神经病靶标酯酶

某些有机磷酸酯 (ｏｒｇａｎｏｐｈｏｓｐｈｏｒｕｓｅｓｔｅｒｓ ,ＯＰｓ)可使人及其他敏感动物患一种迟发性神经病 ,即有机磷诱导的迟发性多神经病(ｏｒｇａｎｏｐｈｏｐｈｏｒｕｓｅｓｔｅｒ ｉｎｄｕｃｅｄｄｅｌａｙｅｄｐｏｌｙｎｅｕ ｒｏｐａｔｈｙ,ＯＰＩＤＰ) ,这种病以步态失调、下肢麻痹以及脊髓与外周神经轴突变性为基本特征 ,症状出现前一般有 1～ 3周的潜伏期。一般认为 ,ＯＰＩＤＰ是由于神经毒性ＯＰｓ共价修饰神经病靶标酯酶 (ｎｅｕｒｏｐａｔｈｙｔａｒｇｅｔｅｓｔｅｒａｓｅ ,ＮＴＥ)引起 ,ＮＴＥ的催化活性被抑制和…     

甲胺磷诱发母鸡迟发性神经毒性模型

以成年鸡为实验动物,对甲胺磷原药诱发鸡的迟发性神经毒性进行了研究。检测了甲胺磷对鸡脑神经病靶标酯酶（NTE）的体外抑制情况以及急性中毒后期鸡神经组织NTE活性变化。毒性试验发现,甲胺磷对京白母鸡（Gallus domestics）的毒性主要表现为急性中毒,未见有明显的迟发性神经毒性症状。结果表明,本实验未能通过经口及经皮两种染毒途径在母鸡上建立甲胺磷诱发的迟发性神经毒性模型。     

神经毒性酯酶的测定方法

有机磷杀虫剂引起动物迟发性神经毒性问题正日益受到重视。在生产上必须对所使用的农药评价它对人及非靶标生物可能发生的危险及应用后的潜在影响。迟发性神经毒性是其中的一个重要指标。Johnson[1～3]用母鸡鸡脑作材料,研究有机磷化合物的迟发性神经毒性问题,发现只有当鸡脑中水解苯基乙酸苯酯或戊酸苯酯的神经毒性酯酶被抑制时,才出现迟发性神经毒性的综合症状。而在急性或慢性中感时,该酶不受抑制。因此可通过测定神经毒性酯酶是否受抑制来作为有机磷化合物近发性神经毒性的部分测定指标。我们基本上按Johnson的方法[2]并加以改进,…     

敌百虫对鸡诱导迟发性神经毒性的研究

通过敌百虫对成年来航母鸡的毒性试验发现，敌百虫对成年母鸡的毒性机理为急性中毒，未见有迟发性神经毒性作用。     

神经病靶标酯酶的特性

神经病靶标酯酶(NTE)是在研究有机磷引起的迟发性神经病的过程中被发现的。研究表明,NTE是一种主要存在于神经元内质网上的跨膜蛋白,其本质是具有磷脂酶B催化功能的磷脂酶,在细胞内调节磷脂酰胆碱的代谢。NTE是哺乳动物胚胎发育所必需的蛋白质,脑特异性缺失NTE会导致神经退行性症状的出现。NTE作为有机磷的作用位点,在不同的生物中可能通过不同的机制引发不同的毒性症状。     

扩散性抑制对脑缺血后海马迟发性神经元死亡的影响

目的为了研究阻断大鼠局灶性脑缺血诱导的扩散性抑制对同侧海马迟发性神经元死亡的影响。方法颈内动脉插线法制备大鼠大脑中动脉缺血再灌注模型,采用电生理学方法记录扩散性抑制波,尼氏染色和TUNEL染色检测海马迟发性神经元死亡;观察阻断局灶性脑缺血再灌注诱导的扩散性抑制对海马迟发性神经元死亡的影响。结果不给予SD阻断剂,大脑中动脉缺血模型有39%的动物出现海马迟发性神经元死亡;用MK-801阻断扩散性抑制后仅10%的动物出现海马迟发性神经元死亡,机率明显减小。结论局灶性脑缺血引起的海马迟发性神经元死亡可能与扩散性抑制由缺血区不断向远隔部位播散有关。     

口服三邻甲苯基磷酸酯对成年母鸡卵壳腺ATP酶及血清β—葡萄糖醛酸酶活性影响

本研究测定了成年来航母鸡口服ＴＯＣＰ（７５０ｍｇ／ｋｇ）引起的迟发性神经毒性、卵壳腺钙ＡＴＰ酶及钙镁ＡＴＰ酶的活性。在为期１０天的试验中,染毒鸡在给药后的第８～１０天出现迟发性神经毒性症状：表现为轻度步态失调,而对照鸡则自始至终未见有此类症状表现。染毒后７～１０天取样,试验鸡的卵壳腺钙ＡＴＰ酶及钙镁ＡＴＰ酶活性与对照相比无明显变化（Ｐ＞００５）,血清β葡萄糖醛酸酶活性两组间亦无明显差异（Ｐ＞００５）,以上结果表明,虽然ＴＯＣＰ可诱导成年母鸡产生迟发性神经毒性,并影响其产蛋性能,导致产包括软壳蛋在内的异常蛋,但其发生机理可能与卵壳腺的钙ＡＴＰ酶活性无直接关联,至少在接触药物７～１０天范围尚监测不到药物对卵壳腺钙ＡＴＰ酶及钙镁ＡＴＰ酶活性的影响。此外,在上述取样时间点,亦未见有血清β葡萄糖醛酸酶活性的改变,提示ＯＰＩＤＰ的发生机制不涉及β葡萄糖醛酸酶。     

家兔迟发性面瘫模型建立及药物干预研究

目的：优化迟发性面瘫的建模方法,并对药物的神经保护作用进行观察。方法：家兔48只共96侧面神经,分A、B、C、D4个实验组,以一侧面神经进行实验处理,另一侧为自身对照。A组：直视下钳夹损伤桥池段面神经;B组：直视下向桥小脑角注射动脉血,以诱导血管痉挛;C组：处理因素=A组＋B组;D组：在C组基础上,应用药物（强的松＋丹参＋维生素BI＋维生素B12）干预。观察家兔面瘫,并做面神经病理切片,比较各组间迟发性面瘫发生率、面瘫持续时间及预后。结果：面瘫发生情况：A组6只家兔（6／11,54．5％）出现迟发性面瘫;平均面瘫持续时间为13．2天。B组有2只（2／12,16．7％）出现迟发性面瘫,平均持续8天。C组6只（6／12,50％）家兔出现迟发性面瘫,平均持续14.3天。D组4只（4／12,33．33％）出现迟发性面瘫,平均持续6天。所有自身对照侧均无面瘫发生。病理：各组均见神经纤维水肿;A、c两组呈高度水肿改变,神经束周围结构紊乱;B组见神经内血管细小,而水肿较A、C两组轻微;D组呈轻度水肿改变。结论：C组出现迟发性面瘫几率高,是较好的模型;联合应用强的松、丹参、维生素B1、维生素B12虽不能防止迟发性面瘫发生,但可使迟发性面瘫病程明显缩短。     

三甲基苯基磷酸酯对神经毒性酯酶的抑制及其酶促动力学分析

以可使人和敏感动物产生迟发性神经毒性的有机磷化合物三甲基苯基磷酸酯（TOCP）为测试药物,研究其在体外对成年产卵来航母鸡不同神经组织神经毒性酯酶（NTE）活性抑制的敏感性及其抑制的动力学．结果表明,外周神经NTE对于TOCP的抑制比中枢神经NTE敏感得多．TOCP对鸡脑、脊髓和坐骨神经中NTE抑制的I50值．分别为：1．9323、2．3950和0．0035mmol／L．NTE酶促动力学研究显示,鸡脑NTE催化分解底物戊酸苯酯（PV）的Vmax为62．10nmol·min-1·mg-1,Km为0．92mmol／L．TOCP对鸡脑NTE的抑制属竞争性抑制类型,并有"底物抑制"现象．     

家兔迟发性面瘫模型建立及药物干预研究

目的:优化迟发性面瘫的建模方法,并对药物的神经保护作用进行观察。方法:家兔48只共96侧面神经,分A、B、C、D 4个实验组,以一侧面神经进行实验处理,另一侧为自身对照。A组:直视下钳夹损伤桥池段面神经;B组:直视下向桥小脑角注射动脉血,以诱导血管痉挛;C组:处理因素=A组+B组;D组:在C组基础上,应用药物(强的松+丹参+维生素B1+维生素B12)干预。观察家兔面瘫,并做面神经病理切片,比较各组间迟发性面瘫发生率、面瘫持续时间及预后。结果:面瘫发生情况:A组6只家兔(6/11,54.5%)出现迟发性面瘫;平均面瘫持续时间为13.2天。B组有2只(2/12,16.7%)出现迟发性面瘫,平均持续8天。C组6只(6/12,50%)家兔出现迟发性面瘫,平均持续14.3天。D组4只(4/12,33.33%)出现迟发性面瘫,平均持续6天。所有自身对照侧均无面瘫发生。病理:各组均见神经纤维水肿;A、C两组呈高度水肿改变,神经束周围结构紊乱;B组见神经内血管细小,而水肿较A、C两组轻微;D组呈轻度水肿改变。结论:C组出现迟发性面瘫几率高,是较好的模型;联合应用强的松、丹参、维生素B1、维生素B12虽不能防止迟发性面瘫发生,但可使迟发性面瘫病程明显缩短。     

Genetic epidemiology of sensorimotor polyneuropathy with or without agenesis of the corpus callosum in northeastern Quebec

Sensorimotor polyneuropathy with or without agenesis of the corpus callosum (McKusick number 218000) is a disorder that has a high frequency in Saguenay-Lac-St-Jean (SLSJ), a geographically isolated region of northeastern Quebec. The incidence at birth and the carrier rate were estimated, respectively, at 1/2117 liveborns and 1/23 inhabitants. Remote consanguinity was found in several polyneuropathic families while the mean kinship coefficient was 2.7 times higher in the polyneuropathic group than in control groups. The birth places of the individuals with sensorimotor polyneuropathy and their parents did not show a clustered nonuniform distribution. The genealogical reconstruction suggests that the high incidence of polyneuropathy in SLSJ is likely to be the result of a founder effect. It also suggests that a unique mutation accounts for most, if not all, of the cases of sensorimotor polyneuropathy known in this region.     

The diabetic polyneuropathy. I. Relation between impaired function in peripheral nerves and clinical findings

789 patients with diabetes mellitus were studied by clinical and electroneurographical investigation. Motor and sensory conduction velocities of the median nerve and motor conduction velocity of the tibial nerve were determined. 86.1% of the patients suffered from juvenile diabetes, and 13.9% from maturity onset diabetes. Average duration of the disease was 9.5 years, average age of the patients was 26.7 years. Clinical signs of polyneuropathy were found in 19.1%. In 40.9% of the patients at least one of 3 conduction velocities was found to be delayed. Patients with clinical signs of polyneuropathy exhibited delayed nerve conduction velocities and delayed distal latencies. Diagnosis of polyneuropathy almost with certainty is possible by determining the three nerve conduction velocities and the three corresponding distal latencies. 22% of patients without clinical signs of polyneuropathy exhibited electroneurographical signs of impaired peripheral nerve function. Heredity, body weight, lipid metabolism, actual metabolic balance, and treatment were found to be without any significant influence on nerve conduction velocity.     

Association of polymorphic markers of lipid metabolism genes with diabetic polyneuropathy in type 1 diabetes mellitus

The aim of this study was the search of association with diabetic polyneuropathy of the polymorphic markers epsilon2/epsilon3/epsilon4 of apolipoprotein E (APOE) and I/D of apolipoprotein B (APOB) genes in groups of type 1 diabetes patients with diabetic polyneuropathy (n = 86) and without its clinical signs (n = 94). We have not found significant association with diabetic polyneuropathy (DPN) of epsilon2/epsilon3/epsilon4 marker of APOE gene. However the comparison of allele and genotype frequencies of I/D marker of APOB gene showed that the carriers of I allele and II genotype had higher risk (OR = 1.66 and 2.01, relatively; p < 0.027), whereas the carriers of D allele had lower risk of DPN (OR = 0.60; p < 0.018). Our findings show that APOB gene, encoding one of the main components of lipid metabolism system, is involved into the diabetic polyneuropathy development in type 1 diabetes mellitus.     

Assessment of Paclitaxel Induced Sensory Polyneuropathy with “Catwalk” Automated Gait Analysis in Mice

Neuropathic pain as a symptom of sensory nerve damage is a frequent side effect of chemotherapy. The most common behavioral observation in animal models of chemotherapy induced polyneuropathy is the development of mechanical allodynia, which is quantified with von Frey filaments. The data from one study, however, cannot be easily compared with other studies owing to influences of environmental factors, inter-rater variability and differences in test paradigms. To overcome these limitations, automated quantitative gait analysis was proposed as an alternative, but its usefulness for assessing animals suffering from polyneuropathy has remained unclear. In the present study, we used a novel mouse model of paclitaxel induced polyneuropathy to compare results from electrophysiology and the von Frey method to gait alterations measured with the Catwalk test. To mimic recently improved clinical treatment strategies of gynecological malignancies, we established a mouse model of dose-dense paclitaxel therapy on the common C57Bl/6 background. In this model paclitaxel treated animals developed mechanical allodynia as well as reduced caudal sensory nerve action potential amplitudes indicative of a sensory polyneuropathy. Gait analysis with the Catwalk method detected distinct alterations of gait parameters in animals suffering from sensory neuropathy, revealing a minimized contact of the hind paws with the floor. Treatment of mechanical allodynia with gabapentin improved altered dynamic gait parameters. This study establishes a novel mouse model for investigating the side effects of dose-dense paclitaxel therapy and underlines the usefulness of automated gait analysis as an additional easy-to-use objective test for evaluating painful sensory polyneuropathy.     

The POEMS syndrome with coexisting endocrinopathy--case report

We present a case of a woman with unique multisystem disorder--POEMS syndrome and endocrine abnormalities coexisting with it. The POEMS acronym comprises the dominant features: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M protein), skin changes. Association between plasma cell dyscrasia and polyneuropathy, was described in 1956 year by Crow. The main features were coined in the acronym POEMS by Bardwick in 1980 year. The polysymptomatic clinical picture, progressive course and no-concurrent manifestations of main features impede the diagnosis. In this case, the first symptoms were the sensomotor polyneuropathy, peripheral oedema, osteosclerotic bone lesions, skin changes, organomegaly. They preceded diagnosis by 3 years. The first endocrinopathy was hypothyroidism. Definite diagnosis was delayed because we couldn't detect the presence of M protein. Immunoelectrophoresis didn't detect it, but analysis by immunofixation detected M protein in serum and urine. Within 3 years of the first symptoms, she developed hypogonadism hypergonadotropic. At first, the monotherapy with corticosteroids was used, then--melfalan with prednisone. Due to the progression of the disease, a thalidomide was used in therapy (it is anti-VEGF agent). One of the side effects of the treatment of thalidomide is the progression of polyneuropathy, which was observed in this patient. After finishing this therapy she received chemotherapy. This case report imposes the necessity of constants observation of patients with POEMS syndrome because there is a possibility of their developing other disorders. In the event of coexistence polyneuropathy and plasma cell dyscrasia, this disease should be taken into consideration.     

Acute inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alfa-2a in a patient with chronic hepatitis C virus infection: a case report

ABSTRACT: INTRODUCTION: The combination of polyethylene glycol (PEG)ylated interferon (pegylated interferon) and ribavirin has been shown to be an effective treatment for chronic hepatitis C virus. In general, common side effects related to this combination therapy are mild and are well tolerated. However, peripheral neuropathy including demyelinating polyneuropathy related to PEG-interferon alpha2a (pegylated interferon alfa-2a) is extremely rare. In the literature, only one case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon alpha2a has been published previously. CASE PRESENTATION: To the best of our knowledge we present only the second case of acute inflammatory demyelinating polyneuropathy related to PEG-interferon alpha2a, occurring in a 63-year-old Caucasian man. He developed tingling, numbness, and weakness of his upper and lower extremities with acute neurological deficits after five weeks of a combination therapy with PEG-interferon alpha2a and ribavirin for chronic hepatitis C virus infection. His clinical course, neurological findings, and his electromyogram results were all consistent with acute inflammatory demyelinating polyneuropathy. Our patient recovered completely after interferon was stopped and symptomatic treatment and a further electromyogram showed a disappearance of neuropathy. Four weeks later, PEG-interferon alpha2a was reintroduced with a gradually increasing dose without any reappearance of neurological symptoms allowing hepatitis C seroconversion. CONCLUSIONS: Recognition of this rare yet possible presentation is important for early and accurate diagnosis and treatment. This case report also suggests that the reintroduction of PEGylated interferon in patients who had presented with acute inflammatory demyelinating polyneuropathy related to interferon alpha may be safe, but this must be confirmed by further studies.     

Parameters of action potentials of motor units in diabetic patients as determined by electromyography using skin surface leads

Motor units were studied in children by means of electromyography using skin surface leads. In the control group of healthy children, 295 action potentials typical of the age dynamics were recorded from motor units. In the group of children with type I diabetes mellitus and diabetic polyneuropathy, a higher amplitude and a longer duration of motor unit action potentials than in the control group, which are typical of diabetic polyneuropathy, were observed.     

Diabetic polyneuropathy. 4. Synopsis of electroneurographic findings in diabetics]

Sensory conduction velocity of the median nerve, motor conduction velocity of both median and tibial nerves, and corresponding distal laterncies are sufficient parameters to establish the diagnosis of polyneuropathy almost with certainty. Considering these six parameters yielded in detection of peripheral nerve dysfunction in 22% of diabetic patients who were free from clinical signs of polyneuropathy. Electroneurographical findings in 340 out of 677 patients with diabetes mellitus were interpreted as evidence of segmental demyelination. Within this group there was the majority of patients with clinical signs of polyneuropathy and with subclinical signs of peripheral nerve dysfunction. There existed a positive correlation between signs of nerve dysfunction with angiopathy, age and duration of the disease. A second group consisting of 243 diabetics with signs of incipient segmental demyelination with or without signs of axonaal degeneration mainly included juvenile patients with a short duration of the disease and with a low frequency of angiopathy.     

Ghrelin reverses experimental diabetic neuropathy in mice

Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. We investigated the pharmacological potential of ghrelin in the treatment of polyneuropathy in uncontrolled streptozotocin (STZ)-induced diabetes in mice. Ghrelin or desacyl-ghrelin was administered daily for 4 weeks after STZ-induced diabetic polyneuropathy had developed. Ghrelin administration did not alter food intake, body weight gain, blood glucose levels, or plasma insulin levels when compared with mice given saline or desacyl-ghrelin administration. Ghrelin administration ameliorated reductions in motor and sensory nerve conduction velocities in diabetic mice and normalized their temperature sensation and plasma concentrations of 8-isoprostaglandin α, an oxidative stress marker. Desacyl-ghrelin failed to have any effect. Ghrelin administration in a mouse model of diabetes ameliorated polyneuropathy. Thus, ghrelin’s effects represent a novel therapeutic paradigm for the treatment of this otherwise intractable disorder.     

Heterogeneity of antibody specificity in Taiwanese patients with polyneuropathy and IgM paraproteinemia

About half of the Caucasian patients with chronic polyneuropathy and IgM paraproteinemia show serum anti-myelin-associated glycoprotein (MAG) and anti-sulfoglucuronosyl glycosphingolipid (SGGLs) activities. These antibody activities have been demonstrated to react with a carbohydrate epitope known as the HNK-1 or sulfoglucuronic acid (SGA) epitope. However, in Asian populations the occurrence of serum anti-SGA activities has been reported to be relatively rare. We investigated 5 cases of chronic polyneuropathy with IgM paraproteinemia from Taiwan and found that 3 of them had high-titer serum anti-SGA (SGGL/MAG) antibody activities. The clinical symptoms of these 3 patients were consistent with sensory dominant polyneuropathy with a severer involvement of the lower limbs than of the upper limbs. Electromyography and nerve conduction studies revealed severe sensory nerve involvement (no response in 3 cases) and moderate slowing of motor conduction velocity (MCV) without conduction block. The decrease in MCV correlated well with anti-SGA antibody titer (less than 30 m/s with the titration of 1:12,800, normal 55–60 m/s). Pathological findings showed active demyelinating polyneuropathy with myelin ovoid and myelinated fiber loss. Our data suggest that anti-SGGL antibody activities may not be very rare among Asian populations. Additionally, there seems an intriguing possibility that the titer of this antibody correlates with the severity of peripheral nerve involvement in patients of demyelinating polyneuropathy with IgM paraproteinemia.