A B S T R A C T The importance of ceruloplasmin in iron metabolism was studied in swine made hypoceruloplasminemic by copper deprivation. When the plasma ceruloplasmin level fell below 1% of normal, cell-to-plasma iron flow became sufficiently impaired to cause hypoferremia, even though total body iron stores were normal. When ceruloplasmin was administered to such animals, plasma iron increased immediately and continued to rise at a rate proportional to the logarithm of the ceruloplasmin dose. The administration of inorganic copper induced increases in plasma iron only after ceruloplasmin appeared in the circulation. Thus, ceruloplasmin appeared to be essential to the normal movement of iron from cells to plasma.Studies designed to define the mechanism of action of ceruloplasmin were based on the in vitro observation that ceruloplasmin behaves as an enzyme (ferroxidase) that catalyzes oxidation of ferrous iron. Retention of injected ferrous iron in the plasma of ceruloplasmin-deficient swine was significantly less than that of ferric iron, reflecting impaired transferrin iron binding. Rat ceruloplasmin, which has little ferroxidase activity, was much less effective than porcine or human ceruloplasmin in inducing increases in plasma iron. These observations suggest that ceruloplasmin acts by virtue of its ferroxidase activity.Eight patients with Wilson's disease were evaluated in order to investigate iron metabolism in a disorder characterized by reduced ceruloplasmin levels. Evidence of iron deficiency was found in six of these, and in five of the six, plasma ceruloplasmin was less than 5% of normal. In comparison, the two patients without evidence of iron deficiency had ceruloplasmin levels of 11 and 18% of normal. It is suggested that iron deficiency tends to occur in those patients with Wilson's disease who have the severest degrees of hypoceruloplasminemia, possibly because of defective transfer of iron from intestinal mucosal cells to plasma.Portions of this work were reported previously in abstract form (1970. J. Clin. Invest. 49: 55 a.) Dr. Lee is a Markle Scholar in Academic Medicine.

Testicular function was assessed in 32 patients who received standard chemotherapy regimens for disseminated lymphomas. Thirty-one had evidence of germ cell damage, as assessed by the finding of azoospermia and/or high plasma levels of follicle-stimulating hormone (FSH). In addition, five patients had persistently low plasma testosterone levels associated in three with elevated plasma luteinising hormone (LH) levels. Reproductive function did not recover in any patient while chemotherapy continued. Cessation of therapy was possible in 16 patients with prolonged remissions of disease. Among these, recovery of germinal epithelium differed greatly between the cyclophosphamide / vincristine / prednisone treated group and the mustine/procarbazine/vincristine/prednisone treated group. Seventy per cent of the former patients had evidence of recovery after 34 months of follow-up while only one (17%) of the latter had begun to recover at 52 months post-therapy. Serial measurement of plasma FSH levels proved useful in predicting likely recovery of spermatogenesis.

Summary Serum ferritin levels were monitored in guinea‐pigs rendered scorbutic by dietary deprivation of ascorbic acid (AA). Hepatic and splenic concentrations of AA fell rapidly during the first 8 d of deprivation, and then declined more slowly to reach approximately 10% of control values after 14 d. Normal levels of serum ferritin (geometric mean, 324 μg/1) were observed for 20 d but a significant fall occurred between days 20 and 23 of deficiency (143 γg/1; P<0·05). Intramuscular administration of iron dextran to scorbutic animals (75 mg Fe per kg body weight) resulted in a non‐significant elevation of serum ferritin levels (geometric mean, 470 μg/1; P>0·1). In control animals, the same dose of iron dextran caused a 10‐fold rise in serum ferritin levels (3400 μg/1). A single subcutaneous dose of AA (75 mg/kg weight) given to scorbutic animals caused a significant rise in serum ferritin levels to 599 μg/1 (P<0·001) but had no effect in control animals. The same dose of AA given to iron loaded, scorbutic animals elevated serum ferritin levels from 554 μg/1 to 1297 μg/1 (P<0·025). Thus, AA deficiency in guinea‐pigs caused serum ferritin levels to fall and blocked the rise in serum ferritin levels observed in response to acute iron loading in control animals. Adequate tissue concentrations of AA appeared to be necessary for the maintenance of a quantitative correlation between tissue iron stores and serum ferritin levels. The mechanisms by which AA influences serum ferritin levels are at present unknown.

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