Characteristics and localisation of 125I ion binding in mammalian airways

We have examined some of the binding characteristics and the autoradiographic distribution of binding sites for Na125I (I-Na) in airway tissue from the guinea-pig, monkey, pig, rat, mouse and from man. Basal I-Na (100 pM) binding levels were extremely low. However, in the presence of ascorbic acid (10 microM) or dithiothreitol (10 microM), I-Na binding was markedly increased in guinea-pig trachea, with lesser increases detected in monkey and rat trachea and in monkey and human bronchus. In guinea-pig trachea, ascorbic acid-induced I-Na binding was not saturable within the concentration range 100-620 pM and could not be reduced by washout. Autoradiography revealed that in central airways, I-Na binding was localized at or near the interface of the airway epithelium and submucosa in small clusters, apparently involving one or two cells per focus. The physiological significance of these binding sites is yet to be established, although they may be involved in intracellular iodine storage.     

Measuring clinical outcome

At the present time, there are many fundamental issues coming from the Department of Health or from other national organizations, which will have an effect on the future development of the dietetic profession. The British Diatetic Association (BDA) Professional Development Committee will consider these issues, as and when appropriate, and will publish the information in the form of Briefing Papers.
The first Briefing Paper on 'Quality Assurance' was published by the BDA in November 1989. The second on 'Measuring clinical outcome' is published below. In each case the opinion of BDA members and specialist groups has been sought and the Professional Development Committee wishes to thank individuals and the specialist groups for their comments.
The Briefing Papers are intended to provide information and promote discussion among the membership. I would welcome further comments from readers, which may be directed to the British Dietetic Association Office.     

Postexercise late-onset hypoglycemia in insulin-dependent diabetic patients

A new clinical entity that is prevalent in young type I (insulin-dependent) diabetic patients, postexercise late-onset (PEL) hypoglycemia, is described. A prospective case-finding study suggested that PEL hypoglycemia occurred in 48 of approximately 300 diabetic type I patients who were diagnosed as diabetic before age 20 yr and who were monitored for up to 2 yr. Typically, hypoglycemia was nocturnal and occurred 6-15 h after the completion of unusually strenuous exercise or play. In more than half the cases the hypoglycemia resulted in loss of consciousness or seizures and necessitated treatment with subcutaneous glucagon or intravenous glucose and/or attendance by a health professional. The hypoglycemia was not limited to patients in good or excellent metabolic control and often occurred after a single bout of exercise in patients unaccustomed to exercise or in athletic patients who were making the transition from an untrained to a trained state. Surprisingly, 12 of the patients who experienced nocturnal PEL hypoglycemia were not using significant amounts of insulin that peaked at night. Type I diabetic patients should be made aware of the possibility of PEL hypoglycemia to enable them to make adjustments in their management plans in anticipation of unusually strenuous exercise, so that they may attempt to minimize or avoid late-onset hypoglycemia.     

The mechanism of aphidicolin bioinactivation by rat liver in vitro systems

1. Aphidicolin is shown to undergo rapid metabolism by rat-liver microsomes resulting in its inactivation and loss of its DNA polymerase alpha/delta inhibition. Metabolism of aphidicolin was not observed with cytosolic enzymes of rat liver and was inconsistent with the involvement of microsomal 3 alpha-hydroxysteroid oxidoreductases. 2. Rates of aphidicolin inactivation as a function of microsomal enzyme induction (per nmol cytochrome P-450) followed the order: untreated microsomes greater than dexamethasone-induced greater than phenobarbital-induced greater than beta-naphthoflavone-induced greater than clofibrate-induced. 3. The principal metabolic process, constituting greater than 90% of the metabolic profile, produces 3-ketoaphidicolin 2, which exhibits approximately 10% of the activity of aphidicolin in inhibition of DNA polymerase alpha. This metabolic transformation, the oxidation of an alcohol to a ketone, is an unusual, but not unique conversion, for cytochrome P-450. 4. 3-Ketoaphidicolin 2 is an intermediate and ultimately undergoes 18-dehydroxymethylation to produce 18-noraphidicolinones 3, which are inactive in the inhibition of DNA polymerase alpha. 5. A specific constitutive cytochrome P-450 isozyme, involved in endogenous steroid regulation, was implicated as the species responsible for aphidicolin metabolism in vitro.     

Growth suppression in the Trichuris dysentery syndrome

The Trichuris Dysentery Syndrome (Ramsey, 1962) is an insidious, chronic condition which has clinical features similar to Crohn's ileocolitis and ulcerative colitis, diseases similarly associated with growth retardation. The attained heights and weights of 19 children at the time of diagnosis of intens, -2.4 Standard Deviation (Z) scores from the Tanner-Whitehouse median with weight, adjusted for height-age, -1.3 Z. We present data on the growth velocities of 11 of the children in the half-year following worm expulsion by mebendazole. These children returned to their home environments without food supplementation or close follow-up, but showed an average height velocity of +5.5 Z and weight velocity (for height-age) of +2.4 Z. Of 8 children with unequivocal height spurts only 3 had any weight spurt. We suggest that the pattern of catch-up growth points to the existence of some specific link between allergy or inflammation in the lower intestinal tract and suppression of linear growth, rather than to stunting due to general deprivation and undernutrition.     

Diet and phenylketonuria: time for change?

This article is a report of a meeting of dietitians held on 15 September 1992 in Birmingham to discuss the recommendations of a 'Medical Research Council Working Party on the Dietary Management of Phenylketonuria'. (Contributions on the day of the meeting came from Judith Houghton, Eleanor Weetch, Isabel Smith, Sheena Laing, Ruth Watling, John Walter, Rodney Pollitt.)