A review of some of the seminal studies of metabolism during various infections indicates that similar patterns of metabolic alterations occur during these illnesses. This patterned metabolic array occurs whether the infection is caused by a gram-positive or a gram-negative bacterium, a rickettsia or a virus, or is respiratory or systemic. In all instances, the previously healthy host responds to infection with cytokine-mediated alterations that appear to occur in proportion to the infectious challenge and to the likelihood of death. These alterations also can occur in the vaccinated host, if the infectious challenge is sufficiently great. Because of their widespread occurrence and seemingly ingrained status, these metabolic alterations may be presumed to be of survival benefit to the host. Whether this patterned array of metabolic sequelae is of benefit to the host, or even to the species, its widespread and systematic occurrence allows it to be of value in assessing the safety and efficacy of vaccines and drugs to prevent or treat a wide variety of infections. In this era of bioterrorism, wherein drugs and vaccines may have to be approved for human use without clinical trials and solely on the basis of animal data, these cytokine-mediated metabolic sequelae can aid in the rational selection of drug and vaccine candidates.

Hextend is a new plasma volume expander containing 6% hydroxyethyl starch in a physiologically balanced medium. This open-label volunteer study demonstrated that it has pharmacokinetic and pharmacodynamic profiles similar to those of established HES.

No abstract

( oncentrutions, of most amino acids and of zinc in serum were depressed during periods of incubation and illness in I11 volunteers who developed symptoms after an oral dose of 105 virulent Salmonellai typhiosa. WVhen a 1.0-mi sample of sterile serum from volunteers who were ill with typhoid fever was injected into normal rats, it stimulated a prompt and significant depression of the concentration of zinc in the rats' sera and a flux of amino acids into thcir livers. These observations support the hypothesis that an endogenous factor (similar to cndogenous pyrogen released by polymorphonuclear leukocytes) was present in the blood during typhoid feve and served as a mediator for the observed depression in zinc and amino acids in serum. The magnitude and pattern of infect ion-related dep-osiion in individual amino acids in serum may he. in part, a function of the amount of endogenous mediator released and of' the rates of utilization of amino acids by tissues.[he period of symptomatic febrile illness during cantly altered in whole blood of volunteers ina ceeneralized infectiotis process is accompanied fected with Salmnone'lla I 'yphosa (S. I "vphi) [2]. A by prominent catabolic events that lead to a negasimilar depression in the total free amino acids tihe halanct ýrl nitrogen and other elements in the in whole blood or serum has been observed durbo~dy 111. Hosi~ever. many other infection-related ing prospective studies in volunteers infected with biochemical changes in the host appear ty-develop Pastettrella tilare'nsis 131, live, attenuated (vaclong before the onset of fever and symptoms of cine strain) Venezuelan equine encephalitis illness and to he anabolic rather than catabolic (VEE) virus 141, or sandfly-fever virus 151. in nature. Little is known about the role of these Serum zinc was also depressed during the periods \er\ early biochemical responses of the host or of incubation and clinikal illness of several bacthe tinderlying mechanisms that initiate them.terial and viral infections, while serum copper f'otal concentrations of amino acids were signifivalues became elevated during the latter stages of the same illnesses 15. 6].Recent studies in experimental animals sug- tissues. The use of a 1 'C-labeled. nonmetabolizable I \periP'w.,s invok~ing humans reported in this paper amino-acid analog, Il-aminocyclopentane-lI-car%kcr : L'oserned b% the principle%. policies, and rules for boxylic acid (cycloleucine) in rats exposed to