Suffocation of nerve fibers by living nanovesicles: a model simulation--part II

Nanobacteria may cause peripheral neuropathy by adhesion to the perineurium. This hypothesis receives support from five independent observations: (1) identification of perineurial apatite in diabetic patients with peripheral neuropathy, (2) massive presence of nanobacteria in a diabetic patient, (3) beneficial effect of lasers on peripheral neuropathy, (4) model simulation indicating that perineurial deposition and attachment of nanobacteria is encouraged by both their size and chemical nature, and (5) transient inhibition of neural function by apatite. Initial deposition of (stressed) nanobacteria is promoted by a slime thought to consist of proteins, calcium, and phosphate, and is most likely followed by an immobilization phase, mediated by a bioadhesive capacity of the apatite. Proteomics may hold the key to control both attachment processes.     

Could reduced bone mineral densities in HIV be caused by nanobacteria?

From the observations of different research groups reporting on reduced bone mineral density (BMD) and on a pronounced tendency for kidney stone formation, both in HIV-infected patients, and from results achieved in the treatment of severest peripheral neuropathy with lasers, it is concluded that nanobacteria (NB) could actively contribute to the reduction of BMD. A reduced BMD could primarily stem from NB, extracting calcium and phosphate from blood, affecting the calcium and phosphate homeostasis in humans.     

Prevalence and clinical characteristics of diabetic peripheral neuropathy in hospital patients with Type 2 diabetes in Korea

Diabet. Med. 29, e290-e296 (2012) ABSTRACT: Aims Diabetic peripheral neuropathy is a common complication of diabetes. This cross-sectional study investigated the prevalence and clinical characteristics of this neuropathy in patients with Type?2 diabetic mellitus treated at hospitals in Korea. Methods Questionnaires and medical records were used to collect data on 4000 patients with Type?2 diabetes from the diabetes clinics of 40 hospitals throughout Korea. Diabetic peripheral neuropathy was diagnosed based on a review of medical records or using the Michigan Neuropathy Screening Instrument score and monofilament test. Results The prevalence of neuropathy was 33.5% (n?=?1338). Multivariate analysis revealed that age, female sex, diabetes duration, lower glycated haemoglobin, treatment with oral hypoglycaemic agents or insulin, presence of retinopathy, history of cerebrovascular or peripheral arterial disease, presence of hypertension or dyslipidaemia, and history of foot ulcer were independently associated with diabetic peripheral neuropathy. Of the patients with neuropathy, 69.8% were treated for the condition and only 12.6% were aware of their neuropathy. Conclusion There was a high prevalence of peripheral neuropathy in patients with Type?2 diabetes in Korea and those patients were far more likely to have complications or co-morbidities. The proper management of diabetic peripheral neuropathy deserves attention from clinicians to ensure better management of diabetes in Korea.     

Primordial proteins and HIV-Part II

Nanobacteria are suspected to be responsible for a number of diseases, i.e., kidney stones, heart disease, ovarian cancer, peripheral neuropathy, and reduced bone mineral density. Being protected by a mineral shell consisting of apatite, the nanovesicles can enter eukaryotic cells. Depending on the host's stress level, nanobacteria may carry a substantial layer of a protein based slime, instrumental in collecting calcium phosphate from the environment. Calcium phosphate is known to mediate the uptake of nucleic acids by eukaryotic cells. Surprisingly, a pathogenic effect of nanobacteria in HIV can be derived primarily from the trafficking of calcium phosphate in HIV infected cells, performed by primordial proteins. The inescapable conclusion is that nanobacteria could promote genetic diversity in HIV.     

Characterization of Granulations of Calcium and Apatite in Serum as Pleomorphic Mineralo-Protein Complexes and as Precursors of Putative Nanobacteria

Calcium and apatite granulations are demonstrated here to form in both human and fetal bovine serum in response to the simple addition of either calcium or phosphate, or a combination of both. These granulations are shown to represent precipitating complexes of protein and hydroxyapatite (HAP) that display marked pleomorphism, appearing as round, laminated particles, spindles, and films. These same complexes can be found in normal untreated serum, albeit at much lower amounts, and appear to result from the progressive binding of serum proteins with apatite until reaching saturation, upon which the mineralo-protein complexes precipitate. Chemically and morphologically, these complexes are virtually identical to the so-called nanobacteria (NB) implicated in numerous diseases and considered unusual for their small size, pleomorphism, and the presence of HAP. Like NB, serum granulations can seed particles upon transfer to serum-free medium, and their main protein constituents include albumin, complement components 3 and 4A, fetuin-A, and apolipoproteins A1 and B100, as well as other calcium and apatite binding proteins found in the serum. However, these serum mineralo-protein complexes are formed from the direct chemical binding of inorganic and organic phases, bypassing the need for any biological processes, including the long cultivation in cell culture conditions deemed necessary for the demonstration of NB. Thus, these serum granulations may result from physiologically inherent processes that become amplified with calcium phosphate loading or when subjected to culturing in medium. They may be viewed as simple mineralo-protein complexes formed from the deployment of calcification-inhibitory pathways used by the body to cope with excess calcium phosphate so as to prevent unwarranted calcification. Rather than representing novel pathophysiological mechanisms or exotic lifeforms, these results indicate that the entities described earlier as NB most likely originate from calcium and apatite binding factors in the serum, presumably calcification inhibitors, that upon saturation, form seeds for HAP deposition and growth. These calcium granulations are similar to those found in organisms throughout nature and may represent the products of more general calcium regulation pathways involved in the control of calcium storage, retrieval, tissue deposition, and disposal.     

CRP、PTH、Alb及Hb水平变化与尿毒症周围神经病变程度的相关性

摘要 目的：探讨C反应蛋白（CRP）、甲状旁腺素（PTH）、血清白蛋白（Alb）及血红蛋白（Hb）水平变化与尿毒症周围神经病变程度的相关性。方法：选取我院2019年4月到2022年4月收治的340例需要进行维持性血液透析治疗的尿毒症患者作为研究对象,依照是否存在周围型神经病变的情况分为非神经病变组（n=132）和神经病变组（n=208）。对比两组患者的临床相关资料,CRP、PTH、Alb及Hb水平变化,其他血清指标变化,并分析CRP、PTH、Alb及Hb水平变化与尿毒症周围神经病变程度的相关性。结果：两组患者高血压患病人数对比无差异（P＞0.05）,两组患者的糖尿病患病人数、血液透析频率以及血液透析时间对比差异显著（P<0.05）;神经病变组患者的CRP、PTH水平明显高于非神经病编组（P＜0.05）,神经病变组患者的Alb、Hb水平明显低于非神经病变组（P＜0.05）;两组患者血浆胆固醇（CHO）、红细胞（RBC）、三酰甘油（TG）、血肌酐（SCr）水平对比无显著差异（P＞0.05）,神经病变组患者血清前白蛋白（PA）、二氧化碳结合力（CO2CP）水平低于非神经病变组,神经病变组患者血清BUN、FBG水平高于非神经病变组（P＜0.05）;Spearman相关分析结果显示：CRP、PTH与尿毒症周围神经病变程度呈正相关（P＜0.05）,Alb、Hb与尿毒症周围神经病变程度呈负相关（P＜0.05）。结论：CRP、PTH、Alb及Hb水平变化与尿毒症周围神经病变程度具有明显关系,可以用于判断尿毒症患者的周围神经病变程度。而且尿毒症周围神经病变患者多数原发疾病为糖尿病,血液透析频率较低,维持血液透析时间较长。     

Suffocation of nerve fibers by living nanovesicles: a model simulation

A model using nanospheres to allow the simulation of the nonspecific interaction of nanobacteria (NB), one with another or with body tissues, is established. Depending primarily on their concentrations and stress levels, these apatite nanovesicles may nucleate thrombogenic conglomerates in blood, or self-assemble to dense nanoclay layers on surfaces in the body. Partial or total encapsulation of nerve fiber bundles by such mineral layers may interrupt the metabolic exchanges between the surrounded tissue and its immediate environment and may restrict signaling processes. The presented model could provide detailed insight into plaque formation triggered by NB, and the parameters encouraging it.     

Putative Nanobacteria Represent Physiological Remnants and Culture By-Products of Normal Calcium Homeostasis

Putative living entities called nanobacteria (NB) are unusual for their small sizes (50–500 nm), pleomorphic nature, and accumulation of hydroxyapatite (HAP), and have been implicated in numerous diseases involving extraskeletal calcification. By adding precipitating ions to cell culture medium containing serum, mineral nanoparticles are generated that are morphologically and chemically identical to the so-called NB. These nanoparticles are shown here to be formed of amorphous mineral complexes containing calcium as well as other ions like carbonate, which then rapidly acquire phosphate, forming HAP. The main constituent proteins of serum-derived NB are albumin, fetuin-A, and apolipoprotein A1, but their involvement appears circumstantial since so-called NB from different body fluids harbor other proteins. Accordingly, by passage through various culture media, the protein composition of these particles can be modulated. Immunoblotting experiments reveal that antibodies deemed specific for NB react in fact with either albumin, fetuin-A, or both, indicating that previous studies using these reagents may have detected these serum proteins from the same as well as different species, with human tissue nanoparticles presumably absorbing bovine serum antigens from the culture medium. Both fetal bovine serum and human serum, used earlier by other investigators as sources of NB, paradoxically inhibit the formation of these entities, and this inhibition is trypsin-sensitive, indicating a role for proteins in this inhibitory process. Fetuin-A, and to a lesser degree albumin, inhibit nanoparticle formation, an inhibition that is overcome with time, ending with formation of the so-called NB. Together, these data demonstrate that NB are most likely formed by calcium or apatite crystallization inhibitors that are somehow overwhelmed by excess calcium or calcium phosphate found in culture medium or in body fluids, thereby becoming seeds for calcification. The structures described earlier as NB may thus represent remnants and by-products of physiological mechanisms used for calcium homeostasis, a concept which explains the vast body of NB literature as well as explains the true origin of NB as lifeless protein-mineralo entities with questionable role in pathogenesis.     

Insulin-Induced Hypoglycemic Peripheral Motor Neuropathy in Spontaneously Diabetic WBN/Kob Rats

Intensive insulin therapy can lead to hypoglycemia, with patients sometimes developing hypoglycemic neuropathy. Spontaneously diabetic Wistar Bonn Kobori (WBN/Kob) rats develop diabetic peripheral motor neuropathy characterized by segmental demyelination and axonal degeneration. We examined the short-term effects of hypoglycemia on neuropathic changes in these rats. Spontaneous diabetic WBN/Kob rats received insulin implants for 40 d and were divided into 3 groups based on blood glucose levels: group N, normoglycemic to slightly hyperglycemic (150 to 250 mg/dL); group H, hypoglycemic to slightly hyperglycemic (50 to 200 mg/dL); and group D, nontreated spontaneously diabetic (350 to 420 mg/dL). Conduction velocity was measured in sciatic–tibial motor nerves; these nerves also underwent qualitative and quantitative histomorphologic analysis. Conduction velocity was not significantly different in N, D, and H groups. Morphologic analysis of the sciatic nerves of H rats showed severe changes, including axonal degeneration, myelin distention, and endoneurial fibrosis, that tended to occur in large, myelinated fibers. N and D rats showed relatively mild changes. The degree and distribution of degenerated nerve fibers in H rats were significantly higher than in N and D rats. These results suggest that hypoglycemia of less than 50 mg/dL induced severe peripheral neuropathy. Hypoglycemic lesions differed from the hyperglycemic lesions in diabetic WBN/Kob rats. This rat strain is an appropriate model for investigating the hypoglycemic peripheral neuropathy that can be associated with a diabetic condition.Peripheral neuropathy is a leading complication of diabetes mellitus. Although its exact pathogenesis is not fully understood, chronic hyperglycemia and resultant microenvironmental changes in peripheral nerve tissue contribute to the development of neuropathy.⁵ Therefore, intensive insulin therapy is needed to prevent such complications in patients with type 1 diabetes. However, intensive insulin therapy can lead to hypoglycemia, with patients sometimes developing hypoglycemic peripheral neuropathy.⁸Although experimental hypoglycemic peripheral neuropathy has been studied by using animal models of type 1 diabetes, few studies have included morphologic analyses.^4,7,14,15 These studies showed that hypoglycemia causes axonopathy involving both degenerative and regenerative events. However, hyperglycemic peripheral neuropathy characterized by axonal atrophy has also been induced in diabetic animal models, such that the hyperglycemic changes in these models were similar to hypoglycemic changes. Diabetic WBN/Kob rats spontaneously develop diabetic peripheral motor neuropathy characterized by segmental demyelination and secondary axonal degeneration.^12,13,19 Morphologic changes in diabetic peripheral motor neuropathy are characterized by various degenerative and regenerative changes in myelin sheath, demyelination, and a shift toward axons of smaller diameter. Therefore, WBN/Kob rats may be useful for distinguishing hyperglycemic from hypoglycemic changes. In addition, the threshold of hypoglycemia that induces the morphologic and clinical changes characteristic of peripheral neuropathy in diabetic animals remains unclear.¹⁴ In the present study, we investigated the effects of short-term hypoglycemia on peripheral neuropathic changes in diabetic WBN/Kob rats.     

Cerebral responses elicited by stimulation of the vesico-urethral junction (VUJ) in diabetics

To investigate the involvement of the visceral afferent nerves in diabetes mellitus, we enrolled 46 male patients in a study, examining the cerebral potentials evoked by stimulation of the vesico-urethral junction (VUJ CEP) and the pudendal (penile CEP) and posterior tibial nerves (tibial CEP). The age range was 23–67 (mean 45.8) years. The epithelial surface of the vesico-urethral junction was stimulated bipolarly with an electrode attached to a specially produced Foley catheter. Cerebral responses were recorded bipolarly at vertex.VUJ CEPs were absent (27 patients) or protracted and/ or of low amplitude (4 patients) (total 31 patients; 67.8%). Penile CEP and/or tibial CEP could be obtained in all cases; however, protracted P1 peak latencies were detected in 15 (32.8%). The abnormalities of VUJ CEP did not correlate with the presence of peripheral neuropathy, while the abnormalities of penile CEP and/or tibial CEP invariably coincided with the presence of peripheral neuropathy. Although neither age nor the duration of diabetes correlated with abnormal CEPs as determined by any of the tests, insulin dependence correlated with abnormal penile CEP and to a lesser extent with VUJ CEP.We conclude that VUJ CEP is informative in evaluating the physiological condition of visceral afferents, and can be used in diagnosis of the early involvement of visceral afferents in diabetes mellitus.     

Antibodies to L-periaxin in sera of patients with peripheral neuropathy produce experimental sensory nerve conduction deficits

L-Periaxin is a PDZ-domain protein localized to the plasma membrane of myelinating Schwann cells and plays a key role in the stabilization of mature myelin in peripheral nerves. Mutations in L-periaxin have recently been described in some patients with demyelinating peripheral neuropathy, suggesting that disruption of L-periaxin function may result in nerve injury. In this study, we report the presence of autoantibodies to L-periaxin in sera from two of 12 patients with diabetes mellitus (type 2)-associated neuropathy and three of 17 patients with IgG monoclonal gammopathy of undetermined significance (MGUS) neuropathy, an autoimmune peripheral nerve disorder. By comparison, anti-L-periaxin antibodies were not present in sera from nine patients with IgM MGUS neuropathy or in sera from 10 healthy control subjects. The effect of anti-L-periaxin serum antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti-L-periaxin antibody, but not sera from age-matched control subjects, injected into the endoneurium of rat sciatic nerve significantly (p < 0.005, n = 3) attenuated sensory-evoked compound muscle action potential (CMAP) amplitudes in the absence of temporal dispersion. In contrast, motor-evoked CMAP amplitudes and latencies were not affected by intraneural injection of sera containing anti-L-periaxin antibody. Light and electron microscopy of anti-L-periaxin serum-injected nerves showed morphologic evidence of demyelination and axon enlargement. Depleting sera of anti-L-periaxin antibodies neutralized the serum-mediated effects on nerve function and nerve morphology. Together, these data support anti-L-periaxin antibody as the pathologic agent in these serum samples. We suggest that anti-L-periaxin antibodies, when present in sera of patients with IgG MGUS- or diabetes-associated peripheral neuropathy, may elicit sensory nerve conduction deficits.     

Neuromuscular diseases of AIDS

Neuromuscular diseases are common in acquired immune deficiency syndrome (AIDS). Although the clinical incidence of peripheral neuropathy has not been systematically studied, various reports suggest that up to 40% of AIDS patients have clinical symptoms. Biopsy and autopsy studies have shown an inflammatory neuropathy with a variable component of demyelination and axonal loss. Evidence of direct involvement by the human immunodeficiency virus (HIV) is scant. Immunosuppression followed by cytomegalovirus (CMV) infection appears to be a direct cause of polyradiculoneuropathy and perhaps other forms of peripheral neuropathy in AIDS. The clinical incidence of myopathy in AIDS is less clear, and clinically less appreciated than the neuropathy. Scattered reports have identified an inflammatory myopathy that does not appear to be due to direct HIV infection, but could be mediated by another human retrovirus. HIV seropositive patients being treated with antiviral drugs develop a unique set of neuromuscular diseases that must be distinguished from the non-drug-related conditions.     

Treatment of symptomatic diabetic neuropathy by surgical decompression of multiple peripheral nerves.

Symptomatic diabetic sensorimotor polyneuropathy is considered progressive and irreversible. The hypothesis that symptoms of diabetic neuropathy may be due to entrapment of peripheral nerves was investigated in a prospective study from 1982 to 1988 in which diabetics (38 type I, 22 type II) had surgical decompression of 154 peripheral nerves in 51 upper extremities and 31 lower extremities. Mean postoperative follow-up was 30 months (range 6 to 83 months). Considering the entire series, an excellent final result was noted for motor function in 44 percent and for sensory function in 67 percent of the decompressed nerves. Ten percent of the patients were not improved, and 2 percent were worse in sensorimotor function. Upper extremity nerve decompressions achieved better results than lower extremity nerve decompressions. Improvement in postoperative electrodiagnostic studies varied in relationship to the preoperative electrodiagnosis. Improvement was noted in 100 percent of those nerves with the preoperative diagnosis of "localized entrapment," 80 percent for "peripheral neuropathy with superimposed entrapment," and 50 percent for "peripheral neuropathy." Progressive neuropathy occurred in a nontreated limb of 50 percent of those patients whose surgically treated limb maintained improvement. The results of this study suggest that symptoms of sensorimotor diabetic neuropathy may be due partly to compression of multiple peripheral nerves. The results further suggest that surgical decompression of such nerves may result in symptomatic improvement.     

Neuropathy Associated with Hepatitis in Patients Maintained on Haemodialysis

During a study of peripheral nerve function in chronic renal failure, 11 patients who were being treated by chronic intermittent haemodialysis developed serum hepatitis. Before the infection there was a trend towards improvement in nerve conduction velocities. A pronounced deterioration in the conduction velocities in motor fibres of peripheral nerves occurred in association with hepatitis. In the months after recovery from the infection there was again a trend towards improvement in conduction velocities. We suggest that this reflects the occurrence of a peripheral neuropathy which is at least in part demyelinating. The neuropathy is related to the serum hepatitis, but its pathogenesis is indeterminate.     

High-Resolution Array CGH Profiling Identifies Na/K Transporting ATPase Interacting 2 (NKAIN2) as a Predisposing Candidate Gene in Neuroblastoma

Neuroblastoma (NB), the most common solid cancer in early childhood, usually occurs sporadically but also its familial occurance is known in 1-2% of NB patients. Germline mutations in the ALK and PHOX2B genes have been found in a subset of familial NBs. However, because some individuals harbouring mutations in these genes do not develop this tumor, additional genetic alterations appear to be required for NB pathogenesis. Herein, we studied an Italian family with three NB patients, two siblings and a first cousin, carrying an ALK germline-activating mutation R1192P, that was inherited from their unaffected mothers and with no mutations in the PHOX2B gene. A comparison between somatic and germline DNA copy number changes in the two affected siblings by a high resolution array-based Comparative Genomic Hybridization (CGH) analysis revealed a germline gain at NKAIN2 (Na/K transporting ATPase interacting 2) locus in one of the sibling, that was inherited from the parent who does not carry the ALK mutation. Surprisingly, NKAIN2 was expressed at high levels also in the affected sibling that lacks the genomic gain at this locus, clearly suggesting the existance of other regulatory mechanisms. High levels of NKAIN2 were detected in the MYCN-amplified NB cell lines and in the most aggressive NB lesions as well as in the peripheral blood of a large cohort of NB patients. Consistent with a role of NKAIN2 in NB development, NKAIN2 was down-regulated during all-trans retinoic acid differentiation in two NB cell lines. Taken together, these data indicate a potential role of NKAIN2 gene in NB growth and differentiation.     

Effect of chronic lithium on mechanical sensitivity and trabecular bone loss induced by type-1 diabetes mellitus in mice

BioMetals - Type-1 diabetes mellitus (T1DM) is a chronic condition characterized by long-term hyperglycemia that results in several complications such as painful peripheral neuropathy, bone...     

Elevated neurofilament light chain (NFL) mRNA levels in prediabetic peripheral neuropathy

Evidence suggests that peripheral nerve injury occurs during the early stages of disease with mild glycemic dysregulation. Two proteins, neuron-specific enolase (NSE) and neurofilament light chain (NFL), have been examined previously as possible markers of neuronal damage in the pathophysiology of neuropathies. Herein, we aimed to determine the potential value of circulatory NSE and NFL mRNA levels in prediabetic patients and in those with peripheral neuropathy. This prospective clinical study included 45 prediabetic patients and 30 age- and sex-matched controls. All prediabetic patients were assessed with respect to diabetes-related microvascular complications, such as peripheral neuropathy, retinopathy and nephropathy. mRNA levels of NSE and NFL were determined in the blood by real-time polymerase chain reaction. NSE mRNA levels were similar between prediabetic and control groups (p > 0.05), whereas NFL mRNA levels were significantly higher in prediabetics than in controls (p < 0.001). NSE mRNA levels did not significantly differ between prediabetic patients with and without peripheral neuropathy (p > 0.05), while NFL mRNA levels were significantly higher in prediabetics with peripheral neuropathy than in those without (p = 0.038). According to correlation analysis, NFL mRNA levels were positively correlated with the Douleur Neuropathique 4 questionnaire score in prediabetic patients (r = 0.302, p = 0.044). This is the first study to suggest blood NFL mRNA as a surrogate marker for early prediction of prediabetic peripheral neuropathy, while NSE mRNA levels may be of no diagnostic value in prediabetic patients.     

Alterations in circulating angiogenic and anti‐angiogenic factors in type 2 diabetic patients with neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. There is an increased attention directed towards the role of angiogenic factors including vascular endothelial growth factor (VEGF) and anti‐angiogenic factors including soluble endoglin (sEng) as contributors to diabetic microvascular complications including neuropathy. The purposes of this study were to determine the role of these angiogenesis regulators in the prognosis of DPN. The study group included 60 patients with type 2 diabetes mellitus (T2DM) and 20 clinically healthy individuals. The patients were divided into two groups. Group I included 20 T2DM patients without peripheral neuropathy, and Group II consisted of 40 T2DM patients with DPN. In all groups, plasma VEGF, sEng and endothelin‐1 (ET‐1), nitric oxide and ET‐1 mRNA were estimated. Plasma levels of VEGF, sEng, ET‐1 and nitric oxide were significantly elevated in diabetic patients (Groups I and II) compared with healthy control subjects, with a higher increase in their levels in patients with DPN compared with diabetic patients without peripheral neuropathy. Measurement of plasma levels of angiogenesis‐related biomarkers in high‐risk diabetic patients might identify who later develop DPN, thus providing opportunities for early detection and targets for novel treatments. Copyright © 2013 John Wiley & Sons, Ltd.     

Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats

Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain. For this reason, the present study was aimed to address the induction of pain modalities and spinal glial expression after streptozotocin injection as compared with that of zymosan inflammation in the rat. Evaluation of pain behavior by either thermal or mechanical stimuli was performed at 3 weeks or 5 hours after either intravenous streptozotocin or zymosan. Degrees of pain were divided into 4 groups: severe, moderate, mild, and non-pain induction. On the mechanical allodynia test, zymosan evoked predominantly a severe type of pain, whereas streptozotocin induced a weak degree of pain (severe+moderate: 57.1%). Although zymosan did not evoke cold allodynia, streptozotocin evoked stronger pain behavior, compared with zymosan (severe+moderate: 50.0%). On the other hand, the high incidence of thermal hyperalgesia (severe+moderate: 90.0%) and mechanical hyperalgesia (severe+moderate: 85.7%) by streptozotocin was observed, as similar to that of zymosan. In the spinal cord, the increase of microglia and astrocyte was evident by streptozotocin, only microglia was activated by zymosan. Therefore, it is recommended that the selection of mechanical and thermal hyperalgesia is suitable for the evaluation of streptozotocin induced diabetic peripheral neuropathy. Moreover, spinal glial activation may be considered an important factor.     

Characterization of a phospholipid antigen reacting with serum antibody in patients with peripheral neuropathies and paraproteinemia

A phospholipid antigen that reacted with the serum antibody from a patient with peripheral neuropathy and paraproteinemia with both impaired sensory and motor functions, but not with sera from patients with only impaired sensory functions and healthy controls, was purified from bovine cauda equina as a minor component with a concentration of about 0.6 µg per gram wet-weight tissue. The structure of the phospholipid was characterized as lysophosphatidylinositol by means of thin-layer chromatography, gas–liquid chromatography, and negative-ion fast-atom-bombardment mass spectrometry. The major fatty acid component of this phospholipid was stearic acid (> 81%). Our data suggest the possible involvement of a lysophospholipid antigen in the immunopathogenesis of peripheral neuropathies with severe motor and sensory dysfunctions. There is an intriguing possibility that the difference in immunoreactivity of serum antibodies may underlie the differential clinical manifestations in patients with peripheral neuropathy and paraproteinemia.