Elevated intrathecal antibodies against the medium neurofilament subunit in multiple sclerosis.

Neurofilaments are cytoskeletal proteins localized within axons, which may interact with the immune system during and following tissue destruction in multiple sclerosis (MS). Antibodies against the medium neurofilament subunit synthesized intrathecally may reflect axonal damage in MS patients. Both immunoglobulin G (IgG) and M (IgM) responses against the purified native medium subunit of neurofilaments (NFM) using enzyme-linked immunosorbent assay (ELISA) were determined in paired serum and cerebrospinal fluid samples obtained from 49 MS patients, 16 normal controls (CN), 21 control patients with miscellaneous diseases (CD) and 14 patients with neurodegenerative disorders (CDEG). Intrathecal production of IgM and IgG antibodies to NFM were elevated in MS patients compared with the CN or CD groups (p<0.04 for IgM, p<0.01 for IgG). The increase was present in all the MS courses (relapsing-remitting, primary and secondary progressive). Similar local anti-NFM IgG and IgM synthesis occurred in the MS and CDEG groups. MS patients with short and long disease duration did not differ in terms of their anti-NFM IgM and IgG responses. Repeated examinations showed stable intrathecal anti-NFM production. Intrathecal IgG and IgM antibodies against NFM were increased in MS patients and may serve as a potential marker for axonal pathology. The extent of anti-NFM levels did not correspond to any individualized clinical profiles of MS patients.

Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients.

BACKGROUND: The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. METHODS: 29 HD patients were randomized into two groups: 15 patients were treated orally with 400 mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical--TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. RESULTS: Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23+/-11.94 vs. 11.41+/-1.94 mIU/L, p<0.001; CRP: 5.20+/-3.50 vs. 3.40+/-3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. CONCLUSION: Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.

Advanced glycation end-products in patients with chronic alcohol misuse.

AIMS: The aim of our study was to determine serum levels of advanced glycation end-products (AGE) in patients with chronic alcohol misuse and to examine their relationship to markers of nutrition and inflammation. METHODS: The study group consisted of 23 heavy alcohol drinkers treated for chronic alcohol misuse and 22 healthy controls. Studied parameters included AGE (fluorescence, CML - carboxymethyllysine and pentosidine), lipids, glucose, albumin, leptin, prealbumin, C-reactive protein (CRP) and pregnancy-associated plasma protein A (PAPP-A). RESULTS: AGE fluorescence was significantly higher in chronic alcoholic patients than in healthy subjects (4.3 +/- 0.7 x 10(3) vs 3.7 +/- 0.5 x 10(3) AU/g protein, P < 0.005), while CML was only slightly but not significantly elevated (569.1 +/- 106.6 vs 545.5 +/- 85.8 microg/l) and pentosidine levels did not differ (105.4 +/- 29 vs 102.2 +/- 23 nmol/l). In alcoholics, AGE correlate significantly negatively with leptin (r = -0.46, P < 0.05) and pentosidine with prealbumin (r = -0.43, P < 0.05), otherwise there was no relationship between AGE and other biochemical parameters (glucose, cholesterol, albumin, CRP, PAPP-A). CONCLUSION: Our findings suggest a more complex relationship among advanced glycation, oxidative stress and metabolism of ethanol and their link to nutrition and nutrition-associated parameters. AGE as a result of oxidative stress might be similarly linked to increased cardiovascular risk of heavy alcohol drinkers, as are malnutrition and inflammation; however, further studies are needed to confirm this hypothesis.

Increased levels of pregnancy-associated plasma protein-A in patients with hypercholesterolemia: the effect of atorvastatin treatment.

BACKGROUND: Serum levels of pregnancy-associated plasma protein-A (PAPP-A) have recently been linked to plaque instability and are increased in acute coronary syndromes. The relation between PAPP-A levels and coronary risk factors, namely blood lipids, has not been studied to date. We have therefore investigated whether serum PAPP-A levels are increased in asymptomatic hypercholesterolemic subjects and whether PAPP-A levels are influenced by atorvastatin therapy. METHODS: We examined 27 subjects with isolated hypercholesterolemia free of manifest vascular disease and 29 age-matched healthy control subjects. Patients were examined at baseline and after 10 weeks of atorvastatin treatment (20 mg/d). RESULTS: In untreated hypercholesterolemic subjects, PAPP-A levels were significantly higher than in control subjects (8.02 +/- 1.86 mU/L vs 6.50 +/- 2.54 mU/L, P =.018). There was no correlation between PAPP-A levels and serum lipid levels. Atorvastatin treatment reduced total and LDL-cholesterol by 31% and 40%, respectively. Despite this profound lipid lowering, there was no significant change in the serum PAPP-A levels. CONCLUSIONS: PAPP-A levels are elevated in hypercholesterolemic subjects without clinical signs of atherosclerosis. PAPP-A may therefore not only reflect plaque instability but also serve as a marker of total atherosclerotic burden in asymptomatic subjects with hyperlipidemia. However, PAPP-A levels are not influenced by atorvastatin treatment.

Glycoxidation and inflammation in chronic haemodialysis patients.

BACKGROUND: Uraemia and haemodialysis treatment are associated with microinflammation and oxidative as well as carbonyl stress, which result in enhanced formation of glycoxidation products. Although both glycoxidation and inflammation can contribute to severe vascular and cardiovascular complications, the role that these pathogenic mechanisms play in the complex response of the whole organism remains to be elucidated. METHODS: We performed a cross-sectional study in 34 clinically stable chronic haemodialysis patients and in 14 healthy controls while determining serum concentrations of pentosidine, fluorescent advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs) and acute phase reactants. We further assessed the relationship between these glycoxidation products and parameters of inflammation. RESULTS: Glycoxidation products as well as certain acute phase reactants were elevated in haemodialysis patients. There were significant correlations between AOPPs and inflammatory parameters such as orosomucoid (0.39, P < 0.05), fibrinogen (0.49, P < 0.05) and pregnancy-associated protein A (PAPP-A; 0.46, P < 0.05), but no correlations between pentosidine or fluorescent AGEs and any of the inflammatory parameters. CONCLUSION: Oxidative damage showed a closer relationship to inflammation than advanced glycation (glycoxidation). AOPPs may represent a superior acute biochemical marker, whereas AGEs may better describe chronic long-lasting damage.