Rafael Santini

THE PTEROYLGLUTAMATE COMPONENTS OF AMERICAN DIETS AS DETERMINED BY CHROMATOGRAPHIC FRACTIONATION

Folic acid activity, as determined by conventional bacteriological assay procedures, reflects the presence of a number of compounds other than pteroylglutamic acid (PGA). For example, one popular test organism, Streptococcus fecalis, will show a growth response in folic acid free medium to at least ten derivatives of PGA in addition to thymine, hypoxanthine, theobromine, guanidine, uric acid, and several other related compounds (1). Another organism, Lactobacillus casei, shows growth with a somewhat wider range of PGA derivatives, including both methylated and triglutamate forms that do not support growth of S. fecalis (2). Under these circumstances, the practice of expressing the growth-supporting ability of crude dietary materials in terms of a single reference standard may not give a true indication of the PGAcontent of foods, because food may contain a mixture of compounds with folic acidlike activity (3). Nevertheless, most dietary tables on the folic acid content of foods are based on such assays. The discrepancy between the amount of folic acid activity in diets and the amount of pure PGA required for the treatment of tropical sprue has led to the suggestion that humans may have a specific requirement for PGA (3). It therefore seemed important to assess the quantity of PGA available in the unsubstituted form from ordinary foods and to investigate the amount of folic acidlike activity that is present in forms other than pure PGA. A method has been employed in which factors with folic acid-like activity are chemically

The Xylose Tolerance Test with a Five-Gram Dose

Summary A modification of the xylose tolerance test employing a 5-gm. dose has been proposed. This dosage gives results comparable to the original test in malabsorption states but eliminates the side effects encountered with the original procedure.

Studies on the Oral and Parenteral Administration of D(+)xylose

THE absorption of xylose by the mammalian intestine was studied by Cori1 as long ago as 1925, and has recently been the subject of renewed interest in connection with studies of malabsorption syndr...

Congenital isolated defect of folic acid absorption

A Caucasian girl with persistent diarrhea and severe megaloblastc anemia diagnosed at age three months failed to respond to oral treatment with folic acid, but there was prompt hematologic and gastrointestinal response following intramuscular administration of folic acid. Evaluation at age 11 years revealed signs of folate deficiency and low serum and whole blood folate avalues. Serum folic acid values were not increased during folic acid and citrovorum factor absorption tests or following administration of 40 or 100 mg. of folic acid orally on separate occasions. Intestinal absorption test results and the jejunal and gastric mucosa were normal. These studies demonstrate an alteration in the normal mechanism of absorption of both physiologic and pharmacologic doses of pteroylglytamic acid.

THE ABSORPTION OF GLYCINE AND ITS CONVERSION TO SERINE IN PATIENTS WITH SPRUE

Glycine has been used for many years as an orally administered test substance in the study of intestinal absorption. Most authors have utilized a technique measuring the total amino acid nitrogen of the blood at intervals after an oral dose of glycine, with the assumption that increases reflect the amount of glycine absorbed. Althausen, Doig, Uyeyama, and Weiden (1) have demonstrated the validity of this technique, but nevertheless concluded that absorptive tests for proteins and fats generally indicate greater impairment of absorption than do nutritional balance studies (2). There have been conflicting reports concerning the absorption of glycine in patients with sprue, although recent work suggests impaired absorption of virtually every normally absorbable substance , including sodium chloride (3). In 1935, Heath and Fullerton (4) noted similar curves of blood amino acid nitrogen after either oral or intravenous administration of glycine to patients with impaired absorption. They noted that about 75 per cent of an injected dose of glycine disappeared from the blood within four or five minutes. They concluded that glycine is without value in studying the absorptive capacity of the intestine. However, Erf and Rhoads (5) in 1940 presented evidence suggesting that glycine is absorbed from the gastrointestinal tract more slowly in patients with sprue or pernicious anemia than in normal subjects. Evidence of this abnormality was not demonstrable in the same patients after remission was induced with liver extract. Drew, Dixon, and Samuel (6) found satisfactory absorption of glycine in five patients with sprue in a convalescent state. In the investigations which form the basis of this repQrt chemical determinations of glycine and serine were carried out, in addition to the usual total amino acid nitrogen determination, in plasma from normal subjects and patients with sprue. This procedure was undertaken because of the role of folic acid in the conversion of glycine to serine and because of presumptive evidence that tropical sprue patients are deficient in this vitamin. The belief that such patients may be deficient in folic acid stems from observations that: 1) they show prompt clinical improvement with the sole addition of folic acid to a protein-poor, vitamin-deficient diet (7), and 2) there is a greatly diminished urinary excretion of folic acid by sprue patients (8). Das Gupta, Chatterjea, and Basu (9) believe that nutritional macrocytic anemia, sometimes considered as synonymous with sprue, results primarily from a deficiency of folic acid. It was postulated at …

Laboratory criteria for the diagnosis of tropical sprue in Puerto Rico

To establish a diagnosis of tropical sprue, readily and accurately, based on clinical manifestations, the xylose absorption test, a jejunal biopsy, and a bone marrow examination are recommended. Fasting serum folic acid, serum vitamin B12, and whole blood folate levels are added to complete the patients work up and to confirm the diagnosis.

Congential defect in folic acid absorption

A Caucasian girl was noted to have persistent diarrhea and progressive pallor since age of two months. Hematologic evaluation at 3 months revealed anemia of 6.0 gm/100 ml and severe megaloblastic erythropoiesis. She failed to respond to oral treatment with folic acid, but she had a prompt hematologic and gastrointestinal response with folic acid I.M. She remained free of anemia and diarrhea and kept growing and developing adequately while receiving parenteral therapy with folic acid. Anorexia and severe stomatitis and glossitis developed regularly three to four weeks after the administration of 15 mg of folic acid I.M. Evaluation at age 11 yrs., 3 weeks after the last dose of folic acid I.M., revealed a normal girl except for moderate stomatitis and glossitis and some hypersegmented PMN leukocytes. Her serum and whole blood folates were 2.0 and 60 ng/ml, respectively, and the serum B-12 was 500 pg/ml. Intestinal absorption tests were normal. Gastric and jejunal biopsies revealed normal mucosa. Folic acid and citrovorum factor absorption tests with 5 mg doses showed flat curves. Forty mg. of folic acid orally also failed to produce an increase in serum folate or to control the early signs and symptoms of folic acid deficiency. The clearance of folate after the administration of 5 mg. of folic acid intravenously was normal, but the urinary excretion of folate was unusually low (100 μgm) in 8 hours. Studies for the presence of a folate inhibitor in the plasma were negative. These studies demonstrate an alteration in the normal mechanism of absorption of both physiologic and pharmacologic doses of folate compounds and suggest also a defective metabolism of folate in the tissues.