ACE activity is modulated by kinin B2 receptor

Angiotensin-converting enzyme (ACE) is an ectoprotein able to modulate the activity of a plethora of compounds, among them angiotensin I and bradykinin. Despite several decades of research, new aspects of the mechanism of action of ACE have been elucidated, expanding our understanding of its role not only in cardiovascular regulation but also in different areas. Recent findings have ascribed an important role for ACE/kinin B(2) receptor heterodimerization in the pharmacological properties of the receptor. In this work, we tested the hypothesis that this interaction also affects ACE enzymatic activity. ACE catalytic activity was analyzed in Chinese hamster ovary cell monolayers coexpressing the somatic form of the enzyme and the receptor coding region using as substrate the fluorescence resonance energy transfer peptide Abz-FRK(Dnp)P-OH. Results show that the coexpression of the kinin B(2) receptor leads to an augmentation in ACE activity. In addition, this effect could be blocked by the B(2) receptor antagonist icatibant. The hypothesis was also tested in endothelial cells, a more physiological system, where both proteins are naturally expressed. Endothelial cells from genetically ablated kinin B(2) receptor mice showed a decreased ACE activity when compared with wild-type mice cells. In summary, this is the first report showing that the ACE/kinin B(2) receptor interaction modulates ACE activity. Taking into account the interplay among ACE, ACE inhibitors, and kinin receptors, we believe that these results will shed new light into the arena of the controversial search for the mechanism controlling these interactions.     

Expression of angiotensin I-converting enzymes and bradykinin B2 receptors in mouse inner medullary-collecting duct cells

We described in mouse inner medullary-collecting duct cells (mIMCD-3) the somatic and the N-domain ACE synthesis and its interaction with the kallikrein-kinin system co-localized in the same cells. We purified two ACE forms from culture medium, M1 (130 kDa) and M2 (N-domain, 60 kDa), and cellular lysate, C1 (130 kDa) and C2 (N-domain, 60 kDa). Captopril and enalaprilat inhibited the purified enzymes. The immunofluorescence studies indicated that ACE is present in the membrane, cytoplasm and in the cell nucleus. Kinin B1 and B2 receptors were detected by immunofluorescence and showed to be activated by BK and DesR9 BK, increasing the acidification rate which was enhanced in the presence of enalaprilat. The presence of secreted and intracellular ACE in mIMCD-3 confirmed the hypothesis previously proposed by our group for a new site of ACE secretion in the collecting duct.     

Effect of angiotensin converting enzyme inhibitor enalapril on body weight and composition in young rats

Obesity is considered a worldwide public health problem showing an increased prevalence in developing countries, with urgent need for new and more efficient drugs and therapies. Enalapril, an angiotensin-I converting enzyme inhibitor (ACEi), is classically used in anti-hypertensive therapies, however, earlier publications have shown that this drug could also have significant impact on body weight in rats as well as in humans, besides reducing blood pressure. The effect of this drug in the white adipose tissue has been neglected for long time, even considering that most components of the renin-angiotensin and kallikrein-kinin system are expressed in this tissue. Furthermore, the adipose tissue is considered today as one of the most important sites for endocrine/inflammatory regulation of appetite and energy output and AngII has been linked to the metabolism in this tissue. Therefore, we analyzed the influence of chronic enalapril treatment in normotensive rats at earlier ages, evaluating body weight, energy homeostasis, lipid profile and serum levels of the hormones leptin and insulin, in the presence of a standard or a palatable hyperlipidic diet regimen for one month. Our results show that enalapril treatment is able to reduce body fat on both diets, without alteration in serum lipid profile. Furthermore, animals receiving enalapril showed reduction in food intake, leptin level and energy intake. In summary, these findings show for the first time that the ACEi enalapril reduces body fat in young normotensive rats and highlights a novel target to treat obesity and associated diseases.     

Allocation of health care resources in the neonatal and perinatal area �CCPS Symposium 1996

There have been publically expressed concerns about the costs and allocation of neonatal and perinatal health care resources in Canada and elsewhere for the past 15 years. This paper reports information from a symposium held during the 1996 Canadian Paediatric Society (CPS) annual meeting sponsored by the CPS Section on Perinatal Medicine. Experts in perinatal epidemiology, health care economics, public policy and finance, and consumer perspectives on the outcomes of neonatal and perinatal intensive care explored the following questions: How should the need for health care resources in the neonatal and perinatal area be objectively determined? When there are competing needs between the maternal-newborn area and other areas, how should these be rationalized? What evidence should be used (or should be available) to support the present use of resources? What evidence should be available (or is needed) to change or introduce new uses of resources? The conclusions indicated that there are no generally accepted methods to determine the allocation of health care resources but that considerations need to include population characteristics, desired outcomes, achievable results, values, ethics, legalities, cost-benefit analyses and political objectives. Information from families and adolescents who required the use of high technology and/or high cost programs will contribute individual, family and societal values that complement cost-efficacy analyses.     

含栅栏状肉芽肿样小体(巨菊形团)的低度恶性纤维肉瘤--报道1例转移病例

自Ｌａｎｅ等 1997年详细报道了ＨＳＣＴＧＲ后 ,一直没有该肿瘤转移潜能的证据 ,该文报道 1例 2 8岁女性右上臂三角肌内ＨＳＣＴＧＲ(8 7ｃｍ× 5 5ｃｍ× 4 0ｃｍ大小 ) ,术后 4年右肺转移 ,并于 6年后行肺部手术 ,取出 0 6ｃｍ～ 1 2ｃｍ大小转移性结节 3枚。肿瘤从大体形态到超微结构及免疫组化表现与前文相似。本文总结出该病光镜下由梭形细胞为主 ,构成 3种图像 :①纤维瘤样区 ,为肿瘤的主要成分 ,无核分裂象 ;②细胞区 ,细胞丰富 ,核浓染 ,胶原减少 ,罕见核分裂象 ;③特征性病变 (有诊断意义 ) ,即由丰富细胞核环绕的玻璃样变小体 …     

Patel S,Turner PR,Stubberfield C,Barry E,Rohlff CR,Stamps A,McKenzie E,Young K,Tyson K,Terrett J,Box G,Eccles S,Page MJ. Hyaluronidase gene profiling and role of HYAL‐1 overexpression in an orthotopic model of prostate cancer. International Journal of Cancer 2002;97(4): 416–424.

The original article to which this Erratum refers was published in International Journal of Cancer; 2002; 97(4) 416–422.     

Effect of intravenous immunoglobulin on inhibiting peripheral blood lymphocyte apoptosis in acute Kawasaki disease

This study aimed to explore the therapeutic mechanism of intravenous immunoglobulin (IVIG) for Kawasaki disease (KD). Peripheral blood lymphocytes (PBLs) obtained from 26 children with KD and 20 age-matched healthy children were stimulated with anti-CD3 monoclonal antibody (mAb), and the percentage of apoptotic cells and DNA fragmentation were assayed at 0, 12, 24, 48 and 72 h in vitro. The patients were divided into two groups: one treated with aspirin combined with IVIG (n = 16) and one treated with aspirin alone (n = 10). PBLs were stimulated by phytohaemagglutinin to evaluate the lymphocyte proliferative response. Compared with normal controls, the apoptotic cell percentage and the DNA fragmentation were markedly decreased (p < 0.001) and delayed in PBLs from KD patients. After IVIG treatment, the decreased percentage of apoptotic cell and delayed DNA fragmentation were restored to the state of the normal controls, accompanied by a fast clinical remission compared with the aspirin-alone group. The lymphocyte proliferative response was also decreased 3-5 d after IVIG therapy (p < 0.001). Conclusion: The results suggest that decreased PBL apoptosis may be involved in the pathogenesis of KD. The therapeutic mechanism of IVIG in KD may be partially due to the reversal of the inhibited lymphocyte apoptosis, and may have implications for other autoimmune diseases with inefficient lymphocyte apoptosis.     

Refrigerated storage of lyophilized and rehydrated, lyophilized human red cells

Human red cells (RBCs) were collected in CPDA-1 and then freeze-dried in lyoprotective solution. The lyophilized RBCs were then stored at -20 degrees C for 7 days. At the end of the storage period, the lyophilized RBCs were rehydrated and washed in dextrose saline. The washed, reconstituted, lyophilized RBCs were resuspended in final wash solutions of ADSOL, CPDA-1, or a special additive solution containing glucose, citrate, phosphate, adenine, and mannitol, and then they were stored at 4 degrees C for an additional 7 days. The main purpose of this study was to determine whether human RBCs can be lyophilized in such a manner that normal metabolic, rheologic, and cellular properties are maintained during rehydration and subsequent storage in standard blood bank preservative solutions. Our results show that reconstituted, lyophilized RBCs maintained levels of ATP, 2,3 DPG, lactate, and cellular properties that are equal to or better than those in control nonlyophilized RBCs stored for a comparable period in CPDA-1. Reconstituted, lyophilized RBCs stored at 4 degrees C after rehydration also show better maintenance of ATP, 2,3 DPG, and lactate than do control RBCs stored in the same preservative solutions for comparable periods.     

经皮椎体注入骨水泥治疗老年脊椎骨质疏松压缩性骨折

目的:观察经皮椎体内注入骨水泥(聚甲基丙烯酸甲酯)治疗脊椎骨质疏松压缩性骨折的疗效。方法:自2005-06/2006-06吉林大学中日联谊医院骨科及大庆龙南医院骨科对35例40个椎体的骨质疏松压缩性骨折患者使用经皮椎体内注射骨水泥,行椎体成形术。成形材料:美国KYPHON公司生产的骨水泥,生产准许号:(GB/T19001-2000和YY/T0287-1996)。结果:35例患者均参加随访6个月。术后均未出现骨水泥外漏、脊髓或马尾神经损伤等并发症。35例患者中5例出现穿刺部位局部疼痛,服用镇痛药物后均缓解。疼痛完全消失25例,占71.4%;明显缓解8例,占22.6%;轻度缓解2例,占6.0%;无缓解0例。15例患者在术后72h内均能下床活动。术后未再发生压缩性骨折及疼痛。结论:经皮椎体注入骨水泥可以有效改善椎体骨质疏松压缩性骨折患者疼痛症状,随访6个月未出现充填剂不良性宿主反应,临床疗效较好。