自体血小板凝胶在糖尿病足溃疡治疗中的应用研究

目的 观察自体富血小板凝胶治疗糖尿病足溃疡（DFU）的疗效. 方法 72例DFU患者按照数字随机法分为两组.治疗组采用自体富血小板凝胶外敷;对照组采用常规疗法.比较两组DFU治愈率、好转率及愈合时间. 结果 两组间年龄、糖尿病病程、FPG、FIns、HbA1c、稳态模型评估胰岛素抵抗指数（HOMA-IR）、BMI、TG、TC、LDL-C、HDL-C、溃疡面积及溃疡体积比较差异均无统计学意义（P＞0.05）.两组Wagner Ⅰ级DFU治疗的疗效比较差异均无统计学意义（P＞0.05）.在WagnerⅡ、Ⅲ级DFU病例中,治疗组治愈率（66.7％、70.0％）、总有效率（94.4％、90.0％）均高于对照组（治愈率：26.3％、57.9％;总有效率：10.0％、30.0％）（P＜0.05）;治疗组Wagner Ⅰ～Ⅲ级DFU愈合时间均短于对照组[WagnerⅠ级：（14.75±1.82） vs （22.00±1.63）d;WagnerⅡ级：（27.12±2.15） vs （34.93±1.44）d;WagnerⅢ级：（41.89±3.22） vs （53.83±1.17）d] （P＜0.05）. 结论 自体富血小板凝胶可能具有促进DFU愈合的作用.     

DFU对骨肉瘤细胞增殖和侵袭能力的影响

目的 观察选择性环氧合酶-2抑制剂DFU对人骨肉瘤细胞株MG-63增殖和侵袭能力的影响及其对Ang-2基因表达的调控.方法 体外培养骨肉瘤细胞株MG-63,免疫荧光法检测Ang-2在MG-63细胞中的表达,应用噻唑蓝(MTT)比色法和形态学检测研究不同浓度DFU对骨肉瘤细胞株MG-63的生长抑制作用,Boyden小室体外侵袭实验检测其对骨肉瘤细胞侵袭能力的影响,RT-PCR法分析DFU对骨肉瘤细胞株MG-63中Ang-2基因表达的影响.结果 免疫荧光染色结果显示Ang-2在骨肉瘤细胞株MG-63中呈阳性染色,MTT法和形态学检测提示DFU可抑制骨肉瘤细胞株MG-63的增殖,并具有剂量依赖性,在DFU浓度为200 μmol/L时,对细胞生长有明显的抑制作用.Boyden小室体外侵袭实验显示DFU可降低骨肉瘤细胞的侵袭能力,在DFU浓度为200 μmol/L时,作用最显著.逆转录-聚合酶链反应(RT-PCR)分析显示经DFU作用后的骨肉瘤细胞株MG-63表达Ang-2较用药前明显下降.结论 DFU对骨肉瘤细胞株MG-63的增殖有抑制作用,其可能通过抑制Ang-2的表达,降低其侵袭能力.     

糖尿病周围神经病变和血管病变对糖尿病足溃疡的相互作用及相关性探讨

目的 探讨糖尿病足溃疡（DFU）发生的危险因素,分析糖尿病周围神经病变（DPN）和糖尿病血管病变（PAD）与DFU的相互作用.方法 选取T2DM患者278例,按其是否合并DFU分成糖尿病足溃疡组（DFU,102例）和糖尿病非足溃疡组（NDFU,176例）,回顾性分析两组生化特征和并发症情况.采用Logistic回归分析DFU发生的危险因素,并通过相对超额危险度比（RERI）,归因比（AP）和相互作用指数（S）评价DPN与PAD的相加相互作用.结果 与NDFU组比较,DFU组HbA1c和纤维蛋白原（FIB）水平,DR、DPN和PAD发生率均升高,血红蛋白（Hb）、血白蛋白（Alb）、TC和LDL-C降低（P＜0.05）.Logistic回归分析显示,DFU相关影响因素有：HbA1 c、DPN、PAD、Hb、Alb和FIB（OR分别为1.41、3.66、3.00、0.98、0.79和2.51）.DPN和PAD对DFU的相加相互作用指标RERI、AP和S分别为3.45（95％CI：1.22～8.56）、0.29（95％CI：0.02～0.58）和1.45（95％CI：1.03～4.96）.结论 血糖控制欠佳、合并DPN和PAD、营养不良及FIB代谢失衡是DFU发生的主要危险因素.DPN和PAD对DFU存在相加相互作用,同时患有DPN和PAD可增加DFU的患病风险.     

Establishing a multidisciplinary partnership integrating podiatric care into the Quebec public health-care system to improve diabetic foot outcomes: A retrospective cohort

Diabetic foot ulcers (DFUs) are one of the main complications of diabetes affecting many Canadians that need to be effectively managed. There is limited data concerning outcomes of Canadian patients with DFUs treated with a team approach in the public health system. Podiatrists are known to be key members of a multidisciplinary team approach to DFUs management, but in Quebec, Canada, they are only available in private practice. The aim of this study is to evaluate diabetic foot outcomes after integrating podiatric care into in-hospital wound care clinic settings. A 12-month retrospective cohort study was conducted into a new organization named the Pododiabetology University Center (PUC), which is described in this article. Healing rate and healing time were the outcomes measured. The analysis was performed by comparing data collected before and after the integration of the podiatrists. Preliminary results indicate that 73.2% of DFUs (n = 52) healed in an average of 19.8 weeks (time to wound closure). Previous data collected on 15 individuals before the integration of podiatric care showed a 27.3% of DFUs resolved in 44.6 weeks. The findings suggest that a patient with DFUs who receives wound care from a multidisciplinary team that includes a podiatrist can improve both their healing rate and time. An integrated multidisciplinary approach including podiatrists for patients affected by acute DFU is highly suggested in the literature in order to reduce the number of hospitalizations, amputations and financial burden, which are variables that could be evaluated in further studies.     

The highly selective cyclooxygenase-2 inhibitor DFU is neuroprotective when given several hours after transient cerebral ischemia in gerbils

Several studies suggest that cyclooxygenase-2 contributes to the delayed progression of ischemic brain damage. In this study we examined whether the highly selective cyclooxygenase-2 inhibitor DFU reduces neuronal damage when administered several hours after 5 min of transient forebrain ischemia in gerbils. The extent of ischemic injury was assessed behaviorally by measuring the increases in locomotor activity and by histopathological evaluation of the extent of CA1 hippocampal pyramidal cell injury 7 days after ischemia. DFU treatment (10 mg/kg, p.o.) significantly reduced hippocampal neuronal damage even if the treatment is delayed until 12 h after ischemia. These results suggest that selective cyclooxygenase-2 inhibitors may be a valuable therapeutic strategy for ischemic brain injury.     

Anti-apoptotic effect of HIV protease inhibitors via direct inhibition of calpain

Treatment with drugs designed to inhibit the HIV protease ameliorates immune functions in AIDS patients, reducing cell deletion by apoptosis even in the absence of inhibition of viral spread. This suggests that they interact with the intrinsic apoptotic signaling. We found that caspases, the main executioner of the apoptotic process, are not directly inhibited. In search for the mechanism responsible for their anti-apoptotic effect, we have found that indinavir and ritonavir are able to inhibit apoptosis only in those cell systems where apoptosis involves the activation of calpains. They directly inhibit a calpain-like activity expressed in lysates from apoptotic cells, to the same extent as commercially available calpain inhibitor 1. In in vitro assays with purified calpains, indinavir and ritonavir strongly inhibit m-calpain, and moderately mu-calpain. These results have great therapeutic implications, going beyond AIDS treatment, since many degenerative disorders involve abnormal calpain activation, indicating calpain as an ideal pharmacological target. Indinavir and ritonavir, potent m-calpain inhibitors, largely used since several years on humans without important negative side effects, may become powerful tools against those pathologies.     

A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory mediators in osteoarthritis

ITB (6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo[2',3':1,5]-1,2,4-triazolo[4,3-a]-1,3,5-benzotriazepine) is a novel inhibitor of cyclo-oxygenase-2 (COX-2) with antiinflammatory activity in animal models. In the present study, we investigated the effect of this compound on the production of catabolic or antiinflammatory mediators in osteoarthritis (OA) cartilage. In OA cartilage explants, ITB inhibited the production of prostaglandin E(2) (PGE(2)), tumour necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-13 (MMP-13) in a concentration-dependent manner, whereas nitrite was partially reduced. On the contrary, ITB increased the production of interleukin (IL)-10 and the expression of heme oxygenase-1 (HO-1). ITB inhibited the production of catabolic mediators at concentrations able to increase IL-10 and HO-1 in OA cartilage, suggesting that this compound may be useful in the prevention of cartilage degradation.