Blood Thiamine Levels Research Articles

Thiamine-responsive megaloblastic anemia

An 11-year-old Caucasian girl is presented who had a megaloblastic anemia responsive only to thiamine. Other abnormalities included diabetes mellitus, aminoaciduria, and sensorineural deafness. Initially the anemia, refractory to vitamin B 12 and folic acid therapy, responded to administration of a multiple vitamin preparation. Vitamin supplementation was withdrawn followed by a recurrence of anemia 3½ months later. The implicated vitamins were then administered sequentially. A reticulocytosis followed administration of thiamine. Anemia again recurred 4 months after cessation of vitamin supplementation. On this occasion the anemia was corrected by the oral administration of 20 mg. thiamine daily. Thiamine blood levels and activities of 3 thiamine-dependent enzymes of the patient's blood cells were normal, excluding a generalized defect of thiamine metabolism. The patient therefore appeared to have a thiamine-dependent megaloblastic anemia. This represents the first demonstration of a role for this vitamin in DNA metabolism.

Synthesis of O-benzoylthiamine disulfide monosulfoxide and its biological properties.

1. Monosulfoxides of symmetrical disulfide-type thiamine derivatives were synthesized by oxidation with perbenzoic acid instead of H2O2. As a solvent, acetic acid or acetic acid in chloroform gave better results than chloroform alone. The oxidation products thus obtained were identified as monosulfoxides of symmetrical disulfide-type thiamine derivatives by elementany analyses, ultraviolet and infrared absorption spectra and HI reaction.2. One molecule of O-benzoylthiamine disulfide monosulfoxide (BTDSO) was found to be reduced with excess cysteine (pH 8.5-9) or Na2S2O3 (pH 4-5) to two molecules of free thiamine. Preventive test of BTDSO in thiamine-deficient lovebirds showed the same activity as thiamine, OBT and BTDS. Biologically, one molecule of monosultoxide was estimated to correspond to two molecules of thiamine.3. When BTDSO was orally and intravenously administered in rabbits, the blood thiamine level was higher and retained longer than in the case of thiamine and BTDS.

Biological properties of a new thiamine derivative, cyclocarbothiamine.

Cyclocarbothiamine, a new thiamine derivative obtained by the reaction of thiamine with phosgene, was found to have a number of advantages over thiamine in its biological properties.1. Its thiamine activity was indistinguishable from that of thiamine when examined in vivo with rats and rice-birds.2. Oral administration of cyclocarbothiamine resulted in far higher thiamine contents in the rabbit blood as well as in the liver and kidney of rats. Marked increase was observed also in blood cocarboxylase levels of rabbits.These data indicate that, as against thiamine, cyclocarbothiamine is absorbed from the intestine in large quantities.3. Intravenously injected cyclocarbothiamine similarly brought about higher blood thiamine levels in rabbits than did thiamine and its urinary excretion was delayed.4. Unlike thiamine, cyclocarbothiamine was not decomposed by either thiaminase I of Bacillus thiaminolyticus or thiaminase II of Bacillus aneurinolyticus.

AFFINITY OF THIAMINE PROPYL DISULFIDE-S35 TO BLOOD.

In order to investigate in detail the increase in blood thiamine level after administration of thiamine propyl disulfide, TPD-S35 (outer), and TPD-S35 (inner), and of thiamine-S35 in rabbits, the distribution of S35 in the blood was examined and the following interesting findings were obtained.1. The thiamine part of TPD was shown to be found in large quantities in blood cells, while the majority of S35 was found in plasma after oral or parenteral administration of TPD-S35 (outer).2. S35 was found in the albumin fraction rather than in the globulin fraction of plasma after administration of TPD-S35.3. After parenteral administration of TPD-S35 (inner), S35 was found mainly in blood cells, and extremely poorly in plasma.4. The SH group in blood cells is shown to be involved in the mechanism of the penetration of the thiamine part of TPD into blood cells.5. S35 was increased in blood cells after oral administration of TPD-S35 (inner), though it was less than after subcutaneous injection, whereas the increase in S35 was scarcely noted in blood cells after administration of thiamine-S35. The finding suggests that TPD passes through the intestinal tract without alternation.

BIOCHEMICAL STUDIES ON VITAMIN METABOLISMS IN POULTRY URINE

1. Thiamine-deficient poults operated to have artificial anus were used, and the thiamine levels in blood and urine of the birds were studied.2. At first, a control test of determining the radioactivity excretion in the droppings after oral administration of thiamine-S35 or TPD-S35 was carried out in ordinary intact poults. The radioactivity excretion in the droppings was found to be greater in the case of thiamine-S35 than in that of TPD-S35.3. S35-Radioactivity excretion in the urine and feces after administration of thiamine-S35 in the poults operated to have artificial anus was studied. Greater urinary excretion of the radioactivity was seen in the poults receiving thiamine-S35, whereas it was very poor in the birds receiving TPD-S35. Further, the proportion of the radioactivity excretion in urine and feces was determined. The more the intake of thiamine-S35, the higher the fecal excretion of the radioactivity. In addition, the radioactivity distribution in various tissues was always higher in the poults receiving TPD-S35 than those receiving thiamine-S35.4. The relative urinary excretion of thiamine-S35 was extremely lower than that of S35.5. In the control tests for thiamine-S35 excretion in the droppings of the thiamine-deficient poults without operation, total excretion of thiamine was rather low as compared with the radioactivity excreted in the droppings.6. In the tests for relative thiamine-S35 excretion to the total radioactivity in urine and feces in thiamine-defiicient poults having artificial anus showed that higher urinary excretion of the radioactivity was seen in the birds orally receiving thiamine-S35, whereas the total excretion of thiamine in urine was extremely low in the poults receiving thiamine-S35.These findings suggest a marked decomposition of thiamine in the digestive tract of poults.

Comparative clinical studies on the effect of thiamine and cocarboxylase.

Comparative clinical studies on the effect of thiamine and cocarboxylase wereconducted using the Sawada urine test, liver function test (Miyaji's phenol-FeCl3 test), rise in blood thiamine level, urinary thiamine excretion, transfer of thiamine into erythrocytes, santonin detoxification test and esterification of thiamine following administration of insulin as criteria. The following results were obtained:1. There was litttle difference in effect between thiamine and cocarboxylase using the three-hour method of the urine test. With the one-hour method, however, cocarboxylase was found to have a superior effect, the difference being fairly significant. With the phenol-FeCl3 test, cocarboxylase was found to be superior without exception.2. Under the conditions of this experiment, no difference between thiamine and cocarboxylase was detected in regards to their effect on blood thiamine level and urinary thiamine excretion.3. There was scarcely any transfer of thiamine or cocarboxylase into erythrocytes in an in vitro experiment.4. Thiamine had little effect on the detoxification of santonin in rabbits, whereas cocarboxylase as well as thiamine propyl disulfide manifested an intensive beneficial effect.5. When thiamine is injected in a diabetic patient following insulin injection, there is a rise in the esterified thiamine level in the blood and a decrease in urinary thiamine excretion as compared with the non-loaded experiment.

B-Vitamin Levels in the Blood of Young Dairy Calves Fed a Milk Replacement Diet with and without Aureomycin1,2

Summary The blood levels of thiamine, riboflavin, pantothenic acid, niacin, and vitamin B 12 activity were determined for ten male and ten female Holstein calves at 4 days of age. No significant differences between sexes were observed. Eight Holstein calves at 4 days of age were placed on a milk replacement diet and were assigned to two comparable groups, one of which received aureomycin orally (40mg. daily per calf for 7 weeks, 80mg. daily per calf from 8 to 12 weeks) while the other served as a control. Venous blood samples drawn at the beginning of the experiment and at 1, 2, 4, 8, and 12 weeks thereafter were analyzed for thiamine, riboflavin, niacin, pantothenic acid, and vitamin B 12 . No significant differences in the blood levels of these vitamins were found between the two groups of animals. Moreover, no apparent differences were observed between male and female calves. Certain trends in the B-vitamin blood levels with age are evident.

Vitamin Studies in Middle-Aged and Old Individuals

Summary The literature concerning the effects of deficiency states on the appearance of gastrointestinal radiograms has been briefly reviewed. Roentgenological examinations of the gastro-intestinal tract were performed in 20 middle-aged and elderly individuals with normal blood thiamine levels, and in 20 patients with blood thiamine concentrations below 2.4 micrograms per cent. The latter group was re-examined 3 months later when the blood thiamine level had been returned to normal by oral administration of thiamine hydrochloride, at which time most of the clinical signs had disappeared. No significant radiological abnormalities were observed in either of the groups examined. These findings do not exclude the possibility that a more severe grade of thiamine deficiency may be accompanied by radiological evidence of gastrointestinal abnormality.

Nutrition Survey and Tests in Bataan, Philippines

A nutrition survey by microchemical methods has been made in Bataan on 202 persons. Three-fourths of the group had been classified by an earlier clinical survey on the basis of severity of beriberi symptoms. One-fourth were regarded as normal individuals exhibiting no symptoms of beriberi. Initial blood thiamine levels were established as a baseline for measuring improvement after the population has consumed enriched rice over a period of time. Evidence of nutritional deficiency due to lack of thiamine was found in the low blood and low urinary thiamine levels of the population sample. The average blood thiamine of all persons was 3.6 μg per 100 ml of blood; of the non-symptomatic group, 4.0 μg. A progressive decrease in the average value for each group occurred with the increasing severity of signs and symptoms of beriberi. Statistically significant differences in blood thiamine were found between the nonsymptomatic group and the frank and suspected beriberi groups. Similarly significant differences were evident between the combined frank and suspected classes and the combined non-symptomatic and doubtful groups. The calculated red blood cell thiamine levels did not exhibit differences between these groups. The serum protein and hemoglobin levels and the hematocrit values showed progressive decrease with increasing severity of the signs and symptoms of beriberi. Concurrent low levels in blood thiamine, serum protein, and hemoglobin suggest an interrelation among these factors which may be pertinent to the appearance of symptoms of beriberi. Evidence of multiple dietary deficiencies in Bataan was found in the levels of other nutrients in blood or serum. Widespread anemia was evident from the low hemoglobin and hematocrit values, probably as a result of chronic deficiencies of iron and several members of the B complex. Serum protein levels fell in the lower range of normal. The lowest levels occurred in the frank beriberi group of pregnant women. Serum vitamin A levels were normal. Serum vitamin C and carotene concentrations were very low, apparently reflecting a low consumption of fresh fruits and vegetables. The lowest vitamin C levels were found in the group of lactating women.