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Serum Zinc, Iron, and Copper Concentrations ... - Clinical Chemistry

Serum Zinc, Iron, and Copper Concentrations ... - Clinical Chemistry

Serum Zinc, Iron, and Copper Concentrations ... - Clinical

diN. CHEM. 21/4, 528-532(1975) Serum Zinc, Iron, and Copper Concentrations during Typhoid Fever in Man: Effect of Chioramphenicol Therapy Robert S. Pekarek,’ R. M. Kluge,2 H. L. DuPont,3 R. W. Wannemacher, Jr., R. B. Hornlck, K. A. Bostlan, and W. R. Belsel In volunteers experimentally infected with Salmonella fyphi, serum iron and zinc concentrations became significantly depressed and there was a concomitant rise in serum copper before the onset of overt clinical illness. However, after several days of fever and the initiation of chloramphenicol therapy, serum iron and zinc concentrations significantly increased. Additional studies-In volunteers with typhoid fever treated with ohIoramphenicol, In a volunteer with typhoid fever receiving cefazolin and gentamicin, and in untreated rhesus monkeys Infected with Salmonella typhimurium-provkied evidence that the Increase in serum ironconcentration during the febrile phase was the result of chioramphenicol therapy, whereas the Increase in serum zinc concentrations was a disease-related phenomenon. The importance of trace-metal monitoring during infectious disease and chemotherapy is discussed. Additional Keyphras.: trace elements and infectious disease U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Md. 21701; and The Division of Infectious Diseases, University of Maryland School of Medicine, Baltimore, Md. 21201. These investigations were conducted in conjunction with a continuing study of the pathogenesis, diagnosis, prophylaxis, and therapy of infectious disease. These tests were governed by the principles and rules for medical volunteers established by the Declaration of Helsinki. The Human Experimentation Committee at the University of Maryland has approved this study and both oral and written consent were obtained from each volunteer. The investigations were also supervised by the Commission on Epidemiological Survey of the Armed Forces Epidemiological Board. In conducting the research described in this report, the investigators adhered to the “Guide for the Laboratory Animal Facilities and Care,” as promulgated by the Committee on the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Academy of Sciences-National Research Council. The facilities are fully accredited by the American Association of Accreditation of Laboratory Animal Care. ‘Present address: USDA, ARS, Human Nutrition Laboratory, 2420 2nd Ave. N., P. 0. Box D, University Station, Grand Forks, N. D. 58201. address: Division of Infectious Diseases, Department of Medicine, University of Florida College of Medicine, Gainesville, Fla. 32610. 3Present address: Division of Infectious Diseases, University of Texas, Medical School, Houston, Tex. 70025. Received Nov. 12, 1974; accepted Dec. 16, 1974. 528 CLINICAL CHEMISTRY, Vol.21. No.4, 1975 Significant alterations in host zinc, iron, and copper metabolism occur during various acute and chronic infectious diseases (1-3). Prospective studies in man demonstrated that such alterations begin early in the incubation period after exposure to either bacterial or viral organisms (4, 5). As shown in laboratory animals, these infection-induced changes represent a rapid redistribution of the metals within the various tissues of the host (6, 7). Beside infection-induced alterations in trace-metal metabolism, various drugs also can produce significant changes. For example, administration of chioramphenicol produces increased serum iron concentrations and an increase in the saturation of transferrin, even in the absence of such recognized but infrequent complications as aplastic anemia or other forms of hematopoietic toxicity (8, 9). Because the serum trace-metal profiles induced by various infectious diseases, in conjuz*ction with other clinical data, may have potential diagnostic and prognostic usefulness, it is important to establish and differentiate the alterations produced by a particular infectious illness from those that may be induced by chemotherapy. Therefore, as an ancillary and incidental part of a continuing series of investigations into the efficacy of new experimental typhoid vaccines (10, 11), the opportunity arose to study the sequential effects of typhoid fever on zinc, iron, and copper concentrations in the serum of experimentally infected volunteers. In addition, these investigations also afforded the opportunity to study the effect of chioramphenicol treatment on these trace-metals in serum, to see if particular patterns of concentration could provide useful criteria for screening potential toxic effects of chemotherapy during an infectious illness. For further comparison, we sequentially determined serum trace-metal concentrations in untreated rhesus monkeys infected with Salmonella typhimurium. MaterIals and Methods Study 1. Nineteen healthy men, inmates of the

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