RESUMEN
To investigate the aetiology of chronic idiopathic axonal polyneuropathy (CIAP), 50 consecutive patients were compared with 50 control subjects from the same region. There were 22 patients with painful neuropathy and 28 without pain, 26 with sensory neuropathy and 24 with sensory and motor neuropathy. The typical picture was a gradually progressive sensory or sensory and motor neuropathy. It caused mild or sometimes moderate disability, and reduced the quality of life. There was no evidence that alcohol, venous insufficiency, arterial disease or antibodies to peripheral nerve antigens played a significant part. There was a possible history of peripheral neuropathy in the first or second-degree relatives of six patients and no controls (P = 0.01), and claw toes were present in 12 patients and four controls (P = 0.03). Thirty-two per cent of the patients and 14% of the controls had impaired glucose tolerance or fasting hyperglycaemia but, after adjusting for age and sex, the difference was not significant (P = 0.45), even in the painful neuropathy subgroup. The mean (SD) fasting insulin concentrations were significantly (P = 0.01) higher in the patients [75.9 (44.4) mmol/l] than the controls [47.3 (37.9) mmol/l], and the mean was higher still in the painful neuropathy subgroup [92.2 (37.1) mmol/l] (P < 0.0001). However, insulin resistance as assessed using the homeostasis model assessment formula was not significantly greater in the patients, even in those with pain, than the controls. After adjustment for body mass index as well as age and sex, there was no significant difference in the serum cholesterol concentrations, but there were significantly higher triglyceride concentrations in the patients [mean 1.90 (1.41) mmol/l] than the controls [mean 1.25 (0.79] mmol/l) (P = 0.02). In the patients with painful peripheral neuropathy, the mean triglyceride concentration was 2.37 (1.72), which was even more significantly greater compared with the controls (P = 0.003). In conclusion, CIAP is a heterogeneous condition. A logistic regression analysis identified environmental toxin exposure and hypertriglyceridaemia, but not glucose intolerance or alcohol overuse as significant risk factors that deserve further investigation as possible causes of CIAP.
Asunto(s)
Polineuropatías/etiología , Anciano , Antropometría , Ácido Ascórbico/sangre , Autoanticuerpos/sangre , Estudios de Casos y Controles , Evaluación de la Discapacidad , Femenino , Intolerancia a la Glucosa/complicaciones , Sustancias Peligrosas/toxicidad , Humanos , Hipertrigliceridemia/complicaciones , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Dolor/etiología , Polineuropatías/genética , Polineuropatías/fisiopatología , Calidad de Vida , Factores de Riesgo , Vitamina E/sangreRESUMEN
Previously, we have investigated the potential for a pro-oxidant interaction of iron and ascorbate in vivo in iron and ascorbate cosupplementation or ascorbate supplementation studies. In this study, for the first time, the effects of iron supplementation on oxidative damage to DNA in healthy individuals with plasma ascorbate levels at the upper end of the normal range were examined. Forty female and male volunteers (mean plasma ascorbate approximately equal to 70 micromol/L) were supplemented with a daily dose of syrup (ferrous glycine sulphate equivalent to 12.5 mg iron) for 6 weeks. Serum ferritin, transferrin bound iron, % saturation of transferrin and plasma ascorbate were assessed and the mean dietary intakes of all subjects were estimated through food frequency questionnaires. Oxidative damage to DNA bases from white blood cells was measured by gas chromatography/mass spectrometry with selected-ion monitoring (GC/MS-SIM), using isotope-labelled standards for quantification. Iron supplementation did not affect any of the iron status parameters. There were also no detrimental effects, over the period under investigation, in terms of oxidative damage to DNA. However, the effects of larger doses or of longer supplementation periods should also be investigated.
Asunto(s)
Ácido Ascórbico/sangre , Daño del ADN/efectos de los fármacos , Suplementos Dietéticos/efectos adversos , Hierro/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Adulto , Femenino , Ferritinas/sangre , Humanos , Masculino , Persona de Mediana Edad , Transferrina/metabolismoRESUMEN
The comparison was undertaken between the effects of ascorbate versus ascorbate plus iron supplementation on DNA damage. Twenty healthy subjects with initial levels of plasma ascorbate of 67.2 +/- 23.3 micromol/l were randomly assigned to and cycled through one of three supplementation regimes: placebo, 260 mg/d ascorbate, 260 mg/d ascorbate plus 14 mg/d iron for 6 weeks separated by 8-week washout periods. Supplementation did not cause a rise in total oxidative DNA damage measured by GC-MS. However, a significant decrease occurred in levels of 8-oxo-7,8-dihydroguanine by ascorbate supplementation and 5-hydroxymethyl uracil by both ascorbate and ascorbate plus iron supplementation, relative to the pre-supplemental levels but not to the placebo group. In addition, levels of 5-hydroxymethyl hydantoin and 5-hydroxy cytosine increased significantly, only relative to pre-supplementation, by ascorbate plus iron treatment. No compelling evidence for a pro-oxidant effect of ascorbate supplementation, in the presence or absence of iron, on DNA base damage was observed.
Asunto(s)
Ácido Ascórbico/farmacología , Daño del ADN , ADN/efectos de los fármacos , Hierro/farmacología , Oxidantes/farmacología , Adulto , Análisis de Varianza , Ácido Ascórbico/sangre , Estudios Cruzados , ADN/metabolismo , Dieta , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Ingestión de Alimentos , Femenino , Humanos , Hierro/sangre , Masculino , Persona de Mediana EdadRESUMEN
A method for the screening of antioxidant activity is reported as a decolorization assay applicable to both lipophilic and hydrophilic antioxidants, including flavonoids, hydroxycinnamates, carotenoids, and plasma antioxidants. The pre-formed radical monocation of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+) is generated by oxidation of ABTS with potassium persulfate and is reduced in the presence of such hydrogen-donating antioxidants. The influences of both the concentration of antioxidant and duration of reaction on the inhibition of the radical cation absorption are taken into account when determining the antioxidant activity. This assay clearly improves the original TEAC assay (the ferryl myoglobin/ABTS assay) for the determination of antioxidant activity in a number of ways. First, the chemistry involves the direct generation of the ABTS radical monocation with no involvement of an intermediary radical. Second, it is a decolorization assay; thus the radical cation is pre-formed prior to addition of antioxidant test systems, rather than the generation of the radical taking place continually in the presence of the antioxidant. Hence the results obtained with the improved system may not always be directly comparable with those obtained using the original TEAC assay. Third, it is applicable to both aqueous and lipophilic systems.