R. P. H. Thompson

The mode of action of the aminosalicylates in inflammatory bowel disease

Sulphasalazine and other 5‐aminosalicylic acid (5‐ASA)‐containing drugs are used in the treatment of acute inflammatory bowel disease and in the maintenance of clinical remission. Despite their use for over 50 years, the mechanism of action of this class of drugs remains uncertain, although a number of possibilities are discussed in this review. It seems likely that the aminosalicylates are important free radical scavengers, can reduce leukotriene production and can inhibit the cellular release of interleukin‐1, all of which are likely to be important in reducing the acute inflammatory response in inflammatory bowel disease, The effects of these drugs on prostaglandin production are more contentious, but it appears that 10‐5 to 10‐4 M concentrations stimulate production of prostaglandins which may be cytoprotective, while higher doses of these drugs inhibit prostaglandin production. The aminosalicylates may maintain remission in inflammatory bowel disease by preventing leucocyte recruitment into the bowel wall. The drugs inhibit the chemotactic response to leukotriene B4, reduce the synthesis of platelet activating factor and also inhibit leucocyte adhesion molecule upregulation.

A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis

In a placebo‐controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n= 16), super evening primrose oil (n= 19), or olive oil as placebo (n= 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red‐cell membrane concentrations of eicosapentaenoic acid (EPA) at 3 months by three‐fold and at 6 months by four‐fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red‐cell membrane concentrations of dihomogamma‐linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell‐membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit.

Experience with transjugular liver biopsy.

The results of 193 transjugular liver biopsies performed with a modified needle are described. An adequate specimen was obtained in 97%, and complications were rare, although puncture of the liver capsule does occur and caused bleeding in two patients. Fever after the procedure was reduced by ultrasonic cleaning of the needle. Although not easy, this technique is safe and preferable in the management of selected patients, but in most patients percutaneous biopsy is to be preferred.

Oral iron and the bioavailability of zinc.

The oral bioavailability of zinc was studied in nonpregnant adults before and 24 hours after two weeks of oral supplementation with iron and folic acid. Bioavailability was greatly reduced, and the shape of the plasma curves suggested that this was due to impairment of the intestinal absorption of zinc. The findings suggest that the reduced bioavailability of zinc occurs because of interelement competition in the bowel wall. This might induce zinc depletion.

Clearance of refractory bile duct stones with extracorporeal shockwave lithotripsy

BACKGROUND Extracorporeal shockwave lithotripsy (ESWL) has been used since the mid-1980s to fragment bile duct stones which cannot be removed endoscopically. Early machines required general anaesthesia and immersion in a waterbath. AIMS To investigate the effectiveness of the third generation Storz Modulith SL20 lithotriptor in fragmenting bile duct stones that could not be cleared by mechanical lithotripsy. METHODS Eighty three patients with retained bile duct stones were treated. All patients received intravenous benzodiazepine sedation and pethidine analgesia. Stones were targeted by fluoroscopy following injection of contrast via a nasobiliary drain or T tube. Residual fragments were cleared at endoscopic retrograde cholangiopancreatography. RESULTS Complete stone clearance was achieved in 69 (83%) patients and in 18 of 24 patients (75%) who required more than one ESWL treatment. Stone clearance was achieved in all nine patients (100%) with intrahepatic stones and also in nine patients (100%) referred following surgical exploration of the bile duct. Complications included six cases of cholangitis and one perinephric haematoma which resolved spontaneously. CONCLUSION Using the Storz Modulith, 83% of refractory bile duct calculi were cleared with a low rate of complications. These results confirm that ESWL is an excellent alternative to surgery in those patients in whom endoscopic techniques have failed.

Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron

Oral iron supplements, which are usually in the form of ferrous (Fe2+) salts, are toxic to the gastrointestinal mucosa, and so intolerance is common, resulting in poor compliance and failure of treatment. The sugar derivative maltol strongly chelates iron, rendering it available for absorption and stabilized in the less toxic ferric (Fe3+) form.

Regulation of metal absorption in the gastrointestinal tract.

In this century industrial changes have greatly increased our exposure to many metals but fortunately their intestinal absorption is highly selective. For example, only 0O1% of the toxic metal aluminium is absorbed, whereas the group 1A elements such as sodium and potassium are nearly completely absorbed.2 3 The principles underlying the absorption of metals are relevant to many nutrients and drugs, but the specific factors that regulate the absorption of metals are determined by their atomic structure, because this determines the chemical properties of the element and therefore its physiological function and metabolism. Hence, we start with simplified in vitro models and develop them to describe the complex mechanisms that determine selectivity of metal absorption from the gastrointestinal tract.

Zinc in the fetus and newborn.

ABSTRACT. The growing fetus and infant are at risk of becoming deficient of zinc, an adequate supply of which is essential for normal growth and development. Mild maternal zinc depletion was strongly associated with intrauterine growth retardation. Low levels of zinc in maternal plasma and poor placental perfusion reduced the materno‐fetal transfer of zinc. Mean maternal dietary intake of zinc was 60% recommended daily allowance and mothers of small‐for‐gestational‐age (SGA) babies consumed significantly less zinc than mothers of appropriate‐for‐gestational‐age babies. In addition, iron/folate supplements, which are often routinely prescribed during pregnancy, despite dietary intakes of iron and folate being adequate, significantly decreased the oral bio‐availability of zinc in pregnant women. Zinc supplementation may be beneficial to women at risk of delivering SGA babies. Zinc requirements and interactions are also important to consider when designing mineral supplements for preterm babies, infant formulae and food fortification in developing countries.

Red cell lipid peroxidation and antioxidant enzymes in iron deficiency

Abstract:u2002 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.

Reduced leucocyte zinc in liver disease.

The zinc content of peripheral blood leucocytes has been measured in normal controls and in three groups of patients with liver disease. A significant reduction in leucocyte zinc, but not erythrocyte zinc, was observed in patients with primary biliary cirrhosis, alcoholic cirrhosis, and active chronic hepatitis. It is suggested that the nucleated tissues of some patients with liver disease are therefore zinc deficient, and that leucocyte zinc may prove of value in the assessment of the zinc status of such patients.