Jerry Kelleher

The gastrointestinal absorption of paracetamol in the rat.

The absorption of [3H]paracetamol by rat small intestine, colon and stomach was studied in vivo and in vitro. Small intestinal in vivo studies, using a wide range of drug concentrations, showed that absorption was efficient and uniform throughout the small bowel, no site showing preferential absorption. Double reciprocal and direct plots indicated first order kinetics. The pattern was not observed when uptake was occurring from high concentrations of paracetamol in suspension. Gastric and colonic in vivo studies showed that there was appreciable absorption of [3H]paracetamol from these sites. In vitro studies using everted intestinal sacs showed no effect on paracetamol transfer when the incubation temperature was lowered to 10 °C or when iodoacetate (5 times 10−2m) and 2.4 dinitrophenol (5 times 10−4m) was added to the incubation medium. There was, however, a significant reduction in transfer of paracetamol against a concentration gradient of 10:1 applied across the mucosa. These data suggest that the uptake of paracetamol is by a passive transport process and confirm the efficiency of paracetamol absorption observed indirectly by others.

The effects of acute infection on indices of zinc status

Various indices of zinc status were assessed in 12 patients with acute urinary tract or chest infections on Day 1 and Day 7 of the infection. Leucocyte counts were raised on Day 1 but had returned to near normal by Day 7. Plasma zinc was decreased on Day 1 in conjunction with depressed plasma albumin concentrations (r = 0.71, p < 0.001) but both had returned to normal by Day 7. Mononuclear cell zinc was raised in all patients on Day 1 compared to Day 7 and control values, but polymorphonuclear cell zinc remained unchanged. However, polymorphonuclear cell alkaline phosphatase activity was grossly increased on Day 1 and correlated with leucocyte count (r = 0.61, p < 0.01). Plasma alkaline phosphatase activity was variable. These results indicate that in patients with infections measurement of plasma mononuclear cell zinc concentration and alkaline phosphatase activity are misleading indicators of zinc status. Polymorphonuclear cell zinc is unaffected by leucocytosis, inflammation and stress and may therefore provide a more reliable index of zinc status in such patients.

The effect of dietary vitamin E deficiency on plasma zinc and copper concentrations

Vitamin E and zinc have a number of functions in common, including membrane stabilisation, antioxidant function and modulation of prostaglandin metabolism. Previous studies have shown vitamin E malabsorption during zinc depletion and it appears that there is an interaction between the two nutrients. In this study we have investigated whether vitamin E deficiency affects zinc and copper concentrations in experimental animals. Male Wistar rats were maintained on a vitamin E deficient diet for either 6 or 10 months. At the end of the experimental period all animals had undetectable plasma vitamin E levels and increased red cell fragility. Plasma zinc concentrations were significantly reduced in all vitamin E deficient animals compared to control rats (p<0.002) and copper levels were reciprocally elevated (p<0.002). It appears likely that decreased zinc levels may represent redistribution of circulating zinc to tissues and cells as a secondary antioxidant, or for membrane stabilisation or prostaglandin synthesis.

The effect of zinc and vitamin C supplementation on the immune status of patients with Crohn's disease

The immune status of 29 patients with Crohns disease given oral supplements of Vitamin C, zinc or placebo for three-week periods was studied. Collectively, the patients showed T-cell hyporesponsiveness, as assessed by phytohaemagglutinin stimulation, which was significantly improved by Vitamin C. Both monocyte function, as assessed by latex phagocytosis, and pan T-Cell number were significantly reduced and were not influenced by supplementation. Humoral immunity, assessed by pokeweed mitogen-induced immunoglobulin synthesis, was normal and remained unchanged. Vitamin C supplements improved T-cell function in Crohns disease, whereas neither Vitamin C nor zinc had a measurable effect on humoral immunity.

Leucocyte zinc in non-Hodgkin's lymphoma and Hodgkin's disease.

Zinc status and the effect of zinc supplementation were assessed in groups of patients with non-Hodgkins lymphoma and Hodgkins disease; patients were either untreated or in remission. In the patients in remission, plasma zinc was normal; and whereas 30% of untreated patients had low plasma zinc, the group as a whole did not differ from normal. For mononuclear cell zinc, the range of values in the disease group was far wider than in controls, but there was no significant difference between the means of the groups. Granulocyte zinc was significantly lower in both the groups of patients in remission from non-Hodgkins lymphoma and Hodgkins disease compared with the control group. Significant increases were found in the plasma copper, ceruloplasmin, and the copper-to-zinc ratio in several of the patient groups. Plasma zinc increased by 23% with zinc supplementation (50 mg elemental Zn/day), but there was no effect on mononuclear cell or granulocyte zinc. Apart from granulocyte zinc, there is little evidence of zinc deficiency in non-Hodgkins lymphoma or Hodgkins disease. However, the presence of depleted granulocyte zinc levels could modify the immune function of this cell population.

Nicotine and Smoking in Patients with Ulcerative Colitis

Few patients with ulcerative colitis smoke. We have demonstrated that smoking affects colonic mucus production and human immune mechanisms in vitro and this may have relevance to the pathogenesis of the disease. There is anecdotal evidence to suggest that nicotine may be the active moiety associated with smoking responsible for these effects, but we have been unable to confirm this in in vitro test systems.

The effect of cigarette smoking on in vitro colonic immunoglobulin production in inflammatory bowel disease

Cigarette smoking is an important factor in the epidemiology of inflammatory bowel disease (IBD). Studies have shown that patients with ulcerative colitis (UC) tend to be non-smokers, while patients with Crohn’s disease (CD) tend to contain more smokers than control groups [l]. Both peripheral and mucosal immunoglobulin secretion are altered in IBD, with the number and production capacity of the plasma cells responsible for IgG, IgM and, in particular, IgA production being altered [2]. Peripheral immunoglobulin production is also influenced by cigarette smoking, with smokers having a reduced serum level of IgA, G and M compared with non-smokers [3]. The aim of this study was to determine whether in vitro colonic mucosal immunoglobulin production is influenced by smoking habit in patients with IBD and in controls.