WITH increasing frequency, the human neutrophil is being implicated as a mediator of tissue-destructive events in inflammatory diseases ranging from rheumatoid arthritis and myocardial reperfusion injury to respiratory distress syndromes, blistering skin disorders, and ulcerative colitis.1 , 2 In each of these diseases, as well as a variety of other acute inflammatory disorders, important components of these pathologic processes are being linked to the neutrophil's ability to release a complex assortment of agents that can destroy normal cells and dissolve connective tissues. Although these toxins normally defend the host against invading microbes, the neutrophil has little intrinsic ability to differentiate between foreign . . .

Tissue Destruction by Neutrophils

The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenylhydrazine derivative of dehydroascorbic acid

Gout

SCOPE OF THIS REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 BIOSYNTHESIS AND REQUIREMENTS OF ASCORBIC ACID . . . . . . . . . . . . . . . . . . . . . . . . . 366 METABOLISM OF ASCORBATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367 ACTIONS AND FUNCTIONS OF ASCORBATE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368 DOPAMINE !3-HYDROXYLASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . 372 PEPTIDYL GLYCINE a-AMIDATING MONOOXYGENASE... . . . . . . . . . . . . . . . . . . . . . . . . . . . 373 4-HYDROXYPHENYLPYRUV ATE DIOXYGENASE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374 PROL YL AND L YSYL HYDROXYLASES FOR COLLAGENS . . . . . . . . . . . . . . . . . . . . . . . . . . . 376 HYDROXYLATION OF OTHER PROTEINS . . . .. . . ...... . . . . 383 Elastin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 383 C1q o/ Complement. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384 DIOXYGENASE REACTIONS OF PYRIMIDINES AND NUCLEOSIDES . . . . . . . . . . . . . . 385 CARNITINE PATHWAY HYDROXYLASES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 386 OTHER POSSIBLE FUNCTIONS OF ASCORBATE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391 CONCLUDING REMARKS ... . . ........ . . . . . .. . .. . .. . . ...... .... . . ........ .... ..... . . . . 391

The Biochemical Functions of Ascorbic Acid

ALTHOUGH vitamin C is critical to human physiology1–5, it is not clear how it is taken up into cells. The kinetics of cell and tissue accumulation of ascorbic acid in vitro indicate that the process is mediated by specific transporters at the cell membrane6. Some experimental observations have linked the transport of ascorbic acid with hexose transport systems in mammalian cells, although no clear information is available regarding the specific role(s) of these transporters, if any, in this process7–16. Here we use the Xenopus laevis oocyte expression system to show that the mammalian facilitative hexose transporters are efficient transporters of the oxidized form of vitamin C (dehydroascorbic acid). Two transport pathways, one with low affinity and one with high affinity for dehydroascorbic acid, were found in oocytes expressing the mammalian transporters, and these oocytes accumulated vitamin C against a concentration gradient when supplied with dehydroascorbic acid. We obtained similar results in experiments using normal human neutrophils. These observations indicate that mammalian facilitative hexose transporters are a physiologically significant pathway for the uptake and accumulation of vitamin C by cells, and suggest a mechanism for the accumulation of ascorbic acid against a concentration gradient.

Mammalian facilitative hexose transporters mediate the transport of dehydroascorbic acid

Experimental Human Scurvy.

Since Lanman and Ingalls1demonstrated that vitamin C deficiency led to poor healing of experimental surgical wounds in guinea pigs and after operations on children there has been an increasing recognition by other surgeons (Wolfer2and Holman3) as well as by Lanman that this factor may be of importance in surgical operations on adults. Since vitamin C was isolated by Svirbely and Szent-Gyorgyi4and synthesized by Reichstein and his co-workers5there have been many tests for vitamin C developed for the determination of its content in foods, tissues, urine and blood. It is now realized that certain of the older methods of analysis did not give accurate results, but it is hoped that present methods will be of value within certain rather broad limits. At the time this study was begun two and one-half years ago little was known concerning the vitamin C status of

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John H. Crandon

Papers

Experimental Human Scurvy.

Human experimental scurvy: and the relation of vitamin c deficiency to postoperative pneumonia and to wound healing

Ascorbic acid and human wound healing.

Vitamin C deficiency in an otherwise normal adult.

Perforation of the Ileum Following Late Ileostomy for Ulcerative Colitis