Thiamine-deficient Diet Research Articles

ENHANCED METHYLGLYOXAL TOXICITY IN OXYTHIAMINE INDUCED THIAMINE DEFICIENCY IN MICE.

SummaryIntraperitoneal injection of methylglyoxal was toxic to mice, the LD50 in normal mice after 24 hours being 290 mg/ kg. The cause of death with doses of 400 mg/kg and above appeared to differ from that produced by lower doses. Neither pre-treatment with a thiamine deficient diet nor pyrithiamine significantly affected the toxicity of methylglyoxal. However, pre-treatment with oxythiamine lowered the LD50 of methylglyoxal to 150 mg/kg. Methylglyoxal was not detected in the urine of normal mice given methylglyoxal, nor in the urine, brain or muscle of mice treated with pyrithiamine or oxythiamine or in mice fed a thiamine deficient diet.

The antithiamine effects of amprolium in rats on tissue transketolase activity

Summary The feeding of amprolium to thiamine-adequate rats at a dietary level of 10,000 ppm (approximately 80 times the effective coccidiostat level for chicks) resulted in depressed transketolase activity in erythrocyte hemolyzates and in homogenates of liver, kidney, heart, and intestine. Thiamine deficiency alone resulted in similar but more severe effects in the same tissues. However, the addition of amprolium to thiamine-deficient diets did not result in more severe depressive effects on tissue transketolase activity than did thiamine deficiency alone. Brain transketolase activity was unaffected by either thiamine deficiency or by the administration of amprolium. Thiamine deficiency resulted in retarded growth after 15 days, whether or not amprolium was present. An alternate method for measuring transketolase activity, by the formation of sedoheptulose in the assay system, was presented.

Lipogenesis in adipose tissue of rats fed different diets.

Lipogenesis and glucose uptake by epididymal fat pads of rats fed different diets have been investigated. Lipogenesis was found to be depressed in rats fed high fat, high fat and high protein, thyroid, thiouracil, and thiamine-deficient diets. The same dose of insulin causes varying degrees of lipogenesis in the tissues, depending on the type of diet fed previously. Lipogenesis is above normal in hydrolyzed glucose-cycloacetoacetate-fed rats but glucose uptake is not appreciably affected. The glucose uptake of adipose tissue is significantly depressed in rats fed high fat, high fat with high protein, and vitamin B1 deficient diets, and in rats with hypothyroidism. Both hyperthyroidism and hydrolyzed glucose-cycloacetoacetate feeding increase glucose uptake by the tissue. Alloxan diabetes reduces lipogenesis as well as glucose uptake.

Tissue thiamine changes in rats with experimental trypanosomiasis or malaria

Progressive changes of thiamine content and concentration in the tissues of rats with infections of Trypanosoma rhodesiense or Plasmodium berghei have been described. During the course of infection with P. berghei there was no change in concentration in either the liver or kidney. In the spleens of young rats thiamine concentration doubled, whereas, in older animals an increase of one third was observed. In the blood of infected animals the apparent increase in concentration was not great, because of the attendant anemia. However, an average infected red cell contained three times as much thiamine as a normal erythrocyte and each purified parasite ten times as much. With infections of T. rhodesiense an increased concentration of thiamine was noted in the livers of young animals. During the terminal portion of the infection there was a rise of concentration in the spleens of both young and old rats and a drop in the kidney. In the blood a threefold increase of thiamine concentration occurred which could be related to the rise in parasitemia. Each purified trypanosome contained about twenty times as much thiamine as a single red cell. When animals with infections of T. rhodesiense were fed thiamine deficient diets the changes in thiamine concentration were of the same order as those observed in rats on routine feeding but at a lower level.

Physiological action of ethylthiamine.

1. 20μg ethylthiamine has nearly the same activity as 20μg thiamine on the growth promotion of mice.2. The endogenous respiration of the liver homogenate of the mice receiving ethylthiamine for a long period was nearly the same as that receiving thiamine, without any effect by adding pyruvic acid.3. The respiration-accelerating effect of ethylthiamine pyrophosphate in the washed liver homogenate of mice fed on a thiamine-deficient diet for a long period was less active than that of thiamine pyrophosphate in the presence of pyruvic acid. In catatorulin test, the activity of ethylthiamine was definitely lower than that of thiamine.4. It remains unexplained at present why ethylthiamine has nearly the same growth-promoting activity in animals as thiamine.

The Influence of Orally-Administered Penicillin upon Growth and Liver Thiamine of Growing Germfree and Normal Stock Rats fed a Thiamine-Deficient Diet

The Influence of Orally-Administered Penicillin upon Growth and Liver Thiamine of Growing Germfree and Normal Stock Rats fed a Thiamine-Deficient Diet

The physiologic role of vitamins

T HE simplest classification of nutrients in foodstuffs depends on whether the primary use of the nutrient in the body is for the provision of energy or for the building of structural tissues. If one’s concept of structural elements is in terms of bone and connective tissue with exclusion of particulate matter in the cytoplasm of cells, then the vitamins belong in neither of these two categories. For our purpose today vitamins may be considered provisionally as dietary essentials required with hormones and other products of endogenous origin in the maintenance of the complex equilibria which together make possible a steady state in the organism, a state not of rigid constancy but one quickly adjustable to normal and abnormal stresses. The diversity of the molecular structure of vitamins is striking and it is clear that their function is not dependent on any one common structural configuration or chemical property. Hormones also show such individual variations. However, hormones differ from vitamins in at least two respects. They are not dietary essentials and several have protein structures. Significantly, there is no known instance of a specific protein that is indispensable in the dietary. Whether or not other essential nutrients such as trace minerals, essential amino acids and essential fatty acids should be classed with the vitamin group is largely a matter of arbitrary definition. If desired, trace minerals can be excluded by explicitly describing vitamins as organic compounds. Similarly, essential amino acids can be put in the category of tissue building materials. The unsaturated fatty acid, arachidonic acid, is more of a problem and might easily qualify as a vitamin unless it also is found to function largely in the form of phospholipides or other derivatives used in cell walls and in brain and nerve tissue. However, no advantage is to be gained in the broadening or narrowing of definitions in order to achieve an unnatural or unrealistic pattern of conformity in the classification of nutrients, and this will not be attempted. A discussion of the physiologic role of the vitamins at this time can only be in the nature of an interim report. Despite the detailed information which has accumulated during this last half-century we are now possibly no more than at the beginning of an understanding of these bewildering constituents of food. True, rather precise statements can be made concerning the mechanism of transport of hydrogen atoms by certain riboflavin-containing protein complexes but this gain is matched by our inability to name any chemical reactions through which another vitamin, the antirachitic vitamin, has been proved to facilitate the utilization of food calcium for the formation of bone. True, the role of vitamin A in vision has been nicely delineated but there is a complete lack of recognition of the manner of its beneficent protection of epithelial cells, whether of the eye, the skin, the gastrointestinal tract or the reproductive tract. Research has linked thiamine, nicotinamide and pantothenic acid with the utilization of the carbons of pyruvic acid in the highly important citric acid cycle in animal tissues; yet, in man, beriberi results from a deficiency of thiamine, pellagra from a deficiency of nicotinamide, and no comparable deficiency disease has been associated with pantothenic acid. Although the latter statement possibly is an oversimplification of the situation one may well ask if the facts at hand, as astonishing and as useful as they are, represent only the more easily recognized aspects of the activity of certain of the vitamins. Be that as it may, the fact is that a well characterized, acute syndrome in man, beriberi, can be prevented by the daily addition of approximately 1 mg. of pure thiamine to a thiamine-deficient diet. Similarly, each of the other historically important nutritional deficiency diseases, pellagra, scurvy, xerophthalmia and rickets, can be prevented by the daily addition of appropriate amounts of pure niacinamide, ascorbic acid, vitamin A and vitamin Dz (or D3), respectively, to the corresponding deficient

Some Effects of Thiamine Deficiency and Reduced Caloric Intake on Avoidance Training and on Reactions to Conflict

The present experiment was designed to test four predictions based upon results of our earlier study (Knöpfelmacber et al., 1956) in which we observed some effects of thiamine deficiency and reduced caloric intake on “behaviour under stress” and on learning. The first two predictions stated that thiamine deficiency of a degree not severe enough to produce polyneuritis (a) would not affect the efficiency of conditioning and (b) would not be associated with exaggerated reactions to conflict. The third prediction arose from our previous observations of the effects of “irrelevant drives” on learning and stated that animals on reduced caloric intakes would condition more rapidly as a group than would animals fed ad libitum. The fourth prediction was that reduced caloric intake would not be associated with increased susceptibility to stress. The experiment was identical in its design to our previous study. It required one experimental and two control groups, all matched by a littermate control technique. The experimental group was maintained on a thiamine-deficient diet throughout the entire experimental period. A caloric control group received adequate thiamine, but a food intake reduced to that of the vitamin-deficient animals. A general control group received adequate thiamine and an unrestricted food intake. Because of the effects of thiamine deficiency on caloric intake, food-hunger was never used as a form of motivation. Behaviour in three different situations was studied: in an instrumental conditioning situation involving jumping to a platform to avoid shock; in an avoidance-avoidance conflict situation; and in a second instrumental conditioning situation requiring lever-pressing to avoid shock. The results confirmed some of our predictions, but not others. In general, they indicated that thiamine deficiency of the level we induced did not affect the efficiency of conditioning. This conclusion conforms with the findings of our earlier experiment that the deficiency did not affect maze or discrimination learning, but it is contrary to the observations of certain other investigators. The evidence did suggest that thiamine deficiency was associated with exaggerated reactions during exposure of the animals to conflict, deficient animals tending to show greater response rigidity and “displacement activity.” The divergences in the behaviour of these animals and their paired caloric controls became more noticeable as the number of conflict trials increased. Our prediction that reduced caloric intake would be associated with more rapid conditioning was confirmed. We believe this result suggests that “irrelevant drives” were operating in a manner similar to that reported in our previous study. The overall results support our fourth prediction that reduced caloric intake would not affect reactions to conflict. However, an analysis of behaviour trends during the conflict trials suggests that reduced caloric intake may have affected reactions early during exposure to conflict and only became differentiated from the effects of thiamine deficiency as the duration of exposure increased.

Some Effects of Thiamine Deficiency and Reduced Caloric Intake on “Behaviour under Stress” and on Learning

The main purpose of the investigation was to determine the effects of thiamine deficiency in rats on behaviour under stress and on learning. Since thiamine deficiency reduces food intake, it was necessary to have two control groups. The first received adequate thiamine, but a food intake reduced to that of the vitamin-deficient animals; the second received adequate thiamine and an unrestricted food intake. It was thus possible to study the effects both of thiamine deficiency and of reduced caloric intake on the behaviour variables measured. The experimental group was maintained on a thiamine-deficient diet throughout the entire experimental period. Because of the effects of thiamine deficiency on caloric intake, food-hunger was never used as a form of motivation. Behaviour in four different situations was studied: in Hall's open-field test, in two discrimination situations both involving exposure to insoluble and soluble problems, and in a water maze. Contrary to the findings of several previous studies, there were no significant effects of thiamine deficiency on behaviour prior to the onset of polyneuritis with its debilitating effects on motor co-ordination. There was also no evidence of impairment in any of the behaviour studied which could be attributed to restrictions in caloric intake. This was the case even though the restrictions continued for a period of somewhat more than twelve months. Although these restrictions did not lead to impairment they were associated with certain changes in performance. Animals whose feeding was restricted were more active and, during the soluble phase of one discrimination situation, showed more vicarious trial and error and learned more readily than animals fed ad libitum on the same diet. It is suggested that these differences may be interpreted in terms of the effects of what previous investigators have referred to as “irrelevant drives”.

CARDIAC AUTOMATISM AND CHOLINE ACETYLATION IN RATS ON THIAMINE- AND PANTOTHENIC- ACID-DEFICIENT DIETS

The choline acetylating activity of extracts of the acetone powders of hearts of rats fed on diets deficient in thiamine, in pantothenate, and in thiamine plus pantothenate was found to be the same as it was in rats on a complete synthetic diet, although severe changes in the electrocardiogram (e.c.g.) were present in rats on the two thiamine-deficient diets. These e.c.g. changes were the same as the ones described in rats on diets deficient in other factors besides thiamine. The rats on the pantothenic-acid-deficient diet grew as normals did and no e.c.g. abnormalities were seen in them. The symptoms of thiamine deficiency were attenuated and their appearance delayed when pantothenate also was deleted from the diet.

The disappearance of pyruvic decarboxylase and α-ketoglutaric decarboxylase from pigeon muscles on thiamine-deficient diets

In homogenates of breast muscle and heart muscle acetoin and succinic semialdehyde are final products of the anaerobic metabolism of pyruvate and α-ketoglutarate respectively. Therefore the pyruvic and α-ketoglutaric decarboxylase activities of these muscles could be measured by determining the rates of production of these compounds from pyruvate and α-ketoglutarate added to the homogenates. During thiamine deprivation both activities decreased according to the curves shown in Figs. 1 and 2. Pronounced differences exist between both kinds of muscle regarding the rates of decline of the activities as well as the activities remaining at death. The presence or absence of carbohydrate in the thiamine-free diet also has a marked influence on both phenomena. In general the α-ketoglutaric decarboxylase activity decrease less rapidly than the pyruvic decarboxylase activity. At death the pyruvic decarboxylase activity of breast muscle is much higher on the carbohydrate diet than on the fat diet, while in this regard no difference appeared to exist in heart muscle. Regarding the α-ketoglutaric decarboxylase activity at death, this is also higher on the carbohydrate diet than on the fat diet in breast muscle, while in most cases the reverse was observed in heart muscle. As compared to the normal activity of breast muscle or heart muscle the final percentage decrease of the pyruvic decarboxylase activity is always much greater than that of the α-ketoglutaric decarboxylase activity, but the former also is never completely lost. The apoenzymes are completely maintained in the muscles during most of the period of deficiency; they are only partly lost in the last stages, with the exception of the α-ketoglutaric decarboxylase on the carbohydrate diet.

CARDIAC AUTOMATISM AND CHOLINE ACETYLATION IN RATS ON THIAMINE- AND PANTOTHENIC- ACID-DEFICIENT DIETS

The choline acetylating activity of extracts of the acetone powders of hearts of rats fed on diets deficient in thiamine, in pantothenate, and in thiamine plus pantothenate was found to be the same as it was in rats on a complete synthetic diet, although severe changes in the electrocardiogram (e.c.g.) were present in rats on the two thiamine-deficient diets. These e.c.g. changes were the same as the ones described in rats on diets deficient in other factors besides thiamine. The rats on the pantothenic-acid-deficient diet grew as normals did and no e.c.g. abnormalities were seen in them. The symptoms of thiamine deficiency were attenuated and their appearance delayed when pantothenate also was deleted from the diet.

Physiologic observations on a case of beriberi heart disease, with a note on the acute effects of thiamine

TWENTY-NINE year old white, alcoholic A male entered the hospital with all of the features of circulatory congestion of the type associated with beriberi. He showed massive edema and ascites, a dusky plethora with hot extremities and an overactive heart. The antecubital venous pressure was 310 mm. Hz0 and the calcium gluconate circulation time was 9 seconds arm-to-tongue. An electrocardiogram and the size and configuration of the heart by x-ray were normal. The serum proteins were normal and there was mild anemia. Subsequent liver function studies and liver biopsy revealed moderate portal cirrhosis. He had been drinking for several years, more heavily for the past two months, and his dietary intake had been extremely poor during this entire period. As nearly as could be determined, he had consumed only alcoholic beverages during the past six weeks. The patient was placed on a thiamine deficient diet without salt restriction and kept at normal activity. The first physiologic study was carried out twelve hours after admission.

The influence of carbohydrate on the origin of symptoms and the onset of death in thiamine-deficient pigeons

Former experiments had shown that increased carbohydrate consumption leads to a quicker depletion of the thiamine pyrophosphate stores of pigeons on diets deprived of thiamine. Now thiamine pyrophosphate has been determined in liver, heart, breast muscle and cerebrum immediately after death by vitamin-B 1 deficiency. It appeared that on a carbohydrate-rich diet the content of liver and heart was lower, and the content of breast muscle and cerebrum was higher than on a diet in which carbohydrate was replaced by an isocaloric amount of fat. These results suggest that the rapid depletion of the stores of thiamine pyrophosphate is the only cause of the earlier appearance of symptoms and of the earlier death by introduction of a higher percentage of carbohydrate in the thiamine-deficient diet. There is no reason to assume any toxic effect of carbohydrate or its metabolic intermediates upon the thiamine-deficient organism.

A study of the nutritional defect in Wernicke's syndrome; the effect of a purified diet, thiamine, and other vitamins on the clinical manifestations.

The salient clinical features of Wernicke's syndrome (1) are partial to complete paralysis of extra-ocular muscles (most commonly the external recti), nystagmus, ataxia and mental disturbances. Postmortem examination reveals changes in the nervous structures adjacent to the third and fourth ventricles and the aqueduct. The lesions are characterized by varying degrees of necrosis of both nerve cells and nerve fibers with appropriate reactions of microglia and astrocytes, alteration of the small blood vessels, and in some cases, petechial hemorrhages (2-5). The syndrome is usually associated with chronic alcoholism and for that reason has sometimes been attributed to a neurotoxic effect of the alcohol; but the occurrence of the same clinical sequence in non-alcoholic patients with malnutrition (1, 2, 4-8) has directed attention to nutritional deficiency as the etiological basis. Moreover, similar pathological lesions have been produced in the rat (9, 10), fox (11, 12), and pigeon (3, 9, 13, 14), by maintaining these animals on thiamine-deficient diets.

The influence of carbohydrate on the origin of symptoms and the onset of death in thiamine deficient pigeons

Former experiments had shown that increased carbohydrate consumption leads to a quicker depletion of the thiamine pyrophosphate stores of pigeons on diets deprived of thiamine. Now thiamine pyrophosphate has been determined in liver, heart, breast muscle and cerebrum immediately after death by vitamin-B1 deficiency. It appeared that on a carbohydrate-rich diet the content of liver and heart was lower, and the content of breast muscle and cerebrum was higher than on a diet in which carbohydrate was replaced by an isocaloric amount of fat. These results suggest that the rapid depletion of the stores of thiamine pyrophosphate is the only cause of the earlier appearance of symptoms and of the earlier death by introduction of a higher percentage of carbohydrate in the thiamine-deficient diet. There is no reason to assume any toxic effect of carbohydrate or its metabolic intermediates upon the thiamine-deficient organism.

The thiamine pyrophosphate content of centrifugally-prepared fractions of rat liverhomogenate. The influence of a thiamine-deficient diet

The thiamine pyrophosphate content of centrifugally-prepared fractions of rat liverhomogenate. The influence of a thiamine-deficient diet

Thiamin Deficiency and Susceptibility of Rats and Mice to Infection with Salmonella typhi murium.

Summary(1) Rats and mice kept for a few weeks on a thiamin-deficient diet show diminished resistance to oral Salmonella typhimurium infection.(2) In rats the lowered susceptibility is secondary to inanition. On the other hand, in mice the diminished resistance to Salmonella infection is a primary result of the thiamin deficiency.

THIAMINE DEFICIENT DIET IN TOURNIQUET SHOCK IN RATS

Journal Article Thiamine Deficient Diet in Tourniquet Shock in Rats Get access Nutrition Reviews, Volume 3, Issue 10, October 1945, Pages 316–317, https://doi.org/10.1111/j.1753-4887.1945.tb08502.x Published: 01 October 1945

Non-Availability of Fecal Thiamine in Thiamine Deficiency

SummaryRats maintained on a thiamine-deficient diet excreted essentially the same concentration of thiamine in their stools as did animals receiving 5 or 50 μg of thiamine daily. The output of feces was greatly reduced in the thiamine low group. During the later stages of the depletion the thiamine was present largely in the form of cocarboxy-lase.The fecal thiamine of the deficient rats was not available when administered curatively by the oral route to animals which had plateaued in weight on a thiamine-low diet.