Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Polymorphism of renin-angiotensin system genes in progressive IgA nephropathy

Summary: Clinical studies revealed that angiotensin converting enzyme (ACE) inhibitor reduces proteinuria and attenuates progressive decline in renal function in IgA nephropathy. Recent studies by us and others have demonstrated that the homozygote of the D allele (DD) of the ACE insertion/deletion (I/D) polymorphism is a potential risk factor for poor prognosis in IgA nephropathy, and that this deletion polymorphism predicts the therapeutic efficacy of ACE inhibition on proteinuria and, potentially, on progressive deterioration of renal function in patients with the nephropathy.     

悦您定对原发性高血压患者长期与即刻疗效的观察

观察了悦您定治疗６０例原发性高血压患者的长期疗效，２０例原发性高血压患者的即刻疗效，及用药过程中的个体反应。长期疗效与即刻疗效分析均有明显统计学意义（Ｐ＜０．０１）。两组患者，经临床与相应实验室检查均未发现肝、肾、血液系统伤害性副作用。     

Cough and converting enzyme inhibitors

Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3–7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents.     

血管紧张素转换酶抑制剂在急性心肌梗塞早期的应用

对２５例急性心肌梗塞（ＡＭＩ）并左心功能不全患者早期应用血管紧张素转换酶抑制剂（ＡＣＥＩ）治疗的对照性临床分析，结果：用小剂量的ＡＣＥＩ治疗对患者心率、血压无显著的影响〔治疗前后心率分别为８９．９０±１０．２２次／分与８９．４２±８．１９次／分，血压分别为１５．３７±３．４６／９．７４±２．３２ｋＰａ（１ｋＰａ＝７．５ｍｍＨｇ）〕和１４．９６±２．６０／９．４６±１．７６ｋＰａ〕；对合并轻、中度泵衰竭患者的疗效显著，但对重度泵衰竭的疗效与对照组比较无显著性差异；治疗组恶性心律失常的发生率较对照组减低１３．３８％，警告性室早的发生率治疗组较对照组减少２６．３９％，但Ⅱ°～Ⅲ°房室传导阻滞的发生率治疗组高于对照组；两组４周病死率比较无显著性差异。作者认为：ＡＣＥＩ治疗ＡＭＩ并轻、中度泵衰竭安全有效；ＡＣＥＩ有一定抗心律失常作用，但应注意传导系统的并发症，使用中应注意各种副作用的发生。     

ANGIOTENSIN CONVERTING ENZYME (ACE) INHIBITORS AND KININ METABOLISM: EVIDENCE THAT ACE INHIBITORS MAY INHIBIT A KININASE OTHER THAN ACE

1. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II, and also metabolizes bradykinin-(1–9) to bradykinin-(1–7) and bradykinin-(1–7) to bradykinin-(1–5). Increases in endogenous kinin levels may contribute to the therapeutic effects of ACE inhibitors. 2. ACE inhibitors increase vascular levels of both bradykinin-(1–9) and its ACE cleavage product bradykinin-(1–7), at doses below the threshold for ACE inhibition, leading to the proposal that ACE inhibitors may also inhibit a non-ACE kininase which cleaves both kinin peptides; this non-ACE kininase may be the major pathway of kinin metabolism in the vasculature and some other tissues. 3. In support of this proposal, ACE inhibitors potentiate bradykinin-(1–9) effects at doses which have little or no effect on ACE activity, as indicated by angiotensin I conversion to angiotensin II. ACE inhibitors also potentiate the actions of ACE-resistant kinin analogues, which may be susceptible to metabolism by a non-ACE kininase. 4. Identification and characterization of the putative non-ACE kininase which is inhibited by ACE inhibitors may reveal novel approaches to the tissue-specific modulation of kinin levels.     

Quality of life on enalapril after acute myocardial infarction

Quality of life was assessed 4–6 months after an acutemyocardial infarction in a randomized double-blind study ofenalapril versus placebo. Quality of life was evaluated usingthe Nottingham Health Profile (NHP), the Physical Symptoms DistressIndex (PSDI), the Work Performance Scale (WPS) and the LifeSatisfaction Index (LSI). The study comprised 36 women (aged46–85 years, mean 68) and 96 males (aged 39–81 years,mean 62). Quality of life did not differ significantly between patientstreated with enalapril versus placebo. The scores were (enalaprilvs placebo, mean± SE): average NHP 15.4 ± 2.3vs 17.1 ± 2.3; PSDI 9.5± 1.0 vs 10.8 ±0.9; WPS 19.8 ± 2.0 vs 19.4 ± 1.4; LSI 24.1 ±1.0 vs 22.5 ±1.4. Men reported a better quality of lifethan women on most assessments, and non-smokers and ex-smokersbetter than smokers. Patients with moderate or severe anginapectoris had a worse quality of life measured by PSDI and NHPthan patients with minimal or no angina pectoris. Patients withcongestive heart failure had a higher PSDI than those without(13.6 ± 1.7 vs 9.4 ± 0.7, P<0.05), while nosignificant differences were observed in the NHP scores. In conclusion, quality of life was similar in enalapril andplacebo- treated patients after an acute myocardial infarction.However, it was reduced in patients with angina pectoris orheart failure and in those who continued smoking.     

人参二醇组皂甙对精索静脉曲张大鼠的保护作用及其机制

把56只成年Wistar大鼠分为如下3组:①精索静脉曲张组(VG)30只;②精索静脉曲张人参二醇组皂甙组(VPG)8只;③假手术组(SOG)18只。实验结果表明,人参二醇组皂甙可显著提高精索静脉曲张大鼠睾丸ACE活力并降低睾丸LPO含量,但3组动物睾丸的SOD水平无明显差异。作者认为人参二醇组皂甙可能是通过减少LPO产生以提高ACE活力,从而实现对精索静脉曲张大鼠的保护作用。     

伊那普利治疗糖尿病肾病的临床研究

目的评估伊那普利治疗糖尿病肾病(DN)的临床疗效 ,并探讨其作用机制。方法40例持续微量蛋白尿的非胰岛素依赖型糖尿病(NIDDM)患者随机分为常规治疗组(n=19)和伊那普利治疗组(n=21)。利用 131I -邻碘马尿酸钠测定有效肾血浆流量(ERPF) ;肾小球滤过率(GFR)以内生肌酐清除率表示 ;通过ELISA法测定尿微量蛋白 ,包括白蛋白(ALB)、转铁蛋白(TF)、视黄醇结合蛋白(RBP)和N -乙酰 - β氨基葡萄糖苷酶(NAG)。结果伊那普利治疗组增高的尿ALB、TF、RBP和NAG均显著下降 ;ERPF显著增加 ;增加的滤过分数(FF)显著减低。而常规治疗组这些参数无显著变化。结论伊那普利具有改善DN患者的肾小球血流动力学 ,保护肾小球和肾小管功能的作用