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N A Punchard

Publications and source records attributed to N A Punchard.

25 records · Page 2Linked to original sources
PubMed1992

The effects of sulphasalazine and its metabolites on prostaglandin production by human mononuclear cells.

Although it has been proposed that sulphasalazine (SASP) and its metabolite 5-aminosalicylic acid (5-ASA) act therapeutically by inhibiting production of vasoactive and immunoregulatory prostaglandins (PGs), in previous in vitro studies these drugs have both inhibited and promoted PG production. This study demonstrates that SASP and 5-ASA promote or inhibit peripheral blood mononuclear cell PG production depending upon the PG measured, the concentration of the drug, and whether the cells were stimulated. Sulphapyridine, the other constituent of SASP, only inhibited production. At high concentrations of SASP and 5-ASA the viability of mononuclear cells was reduced. The enhancement of PG production and toxicity was greater with SASP than 5-ASA, while the PGs most affected by SASP were not those most affected by 5-ASA. Thus, in vitro SASP may possess properties other than those of 5-ASA and this may explain the different therapeutic properties of these two compounds.

Aminosalicylic Acids↗
PubMed1992

Expression of adhesion molecules on circulating leucocytes in patients with inflammatory bowel disease.

1. The expression of leucocyte antigens CD11/CD18 and complement receptor 1 was studied on the circulating leucocytes of 13 patients with inflammatory bowel disease and 13 age- and sex-matched healthy control subjects. 2. Monoclonal antibodies against CD11/CD18 and complement receptor 1 were added to leucocyte suspensions from patients and control subjects. Antibody binding was detected using a fluorescein-conjugated rabbit anti-mouse antibody and flow cytometry. The proportions of lymphocytes, monocytes and granulocytes expressing these molecules and the density of antigen expression, measured as mean fluorescence intensity, were determined. 3. There were no differences between patients and control subjects in the mean fluorescence intensity of antibody staining of surface molecules or in the proportion of cells expressing each molecule for any cell type. Analysis of subgroups of patients according to disease type, severity or treatment also showed no difference compared with control subjects. 4. We conclude that failure to identify a population of circulating leucocytes whose adhesion molecules or complement receptors are upregulated may arise because cells are only activated locally within the gut vasculature. Alternatively, structural changes in these molecules, rather than an increase in their number or the expression of other surface glycoproteins, may be more important in mediating adhesive interactions in inflammatory bowel disease.

Adult↗
PubMed1992

The effects of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid on lipid peroxidation in erythrocytes and prostaglandin production by mononuclear cells.

In parallel studies, the effects of 5-aminosalicylic acid (5-ASA) and acetyl-5-aminosalicylic acid (acetyl-5-ASA) on peroxidation of red-cell membrane lipids and production of prostaglandins by peripheral blood mononuclear cells were assessed. 5-ASA at concentrations of 10(-5), 10(-4) and 10(-3) M significantly inhibited erythrocyte lipid peroxidation, measured as malondialdehyde production, by 20%, 56% and 63%, respectively, (P < 0.05, P < 0.002, P < 0.001, respectively) while acetyl-5-ASA had no effect. 10(-5) and 10(-4) M 5-ASA significantly increased production by stimulated peripheral blood mononuclear cells of PGE2 (by 31% and 30%, P < 0.01, P < 0.05, respectively) and PGF2 alpha (by 30% and 25%, P < 0.05, P < 0.01, respectively). 10(-4) M 5-ASA also significantly stimulated prostacyclin production measured as 6KF1 alpha by 10% (P < 0.05). At 10(-3) M 5-ASA there were significant falls in 6KF1 alpha (by 37%) PGE2 (by 45%) and PGF2 alpha (by 47%) (P < 0.01, P < 0.001, P < 0.001, respectively) although this was accompanied by a decrease in cell viability. Acetyl-5-ASA had little effect upon prostaglandin production. 5-ASA scavenges free radicals and stimulates production of cytoprotective prostaglandins.

Aminosalicylic Acids↗
PubMed1991

Red cell lipid peroxidation and antioxidant enzymes in iron deficiency.

Whether iron deficient RBC in humans have a reduced, or an increased, susceptibility to lipid peroxidation was studied in the iron deficiency states of primary proliferative polycythaemia and iron deficiency anaemia and related to changes in the activities of iron-dependent and non-iron dependent antioxidant enzymes. Susceptibility of RBCs to lipid peroxidation was increased when expressed per g Hb. However, this was a result of the low RBC Hb giving an increased membrane lipid: Hb ratio in the incubations. Results were normal when expressed either per cell, or per ml, RBC. Glutathione reductase was normal. Increased RBC superoxide dismutase activity in iron deficiency may be explained by the younger RBC population and reductions in glutathione peroxidase and catalase activities by the microcytic hypochromic changes and the lack of availability of iron, respectively. There is no evidence of an increased susceptibility of RBC to lipid peroxidation in iron deficiency.

Aged↗
PubMed1991

Inhibition of red cell membrane lipid peroxidation by sulphasalazine and 5-aminosalicylic acid.

The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), and sulphapyridine on peroxidation of red cell membrane lipids, measured as malondialdehyde production, were assessed. Sulphasalazine and 5-ASA, at concentrations of 10(-5)-10(-3) M significantly inhibit lipid peroxidation, suggesting an antioxidant action that may explain the efficacy of these drugs in treating inflammatory bowel disease. Sulphapyridine, which is not effective in inflammatory bowel disease inhibited malondialdehyde production at a concentration of 10(-3) M only.

Aminosalicylic Acids↗
PubMed1985

Prostaglandin production and zinc depletion in human pregnancy.

An association between zinc depletion and intrauterine growth retardation might occur through disturbed prostaglandin (PG) synthesis. The zinc content and PG metabolism of leucocytes from control, nonpregnant women and mothers 24-48 h after delivery, were measured and related to fetal growth and maternal smoking. Mothers of small for gestational age babies had lower polymorphonuclear and mononuclear cell zinc contents than mothers of appropriate for gestational age babies or nonpregnant controls. Monocytes were the major leucocytes producing PGs. Mothers of small for gestational age babies had higher PGE2:F2 alpha ratios than mothers of appropriate for gestational age babies. PGF2 alpha production and PGE2:F2 alpha ratio were correlated with tissue zinc status. Monocytes from nonsmokers tended to produce more PGs than those from smokers but the differences were not significant. Mild maternal zinc depletion is not significantly sufficient to alter absolute PG production, but is associated with altered differential production of PGs in human leucocytes. Zinc depletion or malnutrition may contribute to intrauterine growth retardation by affecting placental and/or umbilical PG production.

Adolescent↗