Views on the wisdom of using antioxidant vitamin supplements

In the Forum that follows, four authorities in nutrition and vitaminology present their divergent views on the use of antioxidant vitamin supplements. In this introduction, the basic dilemma between setting RDAs that insure an absence of deficiency symptoms and those that insure optimal health is discussed, as well as other factors that must be considered to reach a consensus on this controversial topic.     

Determination of 8-oxoguanine in human plasma and urine by high-performance liquid chromatography with electrochemical detection

A highly sensitive and selective method for determining 8-oxoguanine in plasma and urine was developed by high-performance liquid chromatography with electrochemical detection. The compound was separated by gradient elution on a C₁₈ reversed-phase column with a mobile phase of acetonitrile and 0.1 M sodium acetate, pH 5.2. 8-Hydroxy-2′-deoxyguanosine was used as internal standard. 8-Oxoguanine was detected electrochemically by setting the potential to +300 mV vs. Pd reference. The sensitivity of the assay was 22 ng/ml with a signal-to-noise ratio of 7:1. The within-day relative standard deviations for 8-oxoguanine quality control samples with concentrations of 3340, 1340 and 84 ng/ml were 3.6, 4.3 and 5.7% for plasma, and 4.1, 4.6 and 6.2% for urine, respectively. The day-to-day relative standard deviations for the same samples were 3.8, 6.8 and 7.1% for plasma, and 3.9, 7.0 and 7.9% for urine, respectively. The method is designed to study the pharmacokinetics and metabolic fate of O⁶-benzylguanine in a phase I clinical trial. Previously, O⁶-benzyl-8-oxoguanine was identified as the primary metabolite of O⁶-benzylguanine in humans. We now demonstrate that 8-oxoguanine is a further metabolite of O⁶-benzylguanine.     

Isolation of a flax (Linum usitatissimum) gene induced during susceptible infection by flax rust (Melampsora lini)

In a susceptible infection of flax ( Linum usitatissimum ), the obligate rust pathogen ( Melampsora lini ) can grow in the leaf without triggering the hypersensitive resistance response. The rust establishes specialized structures (haustoria) in plant mesophyll cells and induces changes in plant subcellular organization. Subtraction hybridization methods were used to isolate cDNA clones of mRNAs that have altered expression in infected leaves. Most of the cDNAs recovered were of fungal origin, but one clone, pFIS1 ( f lax i nducible s equence No. 1), recovered from several independent experiments, was a plant-specified mRNA that showed a 10-fold increase in steady-state levels during susceptible growth. The increase in fis1 mRNA levels was not seen in the resistant reaction (hypersensitive reaction) and the predicted protein sequence (551 amino acids with a predicted molecular weight of 61 kDa) has no similarity to known pathogenesis-related proteins. Searches of sequence data bases showed that fis1 encodes a protein which contains amino acid sequence motifs that are conserved in all previously characterized aldehyde dehydrogenases.     

Effects of slitting the zona pellucida and its subsequent sealing on freeze-thaw survival of Day 7 bovine embryos

The effects of slitting the zona pellucida and its subsequent sealing by either embedding in agar or surrounding with an additional zona pellucida on the development of frozen/thawed Day 7 bovine embryos were investigated in vitro and in vivo. A total of 225 embryos was frozen and thawed rapidly as controls (Group 1), after slitting the zona pellucida (Group 2), after slitting and subsequent sealing of the zona pellucida with agar (Group 3), or after slitting the zona pellucida (Grothen transferring the embryo into an additional zona pellucida (Group 4). The survival rate (embryos classified morphologically as excellent, good, or poor) was 95.1, 95.4, 92.2, and 94.3% for Groupsl, 2, 3, and 4, respectively. Culture of 145 embryos in vitro for 60 h revealed that 57.1, 59.5, 47.4, and 57.1% developed to hatching and hatched blastocysts in Groups 1, 2, 3, and 4, respectively. Within Group 3, however, a significantly (P < 0.05) lower percentage of the embryos continued to develop when the agar was not removed after thawing (31.8%) compared with embryos from which the agar had been removed (68.8%). After nonsurgical transfer of 78 embryos, the pregnancy rate was significantly (P < 0.05) lower (8.3%) with embryos of Group 3 compared with controls (61.5%) or embryos of Group 2 (42.9%). No significant difference existed between controls and embryos of Group 2. We conclude that an intact zona pellucida prior to rapid freezing is not essential for the survival of Day 7 bovine embryos.     

Toxicity of polycyclic aromatic hydrocarbons. V. Protective effect of beta-naphthoflavone against hepatotoxicity induced by diphenaldehyde in rats

Male Sprague-Dawley rats were treated ip with beta-naphthoflavone (40 mg/kg/day) in corn oil or in DMSO for three days. Diphenaldehyde (90 mg/kg in DMSO) was injected ip 24 hr after pretreatment. The increase in the levels of aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase, gamma glutamyl transpeptidase, and lactate dehydrogenase was significantly lower in rats pretreated with BNF. This suggests that the BNF-induced P-450 isozyme systems have a protective effect against the acute hepatotoxicity of diphenaldehyde.     

DXS28 (C7) maps centromeric to DXS68 (L1-4) and DXS67 (B24) by deletion analysis

Complex glycerol kinase deficiency (CGKD) is a contiguous gene syndrome consisting of glycerol kinase deficiency together with Duchenne muscular dystrophy (DMD), congenital adrenal hypoplasia, and/or Aland Island eye disease. Deletion mapping of genomic DNA from patients with CGKD was carried out and allowed definitive ordering of loci DXS28 (C7), DXS68 (L1-4), and DXS67 (B24). Most reports have placed DXS68 centromeric to DXS28 and DXS67 on the basis of the initial mapping of the Iowa patient 3, but others have presented evidence consistent with the placement of DXS28 telomeric to DXS68 and DXS67. Through the use of DNA from CGKD patients with a variety of genomic deletions, this controversy is resolved and the order Xcen...DMD-DXS28-DXS68-DXS67...pter is definitively demonstrated.     

Toxicity of polycyclic aromatic hydrocarbons. VI. Effects of 1-nitropyrene on serum enzyme levels in rats, and protection against it by beta-naphthoflavone and dimethyl sulfoxide

Male Sprague-Dawley rats were pretreated i.p. with corn oil or DMSO (1.5 ml/kg/day), or with beta-naphthoflavone (BNF, 40 mg/kg/day) in corn oil or DMSO for 3 days. 1-Nitropyrene (1-NP, 150 mg/kg) in DMSO was injected i.p. 24 hr after pretreatment. A significant increase in the levels of several serum enzymes was seen in rats pretreated with corn oil alone 24 hr after 1-NP injection. The increase in enzyme activities was significantly reduced by a 3-day pretreatment with DMSO or BNF.