Herman Baker

PERIPHERAL NEUROPATHY OF THE ALCOHOLIC: I, AETIOLOGICAL ROLE OF ANEURIN AND OTHER B-COMPLEX VITAMINS.

Peripheral neuropathy in alcoholics is usually attributed to a lack of aneurin (Victor and Adams, 1961) ; however, it is often not possible to document this relation by diagnostic or thera peutic tests. Demonstration that pantothenic acid (Hodges et al., 1958) or pyridoxine (Biehl and Vilter, 1954) deficiency may cause peripheral nerve dysfunction suggests that lack of these or other B-complex vitamins may also contribute to neuropathy in the malnourished alcoholic. The present investi gation was therefore undertaken to evaluate further the role of aneurin and other B-complex vitamins in the development of this condition. The study consisted of (a) determining circu lating levels of aneurin, riboflavin, nicotinic acid, pantothenic acid, biotin, pyridoxine, vitamin B12, and folie acid in alcoholic patients with and without neuropathy ; and (b) an evaluation of the responsiveness of patients with neuropathy to various members of the B-complex group.

Microbiological Assay Methods for Vitamins

Publisher Summary Vitamins are organic substances of natural origin, required in minute quantities, and their effects are not based on their caloric value, but exclusively on their catalytic nature. Vitamins, especially the water-soluble ones, provide the coenzymes for the most fundamental cellular reactions. Microchemical methods are used for the determination of thiamine, riboflavin, and some fat-soluble vitamins, based on most sensitive colorimetric and fluorometric techniques. Microbiological assays are applicable when a microorganism responds to a metabolite for which physical and chemical determinations are neither sensitive nor specific enough. One must select a microorganism sensitive to the substance under assay—it should be cultivable with ease; the growth response should be easily measurable and the response should be specific; and it should be non-pathogenic. The chapter accounts for the microbiological assay techniques for the determination of vitamins like thiamine, pantothenic acid, nicotinic acid and amide, biotin, inositol, vitamin B 6 , folic acid, folinic acid, and vitamin B 12 in body fluids. The establishment of quantitative methods for the determination of vitamins in body fluids and tissues by microbiological assay techniques should stimulate the search for the significance of vitamins in disease, not only in nutritional deficiency, but also in much wider field of all metabolic disturbances. Functional vitamin deficiencies are produced by malabsorption, by inhibitors of the vitamin function through products of the body, and particularly through drugs and other toxic substances.

Metabolism of Folic Acid and Other Pterin-Pteridine Vitamins

Publisher Summary Pterinoid investigations have steadily extended knowledge of (1) transfer of C 1 groups, (2) biosynthetic and functional connections between folic vitamins and other nitrogenous heterocycles—purines, thymine (or thymidine), riboflavin, vitamins Bs and BIZ, and unconjugated pterins. Ever since F. G. Hopkins looked into the pigments of butterfly wings, these unconjugated pterins (for example xanthopterin and leucopterin) have been a biosynthetic enigma. The advent of folic acid complicated matters. A solution is in sight thanks to other lines of investigation converging: (1) the eye pigments of Drosophilu—classical objects of genetics—are predominantly pterins in some mutants, (2) the flagellate Crithidia fasciculata requires certain unconjugated pterins, PGA apparently being the precursor, and (3) remarkably high concentrations of pterins, some with Crithidiu-factor activity, occur in blue-green algae and are somehow involved in photosynthesis. Evidently, certain unconjugated pterins have an essential, unknown function. This chapter attempts to collate clues to new relationships and functions of pterinoids; its point of departure is the exhaustive treatment of p -aminobenzoic acid (PABA) by Wright and Taormina, and of the folic vitamin family by Stokstad and others. Uses of microbial systems and the comparative biochemistry of pterinoids are emphasized in the chapter.

A comparison of maternal and foetal folic acid and vitamin B12 at parturition.

It had been hoped that the E.EG. record would give objective evidence of. the onset of the transitional phase between sleep and wakefulness; that the rhythm would revert to normal before the patient awoke. This did not occur. Clinical observation gave as early information as did the E.E.G. Two patients admitted to hospital in barbiturate coma were given bemegride, and their course was followed by intermittent E.E.G. recordings. Each patient returned to consciousness while on treatment with bemegride, but the E.E.G. records gave no indication of the depth of coma, and indeed evidence of barbiturate activity on the E.E.G. persisted for many hours after the patient wakened. This confirms the findings of Peacock (1956). The E.E.G. evidence might suggest that bemegride is not a specific barbiturate antagonist, but the site of action of sodium amylobarbitone may be principally in the hypo-

Lesions in folic acid metabolism induced by primidone

Les auteurs ont étudié le mécanisme de la toxicité de la primidone (Mysoline) chez certains microorganismes. Ces recherches montrent que le métabolisme de lacide folique est inhibé par le primidone et cela en trois étapes: (a) la réduction de lacide folique en acide dihydrofolique, (b) le métabolisme des ptéridines nonconjugées et (c) la phosphorylation de la thymidine.

Study of Folic Acid and Vit. B12 in Blood and Urine During Normal Pregnancy.

Summary A comparison of PGA and vit. B12 levels in blood and urine during pregnancy shows that levels of PGA are high, and those of B12 are low. Possible explanations for these findings are discussed.

Vit. B12 in thyrotoxicosis and myxedema.

Summary The whole-blood B12 values in 10 hyperthyroid subjects before and after a load dose of B12 were lower than for a normal and a myxedematous group. The mean 8-hour urinary excretion after B12 administration in hyperthyroid subjects was considerably lower than in the normal and myxedematous groups. These data suggest that B12 turnover and demand is appreciably greater in hyperthyroidism and appreciably lower in myxedema.

Vitamin Levels in Normal Cerebrospinal Fluid.

Summary Using our microbiological assay methods, we established normal ranges in CSF for folic acid, folinic acid, thiamine, cyanocobalamin, pantothenic acid and the Vit. B6-group. The ratios of CSF levels to blood levels of these vitamins are shown in Table 1.

Comparative study of vitamin B12 assay in urine.

Summary The response of Ochromonas malhamensis, Euglena gracilis, and Lactobacillus leichmannii to vit. B12 in normal urine and in urine of patients, given an intramuscular dose of 50 μg of vit. B12 was studied. The “true” vit. B12 values presumably are given by the Ochromonas malhamensis assay. The response of E. gracilis and L, leichmannii to other members of the B12 group and to other metabolites is discussed from the standpoint of how to estimate responses other than O. malhamensis-active B12. Calculations are given for the estimation of interfering metabolites.

Pantothenic acid, thiamine and folic acid levels at parturition.

Summary A comparison of pantothenic acid, thiamine, and PGA serum levels of mothers and infants at parturition shows an approximately 5-fold increase of these vitamins in the fetal circulation. The significance of these findings is discussed.