect was observed at 30 and ...The hypoglycemic activity of an ethanol extract of Hibiscus rosa-sinsnsis was studied in glucose located rats. Afer a single dose of the extract, a slight but insignificant hypoglycemic effect was observed at 30 and 90 min. At 120 min it was mild but significant. After repeated administration of the extract (once a day for seven consecutive days) a statistically significant (P < 0 .001 ) reduction in blood glucose levels was observed at 30, 90 and 120 min after glucose loading. The average hypoglycemic activity, after repeated administration of 250 mg kg-1 leaf extract was 81 %, under similar conditions average activity of tolbutamide was 96%. At 250 mg·kg-1 the efficacy of the extract was found to be 84% of tolbutawhde (100mg·kg- 1 ). Repeated treatment of animals either with tolbutandde a sulphonylurea or H. rosa-sinensis caused a 2-3-fold improvement in glucose tolerance as compared to those receiving only once. These data suggest that the leaf extract acts like tolbutamide and the meehanism of action may be a stimulation of pancreatic hata cells to produce more insulin or an increase of the glycogen deposition in liver. It appeare that the active principle in the tested extract has the sulphonylurea Skeleton in which -SO2-NH-CO- group and the substituents (S1 and S2) may be the possible active sites responsible for its hypolycemic activity.展开更多
The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on...The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus(T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1,and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM.Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.展开更多
<div style="text-align:justify;"> <span style="font-family:Verdana;">Chronic liver disease (CLD) refers to a structural and functional change of the liver, which modifies the pharmacoki...<div style="text-align:justify;"> <span style="font-family:Verdana;">Chronic liver disease (CLD) refers to a structural and functional change of the liver, which modifies the pharmacokinetics of multiple drugs, including hypoglycemic agents. This alteration depends on the severity degree of the liver disease, clinical characteristics of the patient, and comorbidities presence such as kidney disease and drug biochemistry. Insulin is considered a safe therapeutic strategy in patients with CLD, however, for many oral hypoglycemic agents, its use and dose adjustment will depend on the Child-Pugh score, based on the risk of hypoglycemia in this type of patient.</span> </div>展开更多
1文献来源Adusumilli PS,Zauderer MG,Rivière I,et al.A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease,in combination with the anti-PD-1 agent pembrolizum...1文献来源Adusumilli PS,Zauderer MG,Rivière I,et al.A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease,in combination with the anti-PD-1 agent pembrolizumab[J].Cancer Discov,2021,11(11):2748-2763.2证据水平1b。展开更多
BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis...BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.展开更多
文摘Murry et al in 1986 discovered the intrinsic mechanism of profound protection called ischemic preconditioning. The complex cellular signaling cascades underlying this phenomenon remain controversial and are only partially understood. However, evidence suggests that adenosine, released during the initial ischemic insult, activates a variety of G protein-coupled agonists, such as opioids, bradykinin, and catecholamines, resulting in the activation of protein kinases, especially protein kinase C(PKC). This leads to the translocation of PKC from the cytoplasm to the sarcolemma, where it stimulates the opening of the ATP-sensitive K+ channel, which confers resistance to ischemia. It is known that a range of different hypoglycemic agents that activate the same signaling cascades at various cellular levels can interfere with protection from ischemic preconditioning. This review examines the effects of several hypoglycemic agents on myocardial ischemic preconditioning in animal studies and clinical trials.
文摘Diabetes mellitus is the chronic disorder emerging as major world health problem which increases the rate of morbidity and mortality. The aim of the present study was to ascertain patterns of prescription of oral hypoglycemic agents to type 2 diabetic patients attending a university hospital, and to assess patient compliance. A prospective, observational and non comparative study was conducted in 200 established diabetes mellitus type 2 patients attending outpatient department at Majeedia Hospital, New Delhi, India. Prescriptions from registered patients were included in the study. Once the consultation by the physician was over, the prescriptions were reviewed and the patients were interviewed. The information was collected in an inhouse designed documentation proforma. In a pool of 200 type 2 diabetics, more than half were female (n=106, 53%). The mean age of the patients were found to be 50.4 ± 11.7 years and mean body mass index, 25.8 ± 4.4 kg/m2. A total of 432 oral hypoglycemic agents were prescribed to the patients. Highly significant number of patients were prescribed combination therapy, (n=143, 71.5%) as compared to monotherapy (n=57, 28.5%),
文摘肝细胞癌(hepatocellular carcinoma,HCC)是全球高发的恶性肿瘤。程序性死亡蛋白-1(programmed death protein-1,PD-1)/程序性死亡蛋白配体-1(programmed death protein ligand-1,PD-L1)抑制剂可通过阻断T细胞负调节信号,抑制肿瘤细胞免疫逃逸途径,重新激活抗肿瘤免疫应答过程,成为晚期HCC治疗的新手段。然而,长期临床结果显示,采用PD-1/PD-L1抑制剂单药治疗晚期HCC的病人仍存在较高的复发率和转移率。免疫联合疗法是目前针对晚期HCC患者的新的治疗策略,其中PD-1/PD-L1抑制剂联合抗血管内皮生长因子(vascular endothelial growth factor,VEGF)药物在晚期HCC治疗中显示出了良好的疗效和安全性。PD-1/PD-L1抑制剂联合抗VEGF药物可通过参与癌症免疫循环途径抑制肝癌细胞的生长。该文就PD-1/PD-L1抑制剂联合抗VEGF药物在晚期HCC治疗中的临床研究作一综述。
文摘The hypoglycemic activity of an ethanol extract of Hibiscus rosa-sinsnsis was studied in glucose located rats. Afer a single dose of the extract, a slight but insignificant hypoglycemic effect was observed at 30 and 90 min. At 120 min it was mild but significant. After repeated administration of the extract (once a day for seven consecutive days) a statistically significant (P < 0 .001 ) reduction in blood glucose levels was observed at 30, 90 and 120 min after glucose loading. The average hypoglycemic activity, after repeated administration of 250 mg kg-1 leaf extract was 81 %, under similar conditions average activity of tolbutamide was 96%. At 250 mg·kg-1 the efficacy of the extract was found to be 84% of tolbutawhde (100mg·kg- 1 ). Repeated treatment of animals either with tolbutandde a sulphonylurea or H. rosa-sinensis caused a 2-3-fold improvement in glucose tolerance as compared to those receiving only once. These data suggest that the leaf extract acts like tolbutamide and the meehanism of action may be a stimulation of pancreatic hata cells to produce more insulin or an increase of the glycogen deposition in liver. It appeare that the active principle in the tested extract has the sulphonylurea Skeleton in which -SO2-NH-CO- group and the substituents (S1 and S2) may be the possible active sites responsible for its hypolycemic activity.
基金supported by the National Natural Science Foundation of China (No. 82003873 and 81903708)the Postdoctoral Science Foundation of China (No. 2020M681899)the Fundamental Research Funds for the Central Universities (No. 2021QNA7019)。
文摘The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus(T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1,and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM.Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.
文摘<div style="text-align:justify;"> <span style="font-family:Verdana;">Chronic liver disease (CLD) refers to a structural and functional change of the liver, which modifies the pharmacokinetics of multiple drugs, including hypoglycemic agents. This alteration depends on the severity degree of the liver disease, clinical characteristics of the patient, and comorbidities presence such as kidney disease and drug biochemistry. Insulin is considered a safe therapeutic strategy in patients with CLD, however, for many oral hypoglycemic agents, its use and dose adjustment will depend on the Child-Pugh score, based on the risk of hypoglycemia in this type of patient.</span> </div>
文摘1文献来源Adusumilli PS,Zauderer MG,Rivière I,et al.A phase I trial of regional mesothelin-targeted CAR T-cell therapy in patients with malignant pleural disease,in combination with the anti-PD-1 agent pembrolizumab[J].Cancer Discov,2021,11(11):2748-2763.2证据水平1b。
基金Supported by Science and Technology Plan Project of Shaoyang City,No.2022GX4139.
文摘BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.
