D.G. Wickens

The nature of diene conjugation in human serum, bile and duodenal juice

Diene‐conjugated lipids have been located by HPLC in serum, bile and duodenal juice. Whether esterified or not the same predominant fatty acid is responsible for most of the diene conjugation in all of these biological fluids. Initial attempts to generate this fatty acid in pure lipid by classical lipid peroxidation in vitro were unsuccessful. Ultraviolet irradiation of free fatty acids in the presence of protein produced diene‐conjugated lipids similar to those found in vivo. The predominant diene‐conjugated fatty acid in vivo is an isomerised C18:2 compound.

Lipid peroxidation associated with successful thrombolysis

In 50 patients receiving thrombolytic treatment for acute myocardial infarction, peripheral venous blood samples were taken before streptokinase and 2 h later for assay of markers of free radical activity. Coronary arteriography was carried out within 72 h of thrombolysis. In the 42 patients with patent arteries after thrombolysis, the levels of thiobarbituric-acid-reactive material (TBA-RM), which reflects lipid peroxidation by free radicals, rose after streptokinase by 10.5 (SD 9.6) [corrected] nmol/g albumin, whereas in the 8 whose arteries remained occluded TBA-RM fell by 14.7 (8.0) [corrected] nmol/g albumin. There was no significant change in the 18:2 (9,11)/18:2 (9,12) molar ratio, an indicator of lipid isomerisation, either between the groups or after streptokinase. Thus, after successful thrombolysis there is a rise in lipid peroxidation, not seen in patients whose arteries remain occluded. This finding suggests free-radical-mediated damage at the time of reperfusion, and provides indirect evidence of reperfusion injury in man. This study provides evidence associating indicators of free radical activity with documented myocardial reperfusion in man.

Fluorescence changes in human gamma-globulin induced by free-radical activity

Low-intensity ultraviolet irradiation was used to generate free-radical activity in lipid-free human gamma-globulin. The changes were monitored by fluorescence spectroscopy and gel filtration chromatography. The pattern and the effect of thiol compounds, free-radical scavengers and antioxidants point to a free-radical-mediated process. Initial energy uptake was probably in the region of aromatic amino acid residues, followed by complex intramolecular rearrangements. Irradiation led to the formation of molecular species and complexes whose fluorescence characteristics were different from those of native gamma-globulin and indistinguishable from those observed in inflammatory exudates.

LIPID-PEROXIDATION (FREE-RADICAL-OXIDATION) PRODUCTS IN BILE FROM PATIENTS WITH PANCREATIC DISEASE

Serial samples of bile or duodenal or pancreatic secretions from patients with and without pancreatic disease were examined for lipid-peroxidation (free-radical-oxidation) products. Peroxidation products were found in the phospholipid fraction of bile and the free-fatty-acid fraction of duodenal juice but not in pancreatic juice. There was a highly significant difference in the concentration and excretion pattern of these products between the group of patients with pancreatic disease and the control group of patients with miscellaneous abdominal disorders.

DIAGNOSIS OF CERVICAL NEOPLASIA BY THE ESTIMATION OF OCTADECA-9,11-DIENOIC ACID

Exfoliated cells from the precancerous cervix have an increased concentration of octadeca-9,11-dienoic acid, a diene-conjugated isomer of linoleic acid. A high-performance liquid chromatographic method which measures both has been automated. It may form the basis of a sensitive diagnostic test.

Octadeca-9,11-dienoic acid in cervical intraepithelial neoplasia: a colposcopic study.

488 women were studied to evaluate the use of the molar ratio (%MR) of octadeca-9,11-dienoic acid (18:2(9, 11] to linoleic acid (18:2(9, 12] as a new screening method for cervical cancer and pre-cancer. A combination of Papanicolaou cytology, colposcopy and %MR 18:2(9, 11)/18:2(9, 12) were employed. 86 women (17.6%) were found to have histologically proven cervical intraepithelial neoplasia (CIN). The %MR was obtained in 452 cases (92%). There was no significant difference in %MR in cervical cell scrapes from women with or without CIN. The %MR of cervical scrapes in some women with anaerobic vaginosis was significantly elevated suggesting bacterial generation of 18:2(9, 11). The %MR of 18:2(9, 11)/18:2(9, 12) is unsuitable for the diagnosis of cervical intraepithelial neoplasia.

Recognition of cervical neoplasia by the estimation of a free-radical reaction product (octadeca-9,11-dienoic acid) in exfoliated cells

The molar ratio between a diene-conjugated linoleic-acid isomer (18:2(9,11)) and the parent linoleic acid (18:2(9,12)), both esterified as phospholipids, was significantly different in exfoliated cells from normal cervices and from cervices with colposcopic and cytological evidence of precancer. The measurement may provide a simple and perhaps improved alternative to cytological screening.

Recognition of cervical neoplasia by the estimation of a free-radical reaction product (octadeca-9,11-dienoic acid) in biopsy material.

Linoleic acid (18:2(9,12)) and its diene-conjugated isomer (18:2(9,11)) were measured in 65 cervical biopsy samples. Both the 18:2(9,11) concentration and the 18:2(9,11)/18:2(9,12) molar ratio showed highly significant differences between the normal and precancerous groups. Both showed a further significant increase in 4 invasive carcinomas. The findings in histologically normal areas from organs with precancer correlated significantly with the results in the precancerous lesions.

Copper, Free Radicals and Rheumatoid Arthritis

In the last decade considerable evidence has established the importance of free radicals as mediators of the inflammatory response (1–4). Ever since free-radical reactions were first implicated in this process, their relevance to the development of associated pathological changes has been sought. McCord (5) was the first to suggest that such reactions may mediate the joint injury occurring in rheumatoid arthritis (RA); and this has led to the use of superoxide dismutase (SOD) and drugs with SOD-like activity in the treatment of RA and related disorders (6,7).

Recognition of Cervical Neoplasia by the Estimation of a Free-Radical Reaction Product (Octadeca-9,H-Dienoic Acid) In Exfoliated Cells

The molar ratio between a diene-conjugated linoleic-acid isomer (18:2(9,11)) and the parent linoleic acid (18:2(9,12)), both esterified as phospholipids, was significantly different in exfoliated cells from normal cervices and from cervices with colposcopic and cytological evidence of precancer. The measurement may provide a simple and perhaps improved alternative to cytological screening.