Proteins In Nervous Tissue Research Articles

Immunochemical markers of effect under exposure to risk factors causing vibration disease of different etiogenesis: сomparative assessment

In recent years, it has become especially vital to identify prognostic risks of health disorders in workers exposed to harmful occupational factors. This is necessary for substantiating an occupational origin of a disease and biomarkers of exposure and for optimizing the occupational risk assessment methodology. The aim of this study was to compare and analyze immunochemical markers of effect (cytokines, heat shock proteins, and neuronal antibodies (AB)) in blood serum of patients with vibration disease (VD) induced by exposure to different types of vi-bration in order to substantiate the most informative diagnostic risk indicators concerning the disease development and clinical course. Cytokines, heat shock proteins, and antibodies to regulatory proteins of nervous tissue were identified in blood by ELISA tests. We established unidirectional statistically significantly more apparent changes in patients who had VD caused by combined exposure to both whole body vibration and local vibration against those who had VD caused by exposure to local vibration only. These changes included hyperactivated pro-inflammatory reactions of the immune response (IL-1β, TNF-α, INFγ), growing concentrations of antibodies to proteins: S-100, MBP, NF-200, GFAP, and voltage-gated Ca-channel. The differences were that patients with VD under combined exposure to both types of vibration had greater production of pro-inflammatory IL-8 and HSP27 whereas people with VD caused by exposure to local vibration only had a decrease in HSP70 levels. The study results confirmed more apparent neuro-immune inflammation in patients with VD caused by combined exposure to both whole body vibration and local vibration. This may indicate more significant risk factors of the disease and gives an opportunity to identify the most sensitive biomarkers eligible for diagnosing VD of different etiogenesis.

Сравнительная оценка иммунохимических маркеров эффекта при воздействии факторов риска вибрационной болезни различного этиогенеза

In recent years, it has become especially vital to identify prognostic risks of health disorders in workers exposed to harmful occupational factors. This is necessary for substantiating an occupational origin of a disease and biomarkers of exposure and for optimizing the occupational risk assessment methodology. The aim of this study was to compare and analyze immunochemical markers of effect (cytokines, heat shock proteins, and neuronal antibodies (AB)) in blood serum of patients with vibration disease (VD) induced by exposure to different types of vi-bration in order to substantiate the most informative diagnostic risk indicators concerning the disease development and clinical course. Cytokines, heat shock proteins, and antibodies to regulatory proteins of nervous tissue were identified in blood by ELISA tests. We established unidirectional statistically significantly more apparent changes in patients who had VD caused by combined exposure to both whole body vibration and local vibration against those who had VD caused by exposure to local vibration only. These changes included hyperactivated pro-inflammatory reactions of the immune response (IL-1β, TNF-α, INFγ), growing concentrations of antibodies to proteins: S-100, MBP, NF-200, GFAP, and voltage-gated Ca-channel. The differences were that patients with VD under combined exposure to both types of vibration had greater production of pro-inflammatory IL-8 and HSP27 whereas people with VD caused by exposure to local vibration only had a decrease in HSP70 levels. The study results confirmed more apparent neuro-immune inflammation in patients with VD caused by combined exposure to both whole body vibration and local vibration. This may indicate more significant risk factors of the disease and gives an opportunity to identify the most sensitive biomarkers eligible for diagnosing VD of different etiogenesis.

Changes in Neuronal Antibody and S100β Protein Content as a Risk Factor for Occupational Neurointoxication

The production of the vinyl chloride (VC) still extremely popular in many countries of the world today. The aim of this research was to study changes in the content of S100β protein and antibodies to nerve tissue proteins as regulators of the nervous system in workers in the production of vinyl chloride, depending on the severity of the pathological process. Men working in the production of VC were examined. There are 53 healthy trained workers without signs of disorders of neuro-mental status and 26 patients with initial manifestations of neurointoxication with vinyl chloride among them. The concentration of S100β protein and neurotrophic antibodies (NAB) in blood serum was determined by solid-phase enzyme immunoassay. The more pronounced increase in S100β protein was found in persons with initial manifestations of neurointoxication, compared with trained healthy workers. The involvement of autoimmune reactions in the processes of regulation of the nervous system through the production of antibodies (AB) to certain structures of the nervous tissue has been proved. It is shown that the intensity of autoimmune reactions and the spectrum of produced AB working in the production of VC depend on the duration of exposure and the stage of development of the neurointoxication. It was also established that the change in the synthesis of NAB to specific proteins of nervous tissue is associated with the deterioration of neurological status in trained healthy workers. The obtained results allow us to assess the degree of interest of certain structures of the nervous tissue – bioregulators of the nervous system in the development of neurological disorders. Revealed an increase in serum concentrations of NAB to MAG, and in persons with clinical manifestations of asthenic disorder with autonomic dysfunction – NAB to DNA, NAB to S100β in trained healthy workers. These indicators can be regarded as a risk factor for occupational neurointoxication. The results obtained will improve the quality of diagnosis, especially in the early stages of the disease and, as a result, the formation of the most optimal treatment tactics.

Analysis of Protein Markers in Plasma of Patients with Drug Dependence Syndrome: Observational Clinical Study

Background. In drug addiction treatment, the diagnostic process is based on the chemical toxicological determination of the intoxication substrate or its metabolite. Laboratory monitoring and prediction issues that could form the basis of secondary prevention remain unresolved. Specific nervous tissue proteins are considered to be the most promising laboratory markers of drug pathology.Objective — to determine some potential biomarkers of protein-chemical nature in the plasma of patients with drug dependence syndrome.Methods. The study was conducted according to the design of an observational clinical trial at the Narcological Dispensary of Krasnodar Krai in the period from 07.2021 to 07.2022. The main group (group 2) included 31 patients diagnosed with substance dependence syndrome. The control group (group 1, n = 15) consisted of healthy subjects submitted to occupational medical examinations. During the detoxification-stabilization therapy and rehabilitation, 5 proteins were determined in the plasma: brainand glial-derived neurotrophic factors, neuron-specific enolase, alpha-synuclein and calcium-binding protein S100B. Statistical analysis of the data involved the Mann-Whitney test for comparing the values of the control and experimental groups and the Wilcoxon test for comparing the values of one group obtained at different stages of observation. The calculations were carried out using StatPlus version 7 (AnalystSoft Inc., USA).Results. A total of 31 patients were included in the main group, 18 of them were followed up with a diagnosis of opioid dependence syndrome (n = 11) or psychostimulant dependence syndrome (n = 7). Patients dropped out of the study due to their refusal to participate in the study or undergo rehabilitation, or due to relapse of the disease. When admitted to the hospital, patients indicated a 45% decrease in brain-derived neurotrophic factor in the plasma ( p < 0.001), and a 3.9-fold decrease after rehabilitation course ( p < 0.001). Glial-derived neurotrophic factor in the plasma exceeded the controls 1.9 times ( p < 0.001) upon admission to hospital, but rapidly returned to normal values thereafter. Level of neuron-specific enolase in the plasma was also poor, 36% lower than the controls ( p <0.001), but approached the control values by the end of rehabilitation.Conclusion. The study obtained data indicating the changes in neurotrophic factors in the blood plasma of patients with opioid or psychostimulant dependence. The rehabilitation period was marked by a relatively rapid improving level of neurotrophins; however, brain-derived neurotrophic factor remained reduced despite the successful treatment, which may indicate the irreversible changes.

Diagnostic value of IL-17 in neurointoxication with mercury

It is known that sufficient changes are observed in cellular and humoral links of immune system upon chronic exposure vapors of metallic mercury. In previous studies, upon development and in the course of the chronic mercury intoxication (CMI) we revealed pronounced regular changes of inflammatory mediators (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNFα), and showed an important role of autoimmune reactions affecting nervous tissue proteins. Over last 20 years, an increased interest was shown for interleukin 17 (IL-17) and its role in a number of inflammatory and autoimmune diseases. However, there is no data on its role in neurointoxication with mercury. Considering that IL-17 has proinflammatory activity and stimulates production of the individual cytokines, the goal of our work at the next stage of research, was to identify quantitative changes of serum IL-17 in patients with mercury neurointoxication of various severity, aiming to substantiate additional criteria for early and effective diagnosis of the disease.The study was performed in males chronically exposed to metallic mercury vapors with early signs of neurointoxication (n = 37), individuals diagnosed with CMI (n = 40), and “conditionally healthy” men (n = 34). Proper diagnosis confirmed by history of working contacts with a harmful industrial factor, and absence of comorbid pathologies served as inclusion criteria. Statistical processing of the results was carried out using the STATISTICA 6.0 application package (StatSoft, USA). The study has revealed a statistically significant increase in serum IL-17 concentrations, both in the patients with early signs of neurointoxication with metallic mercury vapors, and individuals with CMI, when compared with the comparison group, thus indicating its activation, and being consistent with results of several workers who showed an IL-17 increase in immunoinflammatory diseases. Correlation analysis has shown an association between IL-17 and inflammatory mediators, i.e., the patients with early signs of neurointoxication had an increased production of IL-17 accompanied by an increase in anti-inflammatory IL-10, whereas the CMI patients with an increase in IL-17 concentration showed a decrease in pro-inflammatory TNFα, thus confirming its role in immunopathogenesis of mercury neurointoxication. Further study of IL-17 involvement in the initiation and maintenance of chronic inflammation will not only contribute to better understanding of the disease origin, but also, most importantly, implication of novel, more effective treatments.

Changes in Antibodies against Nervous Tissue Proteins in Patients with Chronic Mercury Intoxication in the Post-Contact Period

Changes in Antibodies against Nervous Tissue Proteins in Patients with Chronic Mercury Intoxication in the Post-Contact Period

Autoantibodies in the serum of post-stroke patients with different clinical outcome

Natural autoantibodies (auto-Abs) of IgG class against nervous tissue proteins, as well as corresponding anti-idiotypic antibodies (AIAbs) are presented in serum of each healthy adult and their content are relatively constant among individuals. In opposite, in patients with disorders of the nervous system serum levels of such AIAbs were often found beyond the normal ranges. Characteristic changes of auto-Abs against protein S100, glial fibrillary acidic protein (GFAP), MP-65 protein and nervous growth factor (NGF) and corresponding immune reactivity were investigated in serum samples obtained from patients with ischemic stroke. Samples for investigation were collected at 3, 10, 21 days after stroke and 6 months later. Forty-two post-stroke patients were examined in acute period of disease and 6 months later. The follow-up was based NIHSS score. Outcomes were assessed with the Bartel Index at 6 month. Severity of post-stroke dementia was defined according to the DSM-IV and NINDS-AIREN. Auto-Abs against S100, GFAP, MP-65 and NGF as well as corresponding AIAbs were determined in patient serum by standard immuno-ferment assay (ELISA). In acute period of disease in 100% of post-stroke patients the serum immune reactivity of auto-Abs and AIAbs against proteins S100, GFAP, MP-65 and NGF were deviated compare to the same characteristics in serum samples of healthy persons ( P < 0.001). Sixth months later the deviations of serum immune reactivity were revealed in most part of post-stroke patients and relations between changed immune reactivity and clinical spate were found. The most characteristic feature of patients with post-stroke dementia was deviations of normal balance between pairs of specific auto-Abs and corresponding AIAbs. Changes in the serum content of auto-Abs against nervous tissue proteins and corresponding AIAbs in post-stroke patients may reflect intensity of reparative processes and probably could be used for prognostic aims of rehabilitation program success.

Influence of industrial vibration on the level of antibodies against regulatory proteins of the nervous tissue

We studied the concentration of antibodies (ABs) to the regulatory proteins of the nervous tissue revealed in the blood serum of healthy men working for a long period of time and of the patients suffering from the vibration-induced disease (VID). A characteristic feature of autoimmune response development in workers who are exposed to vibration for an extensive period of time is the decline in ABs against virtually all examined antigens (AGs), which indicates an overall reduction of immune reactivity in relation to nervous tissue proteins. At the same time, we discovered characteristic changes in certain AB concentrations, both in the spectrum and in the intensity, depending on the severity of a pathologic process. Changes in the AB concentration in long-term workers who do not exhibit signs of any health conditions induced by vibration may indicate nascent changes in the specialized structure of nervous tissue; for VID patients, the presence of changes in the levels of ABs may reflect continuous neuro-destructive processes in nervous tissue.

PROTEIN MARKERS OF THE HYPOXIC-ISCHEMIC INJURY OF THE CENTRAL NERVOUS SYSTEM IN THE PERINATAL PERIOD

Preeclampsia (gestosis) and eclampsia, as well as the acute intranatal hypoxy often act as trigger for the development of the perinatal hypoxic-ischemic brain injury. That is accompanied by such typical structural changes as periventricular leukomalacia (PVL) and intraventricular hemorrhages (IVH). The hypoxic-ischemic brain injury in the perinatal period can have such consequences as hydrocephaly, microcephaly, infantile cerebral paralysis (ICP), epilepsy and motormental retardation. It is not always possible to determine the disease gravity and forecast of the disease by routine methods of clinical, instrumental and laboratory examination. As it is proved, that the perinatal hypoxic-ischemic brain injury is always accompanied by the disruption of Blood-Brain-Barrier (BBB) permeability for neuron-specific proteins (NSP). NSP can be considered as markers of this pathologic process. Nowadays there are more or less details on 120 NSP, namely, non-enzyme neurospecific Са+ -binding proteins; non-enzyme NSP, responsible for adhesion and intercellular recognition processes; соntractile and cytoskeletal nervous tissue proteins; secreted regulatory and transport NSP; myeline proteins and glial NSP. To evaluate BBB status it is expedient to select from the variety of known NSP most studied proteins, being neurons’ and astrocytes’ markers. Such NSP are gliofibrillary acid protein, GFAP and neuronspecific enolase, NSE. In normal conditions the NSP are within BBB and can be almost undeterminable in the blood serum. In case of the BBB permeability disruption NSP penetrate to the peripheral blood flow and can be determined. The dynamic determination of the NSP in the blood serum can be expedient to evaluate the BBB resistance, to determine the degree of the CNS injury and the disease state forecast at children with perinatal hypoxic-ischemic brain injury.

Erratum to: A novel small molecule HSP90 inhibitor, NXD30001, differentially induces heat shock proteins in nervous tissue in culture and in vivo

Erratum to: A novel small molecule HSP90 inhibitor, NXD30001, differentially induces heat shock proteins in nervous tissue in culture and in vivo

A novel small molecule HSP90 inhibitor, NXD30001, differentially induces heat shock proteins in nervous tissue in culture and in vivo.

Heat shock proteins (HSPs) are attractive therapeutic targets for neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), characterized by aberrant formation of protein aggregates. Although motor neurons have a high threshold for activation of HSP genes, HSP90 inhibitors are effective inducers. This study evaluated NXD30001, a novel, small molecule HSP90 inhibitor based on the radicicol backbone, for its ability to induce neuronal HSPs and for efficacy in an experimental model of ALS based on mutations in superoxide-dismutase 1 (SOD1). In motor neurons of dissociated murine spinal cord cultures, NXD30001-induced expression of HSP70/HSPA1 (iHSP70) and its co-chaperone HSP40/DNAJ through activation of HSF1 and exhibited a protective profile against SOD1(G93A) similar to geldanamycin, but with less toxicity. Treatment prevented protein aggregation, mitochondrial fragmentation, and motor neuron death, important features of mutant SOD1 toxicity, but did not effectively prevent aberrant intracellular Ca(2+) accumulation. NXD30001 distributed to brain and spinal cord of wild-type and SOD1(G93A) transgenic mice following intraperitoneal injection; however, unlike in culture, in vivo levels of SOD1 were not reduced. NXD30001-induced expression of iHSP70 in skeletal and cardiac muscle and, to a lesser extent, in kidney, but not in liver, spinal cord, or brain, with either single or repeated administration. NXD30001 is a very useful experimental tool in culture, but these data point to the complex nature of HSP gene regulation in vivo and the necessity for early evaluation of the efficacy of novel HSP inducers in target tissues in vivo.

The functional expression and characterisation of a cysteine peptidase from the invasive stage of the neuropathogenic schistosome Trichobilharzia regenti

A transcriptional product of a gene encoding cathepsin B-like peptidase in the bird schistosome Trichobilharzia regenti was identified and cloned. The enzyme was named TrCB2 due to its 77% sequence similarity to cathepsin B2 from the important human parasite Schistosoma mansoni. The zymogen was expressed in the methylotropic yeast Pichia pastoris; procathepsin B2 underwent self-processing in yeast media. The peptidolytic activity of the recombinant enzyme was characterised using synthetic fluorogenic peptide substrates at optimal pH 6.0. Functional studies using different specific inhibitors proved the typical cathepsin B-like nature of the enzyme. The S2 subsite specificity profile of recombinant TrCB2 was obtained. Using monospecific antibodies against the recombinant enzyme, the presence of cathepsin B2 was confirmed in extracts from cercariae (infective stage) and schistosomula (early post-cercarial stage) of T. regenti on Western blots. Also, cross-reactivity was observed between T. regenti and S. mansoni cathepsins B2 in extracts of cercariae, schistosomula or adults. In T. regenti, the antisera localised the enzyme to post-acetabular penetration glands of cercariae implying an important role in the penetration of host skin. The ability of recombinant TrCB2 to degrade skin, serum and nervous tissue proteins was evident. Elastinolytic activity suggests that the enzyme might functionally substitute the histolytic role of the serine class elastase known from S. mansoni and Schistosoma haematobium but not found in Schistosoma japonicum or in bird schistosomes.

Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury.

BackgroundNF-κB binds to the κB motif to regulate transcription of genes involved in growth, immunity and inflammation, and plays a pivotal role in the production of pro-inflammatory cytokines after nerve injuries. The zinc finger protein ZAS3 also binds to the κB or similar motif. In addition to competition for common DNA sites, in vitro experiments have shown that ZAS3 can inhibit NF-κB via the association with TRAF2 to inhibit the nuclear translocation of NF-κB. However, the physiological significance of the ZAS3-mediated inhibition of NF-κB has not been demonstrated. The purpose of this study is to characterize ZAS3 proteins in nervous tissues and to use spinal nerve ligation, a neuropathic pain model, to demonstrate a functional relationship between ZAS3 and NF-κB.ResultsImmunohistochemical experiments show that ZAS3 is expressed in specific regions of the central and peripheral nervous system. Abundant ZAS3 expression is found in the trigeminal ganglion, hippocampal formation, dorsal root ganglia, and motoneurons. Low levels of ZAS3 expressions are also found in the cerebral cortex and in the grey matter of the spinal cord. In those nervous tissues, ZAS3 is expressed mainly in the cell bodies of neurons and astrocytes. Together with results of Western blot analyses, the data suggest that ZAS3 protein isoforms with differential cellular distribution are produced in a cell-specific manner. Further, neuropathic pain confirmed by persistent mechanical allodynia was manifested in rats seven days after L5 and L6 lumbar spinal nerve ligation. Changes in gene expression, including a decrease in ZAS3 and an increase in the p65 subunit of NF-κB were observed in dorsal root ganglion ipsilateral to the ligation when compared to the contralateral side.ConclusionZAS3 is expressed in nervous tissues involved in cognitive function and pain modulation. The down-regulation of ZAS3 after peripheral nerve injury may lead to activation of NF-κB, allowing Wallerian regeneration and induction of NF-κB-dependent gene expression, including pro-inflammatory cytokines. We propose that reciprocal changes in the expression of ZAS3 and NF-κB might generate neuropathic pain after peripheral nerve injury.

Myocyte enhancer factor-2 transcription factors in neuronal differentiation and survival.

Myocyte enhancer factor-2 (MEF2) transcription factors regulate genes that control critical cellular processes including proliferation, differentiation, and survival. Although MEF2 proteins were first identified as transcription factors that bound A/T rich DNA sequences and controlled muscle-specific genes during myogenic development, it is now apparent that MEF2 transcription factors are also highly expressed in neurons and are critical determinants of neuronal differentiation and fate. Here we focus our discussion on the role of MEF2 proteins in nervous tissue and the regulation of these transcription factors by calcium and phosphorylation signaling pathways.

LR white post-embedding colloidal gold method to immunostain MBP, P0, NF and S100 in glutaraldehyde fixed peripheral nerve tissue.

A variety of immunocytochemical techniques are now widely used for the electron and light microscopic examination of biological samples. They are employed routinely for investigating the role of certain proteins in nervous tissue. Immunoelectron microscopic studies require the tissue to be fixed and embedded in a solid support, which may disrupt cellular structures and destroy crucial antigens. A technique of post-embedding with LR white resin has been developed, and it has been shown that certain antigens tolerate fixation with glutaraldehyde. In this study, we optimized a previous post-embedding method using low-water-miscible low-temperature embedding resin (LR white) to immunostain MBP, P0, NF and S100 proteins in peripheral nerves fixed with a relatively high concentration of glutaraldehyde found to be compatible with the morphology of normally compacted nerve fibers from humans and adult animals. The main difference in the procedures described here from previous ones is the elimination of vibratome sectioning, rendering this immunostaining technique more accessible to neuropathological laboratories using standard equipment for the ultrastructural study of peripheral nerves. It may prove of value for localization and quantification of these proteins in normal and pathological conditions.

Identifying novel proteins in nervous tissue using microsequencing techniques.

Identifying signaling molecules that participate in pathways leading from receptor activation to changes in gene expression in cells is the fundamental focus of many research endeavors. For example, neurotrophins interacting with their trk receptors mediate a number of cellular effects, including cell differentiation, neurite outgrowth, and neuronal survival (1, 2, 3, 4). This results from specific protein-protein interactions in different signaling pathways. The primary aim of many research efforts is to elucidate these signaling pathways by identifying the proteins that participate in them. The most common method for isolating protein-protein interactions is by coimmunoprecipitation of protein complexes from cell lysates, where an appropriate antibody is available. Isolated proteins are separated using polyacrylamide gel electrophoresis and then transferred from the gel to a membrane support and identified using immunoblotting. These techniques have been well documented (see refs. 5, 6, 7, 8). The major drawback of this technique is its inability to find novel proteins. Currently, the best technique available for identifying novel proteins is by chemical or enzymatic fragmentation of isolated proteins in a gel matrix following one- or two-dimensional electrophoresis or after electrotransfer onto a suitable membrane (9,10). In most cases, reverse-phase high-performance liquid chromatography (RP-HPCL) is used to separate the cleavage fragments.

Fatty acid-binding proteins of nervous tissue.

Fatty acid-binding proteins (FABPs) are cytosolic 14-15 kDa proteins, which are supposed to be involved in fatty acid (FA) uptake, transport, and targeting. They may modulate FA concentration and in this way influence function of enzymes, membranes, ion channels and receptors, and gene expression and cellular growth and differentiation. Nine FABP types can be discerned with a specific tissue distribution. In spite of 30-70% amino acid sequence identity, they have a similar tertiary, beta-clam structure in which the FA is bound. Nervous tissue contains four FABP types with a distinct spatio-temporal distribution. Myelin (M)-FABP is only present in the peripheral nerves, brain (B)-FABP and epidermal (E)-FABP mainly in glial cells and neurons, respectively of pre- and perinatal brain, and heart (H)-FABP in adult brain. Possible functions of FABPs in the nervous system are discussed. Binding studies with a range of physiological FA showed no large differences between recombinant proteins of the four human FABP types in binding specificity and affinity, also not for polyunsaturated FA (PUFA). The transfer of FA from fixed liposomes to mitochondria was similarly promoted by the four types. A marked difference in conformational stability was observed with H-FABP > B-FABP > M-FABP > E-FABP. Surface epitopes of H-FABP showed reaction with anti-B-FABP antibodies, but no other cross-reactivity of FABP type and heterologous antibodies was observed. The functional significance of the distinct spatio-temporal pattern of the four FABP types remains to be elucidated.

Reduction of advanced glycation end-product (AGE) levels in nervous tissue proteins of diabetic Lewis rats following islet transplants is related to different durations of poor metabolic control.

Advanced glycation end-products (AGEs) are irreversible compounds which, by abnormally accumulating over proteins as a consequence of diabetic hyperglycaemia, can damage tissues and thus contribute to the pathogenesis of diabetic complications. This study was performed to evaluate whether restoration of euglycaemia by islet transplantation modifies AGE accumulation in central and peripheral nervous tissue proteins and, as a comparison, in proteins from a non-nervous tissue. Two groups of streptozotocin diabetic inbred Lewis rats with 4 (T1) or 8 (T2) months disease duration were grafted into the liver via the portal vein with 1200-1500 islets freshly isolated from normal Lewis rats. Transplanted rats, age-matched control and diabetic rats studied in parallel, were followed for a further 4-month period. At study conclusion, glycaemia, glycated haemoglobin and body weight were measured in all animals, and an oral glucose tolerance test (OGTT) performed in transplanted rats. AGE levels in cerebral cortex, spinal cord, sciatic nerve proteins and tail tendon collagen were measured by enzyme-linked immunosorbent assay (ELISA). Transplanted animal OGTTs were within normal limits, as were glycaemia and glycated haemoglobin. Diabetic animal AGEs were significantly higher than those of control animals. Protein AGE values were reduced in many transplanted animals compared to diabetic animals, reaching statistical significance in spinal cord (P < 0.05), sciatic nerve (P < 0.02) and tail tendon collagen (P < 0.05) of T1 animals. Thus, return to euglycaemia following islet transplantation after 4 months of diabetes with poor metabolic control reduces AGE accumulation rate in the protein fractions of the mixed and purely peripheral nervous tissues (spinal cord and sciatic nerve, respectively). However, after a double duration of bad metabolic control, a statistically significant AGE reduction has not been achieved in any of the tissues, suggesting the importance of an early therapeutic intervention to prevent the possibly pathological accumulation of AGEs in nervous and other proteins.

Reduction of advanced glycation end-product (AGE) levels in nervous tissue proteins of diabetic Lewis rats following islet transplants is related to different durations of poor metabolic control

Reduction of advanced glycation end-product (AGE) levels in nervous tissue proteins of diabetic Lewis rats following islet transplants is related to different durations of poor metabolic control

Change in the titers of serum IgG-class autoantibodies to some nervous tissue proteins in patients with life-threatening arrhythmias

Titers of autoantibodies to nerve growth factor, water-soluble astrocytic protein S-100, glial fibrillary acidic protein, and MP-65 membrane protein of the nervous cell superfamily of integrins was determined by solid-phase immunoenzyme assay in healthy children and in children with the Romano-Ward and sick sinus syndromes. Immunoreactivity to these antigens was either increased or decreased in 20% of sick children in comparison with that of healthy children of the same age.