40例糖尿病足细菌感染临床分析与护理对策

糖尿病足（DF）是糖尿病患者由于合并神经病变及各种不同程度末梢血管病变而导致下肢感染、溃疡形成和（或）深部组织的破坏。DF作为糖尿病的慢性并发症之一,具有很强的致残性和致死性,细菌感染是促使DF病情加重的一个重要诱因。因此,如何控制糖尿病足细菌感染已成为临床治疗与护理中急需共同解决的难题。笔者通过对糖尿病足细菌感染的临床分析,有的放矢进行诊治和护理,及时缓和和减轻病人痛苦,提高其治愈率。     

干细胞对糖尿病足的治疗研究进展

糖尿病足患者大部分伴有下肢缺血,而缺血是导致糖尿病足溃疡不愈和截肢的最主要原因。传统的治疗方法并不能很好的降低其截肢率,糖尿病足溃疡已经成为世界范围内临床医学的难题。因此,深入研究糖尿病足的发病机制及下肢血管病变特点,探索新的治疗策略及推广应用,具有重要的社会意义。干细胞已经广泛应用于多个领域,其分泌细胞因子促进新生血管生成等机制为治疗糖尿病足提供了可能。本文就近年来干细胞治疗糖尿病足的研究进展作一综述。     

细胞因子水平与糖尿病足的相关性研究

糖尿病足(Diabetic Foot,DF)是下肢远端神经异常和不同程度的周围血管病变相关的足部感染、溃疡和(或)深层组织破坏,是糖尿病常见而又严重的并发症之一。目前临床上提倡预防为主、防治结合方针。大量国内外研究已证实糖尿病足患者细胞因子水平存在明显变化,如胰岛素样生长因子、C反应蛋白、脂联素、抵抗素、白细胞介素-6、集落刺激因子等,且这些细胞因子的变化可作为DF发生的预防以及评估预后的监测指标。促红细胞生成素作为重要的集落刺激因子,具有抗凋亡、抗炎、抗氧化、促进血管生长等作用,目前已用于多种临床疾病的治疗,且对糖尿病并发症具有良好的疗效。本文通过对细胞因子水平与糖尿病足的相关性研究进展作一综述,旨在探索细胞因子用于糖尿病足治疗的可行性及有效性,为改善糖尿病足患者的生活质量提供新的治疗方案。     

糖尿病足围手术期的护理

糖尿病足于1956年由Oakley首先提出。1972年Callerall再次明确其定义：糖尿病足是糖尿病患者因神经病变而失去感觉或因缺血而失去活动能力、合并感染所致的足部疾病。随着糖尿病发病率的增加,糖尿病足群体也在逐渐扩大,甚至达到糖尿病患者的49．5％,因此而被截肢者占到非外伤性截肢的50％。且一侧肢体做了截肢,50％的患者另一侧肢体5年内也不得不截肢。     

糖尿病的细胞治疗

胰岛素产生细胞的缺陷或缺乏导致的Ⅰ型糖尿病是影响人类健康的重大疾病之一。最近细胞移植和组织工程的研究进展,使得糖尿病的细胞替代治疗成为可能,即通过胰岛素产生细胞的移植治疗Ⅰ型糖尿病和某些Ⅱ型糖尿病。但是由于供体细胞缺乏的限制,使得糖尿病的细胞治疗难以广泛开展。胰腺干细胞将成为胰岛素产生细胞的潜在来源。就Ⅰ型糖尿病的发病机制和治疗中存在的问题、胰腺干细胞的分离和分化、胰岛移植治疗糖尿病的局限性和干细胞治疗的必要性、糖尿病细胞治疗的探讨作如下介绍。     

中西医结合治疗糖尿病足78例

糖尿病足（DF）是糖尿病的严重并发症,临床表现为肢体缺血、神经功能障碍和感染。2001-2004年我科对78例DF患者进行X线、彩超、CT检查明确肢体动脉硬化、迂曲、狭窄、闭塞改变者采用中西医结合治疗,取得了满意疗效。现报道如下。     

糖尿病足治疗新进展

糖尿病足溃烂是糖尿病的常见慢性并发症,以高发生率、高致残率、经济负担重,治疗时间长及高死亡率严重影响病人的生活质量甚至威胁生命,我国糖尿病协会于2010年11月14公布我国糖尿病的患病者已达9240万,除此之外糖尿病前期患者已达1.482亿。而在糖尿病患者中糖尿病足的发病率达到1.7%-11.9%;糖尿病患者中有15%的患者一生中有患糖尿病足的倾向,因此对于糖尿病足的治疗显得尤为重要,本文从糖尿病足的病因、机制,微环境变化着手,重点阐述糖尿病足传统的中西医疗法及目前的手术、介入及干细胞治疗方法的近况,旨在探讨各种方法的优点和不足及可开拓的空间,为进一步治疗糖尿病足提供一定的理论依据,为糖尿病足新方法的研究提供一些新的思维方式。     

脐带间充质干细胞移植治疗50例缺血性下肢血管病的临床研究

目的:观察脐带间充质干细胞移植治疗缺血性下肢血管病的临床疗效并观察近期临床效果.方法:50例自愿接收脐带间充质干细胞移植患者中糖尿病足35例,动脉硬化闭塞症10例,血栓性闭塞性脉管炎5例.全部患者均给予静脉输注及局部种植脐带间充质干细胞.术后第7天至6个月定期观察各项指标的变化.结果:治疗1月后,47例(94％)疼痛有不同程度的缓解,46例(92％)患肢冷感明显缓解,45例(90％)患者行走距离延长.6月后30例糖尿病足患者溃疡或足部坏疽痊愈.结论:脐带间充质干细胞移植治疗缺血性下肢血管病是一种简便、安全、有效的治疗方法,其治疗的近期疗效显著,使很多患者免除截肢或降低截肢平面,明显改善患者生活质量.     

干细胞治疗糖尿病研究:进展、挑战和发展前景

糖尿病是一类伴随严重肾衰竭、失明、糖尿病足、高血压和心血管疾病等并发症的代谢性疾病。目前,临床治疗手段均无法实现糖尿病治愈。干细胞可以对失衡的免疫系统进行调节,还能分化为胰岛样分泌细胞,从而为糖尿病治愈提供了可能。本文着重从胰岛样细胞分化、免疫调节和细胞包埋技术入手,总结了干细胞研究和治疗技术在糖尿病中的进展和存在的问题,并对未来的发展进行了展望。     

我国干细胞治疗糖尿病的基础与临床研究

胰岛β细胞功能衰竭和胰岛素抵抗是导致糖尿病发生发展的主要机制,目前的抗糖尿病药物没有针对糖尿病发病的关键环节,只能解除或缓解症状,延缓疾病进展,不能从根本上治愈该疾病.干细胞通过促进胰岛β细胞原位再生,提高胰岛β细胞自噬能力、调节胰岛巨噬细胞功能修复受损的胰岛β细胞以改善胰岛β细胞功能;通过多种途径活化骨骼肌、脂肪和肝脏IRS(1)-AKT-GLUT4信号通路改善外周组织胰岛素抵抗,为糖尿病的精准治疗提供了新的方向.我国研究者针对不同来源的干细胞使用不同输注方式治疗1型糖尿病和2型糖尿病开展了系列研究,取得了良好的临床疗效,且未发生严重不良反应,为干细胞治疗糖尿病的临床应用奠定了基础.     

Effects of umbilical cord blood stem cells on healing factors for diabetic foot injuries

The use of stem or progenitor cells from bone marrow, or peripheral or umbilical cord blood is becoming more common for treatment of diabetic foot problems. These cells promote neovascularization by angiogenic factors and they promote epithelium formation by stimulating cell replication and migration under certain pathological conditions. We investigated the role of CD34 + stem cells from human umbilical cord blood in wound healing using a rat model. Rats were randomly divided into a control group and two groups with diabetes induced by a single dose of 55 mg/kg intraperitoneal streptozocin. Scarred areas 5 mm in diameter were created on the feet of all rats. The diabetic rats constituted the diabetes control group and a diabetes + stem cell group with local injection into the wound site of 0.5 × 106 CD34 + stem cells from human umbilical cord blood. The newly formed skin in the foot wounds following CD34 + stem cell treatment showed significantly improvement by immunohistochemistry and TUNEL staining, and were closer to the wound healing of the control group than the untreated diabetic animals. The increase in FGF expression that accompanied the local injection of CD34 + stem cells indicates that FGF stimulation helped prevent apoptosis. Our findings suggest a promising new treatment approach to diabetic wound healing.     

In vitro glycation of a tissue-engineered wound healing model to mimic diabetic ulcers

Diabetic foot ulcers are a major complication of diabetes that occurs following minor trauma. Diabetes-induced hyperglycemia is a leading factor inducing ulcer formation and manifests notably through the accumulation of advanced glycation end-products (AGEs) such as N-carboxymethyl-lysin. AGEs have a negative impact on angiogenesis, innervation, and reepithelialization causing minor wounds to evolve into chronic ulcers which increases the risks of lower limb amputation. However, the impact of AGEs on wound healing is difficult to model (both in vitro on cells, and in vivo in animals) because it involves a long-term toxic effect. We have developed a tissue-engineered wound healing model made of human keratinocytes, fibroblasts, and endothelial cells cultured in a collagen sponge biomaterial. To mimic the deleterious effects induced by glycation on skin wound healing, the model was treated with 300 µM of glyoxal for 15 days to promote AGEs formation. Glyoxal treatment induced carboxymethyl-lysin accumulation and delayed wound closure in the skin mimicking diabetic ulcers. Moreover, this effect was reversed by the addition of aminoguanidine, an inhibitor of AGEs formation. This in vitro diabetic wound healing model could be a great tool for the screening of new molecules to improve the treatment of diabetic ulcers by preventing glycation.     

Localization of Human Mesenchymal Stem Cells from Umbilical Cord Blood and Their Role in Repair of Diabetic Foot Ulcers in Rats

The aim of this study is to explore the localization of human mesenchymal stem cells from umbilical cord matrix (hMSCs-UC) and the role of these cells in the repair of foot ulcerate tissue in diabetic foot ulcers in rats. A diabetic rat model was established by administering Streptozotocin. Diabetic foot ulceration was defined as non-healing or delayed-healing of empyrosis on the dorsal hind foot after 14 weeks. hMSCs-UC were delivered through the left femoral artery. We evaluated the localization of hMSCs-UC and their role in tissue repair in diabetic foot ulcers by histological analysis, PCR, and immunohistochemical staining. A model for diabetes was established in 54 out of 60 rats (90% success rate) and 27 of these rats were treated with hMSCs-UC. The area of ulceration was significantly and progressively reduced at 7 and 14 days following treatment with hMSCs-UC. This gross observation was strongly supported by the histological changes, including newly developed blood vessels and proliferation of inflammatory cells at 3 days post-treatment, significant increase in granulation tissue at 7 days post-treatment and squamous epithelium or stratified squamous epithelium at 14 days post-treatment. Importantly, human leukocyte antigen type-I (HLA-1) was confirmed in ulcerated tissue by RT-PCR. The expression of cytokeratin 19 was significantly increased in diabetic model rats, with no detectable change in cytokeratin 10. Additionally, both collagens I and III increased in model rats treated with hMSCs-UC, but the ratio of collagen I/III was less significant in treated rats compared with control rats. These results suggest that hMSCs-UC specifically localize to the target ulcerated tissue and may promote the epithelialization of ulcerated tissue by stimulating the release of cytokeratin 19 from keratinocytes and extracellular matrix formation.     

骨髓间充质干细胞外泌体中miRNA在视网膜新生血管形成中的作用及机制

视网膜血管疾病如早产儿视网膜病变、糖尿病视网膜病变和视网膜静脉阻塞等以异常增生的视网膜新生血管为主要病理表现。骨髓间充质干细胞来源外泌体通过旁分泌作用传递生物活性分子介导细胞间的物质与信息交换。其中,miRNA等内容物在传递信息中起关键作用,可调控缺血缺氧环境下内皮细胞的增殖、管腔形成和新生血管的形成。并且能够通过血视网膜屏障而不引起免疫、炎症反应,在眼科疾病治疗中极具潜力。本文总结骨髓间充质干细胞衍生外泌体中miRNA在视网膜新生血管形成中的作用和可能的作用机制,以期为外泌体在眼科疾病诊治中的应用拓宽新思路。     

Transplantation of bone marrow-derived mononuclear cells improves mechanical hyperalgesia, cold allodynia and nerve function in diabetic neuropathy

Relief from painful diabetic neuropathy is an important clinical issue. We have previously shown that the transplantation of cultured endothelial progenitor cells or mesenchymal stem cells ameliorated diabetic neuropathy in rats. In this study, we investigated whether transplantation of freshly isolated bone marrow-derived mononuclear cells (BM-MNCs) alleviates neuropathic pain in the early stage of streptozotocin-induced diabetic rats. Two weeks after STZ injection, BM-MNCs or vehicle saline were injected into the unilateral hind limb muscles. Mechanical hyperalgesia and cold allodynia in SD rats were measured as the number of foot withdrawals to von Frey hair stimulation and acetone application, respectively. Two weeks after the BM-MNC transplantation, sciatic motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), sciatic nerve blood flow (SNBF), mRNA expressions and histology were assessed. The BM-MNC transplantation significantly ameliorated mechanical hyperalgesia and cold allodynia in the BM-MNC-injected side. Furthermore, the slowed MNCV/SNCV and decreased SNBF in diabetic rats were improved in the BM-MNC-injected side. BM-MNC transplantation improved the decreased mRNA expression of NT-3 and number of microvessels in the hind limb muscles. There was no distinct effect of BM-MNC transplantation on the intraepidermal nerve fiber density. These results suggest that autologous transplantation of BM-MNCs could be a novel strategy for the treatment of painful diabetic neuropathy.     

Metformin Induces Cell Cycle Arrest,Reduced Proliferation,Wound Healing Impairment In Vivo and Is Associated to Clinical Outcomes in Diabetic Foot Ulcer Patients

BackgroundSeveral epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation.ResultsMetformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin.ConclusionsMetformin treatment reduces cell proliferation and reduces wound healing in an animal model and affects clinical outcomes in diabetic foot ulcer patients. Chronic use of this drug should be further investigated to provide evidence of their security in association with DFU.     

Comparison of the effect of stem cell therapy and percutaneous transluminal angioplasty on diabetic foot disease in patients with critical limb ischemia

Background aimsThe aim of our study was to compare the effect of autologous stem cell therapy (SCT) and percutaneous transluminal angioplasty (PTA) on diabetic foot disease (DFD) in patients with critical limb ischemia (CLI).MethodsThirty-one patients with DFD and CLI treated by autologous stem cells and 30 patients treated by PTA were included in the study; 23 patients with the same inclusion criteria who could not undergo PTA or SCT formed the control group. Amputation-free survival, transcutaneous oxygen pressure (TcPO₂) and wound healing were assessed over 12 months.ResultsAmputation-free survival after 6 and 12 months was significantly greater in the SCT and PTA groups compared with controls (P = 0.001 and P = 0.0029, respectively) without significant differences between the active treatment groups. Increase in TcPO₂ did not differ between SCT and PTA groups until 12 months (both Ps < 0.05 compared with baseline), whereas TcPO₂ in the control group did not change over the follow-up period. More healed ulcers were observed up to 12 months in the SCT group compared with the PTA and control groups (84 versus 57.7 versus 44.4 %; P = 0.042).ConclusionsOur study showed comparable effects of SCT and PTA on CLI, a major amputation rate that was superior to conservative therapy in patients with diabetic foot and an observable effect of SCT on wound healing. Our results support SCT as a potential promising treatment in patients with CLI and diabetic foot.     

Multiscale phenomena related to diabetic foot

Diabetes is a group of metabolic diseases causing a system disorder, i.e.; it cannot be explained or understood by phenomena on single material scale. The diabetic foot is studied as flexible multibody structure by nonlinear finite element method. The physical and geometrical multiscale heterogeneity is solved by multilevel finite element approach. The diabetic tissue is described by internal coordinate's formalism, as complex multiscale process in tissue. The accompanying problem of the axisymetric wound healing is solved numerically. Some results related to foot deformity, stress and strain concentration and wound healing are presented.