CD 13/APN expression in peripheral blood lymphocytes and skin lesions in patients with advanced psoriasis vulgaris

Objective： To observe the expression of CD13/APN in peripheral blood lymphocytes and skin lesions of patients with advanced psoriasis vulgaris, and discuss its effect on the pathogenesis of psoriasis. Methods： CD 13 expression in peripheral blood lymphocytes and skin lesions was detected by flow cytometry and imrnunohistochemical technique, respectively. Results were compared with those of healthy controls. Results： CD 13 expression was significantly higher in peripheral blood lymphocytes of patients with advanced psoriasis vulgaris than in that of healthy controls, and in skin lesions than in healthy skin tissues. The expression was mainly in the suprabasal layers of skin lesions, and positively correlated to PASI （R 0.78029）. Conclusion： The significantly higher expression of CD13 in peripheral blood lymphocytes and skin lesions of the patients with advanced psoriasis vulgaris probably is related to immunological abnormality, blood vessel abnormality and proliferation of keratinocyte in the pathogenic course of psoriasis. It may be a novel and effective way to treat psoriasis with specific CD13 inhibitors.     

The role of the brain renin–angiotensin system in hypertension: Implications for new treatment

Hypertension affects 26% of adults and is in constant progress related to increased incidence of obesity and diabetes. One-third of hypertensive patients may be successfully treated with one antihypertensive agent, one-third may require two agents and in the remaining patients will need three agents for effective blood pressure (BP) control. The development of new classes of antihypertensive agents with different mechanisms of action therefore remains an important goal. Brain renin–angiotensin system (RAS) hyperactivity has been implicated in hypertension development and maintenance in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III have similar affinities for type 1 (AT1) and type 2 (AT2) Ang II receptors. Following intracerebroventricular (i.c.v.) injection, Ang II and Ang III similarly increase arginine–vasopressin (AVP) release and BP. Blocking the brain RAS may be advantageous as it simultaneously (1) decreases sympathetic tone and consequently vascular resistance, (2) decreases AVP release, reducing blood volume and vascular resistance and (3) blocks angiotensin-induced baroreflex inhibition, decreasing both vascular resistance and cardiac output. However, as Ang II is converted to Ang III in vivo, the exact nature of the active peptide is not precisely determined. We summarize here the main findings identifying AngIII as one of the major effector peptides of the brain RAS in the control of AVP release and BP. Brain AngIII exerts a tonic stimulatory effect on BP in hypertensive rats, identifying brain aminopeptidase A (APA), the enzyme generating brain Ang III, as a potentially candidate target for hypertension treatment. This has led to the development of potent orally active APA inhibitors, such as RB150 — the prototype of a new class of centrally acting antihypertensive agents.     

Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo

Aminopeptidase N (APN/CD13), a 150-kDa metalloproteinase, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression in several human malignancies. In the current study, we investigated the role of APN/CD13 in paclitaxel (PAC)-resistance of ovarian carcinoma (OVCA) cells. We first examined the correlation between APN/CD13 expression and IC50 values of PAC in a variety of OVCA cell lines. Next we investigated whether suppression of APN/CD13 using bestatin, an inhibitor of APN/CD13 activity or the siRNA technique influenced PAC-sensitivity in ES-2 cells, which highly express APN/CD13. Moreover, we investigated the effect of bestatin on peritoneal metastasis using nude mice. We found a negative correlation between APN/CD13 expression and chemosensitivity to PAC in various carcinoma cell lines. Subsequently, we found a significant increase in PAC-sensitivity of APN/CD13 expressing OVCA cells by suppression of this enzyme, using the addition of bestatin or the siRNA technique. Furthermore, in a peritoneal metastasis model using nude mice, combination treatment with PAC and bestatin caused a synergistic increase of survival time compared with PAC alone treatment. (mean survival time: 37.7 +/- 7.0 s and 27.1 +/- 6.6 days, respectively). The present findings showed that APN/CD13 may be involved in decreased sensitivity to PAC in OVCA cells and that the mechanism of this effect involves its enzyme activity at least in part. APN/CD13 may be a therapeutic target for the treatment of OVCA in combination with chemotherapy.     

The effect of Andrographis Paniculata Nees (APN) in alleviating the myocardial ischemic reperfusion injury

Summary In experimental dogs, the effect of APN in alleviating the ischemiareperfusion injury was prominent. Compared with the sustained ischemia group, superoxide dismutase (SOD) in the ischemic region of myocardial tissue in the ischemiareperfusion group was significantly decreased and malondialdehyde (MDA) markedly increased: Ca²⁺ in myocardial cells was increased; and ultrastructural changes of myocardial tissues were severe. In the APN-pretreated ischemia-reperfusion group, on the contrary, all the above parameters showed reversely, i,e., SOD increased, MDA and intracellular Ca²⁺ decreased, the ultrastructure changes were less distorted.     

脂联素在高血压致炎症和心肌纤维化中的作用

目的探讨脂联素在高血压致炎症和心肌纤维化中的作用。方法选取纯合脂联素敲除鼠12只(APN-/-)和野生型小鼠(WT)12只,采用微量泵持续灌注血管紧张素Ⅱ(AngⅡ)[1500 ng/(kg·min),7天]建立高血压模型,对照组给予乙酸溶液微量泵灌注,连续灌注7天,实验随机分成4组,每组6只:野生型小鼠对照组(WT),野生型小鼠+血管紧张素Ⅱ组(WT+AngⅡ),APN-/-对照组(APN-/-),APN-/-+血管紧张素Ⅱ组(APN-/-+AngⅡ),采用小鼠无创血压计测定小鼠尾动脉血压,运用ELISA法检测血清中s ICAM-1、s VCAM-1、v WF的含量,心肌组织Masson染色观察心脏纤维化,α-SMA免疫组化法观察肌成纤维细胞的形成,HE染色观察炎症细胞浸润,Western blot法测定TGF-β、TNF-α蛋白表达。结果与WT组相比,WT+AngⅡ组第二天血压开始升高,连续监测7天,血压均明显升高(P0.05),造模成功。与WT+AngⅡ组相比,APN-/-+AngⅡ组血压显著升高(P0.05),炎症细胞浸润明显增多(P0.05),s ICAM-1、s VCAM-1、v WF含量明显增加,TGF-β、TNF-α表达显著上调,α-SMA+肌成纤维细胞数量增多(P0.05)。结论在高血压致心脏纤维化过程中,脂联素可能有保护血管内皮损伤,抑制炎症反应,进而抑制心脏纤维化。     

“优质护理服务示范病房”的实施与效果

根据2010年1月卫生部下发的“2010年‘优质护理服务示范病房’活动方案”,我区于3月份开始作为试点病区,对护士的工作模式进行了调整,实施了APN连续性护理排班,采用个人与小组包干相结合,实行护士固定分管床位,落实床边工作制、床边记录制等,由分管床位的责任护士对所管病人实施连续整体护理。试行后,护理服务质量与患者满意度大大提高,同时也提高了工作效率,效果良好。     

电针腹部腧穴对单纯性肥胖患者血脂和血清脂联素的影响

目的:观察电针腹部腧穴对单纯性肥胖患者血脂和血清脂联素含量的影响。方法:106例病例随机分为两组,治疗组54例采用电针腹部腧穴疗法,对照组52例采用电针传统体穴疗法,测量两组患者治疗前后的身高、体重,计算体重指数(BMI);测量腰围、臀围,计算腰臀比值;检测血脂、血清脂联素含量。结果:与对照组比较,治疗组腰围、腰臀比降低,总胆固醇、甘油三酯显著下降(P0.05,P0.01),高密度脂蛋白胆固醇明显升高(P0.05)。两组治疗后血清脂联素均明显升高,但治疗组上升尤为明显。结论:电针腹部腧穴较电针传统体穴治疗单纯性肥胖患者有显著优势,适于临床推广应用。     

原发性高血压肾病患者血浆leptin和血清APN及尿mAlb检测的临床意义

目的:探讨了原发性高血压肾病患者血浆瘦素(leptin)和血清脂联素(APN)及尿微量白蛋白(mAlb)水平的变化及意义。方法:应用放射免疫分析、酶联免疫法和化学法对38例原发性高血压肾病患者血浆leptin和血清APN及尿mAlb进行检测,并与35名正常健康人作比较。结果:原发性高血压肾病患者血浆leptin和尿mAlb水平非常显著地高于正常人组(P<0.01)。而血清APN水平则显著地低于正常人组(P<0.01)。血清APN水平与leptin、尿mAlb水平呈显著的负相关(r=-0.4084、-0.5132,P<0.01)。结论:检测原发性高血压肾病患者血浆leptin和血清APN及尿mAlb水平的变化对了解病情、探讨其发病机理、预防和指导用药均有重要的临床价值。     

凉血解毒、活血化瘀法治疗少儿紫癜性肾炎性血尿30例临床观察

目的：观察凉血解毒活血化瘀法治疗小儿紫癜性肾炎性血尿临床疗效。方法：将60例小儿APN急性期血尿患者随机分为中医治疗组(治疗组)30例与西医常规治疗组(对照组)30例,分别给予中医治疗及西医常规治疗,4周后观察血尿改变情况。结果：治疗组总有效率90.00％,对照组总有效率73.33％,两组总体疗效比较,差异具有统计学意义(P<0.05)。结论：凉血解毒活血化瘀法能够有效治疗APN。     

Neoadjuvant chemotherapy modifies serum angiotensinase activities in women with breast cancer

Purpose

The aim of this study was to investigate the putative changes in serum angiotensinase activities (aminopeptidase N, APN; aminopeptidase B, APB; aminopeptidase A, APA; aspartyl aminopeptidase, ASAP) involved in the renin–angiotensin system (RAS) in women with breast cancer treated or not with a neoadjuvant therapy of paclitaxel and anthracycline and in healthy women volunteers.

Methods

We fluorometrically analysed serum APN, APB, APA and ASAP activities using their corresponding aminoacyl-β-naphthylamides as substrates in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline.

Results

When compared with healthy controls, women with breast cancer not treated with neoadjuvant chemotherapy, showed a decrease in angiotensinase activity, which support the putative increase of angiotensin II (Ang II) levels, indicating that the tumour process would favour the development of the disease. Also, an increase in APN and APB activities was observed, which support a role for angiotensin IV (Ang IV). In women treated with a neoadjuvant therapy, we described an increase in ASAP and APA activities, supporting the idea that this treatment increases Ang II catabolism. The resulting decrease in Ang II level could lead to an inhibition of the tumour growth.

Conclusion

Present results show changes in serum angiotensinase activities in women with breast cancer and in women with breast cancer treated with a neoadjuvant therapy of paclitaxel and anthracycline. Therefore, considerable attention should be focused on the development of RAS blockade therapy as a new strategy for breast cancer treatment.