RESTORATION OF NITRIC OXIDE FUNCTION IN HUMAN HYPERLIPIDAEMIA, CONGESTIVE HEART FAILURE AND LIVER CIRRHOSIS

1. There is accumulating evidence for a range of abnormalities in the nitric oxide (NO) signalling cascade in human cardiovascular disorders. 2. In the present review we assess the literature detailing such evidence in early (hyperlipidaemia) and end-stage (heart failure) disease, with emphasis on the mechanisms by which the disturbances are thought to occur. 3. Strategies for the correction of disturbed NO signalling in these states are reviewed and include both prescribed pharmacological interventions, such as lipid-lowering therapy and novel uses of angiotensin-converting enzyme inhibitors, as well as non-pharmacological interventions, such as exercise and dietary supplementation with l -arginine and n-3 polyunsaturated fatty acids. 4. In addition to a decreased production/function of NO, the possible detrimental effects of a chronic elevation in NO production in patients with liver cirrhosis, together with a novel use of antibiotics to correct this perturbation, is outlined.     

Exogenous gamma-linolenic acid alters hormone stimulated cyclic AMP levels in U937 cells

Polyunsaturated fatty acids are selectively cytotoxic in culture. Incorporation of these fatty acids leads to profound changes in membrane fatty acid composition which in turn may alter the activity of transmembrane receptor/effector systems. In U937 cells, hormone stimulated production of cyclic AMP can be reduced by 30% following incubation with gammalinolenic acid (18:3n-6). It is suggested that β-adrenoceptor number, subtype and adenylyl cyclase stimulation may be regulated by alterations in membrane fatty acid composition as a result of changes in the levels of polyunsaturated fatty acids and alterations in eicosanoid production.     

Localization of pancreatic insulinoma: comparison of pre- and intraoperative US with CT and angiography

Methods of preoperative radiologic localization of insulinoma were compared in 52 patients, 44 of whom had solitary tumors. Examinations performed in these 44 patients were preoperative ultrasonography (US) in 28, angiography in 26, and computed tomography in 23. Prospective sensitivities were 61%, 54%, and 30%, respectively. Imaging sensitivities were lower for the eight patients with multiple insulinomas. In 28 of the 44 patients, intraoperative US was performed without the examiner being aware of the surgical findings. The sensitivity was 84%. Four insulinomas were not palpable but were visualized sonographically. The combined sensitivity of intraoperative US and surgical palpation for detecting solitary insulinomas was 100%. High-frequency intraoperative US is valuable for detecting occult solitary insulinomas and considerably useful for determining the proximity of insulinomas to the pancreatic and bile ducts.     

Polyunsaturated fatty acid-induced cytotoxicity against tumor cells and its relationship to lipid peroxidation

The contribution of lipid peroxidation to the killing of human breast cancer cells by gamma-linolenate (GLA) was examined. Other fatty acids of different cytotoxic potential containing 2, 4, 5, and 6 double bonds were also tested for comparison. It was found that the cytotoxic potential varied with the ability of the fatty acids to stimulate the production of superoxide radicals. Neither hydrogen peroxide nor hydroxy radicals are significantly involved in cell killing. As nonspecific indicators of lipid peroxidation, measurements of the loss of unsaturated fatty acid in the phospholipids together with the generation of hydroperoxide breakdown products were done with the use of the thiobarbituric acid test. The results of these experiments showed that the effectiveness of a given fatty acid in killing cancer cells correlated with the intracellular thiobarbituric acid-reactive material (TBARM) content: GLA and arachidonate with 3 and 4 double bonds generated the most TBARM and were the most cytotoxic fatty acids, whereas docosahexaenoate with 6 double bonds was the least effective either in raising TBARM or in killing the malignant cells. Iron and copper accelerated the rate of cell death, whereas antioxidants such as vitamin E and butylated hydroxyanisole inhibited the effect of GLA dose dependently. Indomethacin, an inhibitor of endoperoxide formation, did not reduce either cell kill or TBARM amounts. In contrast, the addition of vitamin E acetate to the cancer cell cultures challenged with eicosapentaenoate reduced both cell killing and TBARM content. These results suggest that the effectiveness of a given fatty acid in killing cancer cells correlated with the extent of lipid peroxidation of the added fatty acid in the cells.     

Complicated pancreatic abscesses: problems in interventional management

Twenty-five patients with grade D or E pancreatitis underwent percutaneous drainage. These patients required multiple computed tomography (CT) examinations, multiple catheter insertions, multiple catheter manipulations, and long-term catheter drainage. Eight of the 25 patients were successfully treated with catheter drainage alone. Sixteen underwent surgical drainage, ten after attempts at percutaneous drainage and six prior to radiologic drainage. Of the ten patients who had initial percutaneous drainage, only four were clinically improved from the drainage procedure alone. Although the fluid component of the abscess was often adequately drained in all ten patients, surgery was required to remove pieces of necrotic debris. Six patients who underwent surgical debridement had residual abscesses in the post-operative period and were all successfully treated with percutaneous drainage. One patient died from unrelated causes. Successful interventional management of patients with pancreatic abscesses requires intensive radiologic intervention and monitoring and may be better served by a combination of radiologic and surgical means.