坎地沙坦联合贝那普利治疗糖尿病肾病并高血压患者的临床研究

目的:探索坎地沙坦联合贝那普利治疗糖尿病肾病(DN)并高血压患者的临床疗效。方法:选择2012年7月至2014年9月我院接收的DN合并高血压患者135例,按照随机数表法将患者分成坎地沙坦组(口服8 mg/d坎地沙坦)、贝那普利组(口服10mg/d贝那普利)和联合用药组(口服8 mg/d坎地沙坦和10 mg/d贝那普利)三组,每组45例,连续治疗12周。比较三组患者治疗前后收缩压(SBP)、舒张压(DBP)、24 h尿微量清蛋白排泄频率(24 h UAER)、尿素氮(BUN)、血钾水平(K+)、血清肌酐(Scr)、肌酐清除率(Ccr)、空腹血糖(FPG)指标变化及不良反应发生率。结果:与治疗前相比,治疗后各组患者的SBP、DBP、24 h UAER及BUN、Scr、Ccr、FPG均显著下降(均P0.05),且联合用药组患者的上述各指标水平明显低于坎地沙坦组和贝那普利组(均P0.05);联合用药组不良反应发生率低于其他两组,但是三组之间差异无统计学意义(P0.05)。结论:坎地沙坦联合贝那普利可以有效改善DN并高血压患者的血压情况及尿蛋白水平,改善患者的肾脏功能,且疗效优于单药治疗,对于临床用药有指导意义。     

坎地沙坦酯治疗老年患者原发性高血压的疗效及安全性分析

目的:探讨坎地沙坦酯治疗老年高血压患者的疗效和安全性。方法:选取我院110例老年原发性高血压患者,随机分为观察组(坎地沙坦酯治疗)和对照组(依那普利治疗),对比分析两组患者药物治疗前、后的动态血压监测及相关指标。结果:经两个月治疗后,两组患者坐位收缩压(SBP)及舒张压(DBP)谷值均较基线明显降低,观察组下降幅度明显大于对照组,差异有统计学意义(P0.05);观察组的总有效率为90.91%,明显高于对照组的76.36%,差异有统计学意义(P0.05)。结论:坎地沙坦酯治疗老年患者原发性高血压疗效显著,可明显降低收缩压和舒张压,是治疗老年性高血压理想的制剂。     

Candesartan attenuates Angiotensin II-induced mesangial cell apoptosis via TLR4/MyD88 pathway

Angiotensin II (Ang II) can stimulate Toll-like receptor 4 (TLR4) expression in mesangial cells (MCs), but the role of TLR4 in the Ang II-induced apoptosis and the effect of candesartan on TLR4 expression remain unclear. Here, we report that Ang II-induced MC apoptosis in a time-dependent manner and up-regulated TLR4/MyD88 expression, and that the intracellular ROS was subsequently increased. We also show that candesartan attenuated the Ang II-induced MC apoptosis, and that this protective effect was dependent on decreased TLR4/MyD88 expression as well as reduced intracellular ROS formation. Furthermore, Ang II increased the apoptosis inducing factor protein level, while candesartan markedly reduced this increase. These results demonstrate that TLR4/MyD88 pathway was involved in the Ang II promoted MC apoptosis, which was related to TLR4/MyD88 mediated oxidative stress. These data also suggest that candesartan exerted anti-apoptotic effect as an antioxidant by modulating this pathway.     

卡托普利联合坎地沙坦对糖尿病肾病患者的疗效及对血浆ET、D-D、Hcy、ADM、FIB水平的影响

目的:研究卡托普利联合坎地沙坦治疗糖尿病肾病患者的临床疗效及对血浆内皮素(Endothelin,ET)、D-二聚体(D-Dimer,D-D)、同型半胱氨酸(Homocysteine,Hcy)、肾上腺髓质素(Adrenal medulla,ADM)、纤维蛋白原(Fibrinogen,FIB)的影响。方法:选择2016年1月至2017年8月在我院治疗的糖尿病肾病患者72例,根据不同的治疗方法分为观察组和对照组。对照组采用卡托普利治疗,观察组在对照组的基础上联用坎地沙坦治疗,观察和比较两组患者的临床治疗效果,治疗前后ET、D-D、Hcy、ADM、FIB水平、肾功能及空腹血糖(fasting plasma glucose,FPG)、餐后2小时血糖浓度(2 hours Plas ma Glucose,2hPG)、糖化血红蛋白(Hemoglobin A1c,HbA1C)水平的变化。结果:治疗后,观察组总有效率为88.89%,明显高于对照组69.44%(P0.05);观察组血浆ET、D-D、Hcy、ADM、FIB、FPG、2hPG、HbA1C水平、24 h尿总蛋白及尿白蛋白排泄率均显著低于对照组(P0.05)。结论:卡托普利联合坎地沙坦治疗糖尿病肾病患者的临床疗效明显优于单用卡托普利治疗,可助于降糖、降压并有效保护患者肾脏功能。     

卡托普利与坎地沙坦对老年糖尿病肾病患者肾功能的影响

目的:研究卡托普利联合坎地沙坦对糖尿病肾病患者肾功能的影响及临床疗效。方法:选择2014年5月-2015年5月我院收治的糖尿病肾病患者90例,根据治疗方法不同分为观察组和对照组。对照组给予卡托普利治疗,观察组在对照组基础上加用坎地沙坦治疗。观察并比较两组患者的临床疗效以及治疗前后空腹血糖、血尿素氮、血肌酐、24 h尿蛋白等水平的变化情况。结果:观察组的治疗总有效率为93.3%,对照组的治疗总有效率为84.4%;观察组患者的临床疗效显著高于对照组,但差异并不具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后的空腹血糖、血尿素氮、血肌酐及24 h尿蛋白水平均显著降低,差异具有统计学意义(P0.05);治疗后,观察组患者的空腹血糖、血尿素氮、血肌酐和24 h尿蛋白值均显著均明显低于对照组,差异均具有统计学意义(P0.05)。结论:卡托普利联合坎地沙坦治疗糖尿病肾病较单独采用卡托普利治疗能够更加有效的改善患者的临床症状,保护患者的肾功能,具有较好的临床疗效。     

赖诺普利联合坎地沙坦治疗心力衰竭合并原发性高血压(英文)

目的:观察和评价赖诺普利联合坎地沙坦治疗心力衰竭(HF)合并原发性高血压(EH)的疗效。方法:将我院收治的EH合并HF患者69例,在给予个体化治疗的基础上随机分为:A组赖诺普利治疗组,B组坎地沙坦治疗组,C组赖诺普利和坎地沙坦联合治疗组,三组疗程均为8周。观察治疗前后的血压、心功能分级、BNP水平、心脏彩色多普勒及肝肾功检查。结果:与对照组比较,联合组的总有效率明显增高,差异有统计学意义;治疗前后所有患者肝肾功能等生化指标未见明显变化。结论:赖诺普利与坎地沙坦联合治疗心力衰竭合并原发性高血压的疗效明显优于单用赖诺普利或坎地沙坦的疗效,且安全性好,值得广泛推广和应用。     

Enzyme-assisted synthesis and structure characterization of glucuronic acid conjugates of losartan, candesartan, and zolarsartan

Three angiotensin II receptor antagonists—losartan, candesartan, and zolarsartan—were investigated. All the compounds, which are structural analogues, are metabolized via conjugation to glucuronic acid. Interestingly, both O- and N-glucuronidation take place, so that regioisomers are formed. One ether O-glucuronide, two acyl O-glucuronides, and five tetrazole-N-glucuronides were biosynthesized, in milligram scale, from the three sartan aglycones. Liver microsomes from bovine, moose, rat, and pig and recombinant human UDP-glucuronosyltransferases were used as catalysts. The synthesized compounds were identified as sartan glucuronides by mass spectrometry, while the sites of glucuronidation were determined by nuclear magnetic resonance spectroscopy. Drug metabolites are needed as standards for pharmaceutical research and, as the present study shows, they can easily be produced with enzymes as catalyst.     

赖诺普利联合坎地沙坦治疗心力衰竭合并原发性高血压

目的：观察和评价赖诺普利联合坎地沙坦治疗心力衰竭（HF）合并原发性高血压（EH）的疗效。方法：将我院收治的EH合并HF患者69例,在给予个体化治疗的基础上随机分为：A组赖诺普利治疗组,B组坎地沙坦治疗组,C组赖诺普利和坎地沙坦联合治疗组,三组疗程均为8周。观察治疗前后的血压、心功能分级、BNP水平、心脏彩色多普勒及肝肾功检查。结果：与对照组比较,联合组的总有效率明显增高,差异有统计学意义;治疗前后所有患者肝肾功能等生化指标未见明显变化。结论：赖诺普利与坎地沙坦联合治疗心力衰竭合并原发性高血压的疗效明显优于单用赖诺普利或坎地沙坦的疗效,且安全性好,值得广泛推广和应用。     

Inhibitors for the hepatitis C virus RNA polymerase explored by SAR with advanced machine learning methods

Hepatitis C virus (HCV) is a global health challenge, affecting approximately 200 million people worldwide. In this study we developed SAR models with advanced machine learning classifiers Random Forest and k Nearest Neighbor Simulated Annealing for 679 small molecules with measured inhibition activity for NS5B genotype 1b. The activity was expressed as a binary value (active/inactive), where actives were considered molecules with IC₅₀ ?0.95 μM. We applied our SAR models to various drug-like databases and identified novel chemical scaffolds for NS5B inhibitors. Subsequent in vitro antiviral assays suggested a new activity for an existing prodrug, Candesartan cilexetil, which is currently used to treat hypertension and heart failure but has not been previously tested for anti-HCV activity. We also identified NS5B inhibitors with two novel non-nucleoside chemical motifs.     

Central angiotensin II stimulates cutaneous water intake behavior via an angiotensin II type-1 receptor pathway in the Japanese tree frog Hyla japonica

Angiotensin II (Ang II) stimulates oral water intake by causing thirst in all terrestrial vertebrates except anurans. Anuran amphibians do not drink orally but absorb water osmotically through ventral skin. In this study, we examined the role of Ang II on the regulation of water-absorption behavior in the Japanese tree frog (Hyla japonica). In fully hydrated frogs, intracerebroventricular (ICV) and intralymphatic sac (ILS) injection of Ang II significantly extended the residence time of water in a dose-dependent manner. Ang II-dependent water uptake was inhibited by ICV pretreatment with an angiotensin II type-1 (AT₁) receptor antagonist but not a type-2 (AT₂) receptor antagonist. These results suggest that Ang II stimulates water-absorption behavior in the tree frog via an AT₁-like but not AT₂-like receptor. We then cloned and characterized cDNA of the tree frog AT₁ receptor from the brain. The tree frog AT₁ receptor cDNA encodes a 361 amino acid residue protein, which is 87% identical to the toad (Bufo marinus) AT₁ receptor and exhibits the functional characteristics of an Ang II receptor. AT₁ receptor mRNAs were found to be present in a number of tissues including brain (especially in the diencephalon), lung, large intestine, kidney and ventral pelvic skin. When tree frogs were exposed to dehydrating conditions, AT₁ receptor mRNA significantly increased in the diencephalon and the rhombencephalon. These data suggest that central Ang II may control water intake behavior via an AT₁ receptor on the diencephalon and rhombencephalon in anuran amphibians and may have implications for water consumption in vertebrates.