1059 in large amounts for the study of biological actiand vity physiological and pathological significance.

prostacyclin

Full details of the chemical

synthesis

and

biological activity

will be



published eteswhere.

Chemistry Department,

University of Pennsylvania, Philadelphia, Philadelphia 19104, U.S.A. Cardeza Foundation and

K. C. NICOLAOU W. E. BARNETTE G. P. GASIC R. L. MAGOLDA W. J. SIPIO M. J. SILVER J. B. SMITH C. M. INGERMAN

Department of Pharmacology, Thomas Jefferson University, Philadelphia

breakdown accelerated. Dopamine reaching the anterior pituitary would fall and prolactin levels would rise. This argument would suggest that inhibition of M.A.o.b with 1-deprenil would be followed by a marked inhibition of prolactin release. If this were found so, the fluctuations of M.A.o.b activity (either in platelets or in brain) would be seen as a mechanism modulating the release pattern of prolactin by interaction with peripherally circulating substances such as adrenaline. The fluctuations in M.A.o.b activity in response to exercise, and possibly in response to stress, may in part account for the conflicting results found by Gold et al. and Mendlewicz et al. It would have been rewarding if the activity of platelet M.A.o. had been measured in all their patients as well as the urinary catecholamine or 3-methoxy-4-hydroxyphenylglycol output as an expression of the extent of the

adrenergic excitation. MECHANISM FOR CONTROL OF PROLACTIN SECRETION

London W6

SiR,—Iread with interest the letter by Dr Mendlewicz and his colleagues (March 19, p. 652) on growth hormone and prolactin response to a levodopa load in affective illness. The apparent disparity between their results and those of Gold et aI.’ illustrates the problems often encountered with endocrine studies in psychiatric patients. I would like to propose a possible mechanism which may affect prolactin release in the experimental situation described by these workers. Prolactin release is thought to be inhibited by dopamine, which reaches the anterior pituitary from the median eminence via a complex of portal veins. This would mean that any mechanism depleting dopamine, either in the hypothalamus or in the portal system, would lead to increased levels of prolactin. I suggest that such

a mechanism exists and is mediated by changing activity of the enzyme monoamine oxidase b (M.A.o.b), of which dopamine is a substrate.2 M.A.o.b is present in platelets and also in certain parts of the brain, but whether the platelet enzyme activity can be used as a marker for the activity of the enzyme in the brain remains controversial,4 although there is circumstantial evidence to support this.3 Low levels of platelet M.A.o. activity have been described in certain categories of depression,’ schizophreniaand the acute phase of migraine.’7 Our studies8 on healthy volunteers who were exercised vigorously showed that there was a significant increase (mean 33%) of platelet M.A.o.b activity during the period of maximum exertion followed by a fall to near resting levels within 10 min of the end of the exercise. This increase in activity is

similar to that found after subcutaneous administration of adrenaline to man.9 Blood taken during the exercise at the same time as that taken for platelet M.A.o.b showed a striking increase in prolactin levels which follows the increase in M.A.o.b activity by about 10 min. This increase is of the order

of 30%. As the platelet M.A.o.b activity rises it is possible that an activation of the enzyme in the brain follows. However, there could be two ways in which this increase in activity could be reflected by a change in dopamine levels. Firstly, turnover of dopamine could be increased in the hypothalamus, causing relative depletion; and, secondly, dopamine already released could be taken up by platelets in the portal circulation and its 1. Gold, P. W., and others. Lancet, 1976, ii, 1308. 2. Glover, V., Sandler, M., Owen, F., Riley, G. J. Nature, 1977, 265, 80. 3. Murphy, D. L., Wyatt, R. J. ibid. 1972, 238, 225. 4. Youdim, M. B. H., Holzbauer, M. J. neurol Transm. 1976, 38, 193. 5. Murphy, D. L., Weiss, R. Am. J. Psychiat. 1972, 128, 1351. 6. Schildkraut, J. J., Herzog, J. M., Orsulak, P. J., Edelman, S. E.,

Shein,

H.M., Frazier, S. H. ibid. p.1351. 7. Glover, V.,

Rose, F. C.,

Sandler, M., Grant, E., Orton, D., Wilkinson, M. Lancet, 1977, i, 391. 8. Gawel, M., Glover, V., Sandler, M., Clifford Rose, F. Clin. Sci. mol. Med.

(in the press). 9. Gentil, V., McCurdy, logy, 1976, 50, 187.

R.

Department of Neurology, Charing Cross Hospital,

L., Alevizos, B., Lader, M. H. Psychopharmaco-

MAREK J. GAWEL

ORAL THERAPY FOR DIARRHŒA

SIR,-We agree with you’ that publication of the World Health Organisation booklet Treatment and Prevention in Diarrhaeal Diseases: a Guide for Use at the Primary Level is a laudable step but we would like to make certain observations which may be of benefit to future editions. The booklet suggests that oral salt and water alone will suffice for diarrhoea therapy (pp. 8, 14, 19); but oral salt/water 6 aggravates severe diarrhoea2-’ unless 2% glucose is added.5 Oral and intravenous therapy should replace intraperitoneal therapy (pp. 15,16) which is ineffective in severe cases.7 The oral formula recommended (p. 27) has not, to our knowledge, been "tested in the field and found to be satisfactory for all diarrhoeas and for patients of all ages", and our evidence suggests that it may not meet that description.89 A formula with a well-developed rationale, based on many studies," 1-1-1 and found satisfactory for all ages contains (mmol/1): glucose 110, sodium 120, potassium 25, bicarbonate 48, and chloride 98 (equivalent, in g/1, to glucose 20, sodium chloride 4.2, potassium chloride 1-8, sodium bicarbonate 4 - 0). Oral therapy rates need clearer definition. The rate for mild of body-weight, p. 27) percases via nasogastric tube (> 12% for cases who drink, and exceeds that identical plexingly exceeds volumes given intravenously for severe diarrhoea with shock. 14 Oral therapy rates are based on established ml/kg/h 11 If weight- or height are unobtainable, or ml/height ratios. 10 however, oral therapy can be given until signs of dehydration disappear and abundant pale urine is produced. If oral therapy cannot be given to a severely dehydrated diarrhoea patient, intravenous therapy is required. At the Cholera Hospital, Dacca, data from thousands of cases indicate a rehydration-time of 1-2 h for shocked patients, rather than 4-6 h as recommended in chart 3. Within 2-6 h maintenance therapy is required to avoid shock from continuing diarrhoea. 1. Lancet, 1976, ii, 697. 2. Latta, T. ibid. 1831-2,i,274.

R. A., Wallace, C. K., Blackwell, R. Q. in Proceedings of Cholera Research Symposium (Honolulu, 1965); p. 299. 4. Nalin, D. R., Cash, R. A., Rahaman, M., Yunus, M. Gut, 1970, 1, 768. 5. Phillips, R. A. Fedn Proc. 1964, 23, 705. 6. Hirschhorn, N., Kinzie, J. L., Sachar, D. B., Northrup, R. S., Taylor, J. O., Ahmad, S. Z., Phillips, R. A. New Engl. J. Med. 1968, 279, 176. 7. Mahalanabis, D., Sack, R. B., Kaplan, J., Jacobs, B., Mondal, A. Bull. Wld Hlth Org. 1970, 42, 837. 8. Nalin, D. R., Cash, R. A. Ann. intern. Med. 1970, 72, 288. 9. Nalin, D. R., Cash, R. A. Proc. 6th int. epidem. Ass. Meet. 1973, p. 1048 10. Nalin, D. R., Cash, R. A., Islam, R., Molla, M., Phillips, R. A. Lancet, 1968, ii, 370. 11. Nalin, D. R., Cash, R. A. J. Pediat. 1971, 78, 366. 12. Nalin, D. R., Cash, R. A. Bull. Wld Hlth Org. 1970, 43, 361. 13. De, S.J. Indian med. Ass. 1975, 65, 230. 14. Nalin, D. R., Rahaman, M. in Current Therapy (edited by H. Conn); p. 18. Philadelphia, 1974. 3.

Phillips,

Mechanism for control of prolactin secretion.

1059 in large amounts for the study of biological actiand vity physiological and pathological significance. prostacyclin Full details of the chemica...
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