Silent cerebral infarction in patients with type 2 diabetic nephropathy. Effects of antiplatelet drug dilazep dihydrochloride

BACKGROUND: To determine whether diabetic nephropathy is a risk factor for silent cerebral infarction and whether antiplatelet drug dilazep dihydrochloride decreases the occurrence of silent cerebral infarction in type 2 diabetes patients with microalbuminuria. METHODS: Two hundred four type 2 diabetes patients (124 men, 80 women; age, median 56 years, range 42-74 years) and 60 healthy age-matched subjects (no diabetes, normal renal function) were recruited for brain magnetic resonance imaging. The diabetes patients included 40 without nephropathy (group A), 42 with microalbuminuria (20-200 microg/min) (group B), 44 with macroalbuminuria (>200 microg/min) and normal renal function (blood creatinine <132.7 micromol/L) (group C), 33 with chronic renal failure but not undergoing haemodialysis (blood creatinine >132.7 micromol/L; mean creatinine 335.9 micromol/L) (group D) and 45 undergoing haemodialysis (duration; median 4 years, range 3-6 years) (group E). RESULTS: Silent cerebral infarction was found in 20, 29, 34, 45, 53 and 8% of group A, B, C, D, E and control patients respectively. The incidence of silent cerebral infarction was increased with diabetic nephropathy. Thirty group B patients with no silent cerebral infarction were divided into two groups: (B1) 15 treated with dilazep dihydrochloride and (B2) 15 not treated with dilazep dihydrochloride. Treatment continued for 24 months. The incidence of silent cerebral infarction was significantly lower in the dilazep-treated patients (6.7%) than in the untreated patients (33.3%) (p < 0.01). CONCLUSIONS: These data suggest that diabetic renal dysfunction increases the risk of silent cerebral infarction and that dilazep dihydrochloride prevents its onset in early type 2 diabetic nephropathy patients.     

Sugar alcohols enhance calcium transport from rat small and large intestine epithelium in vitro

We compared the effect of a variety of sugar alcohols on calcium absorption from the rat small and large intestine in vitro. An Ussing chamber technique was used to determine the net transport of Ca across the epithelium isolated from the jejunum, ileum, cecum, and colon of rats. The concentration of Ca in the serosal and mucosal Tris buffer solution was 1.25 mM and 10 mM, respectively. The Ca concentration in the serosal medium was determined after incubation for 30 min and the net Ca absorption was evaluated. The addition of 0.1–200 mM erythritol, xylitol, sorbitol, maltitol, palatinit, or lactitol to the mucosal medium affected net Ca absorption in the intestinal preparations. Differences in Ca transport were observed between portions of the intestine, but not between sugar alcohols tested. We concluded that sugar alcohols directly affect the epithelial tissue and promote Ca absorption from the small and large intestine in vitro.     

Targeted delivery of adipose‐derived stem cells via acellular dermal matrix enhances wound repair in diabetic rats

Cell‐based therapeutic intervention has emerged as a new approach to accelerate wound closure. Adipose‐derived stem cells (ASCs), as a fascinating cell source, have received much attention in tissue repair and regeneration. In this study we evaluated the potential of acellular dermal matrix (ADM) scaffold serving as a carrier for the delivery of ASCs and investigated its therapeutic effects on wound healing. First, ASCs were isolated and characterized for multidifferentiation potential. ASCs–ADM grafts were then prepared, and ADM scaffold was shown to support the in vitro growth and proliferation of ASCs. Next, we analysed paracrine factors in conditioned medium and found that ASCs–ADM grafts secreted various cytokines, including VEGF, HGF, TGFβ and bFGF. Moreover, ASCs–ADM conditioned medium notably stimulated the migration and proliferation of fibroblasts. In vivo, we established an excisional wound model in diabetic rats which received phosphate‐buffered saline (PBS), ADM or ASCs–ADM grafts, respectively. Our results demonstrated that implantation of ASCs–ADM significantly enhanced tissue regeneration and increased epithelialization, resulting in accelerated wound closure. Immunofluorescence analysis further indicated that capillary density was evidently increased in the ASCs–ADM group compared with the control or ADM group. In addition, western blot analysis showed that ASCs–ADM significantly increased the expression of angiogenic factors, which was consistent with in vitro data. Taken together, our results suggest that targeted delivery of ASCs via ADM scaffold accelerate diabetic wound healing through a paracrine mechanism, with enhanced granulation tissue formation and increased re‐epithelialization and neovascularization. Copyright © 2012 John Wiley & Sons, Ltd.     

Functional recovery guided by an electrospun silk fibroin conduit after sciatic nerve injury in rats

The aim of this study was to evaluate the regenerative capacity of a newly developed nerve guidance conduit using electrospun silk fibroin (SFNC) implanted in a 10‐mm defect of the sciatic nerve in rats. After evaluating the physical properties and cytocompatibility of SFNC in vitro, rats were randomly allocated into three groups: defect only, autograft and SFNC. To compare motor function and abnormal sensation among groups, ankle stance angle (ASA) and severity of autotomy were observed for 10 weeks after injury. Immunostaining with axonal neurofilament (NF) and myelin basic protein (MBP) antibodies were performed to investigate regenerated nerve fibres inside SFNC. ASA increased significantly in the SFNC group at 1, 7 and 10 weeks after injury compared to the defect only group (p < 0.05). At one week, mean ASA of the SFNC group was significantly higher than that of the autograft group (p < 0.05). Onset and severity of autotomy decreased significantly in the SFNC group compared to other groups (p < 0.05). Autotomy in the SFNC group started at 4 weeks and maximally reached toe level. However, the defect only and autograft groups first showed autotomy at 2 and 1 weeks following injury, respectively, and then reached the sole level. Well myelinated nerve fibres stained with NF and MBP were found inside SFNC. In conclusion, SFNC could be helpful in restoring motor function and preventing abnormal sensations after nerve injury. Copyright © 2012 John Wiley & Sons, Ltd.     

下颌骨功能性偏斜对发育期大鼠髁突软骨胶原改建的影响

目的:观察下颌骨功能性偏斜对发育期大鼠髁突软骨内I型、II型以及III型胶原纤维分布及表达的影响。方法:取4周龄雄性SD大鼠40只,随机分为实验组(20只)和正常对照组(20只)。实验组佩戴自制的上切牙金属牙套引导下颌骨功能性右偏,对照组不佩戴任何装置,分别于实验1周、4周取得标本。HE染色及番红-O染色观察髁突软骨组织形态,苦味酸-天狼猩红偏振光染色以及免疫组化染色分别观察髁突软骨内I型、II型、III型胶原纤维含量以及分布表达情况,并进行相关半定量图像分析。结果:HE以及番红-O染色显示,实验1周后实验组牵张侧较正常组髁突软骨厚度显著增加,到4周后两组差异不显著;而实验组受压侧髁突软骨厚度4周后显著下降。天狼猩红染色及免疫组化染色结果显示,I型胶原主要表达在增殖层至成骨细胞层,II型胶原主要表达在软骨细胞层和肥大层。与正常组相比,1周及4周时实验组牵张侧软骨中区I型及II型胶原表达增强;受压侧软骨后区I型及II型胶原表达均显著减少。III型胶原主要表达在软骨纤维层至软骨细胞层,两组间无显著表达差异。结论:下颌骨功能性偏斜导致两侧髁突软骨发生了差异性生长改建,I型及II型胶原参与了改建中软骨内骨化过程。     

3种抗高血压药物治疗高血压伴糖尿病肾病的疗效比较

目的比较氨氯地平、贝那普利和厄贝沙坦单独和联合使用治疗高血压伴糖尿病肾病的疗效及安全性。方法将268例患者按使用的降压药物类型分为氨氯地平组、贝那普利组、厄贝沙坦组、氨氯地平+贝那普利组(氨贝组)、氨氯地平+厄贝沙坦组(氨厄组)。比较各组治疗前后血压、尿微量白蛋白水平及不良反应发生情况。结果治疗后,氨氯地平组、贝那普利组和厄贝沙坦组均能较好地控制血压,贝那普利组和厄贝沙坦组的尿蛋白也有显著下降,但贝那普利组的不良反应发生率相对较高。联合用药组的降压疗效、肾脏保护作用及不良反应发生率均显著优于单药各组。结论氨氯地平、贝那普利和厄贝沙坦均具有明显的降压效果,其中厄贝沙坦降压作用与氨氯地平相当,厄贝沙坦与氨氯地平联用后疗效增强,不良反应少,值得临床使用。     

血浆NGAL和血清CysC在糖尿病肾病早期诊断中的临床价值

目的探讨2型糖尿病(T2DM)患者血浆中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和血清胱抑素C(CysC)的改变及其对糖尿病肾病(DN)的诊断价值。方法选择T2DM患者58例,根据尿微量清蛋白/尿肌酐比值(ACR)分为正常清蛋白尿组(ACR30mg/mmol)和高清蛋白尿组(ACR≥30mg/mmol);另选择40例健康体检者作为对照,测定其血浆NGAL、血清CysC、肾功能、血糖及血脂等水平。结果血浆NGAL和血清CysC水平在对照组、正常清蛋白尿组和高清蛋白尿组中呈逐步增高趋势,差异有统计学意义(P0.05);Pearson相关分析,血浆NGAL与血清CysC、肌酐(CREA)呈正相关(相关系数分别为0.58、0.43、0.66,P0.05);血清CysC与CREA、BUN亦呈正相关(相关系数分别为0.73、0.58,P0.05)。结论 DN患者血浆NGAL与血清CysC水平显著升高,二者呈明显正相关,均与肾损伤程度有关,二者可以作为DN早期无创性诊断指标。     

过氧化氢在门静脉高压症大鼠侧支循环建立中的作用

目的探讨过氧化氢(H2O2)对胆总管结扎诱导的肝硬化门静脉高压症(PHT)大鼠门体侧支循环形成的影响机制。方法胆总管结扎诱导的肝硬化PHT大鼠和假手术组大鼠每天一次腹腔分别注射浓度为10 000 U/kg聚乙二醇过氧化氢酶(PEG-catalase)或生理盐水,共8 d。测定大鼠肠系膜组织H2O2含量,利用彩色微球技术测定门体分流率及相应血流动力学指标。检测大鼠肠系膜组织中血管内皮生长因子(VEGF)及VEGF受体-2(VEGFR-2)蛋白含量。结果肝硬化PHT组大鼠门静脉压力、肠系膜组织H2O2水平及门体分流程度明显高于对照组大鼠。PEG-catalase处理使PHT大鼠门体分流率明显下降,VEGF及VEGFR-2蛋白水平明显降低,内脏高血流动力循环得到明显改善。结论 H2O2在肝硬化PHT内脏高动力循环形成过程中发挥重要作用,这和VEGF介导的血管增生有关。     

Sphingomyelinase-Like Phosphodiesterase 3b Expression Levels Determine Podocyte Injury Phenotypes in Glomerular Disease

Diabetic kidney disease (DKD) is the most common cause of ESRD in the United States. Podocyte injury is an important feature of DKD that is likely to be caused by circulating factors other than glucose. Soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor found to be elevated in the serum of patients with FSGS and causes podocyte αVβ₃ integrin-dependent migration in vitro. Furthermore, αVβ₃ integrin activation occurs in association with decreased podocyte-specific expression of acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3b) in kidney biopsy specimens from patients with FSGS. However, whether suPAR-dependent αVβ₃ integrin activation occurs in diseases other than FSGS and whether there is a direct link between circulating suPAR levels and SMPDL3b expression in podocytes remain to be established. Our data indicate that serum suPAR levels are also elevated in patients with DKD. However, unlike in FSGS, SMPDL3b expression was increased in glomeruli from patients with DKD and DKD sera-treated human podocytes, where it prevented αVβ₃ integrin activation by its interaction with suPAR and led to increased RhoA activity, rendering podocytes more susceptible to apoptosis. In vivo, inhibition of acid sphingomyelinase reduced proteinuria in experimental DKD but not FSGS, indicating that SMPDL3b expression levels determined the podocyte injury phenotype. These observations suggest that SMPDL3b may be an important modulator of podocyte function by shifting suPAR-mediated podocyte injury from a migratory phenotype to an apoptotic phenotype and that it represents a novel therapeutic glomerular disease target.