Peripheral Neuropathy Following Chloroquine Therapy

Four patients were observed who developed similar episodes of peripheral neuropathy following prolonged treatment with chloroquine phosphate. This previously unreported toxic reaction consisted of bilateral loss of knee and ankle reflexes and weakness of the quadriceps muscles. Gradual return to normal followed withdrawal of the chloroquine. Other toxic reactions to the drug are reviewed.     

Peripheral Neuropathy and Experimental Myeloma in the Mouse

SEVERAL forms of generalized and localized peripheral neuropathy have been associated in man with solitary or multiple myeloma^1–3. The cause of the nerve damage, which usually involves segmental demyelination^{4, 5} (that is, a specific lesion of the Schwann cell-myelin sheath) as well as some total nerve fibre degeneration, is unknown and so is its relationship to the protein produced by the abnormal plasma cells. The disorder has been classed as one of the “non-metastatic neurological complications of neoplasms”⁶, a group of mysterious disorders, almost all of unknown cause, which have not so far been reproduced in experimental animals. Recently, histological studies on the peripheral nerves of mice bearing transplanted plasma cell myelomas have shown that tumours secreting a particular type of protein are associated with a similar mixed peripheral neuropathy.     

紫杉醇所致SD大鼠外周神经病变模型的建立

目的 化疗药物所致的外周神经病变（chemotherapy-induced peripheral neuropathy,CIPN）是多种化疗药物的共同而严重的不良反应.目前,国内外最常用的CIPN模型是紫杉醇（PTX）腹腔注射建立的SD大鼠模型,但关于影响CIPN模型建立的相关因素却少有涉及.本实验拟考察影响PTX所致SD大鼠CIPN模型的影响因素,为筛选和研究防治CIPN药物提供理想的动物模型.方法 大鼠隔日一次腹腔注射给予PTX,采用测痛丝致痛行为学实验考察PTX对大鼠机械性异常性疼痛和机械性痛觉过敏的影响,免疫荧光法检测大鼠后足表皮下神经纤维（intraepidermal nerve fiber,IENF）的形态及数目,电子显微镜检测坐骨神经细胞线粒体的形态及数目.结果 隔日腹腔注射2 mg/kgPTX四次对SD大鼠的体重增长无明显影响;给予PTX后,初始体重为200 g的大鼠在34 d的实验周期内未观察到机械性异常性疼痛,仅在第17天出现了一次机械性痛觉过敏;而初始体重为400 g的大鼠则在第17天表现出了机械性异常性疼痛,第8-26天表现出了机械性痛觉过敏,免疫荧光显示PTX处理组大鼠后足表皮下IENF断裂,IENF密度显著降低,电镜观察可见空泡变性的异常线粒体的比例升高,PTX处理组大鼠表现出明显的外周神经病变.结论 初始体重400 g的SD大鼠对PTX所致的外周神经病变较敏感,适合作为PTX所致外周神经病变的模型动物.     

交感皮肤反应在糖尿病周围神经病变诊断中的应用

糖尿病周围神经病变（Diabetic Peripheral Neuropathy,DPN）是糖尿病最常见的并发症之一。由于目前DPN发病机制不清楚、治疗效果不理想,故早诊断、早治疗显得至关重要。有研究指出交感神经皮肤反应（Sympathetic Skin Response,SSR）可作为评价2型糖尿病患者早期周围植物神经功能状态的指标。本文对SSR应用于DPN临床诊断中的检测技术、观测参数进行综述,发现多数研究中指出,在临床应用中SSR波形、波幅以及潜伏期指标的异常率常受到多种因素的影响、会发生很大波动,而电位曲线下面积减少值相对稳定。据此笔者建议在DPN早期临床诊断中以SSR电位曲线下面积减少作为关键参数,辅助参考SSR波形、波幅以及潜伏期指标进行诊断。     

Exenatide Facilitates Recovery from Oxaliplatin-Induced Peripheral Neuropathy in Rats

Background

Oxaliplatin has widely been used as a key drug in the treatment of colorectal cancer; however, it causes peripheral neuropathy. Exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is an incretin mimetic secreted from ileal L cells, which is clinically used to treat type 2 diabetes mellitus. GLP-1 receptor agonists have been reported to exhibit neuroprotective effects on the central and peripheral nervous systems. In this study, we investigated the effects of exenatide on oxaliplatin-induced neuropathy in rats and cultured cells.

Methods

Oxaliplatin (4 mg/kg) was administered intravenously twice per week for 4 weeks, and mechanical allodynia was evaluated using the von Frey test in rats. Axonal degeneration was assessed by toluidine blue staining of sciatic nerves.

Results

Repeated administration of oxaliplatin caused mechanical allodynia from day 14 to 49. Although the co-administration of extended-release exenatide (100 μg/kg) could not inhibit the incidence of oxaliplatin-induced mechanical allodynia, it facilitated recovery from the oxaliplatin-induced neuropathy with reparation of axonal degeneration. Inhibition of neurite outgrowth was evaluated in cultured pheochromocytoma 12 (PC12) cells. Exenatide inhibited oxaliplatin-induced neurite degeneration, but did not affect oxaliplatin-induced cell injury in cultured PC12 cells. Additionally, extended-release exenatide had no effect on the anti-tumor activity of oxaliplatin in cultured murine colon adenocarcinoma 26 (C-26) cells or C-26 cell-implanted mice.

Conclusion

These results suggest that exenatide may be useful for treating peripheral neuropathy induced by oxaliplatin in colorectal cancer patients with type 2 diabetes.     

踝肱指数与糖尿病周围神经病变及中医证候积分的相关性

目的：探讨踝肱指数（ABI）与糖尿病周围神经病变及中医证候积分的相关性。方法：选取我院内分泌科收治辩证以气阴两虚为证型的糖尿病患者66 例,根据踝肱指数实验将患者分为ABI降低组（0.9>ABI>0.5）和ABI 正常组(1.4>ABI>0.9)。记录患者神经病变症状尼龙丝检查以及中医症候评分,分析ABI与糖尿病周围神经病变及中医证候积分的相关性。结果：ABI降低组的糖尿病周围神经病变的患病率高于ABI正常组（P<0.05）。ABI 降低组发麻、针刺感症状的发生率高于ABI 正常组,且有统计学差异（P<0.05）。ABI降低组10 g尼龙丝检查异常者多于ABI正常组,差异显著（P<0.05）。ABI降低组的感觉振动阈值高于ABI正常组（P<0.05）。ABI数值与中医证候积分呈负向直线相关（P<0.05）。结论：糖尿病患者ABI数值与糖尿病周围神经病变和中医证候积分具有相关性。     

Mouse Forward Genetics in the Study of the Peripheral Nervous System and Human Peripheral Neuropathy

Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. Special issue article in honor of Dr. George DeVries.     

光子中医信息疗法治疗糖尿病周围神经病变的临床研究

目的:观察光子中医信息疗法对糖尿病周围神经病变患者的临床疗效。方法:将60例符合入选标准的患者,以1∶1的比例随机分配到治疗组(光子中医信息疗法联合药物组)、对照组(药物组),两组患者均给予糖尿病基础治疗,对照组加甲钴胺口服,每次500μg,每日3次,疗程4周;治疗组在对照组的基础上配合光子中医信息疗法,隔日照射1次,每周3次,6次为1疗程,共2个疗程。治疗前后分别对两组患者的中医临床症状、神经症状体征进行评定,并测定周围神经传导速度及观察血糖变化情况,进行综合疗效评估。结果:治疗组的临床综合疗效明显优于对照组,两组的总有效率比较有显著性差异(P<0.05)。治疗组在中医症状改善、周围神经症状及体征改善、提高周围神经传导速度方面均优于对照组,组间比较均具有显著性差异(P<0.05)。治疗后治疗组空腹血糖、餐后血糖、糖化血红蛋白与治疗前比较均明显降低(P<0.01),对照组治疗前后比较及治疗后组间比较均无显著性差异(P>0.05)。结论:光子中医信息疗法联合药物组相对于药物组在改善DPN患者的临床症状、周围神经症状及体征、神经的传导速度等方面均有良好的优势,同时具有一定的辅助降糖趋势。     

Peripheral Neuropathy with Sympathetic Overactivity from Industrial Contact with Acrylamide

This paper describes the experimental and clinical findings of acrylamide intoxication in a human being. It is believed that this is the first such case to be recorded in the medical literature.Acrylamide is widely used as a “chemical grout”. It is pumped into dirt, clay and stone walls of excavations in a liquid state together with a catalyst, and it then polymerizes to make a watertight shield.This chemical is neurotoxic in its non-polymerized form and can be absorbed through the intact skin, mucous membranes and lungs. In spite of warnings with regard to its handling, this worker became careless, and developed a contact dermatitis and a polyneuropathy with bluish cold extremities which dripped perspiration.In six months'' time after his removal from contact with the chemical the patient made a complete clinical recovery. He was advised not to work with the chemical.     

An Early Diagnostic Tool for Diabetic Peripheral Neuropathy in Rats

The skin’s rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats’ hind paws. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats.     

Diabetic Peripheral Neuropathy: Role of Reactive Oxygen and Nitrogen Species

The prevalence of diabetes has reached epidemic proportions. There are two forms of diabetes: type 1 diabetes mellitus is due to auto-immune-mediated destruction of pancreatic β-cells resulting in absolute insulin deficiency and type 2 diabetes mellitus is due to reduced insulin secretion and or insulin resistance. Both forms of diabetes are characterized by chronic hyperglycemia, leading to the development of diabetic peripheral neuropathy (DPN) and microvascular pathology. DPN is characterized by enhanced or reduced thermal, chemical, and mechanical pain sensitivities. In the long-term, DPN results in peripheral nerve damage and accounts for a substantial number of non-traumatic lower-limb amputations. This review will address the mechanisms, especially the role of reactive oxygen and nitrogen species in the development and progression of DPN.