RESUMEN
BACKGROUND: Panadol Extend (PEx) is an over-the-counter, modified-release formulation of paracetamol. Each 665 mg tablet contains 69% slow-release and 31% immediate-release paracetamol. In simulated human overdose, PEx exhibits lower and later peak serum concentrations and a lower area-under-the-curve (AUC) than comparable doses of immediate-release paracetamol (APAP-IR). The lower AUC might result from incomplete absorption of paracetamol or simultaneous metabolism with absorption. OBJECTIVE: Do differences in pharmacokinetics (PK) between PEx and APAP-IR result from incomplete absorption or simultaneous absorption and metabolism of paracetamol? METHODS: Cross-over study of 80 mg/kg of PEx or APAP-IR in nine volunteers. Serial plasma paracetamol, glucuronide, sulphate and cysteine metabolite estimates performed over 24 h. Peak plasma concentration (Cmax), AUC((0-∞),) time to peak concentration (Tmax) and elimination half-life (t(1/2) ) were compared. RESULTS: PEx exhibited significantly lower paracetamol Cmax (252.33 µmol/L vs 565.56 µmol/L, P= 0.0421), AUC((0-∞)) (2133 µmol/h/L vs 2637 µmol/h/L, P= 0.0004) and delayed Tmax (2.889 h vs 1.389 h, P= 0.0189) than APAP-IR. Sulphate metabolite PK parameters for both preparations, PEx vs APAP-IR, showed similar AUC((0-∞)) (1369 µmol/h/L vs 1089 µmol/h/L), Tmax (3.889 h vs 4.444 h), Cmax (95.889 µmol/L vs 95.889 µmol/L) and t(1/2) (3.895 h vs 3.810 h). Glucuronide metabolite concentrations revealed that PEx produced a lower Cmax (257.44 µmol/L vs 335.22 µmol/L, P= 0.0239) than APAP-IR. All other pharmacokinetic parameters were similar. Cysteine metabolite was not detected. CONCLUSION: There were minor differences between the PK parameters of the two major paracetamol metabolites of these two preparations in simulated overdose. The variability in paracetamol AUC seen between the two preparations in moderate overdose might be explained by concurrent metabolism of paracetamol during slower absorption with PEx.
Asunto(s)
Acetaminofén/farmacocinética , Analgésicos no Narcóticos/farmacocinética , Modelos Biológicos , Medicamentos sin Prescripción/farmacocinética , Mal Uso de Medicamentos de Venta con Receta , Acetaminofén/efectos adversos , Adulto , Analgésicos no Narcóticos/efectos adversos , Área Bajo la Curva , Australia , Estudios Cruzados , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/farmacocinética , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Humanos , Estudios Longitudinales , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Medicamentos sin Prescripción/efectos adversosRESUMEN
BACKGROUND: Panadol Osteo (GlaxoSmithKline) is a modified-release paracetamol formulation marketed in Australia and New Zealand, comprising 33% immediate and 66% sustained-release fractions. In overdose, absorption may be delayed and the paracetamol treatment nomogram can miss potentially toxic paracetamol concentrations if only one serum estimate is taken. We report a massive ingestion of Panadol Osteo with biphasic, prolonged absorption requiring extended treatment with N-acetylcysteine. CASE REPORT: A 72-year-old female presented 2 hours after ingesting 119x665 mg (1 g/kg) of Panadol Osteo and 5x30 mg mirtazepine. The patient was drowsy (GCS14). Activated charcoal was not administered. Her pulse was 70 bpm, BP 149/63 mmHg with an unremarkable physical examination. Two-hour paracetamol concentration was 2628 micromol/L falling to 2216 micromol/L, 4 hours post-ingestion. Admission acid-base status and liver function were normal. N-acetylcysteine was commenced using the standard 21-hour intravenous protocol and continued for 5 days (total dose 700 mg/kg) until paracetamol concentrations were undetectable. Serum paracetamol peaked a second time, 12 hours post-ingestion, at 3040 micromol/L and paracetamol absorption continued for 35 hours post-ingestion. Despite early administration of N-acetylcysteine, serum AST/ALT peaked at 384 and 541 IU/L on day 3 with normal coagulation profile. CONCLUSIONS: Massive ingestion of modified-release paracetamol (Panadol Osteo) may result in biphasic and prolonged paracetamol absorption requiring extended administration of N-acetylcysteine. Current intravenous dosing regimens may not provide enough N-acetylcysteine to effectively metabolise paracetamol to non-toxic adducts.
Asunto(s)
Acetaminofén/efectos adversos , Acetilcisteína/uso terapéutico , Analgésicos no Narcóticos/efectos adversos , Depuradores de Radicales Libres/uso terapéutico , Acetaminofén/administración & dosificación , Acetaminofén/farmacocinética , Anciano , Alanina Transaminasa/sangre , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/farmacocinética , Aspartato Aminotransferasas/sangre , Preparaciones de Acción Retardada , Sobredosis de Droga , Femenino , Humanos , Infusiones IntravenosasRESUMEN
To investigate the pharmacokinetics of naloxone in healthy volunteers, we undertook an open-label crossover study in which six male volunteers received naloxone on five occasions: intravenous (0.8 mg), intramuscular (0.8 mg), intranasal (0.8 mg), intravenous (2 mg), and intranasal (2 mg). Samples were collected for 4 hours after administration for 128 samples in total. A population pharmacokinetic analysis was undertaken using NONMEM. The data were best described by a three-compartment model with first-order absorption for intramuscular and intranasal administration, between-subject variability on clearance and central volume, lean body weight on clearance, and weight on central volume. Relative bioavailability of intramuscular and intranasal naloxone was 36% and 4%, respectively. The final parameter estimates were clearance, 91 L/hr; central volume, 2.87 L; first peripheral compartment volume, 1.49 L, second peripheral compartment volume, 33.6 L; first intercompartmental clearance, 5.66 L/hr; second intercompartmental clearance, 29.8 L/hr; Ka (intramuscular), 0.65; and Ka (intranasal), 1.52. Median time to peak concentration for intramuscular naloxone was 12 minutes and for intranasal, 6 to 9 minutes. A combination of intravenous and intramuscular naloxone provided immediate high and then detectable concentrations for 4 hours. Intranasal naloxone had poor bioavailability compared with intramuscular. Combined intravenous and intramuscular administration may be a useful alternative to naloxone infusions.
Asunto(s)
Naloxona/administración & dosificación , Naloxona/farmacocinética , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/farmacocinética , Administración Intranasal , Adulto , Algoritmos , Área Bajo la Curva , Simulación por Computador , Estudios Cruzados , Interpretación Estadística de Datos , Semivida , Humanos , Inyecciones Intramusculares , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Adulto JovenRESUMEN
OBJECTIVE: While renal failure greatly increases coronary risk, mild renal impairment is not usually considered a major risk factor. To explore this we assessed relations between measures of mild impairment of renal function and coronary artery disease (CAD) together with other risk factors. METHODS AND RESULTS: In 408 consecutive patients aged 75 years or less with angiographically defined normal or obstructed coronary arteries and an estimated glomerular filtration rate (eGFR) >45 mL/min per 1.73 m(2), we assessed relations between severity of CAD and levels of plasma cystatin C, creatinine, eGFR, lipid profile, C-reactive protein (CRP), homocysteine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). With univariate ANOVA, the severity of CAD was significantly associated with all indices of renal function: increased plasma cystatin C (p=0.003) and creatinine (p=0.004) and decreased eGFR (p=0.008). An elevated plasma cystatin C was associated with increases in ADMA, SDMA, CRP, homocysteine and age. ADMA, SDMA, CRP and homocysteine levels were not associated with CAD severity. eGFR was negatively associated only with SDMA and homocysteine. In multivariate analysis, increased plasma cystatin C predicted both the occurrence and the severity of CAD more strongly than other measures of renal function. CONCLUSIONS: We conclude that mild renal impairment detected by elevated cystatin C is associated with both the occurrence and the severity of CAD, independent of the other risk factors we measured and that mild renal impairment results in increased plasma levels of homocysteine, ADMA and SDMA. Our findings suggest a possible mechanistic link between CAD and mild renal impairment in which cystatin C may serve as an early marker for CAD and may also participate directly in atherogenesis.
Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Cistatinas/sangre , Tasa de Filtración Glomerular , Insuficiencia Renal/sangre , Factores de Edad , Anciano , Arginina/análogos & derivados , Arginina/sangre , Biomarcadores/sangre , Estudios de Cohortes , Enfermedad de la Arteria Coronaria/complicaciones , Cistatina C , Femenino , Homocisteína/sangre , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal/complicaciones , Factores de RiesgoRESUMEN
BACKGROUND: Elevated plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide production, are reported to be associated with coronary artery disease (CAD). METHODS: We measured plasma levels of ADMA and related compounds, nitrate+nitrite (NO(x)), total homocysteine (tHCY) and assessed renal function and lipid profiles in 145 patients--75 with triple vessel coronary disease and 70 with no detectable coronary disease. RESULTS: Levels of ADMA, l-arginine, l-arginine/ADMA and plasma NO(x) were not different in the two groups but smokers with triple vessel disease had higher ADMA and lower NO(x) levels than the non-smokers, relationships also present for all smokers and non-smokers in the two groups combined. In all 145 patients ADMA, symmetric dimethylarginine (SDMA) and tHCY levels were significantly higher in patients with glomerular filtration rate (GFR) <81 mL/min/1.73 m(2) than in patients with GFR> or =81 mL/min/1.73 m(2). There was a modest positive correlation between tHCY and ADMA and both were strongly correlated with SDMA which is excreted by the kidney. ADMA, SDMA and tHCY were negatively correlated with GFR. CONCLUSIONS: We suggest that the reported ADMA increases in CAD patients are due to an associated reduction in renal function and to smoking habit.
Asunto(s)
Arginina/análogos & derivados , Enfermedad Coronaria/sangre , Óxido Nítrico Sintasa/antagonistas & inhibidores , Adulto , Anciano , Arginina/sangre , Biomarcadores/sangre , Cromatografía Líquida de Alta Presión , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/fisiopatología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/fisiología , Homocisteína/sangre , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Fumar/efectos adversosRESUMEN
Research on the structural and functional effects of hormone replacement therapy on the brain has produced inconsistent results. This paper reports on cross-sectional associations between hormone replacement therapy use and volumes of brain structures measured using magnetic resonance imaging in 213 postmenopausal women aged 60-64 years recruited from a large population study. Of these, 64 were current hormone replacement therapy users, 69 previous users and 80 had never used hormone replacement therapy. No differences were observed between groups in total grey matter, white matter, hippocampal or amygdalar volumes, severity or volume of white matter hyperintensities, or in different measures of brain atrophy. While acknowledging the limitations of a cross-sectional study, the results argue against hormone replacement therapy being protective against brain changes associated with ageing in women in their early 60s.
Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/efectos de los fármacos , Terapia de Reemplazo de Estrógeno/métodos , Posmenopausia/efectos de los fármacos , Cognición/efectos de la radiación , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Visión Ocular/efectos de los fármacosRESUMEN
BACKGROUND: This study addressed the suggested association between levels of the antioxidants glutathione (GSH), vitamin C and vitamin E in peripheral blood and the histological activity and fibrosis stage in chronic hepatitis C (CHC). We then determined whether regular antioxidant supplementation influenced these antioxidant levels or disease severity. METHODS: Clinical, biochemical, histological and demographic data were collected from 247 CHC patients at the time of liver biopsy. Whole blood total GSH, plasma vitamin C and E were assessed by high-performance liquid chromatography. Statistical analyses were performed to test for associations between the variables and to identify independent predictors for hepatic necroinflammatory and fibrosis scores. RESULTS: GSH and vitamin C, but not vitamin E correlated with both portal/periportal activity (r = -0.19, P = 0.004; r = -0.19, P = 0.009 respectively) and fibrosis stage (r = -0.18, P = 0.007; r = -0.18, P = 0.009 respectively). GSH was an independent negative predictor of portal/periportal inflammation (P = 0.02) and fibrosis (P = 0.01). Vitamin C was an independent negative predictor of fibrosis stage (P = 0.02). Antioxidant intake was associated with higher vitamin C (P < 0.0001) and vitamin E (P = 0.005) levels, but not GSH. CONCLUSIONS: Whole blood GSH and plasma vitamin C are negatively associated with hepatic portal/periportal inflammation and fibrosis stage in CHC. Controlled intervention studies with vitamin C and agents that boost endogenous GSH levels are warranted.
Asunto(s)
Antioxidantes/metabolismo , Hepatitis C Crónica/metabolismo , Cirrosis Hepática/metabolismo , Adolescente , Adulto , Anciano , Antioxidantes/administración & dosificación , Ácido Ascórbico/sangre , Biomarcadores/sangre , Biopsia , Estudios de Cohortes , Suplementos Dietéticos , Femenino , Glutatión/sangre , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Índice de Severidad de la Enfermedad , Carga Viral , Vitamina E/sangreRESUMEN
BACKGROUND: Case control studies have supported a relationship between low folic acid and vitamin B112 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations. METHOD: A random subsample of 412 persons aged 60-64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging. RESULTS: Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. CONCLUSIONS: Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.
Asunto(s)
Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo/epidemiología , Deficiencia de Ácido Fólico/epidemiología , Hiperhomocisteinemia/epidemiología , Deficiencia de Vitamina B 12/epidemiología , Anciano , Antioxidantes/metabolismo , Australia , Encéfalo/patología , Estudios de Casos y Controles , Causalidad , Creatinina/sangre , Estudios Transversales , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/etiología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/etiología , Femenino , Ácido Fólico/sangre , Deficiencia de Ácido Fólico/sangre , Deficiencia de Ácido Fólico/diagnóstico , Indicadores de Salud , Encuestas Epidemiológicas , Homocisteína/sangre , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Determinación de la Personalidad/estadística & datos numéricos , Valor Predictivo de las Pruebas , Psicometría , Valores de Referencia , Estadística como Asunto , Vitamina B 12/sangre , Deficiencia de Vitamina B 12/sangre , Deficiencia de Vitamina B 12/diagnósticoRESUMEN
BACKGROUND: High serum homocysteine (HCY) levels have been associated with thromboembolic cerebrovascular disease, but their relationship to microvascular disease is uncertain. Homocysteine also has a direct neurotoxic effect and has been linked to brain atrophy and an increased risk of Alzheimer disease. OBJECTIVE: To examine the relationship of HCY levels to brain and cognitive measures in a healthy community sample. DESIGN: Cross-sectional study. SETTING: Individuals residing in Canberra and Queanbeyan, Australia, who were participating in the longitudinal PATH Through Life Project. PARTICIPANTS: Individuals aged 60 to 64 years selected randomly from the community, 196 men and 189 women. MAIN OUTCOME MEASURES: Regression coefficients with HCY level as the putative determinant and various magnetic resonance imaging measures (brain atrophy index, ventricle-brain ratios, volume of periventricular and deep white matter hyperintensities) and cognitive measures (information processing speed, verbal memory, fine motor speed) as dependent measures. RESULTS: Homocysteine levels did not have a significant relationship with brain atrophy index or ventricle-brain ratios. High HCY levels were related to increased deep white matter hyperintensities but not periventricular white matter hyperintensities, after correcting for levels of folate, vitamin B(12), creatinine, and thyrotropin; hypertension; smoking; and diabetes, the relationship being significant only in men. Homocysteine levels were related to impairment in verbal memory and fine motor speed but not after the previously mentioned correction. CONCLUSIONS: Total HCY level is independently related to leukoaraiosis in middle-aged men, and this may be functionally relevant in the form of mild cognitive impairment. The remediation of hyperhomocysteinemia should begin early in life if its deleterious effects on the brain are to be prevented.
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Encefalopatías/sangre , Encéfalo/patología , Cognición/fisiología , Homocisteína/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Encefalopatías/diagnóstico por imagen , Encefalopatías/patología , Estudios Transversales , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Radiografía , Análisis de Regresión , Factores SexualesRESUMEN
Measurement of malondialdehyde (MDA) is an important contribution to the assessment of oxidative stress. We report a sensitive and reproducible high-performance liquid chromatography (HPLC) method for measurement of plasma MDA in the assessment of lipid peroxidation. Using methyl malondialdehyde (Me-MDA) as an internal standard with reversed-phase HPLC and UV detection and derivatisation with 2,4 dinitrophenylhydrazine (DNPH), we obtained maximum MDA values with 60-min incubation of 10% plasma with 1 M NaOH at 60 degrees C. The dilution of the plasma and a longer incubation time in the alkaline hydrolysis step greatly improved recovery of MDA from its bound form. Ratios of peak height of MDA/Me-MDA were linear over a range of 0-100 microM with correlation coefficients >0.99. The recovery was 88.5%. Within and between run variations were <4 and <7%, respectively. The mean MDA value measured in 20 healthy volunteers was 13.8 microM (+/-1.32).
Asunto(s)
Malondialdehído/análogos & derivados , Malondialdehído/sangre , Malondialdehído/química , Calibración , Cromatografía Líquida de Alta Presión , Humanos , Hidrazinas , Hidrólisis , Indicadores y Reactivos , Peroxidación de Lípido , Espectrometría de Masas , Control de Calidad , Estándares de Referencia , Reproducibilidad de los Resultados , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
Serum cystatin C more accurately reflects glomerular filtration rate (GFR) in pediatric renal transplant recipients than serum creatinine. Nineteen pediatric renal transplant recipients, 15 male and 4 female, ranging in age from 8.35 yr to 19.06 yr (median 13.52 yr), were enrolled in the study over an 18-month period. Twenty-eight measurements of 99mTc-DTPA GFR were compared with simultaneous measurements of serum cystatin C and Cr. Linear regression analysis, Pearson correlation coefficients and analysis of variance (anova) were used to determine the relationship between creatinine, cystatin C and GFR. The correlation coefficients (R2) for the relationship of 1/Cr to DTPA-GFR and for 1/cystatin C to DTPA-GFR were 0.63 and 0.58, respectively. There was no significant difference between serum cystatin C and serum creatinine as markers of GFR. Serum cystatin C, which costs more to measure than serum creatinine, offers no advantage in monitoring the renal function of pediatric renal transplant recipients.
Asunto(s)
Creatinina/sangre , Cistatinas/sangre , Tasa de Filtración Glomerular , Trasplante de Riñón/fisiología , Adolescente , Adulto , Niño , Cistatina C , Femenino , Humanos , Pruebas de Función Renal , Masculino , Proyectos PilotoRESUMEN
The potential for the carry-over of the cyanobacterial toxin, microcystin-LR, from feed to milk was assessed using four Holstein-Friesian cows in a 4 week feeding trial. Two cows were used as control and the other two dosed daily at increasing weekly concentrations of microcystins from zero to a maximum dosage of 13 microg toxin kg x (-1) d x (-1) (or 7.4 mg toxin day(-1)). The absence of any deviation from the control in terms of physiological response and plasma indicators (total bilirubin, gamma-glutamyl transpeptidase and alkaline phosphatase) suggests that the microcystin-LR dosage did not have a detrimental effect on cattle liver function or milk yield during the course of the study. While the milk production did decrease over the period of the trial, no difference was observed between control and dosed cattle. Protein phosphatase inhibition assays were successfully used to determine the presence of microcystin-LR in prepared milk samples with an average recovery of 88% for samples spiked with 0.6 microg x l(-1) microcystin-LR. The level of microcystin-LR in all milk samples during the trial was less than 0.2 microg x l(-1). This suggests that after digestion, microcystin--LR is either not present in milk or sufficiently modified to render it non-toxic.
Asunto(s)
Toxinas Bacterianas/análisis , Leche/química , Péptidos Cíclicos/análisis , Animales , Toxinas Bacterianas/toxicidad , Biomarcadores , Bovinos , Cromatografía Líquida de Alta Presión , Cianobacterias/química , Femenino , Toxinas Marinas , Microcistinas , Péptidos Cíclicos/toxicidad , Fosfoproteínas Fosfatasas/antagonistas & inhibidores , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
BACKGROUND: Preterm infants are at increased risk of oxidative stress and free-radical mediated diseases partly related to deficient antioxidant state. The purpose of this study was to investigate if maternal supplementation of antioxidant vitamins prior to delivery would reduce the oxidative stress in the mothers and their infants. STUDY DESIGN: A pilot case-control study. PATIENTS AND METHODS: Five mothers at risk of preterm delivery between 30 and 36 weeks were given a daily oral dose of betacarotene 20 mg, vitamin E 167.8 mg and vitamin C 1000 mg until delivery. Plasma levels of MDA and vitamins A, E and beta-carotene were measured prior to treatment in mothers and at delivery in both mothers and neonates. Seven mother-infant pairs comparable in gestation and birthweight acted as controls. RESULTS: In the supplemented group, median maternal plasma MDA at delivery was significantly lower compared to the pretreatment level (1.9 vs. 3.2 micromol/l, p=0.04) and it was also lower than the control group (1.9 vs. 3.65 micromol/l, p<0.001). In the supplemented group, median maternal plasma vitamin E at delivery was significantly higher than the levels prior to treatment (46 vs. 31 micromol/l, p=0.007) in the same group and those at delivery in the control group (46 vs. 30 micromol/l, p=0.03). There was a trend of lower plasma MDA and higher vitamin E at birth in infants born to supplemented mothers, but it did not reach statistical significance. CONCLUSION: A short supplementation of multiple antioxidant vitamins to a small sample of preterm pregnant women reduced the oxidative stress at delivery in mothers and probably in their neonates. Larger studies probably using larger doses are needed to evaluate the efficacy of this strategy.