Amino Acid Studies and Clinical Findings in Normal Adults and Rheumatoid Arthritis Patients Treated With Acth 12

Abstract

Previous publications .from this laboratory ( 1, 2) have reported that rheumatoid arthritis patients who were treated with ACTH (adrenocorticotrophic hormone) and cortisone (17-hydroxy-11-dehydrocorticosterone) exhibited changes in the urinary excretion of certain amino acids. Similar results were found to occur during remission induced by pregnancy (3, 4), and one rheumatoid arthritis patient in remission caused by jaundice showed changes even more striking (5). Significant differences have been reported to exist in plasma concentrations of certain "free" amino acids in untreated rheumatoid arthritis patients and in normal individuals (6) . It was considered important, therefore, to determine whether in this disease changes occur in plasma concentrations concomitantly with remission induced by ACTH therapy and also to establish the effect of ACTH on plasma concentrations and urinary excretion of amino acids in normal adults.Results for six apparent "free" amino acids in the urinary excretion of normal adults and for seven "free" amino acids in plasma of normal individuals treated with ACTH are compared with those from rheumatoid arthritis patients similarly treated. METHODSThe normal control group consisted of four male and four female university students. Immediately before the experiment each student was subjected to a complete physical examination and absence of any disease or obvious metabolic disorder was established. The students ' This work was supported in part by grants from the United States Public Health Service and the Fair Foundation. ACTH was provided by the Armour Laboratories.2A preliminary report of this material was presented before the Federation of American Societies for Experimental Biology, Cleveland, Ohio, April 1951.were not hospitalized but were kept on a closely supervised diet of adequate caloric and vitamin C intake and one which supplied one gram of protein per kilogram of body weight. The source of protein was the same for all subjects and to that extent the amino acid intake was controlled. Following a three-day control period on the diet, 40 mg. of ACTH were administered intramuscularly in three divided doses each day for seven days. Thirtyfive patients were chosen on the basis of an unquestionable diagnosis of rheumatoid arthritis and had been under treatment by the investigators for periods ranging from six months to 15 years. They were hospitalized for observation and study throughout the experiment and were maintained on the same controlled diet as that used for the normal adult group. ACTH was administered intramuscularly in variable dosage of from 40 to 60 mg. daily except for one patient who received a much larger dose. It was determined conclusively that the size of the dose had no measurable effect on the plasma levels of the amino acids assayed. In an effort to accelerate or prolong the favorable effects of ACTH therapy some patients included in this study received supplementary medication. During the control period and/or through the treatment period various agents suc...

Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity.

“…The free blood histidine concentration has been reported to be statistically significantly decreased in patients with rheumatoid arthritis in 10 (1-10) of 11 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) reports. In two reports (3,9), patients with more active rheumatoid arthritis had smaller serum histidine concentrations than patients with less active disease.…”

Investigation of serum amino acid and serum amyloid A concentrations in chickens with amyloid arthropathy

“…The pain associated with arthritis in the experimental group chicks is thought to have resulted in the elevation of phenylalanine in this study. Borden et al (1952) observed an increase in lysine, phenylalanine, and tyrosine, and a decrease in arginine and histidine concentrations in human rheumatoid arthritis patients. In this study, increases in phenylalanine (p 5 0.001) and tyrosine (p 5 0.01) were observed in the experimental group.…”

“…Until today, studies examining amino acid composition in human rheumatoid arthritis patients (Borden et al 1952;Peter et al 1978) and acute-phase proteins of humans (Barker 1984(Barker , 1987 have been conducted. In animals, serum amino acid compositions of rats with arthritis (Sluka and Westlund 1992) and of chickens with AA-amyloidosis have been studied (Landman 1998).…”

NMR-Based Serum Metabolomics Revealed Distinctive Metabolic Patterns in Reactive Arthritis Compared with Rheumatoid Arthritis

“…58 The significantly elevated serum levels of phenylalanine (hyperphenylalaninemia) have also been seen under septic inflammatory conditions. 59 The reduced serum level of phenylalanine has been previously seen in RA patients, 60 suggesting its negative metabolic turnover under infectioninduced inflammatory conditions. Compared with RA, the concomitantly elevated serum levels of BCAAs, glucose, and phenylalanine in ReA clearly suggested the aberrant immune activation and dominance of protein degradation in this postinfection inflammatory arthritis (underlying antigenic cross-reactivity).…”