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PubMed1979

Drugs and vitamin deficiency.

During the past 10 to 20 years it has become increasingly clear that a certain number of drugs may lead to increased vitamin requirements. However, it is unusual for symptomatic avitaminosis to develop, and then only when circumstances are present which in themselves increase the risk of vitamin deficiency. Therapeutic doses of drugs will interfere with the vitamin status only to a restricted degree, provided they are administered for brief periods and to patients receiving a normal supply of vitamins. Most cases of vitamin deficiency have in fact been described in connection with drugs usually taken for a longer period of time by patients who were already in negative vitamin balance as a result of disease or marginal supply of the necessary vitamins. This review describes some of the more important articles covering this topic.

Ascorbic Acid Deficiency↗

PubMedDate not supplied

[Removal of nicotinic acid 7-14C from the body of rats on a varying supply of vitamin PP].

Dynamic was studied for nicotinic acid (NA-7-14C) and its total metabolites excretion with area of animals under different physiological states (standard PP-avitaminosis). Various "efficiency" is shown for systems regulating homeostasis of this vitamin. When it is administered both in the amount close to the physiological dose (50 mg per 1 kg of weight) and exceeding the dose (500 mg per 1 kg of weight). The data obtained make it possible to draw a conclusion that the biological halflife period of Na-7-14C administered in excess of a physiological dose depends mainly on the rate of the unchanged vitamin PP excretion with urea and when it is administered in the physiological amount the period depends on the rate of the acid-metabolic transformations in the organism.

Animals↗

PubMed1979

[Peculiarities of phosphorylation of skeletal muscle troponin under some forms muscle pathologies].

Phosphorylation of rat and rabbit troponin from normal skeletal muscles and from skeletal muscles of animals under avitaminosis, denervation and hypokinesia was studied. Phosphorylation was carried out by cAMP-dependent protein kinase with [gamma-33P] as substrate. The incorporation of labelled phosphorus into troponin T of the damaged muscles was decreased as compared to normal. After preliminary dephosphorylation of troponin by alkaline phosphatase immobilized on Sepharose 4B, the ability of damaged muscle troponin for subsequent phosphorylation was also decreased as compared to the control. It may be thus assumed that there exist conformational changes of troponin under muscular system pathologies.

Alkaline Phosphatase↗

PubMed1979

Biochemical assessment of thiamine nutrition in childhood.

The activity of red cell transketolase and TPP-effect were determined in 1028 infants and children, aged 1 month to 14 years, using a micromethod. All the children were healthy and without evidence of malnutrition. Transketolase activity decreased in the second year of life, followed by a constant increase up to the 6th year. Activity did not change in the next four years, then a steady decrease occurred. TPP-effect was not as stable as transketolase activity, and decreased significantly from years 3 to 5 and increased significantly from years 5 to 7. Beginning with year 10, TPP-effect decreased gradually. 6.6% of all children investigated had marginally deficient TPP-effects and 1.3% were biochemically deficient without clinical signs of avitaminosis. A group of 37 adults had transketolase activities and TPP-effect comparable to those of the 13 year-olds. Effect appeared to be marginal in 5.4% and deficient in 2.7%.

Adolescent↗

PubMedDate not supplied

Keratomalacia.

Xerophthalmia and keratomalacia are public health problems of great magnitude which are usually associated with multiple vitamin and protein deficiencies. The authors report the case of a 27-year-old commune member who subjected herself to a bizarre protein and vitamin deficient diet for many months. This ultimately produced nyctalopia, xerophthalmia and keratomalacia with bilateral corneal perforation. Despite therapy, she remained comatose and expired shortly after admission. Ocular pathological changes included bilateral corneal melting with prolapse of intraocular contents, conjunctival epidermidalization, goblet cell atrophy and thinning of the outer nuclear layer of the retina. It is noted that ocular findings in pure avitaminosis A produced experimentalyy include epithelial atrophy followed by keratinization.

Adult↗

PubMed1990

Effects of beta-carotene on chemically-induced skin tumors in HRA/Skh hairless mice.

In order to evaluate the role of beta-carotene as an inhibitor of skin carcinogenesis, hairless female HRA/Skh mice were treated with the initiator 7,12-dimethylbenz[a]anthracene (DMBA) and with the promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), and were fed a balanced diet free from vitamin A either with or without gavage-administered beta-carotene. There was no evidence of avitaminosis A or differences in body weight in mice deprived of beta-carotene and vitamin A, compared with those given 290 or 1430 IU beta-carotene/kg per day. Mice fed with normal animal feed pellets displayed a significantly higher body weight (28.5 +/- 1.95 g) compared with mice on the special diet (25.7 +/- 1.9 g), and also displayed a higher papilloma yield. However animals on the special diet, fed with beta-carotene from weaning, displayed significantly lower numbers of papillomas per mouse. This lower papilloma yield was evident particularly between 12-24 weeks after commencement of the study, which coincided with the period of maximum tumor yield in DMBA/TPA-treated mice. The characteristic regression of papillomas after that time points to the reversibility of many earlier papillomas, and their dependence on continued TPA administration. Evaluation of carcinomas in mice on the various dietary regimes showed there was no significant difference between any group, including those fed with beta-carotene continuously from weaning. The present results demonstrate that a sustained dietary intake of beta-carotene from 3 weeks of age partially suppressed the growth of papillomas, but did not affect the course of malignant progression in DMBA/TPA-treated HRA/Skh mice. It is evident that beta-carotene predominantly affects TPA-dependent papillomas, which possess reversible properties and have a low probability of progression to form carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2002

Spermatogenesis and blood-testis barrier in rats after long-term Vitamin A deprivation.

It has been established that experimental avitaminosis A in rats results in a 'Sertoli cell-only situation' after about 10 weeks, and that replacing the vitamin immediately reinitiates spermatogenesis. The present study deals with testicular recovery after prolonged deprivation (up to 19 weeks). The Sertoli cell-only situation reached under this condition was thought to be refractory to Vitamin A replacement. However, spermatogenesis did reinitiate about 11 weeks after vitamin restoration, although in an atypical manner. The blood-testis barrier, normally assembled when spermatocytes reaches the zygotene stage, remained under this condition permeable to the lanthanum intercellular tracer. Concomitantly, primary spermatocytes normally found in the adluminal compartment isolated by the barrier (zygotene onward) became massively apoptotic. All the tubules containing early spermatocytes (preleptotene or leptotene cells), normally found in the basal compartment, exhibited normal features with no signs of degeneration. Based on these results, a possible relationship between blood-testis barrier assembly and spermatocyte differentiation is proposed.

Animals↗

PubMedDate not supplied

Phenytoin ameliorates the memory deficit induced in the young chick by ethanol toxicity in association with thiamine deficiency.

The experiments reported in this series of studies demonstrate that thiamine deficiency, induced pharmacologically by oxythiamine (OT) coupled with the acute administration of ethanol can adversely affect memory processing in the young chick. The interaction between the avitaminosis and ethanol neurotoxicity exerted its effects through the inhibition of the development of the intermediate (ITM) stage of memory (i.e., following 10 min after training), consequently affecting development of the long-term stage of memory and leaving the short-term memory stage intact. The amnesic effect of OT-induced thiamine deficiency and exposure to alcohol was ameliorated by the administration of phenytoin [diphenylhydantoin (DPH)] immediately following the training experience. As the ITM stage of memory has been suggested to rely on the activities of Na(+)/K(+) ATPase, and as DPH is a facilitator of Na(+)/K(+) ATPase activity amongst its other actions, it may be that the combined effect of OT and ethanol exposure is by interfering with Na(+)/K(+) ATPase activity, thus undermining the expression and maintenance of the memory in the period from 10 min following aversant training.

Animals↗

PubMed2000

Dyshaemopoiesis in adults: a practical classification for diagnosis and management.

Dyshaemopoiesis is a heterogeneous disease that may be classified into non-clonal and clonal dyshaemopoiesis. Non-clonal dyshaemopoiesis comprises reversible disorders with DNA synthesis impairment in dividing cells of the bone marrow by avitaminosis through various mechanisms or direct DNA damage from multiple causes. Complete haematologic recovery is obtained after vitamin supplementation or suppression of a myelotoxic agent. On the contrary, clonal dyshaemopoiesis is a group of chronic and usually irreversible diseases that may culminate in acute leukaemia (AL). These so called myelodysplastic syndromes (MDS) and their variants may be classified as primary, secondary and other diseases with doubtful clonality. A detailed classification of dyshaemopoiesis in adults may offer partial help in the diagnosis and management of dyshaemopoiesis. Pathobiological studies in progress allow better understanding of MDS and consequently the establishment of new modalities of treatment.

Adult↗

PubMed2000

William Hogarth, unwitting neurochemist?

William Hogarth's famous etching Gin Lane is often used to illustrate the debilitating results of alcohol addiction. Less well known is the companion etching Beer Street in which death, murder and squalor are replaced by health, orderliness and joy. Some 250 years later, the rise of science, and specifically of neurochemical research, has defined how the malnutrition, including avitaminosis, resulting from addiction to distilled spirits (rather than more judicious use of less potent alcoholic beverages) disturbs brain metabolism and function. These two etchings, which have survived for their historical and artistic value, continue to have sociological and clinical relevance.

Alcoholism↗

PubMed2000

[Toxic-metabolic and physically-induced myelopathies].

The differential diagnosis in patients with spinal cord disorders is sometimes very difficult. There is an overview about important toxic-metabolic myelopathies, like drugs, ergotamines, Kichererbsen, avitaminosis, diving accidents and radiation exposition. Beside the cause- and the senso-motoric therapy, disturbances bladder-, bowel-, sexual and cardiovascular disorders needs a specialised therapy.

Decompression Sickness↗

PubMed1966

Nutrition and lysosomal activity. The influence of the vitamin A status on the proteolytic activity of extracts from the livers and kidneys of rats.

1. Young rats were kept for several weeks on a diet deficient in vitamin A. Some were undosed, others were given marginal (25i.u. weekly), adequate (1000i.u. weekly) or excessive (50000i.u. daily) doses of vitamin A acetate. The undosed rats developed signs of vitamin A deficiency, and the overdosed animals had skeletal fractures indicative of hypervitaminosis A. 2. The rats were decapitated. Their livers, and sometimes their kidneys, were homogenized and processed by centrifugal methods to sediment most of the lysosome fractions. Proteolytic activity was measured, after treatment with a detergent, in the whole homogenate (;total' activity), in the pellet obtained after 20min. at 15000g (;bound' activity) and, without treatment with detergent, in the supernatant (;free' activity). 3. In rats suffering from hypervitaminosis A the free activity and to a smaller extent the total activity were increased. Free activity was also raised in most rats suffering from avitaminosis A, but less than in those suffering from hypervitaminosis. 4. The vitamin A status appeared to have little effect on the proteolytic activity of the kidneys. Results for total and free activities, but not for bound activities, were higher than for corresponding liver preparations. 5. Control experiments were done on starved rats and on rats which were pair-fed with hypervitaminotic animals. Short periods of starvation caused an increase in free activity in young rats, but not in adults. The increases caused by starvation were much less than those caused by hypervitaminosis A. 6. For studies of the distribution of vitamin A more complete separation of the subcellular fractions was carried out on the combined livers from several hypervitaminotic rats. The concentration of vitamin A in the lysosome fraction was less than in the liver as a whole. 7. Our finding that the free proteolytic activity of the liver is increased by toxic oral dosing with vitamin A can be considered an extension of the previous observation that proteolytic enzymes are liberated when lysosomes are treated in vitro with vitamin A.

Animals↗

PubMed1967

Nutrition and lysosomal activity. The influence of vitamin E deficiency and its duration on the stability of lysosomes in the kidneys of rats.

1. Experiments on rats were made to find whether the increased liability of the kidney-cortex tubules to autolysis post mortem, which is a well-established abnormality in vitamin E deficiency, can be correlated with changes in lysosomal activity. Parallel observations were made on the development of certain other abnormalities characteristic of avitaminosis E. 2. In rats killed after long periods (8-10 months) of subsistence on a standard vitamin E-deficient diet, containing lard, both the rate of kidney autolysis post mortem and the enzyme activity of lysosome preparations from the fresh tissues were much greater than in controls. A greater percentage difference was usually found in the ;free' enzyme fraction than in ;bound' or ;total' activity. 3. In rats killed after graded periods (3-8 months) of deficiency, two abnormalities (decreased resistance of the erythrocytes to haemolysis, and brown discoloration of the uterus) were already evident at a stage (3-4 months) when the liability to rapid kidney autolysis had not begun. At this point the enzymic activity of kidney extracts differed little between deficient animals and controls given alpha-tocopherol. As the duration of deficiency advanced, parallel increases occurred in the rate of kidney autolysis and in lysosomal instability. 4. When cod-liver oil, rich in polyunsaturated fatty acids but freed from vitamin A, was substituted for lard in the diet, the time (1(1/2) months) required for the inducement of both rapid kidney autolysis and decreased lysosomal stability was greatly shortened. The time for the inducement of brown discoloration of the uterus was not shortened and the kidney abnormalities appeared while the uterus was still normal. 5. Confirmation was thus obtained for the view that the various tissues of the rat respond differently to the relationship between the adequacy of the vitamin E status and the intake of polyunsaturated fatty acids. The kidney-cortex tubules, as evidenced by autolysis post mortem and the corresponding decrease in lysosomal stability, may be classed among those tissues that are most sensitive to the effect of high intakes of polyunsaturated acids.

Animals↗

PubMed1987

Vitamin-A-dependent zinc-binding protein and intestinal absorption of Zn in chicks.

It was demonstrated that the development of experimental avitaminosis A in chicks led to secondary zinc deficiency. The balance of Zn in the chick became negative, while the Zn content of various tissues decreased. Thus in vitamin-A-deficient chicks the serum Zn content was 1258 (SD 26.3) micrograms/l which was considerably lower than 1652 (SD 97.8) micrograms/l in controls. Zn absorption was considerably reduced throughout the entire small intestine of vitamin-A-deficient chicks and most markedly in the ileal region. Within 72 h after retinyl acetate administration Zn absorption was fully restored in this region of the intestine. The 65Zn-binding capacity of soluble proteins, present in the supernatant fraction of ileal-mucosa homogenates of vitamin-A-deficient chicks, was found to increase 2.6 times by 72 h after the administration of a single dose of retinyl acetate. A vitamin-A-dependent Zn-binding protein (ZnBP), absent in vitamin-A-deficient chicks, was isolated from the ileal mucosa after their repletion with vitamin A. Competitive-binding studies (calcium, cadmium, copper) showed the protein to be highly specific for Zn ions. The molecular weight of ZnBP was 83 kDa. The association constant of the protein-Zn complex was 0.8 X 10(6)/mol. The protein was acidic with approximately 20% of its amino acid residues belonging to dicarboxylic acids. ZnBP was found to be a glycoprotein, and it contained hexose as a carbohydrate component. It is suggested that ZnBP is involved in the binding of Zn in the ileal mucosa of chicks.

Animals↗

PubMed1998

Kinetics of redox interaction between substituted 1,4-benzoquinones and ascorbate under aerobic conditions: critical phenomena.

Redox cycling is believed to be the most general molecular mechanism of quinone (Q) cytotoxicity. Along with redox cycling induced by a reductase, a similar process is known to occur via electron transfer from ascorbate (AscH-) to Q with formation of a semiquinone radical (Q.-): (1) Q + AscH- (k1)--> Q.- + Asc.- + H+ (2) Q.- + O2 --> Q + O2.-. The net effect of reactions (1) and (2) provides for the catalytic oxidation of AscH-, with Q serving as a catalyst. In this work, the kinetics of oxygen consumption accompanying this process were studied with several substituted 1,4-benzoquinones (BQ) at 37 degrees C in phosphate buffer, pH 7.40, using the Clark electrode technique. The value of k1 determined from the initial rate of oxygen consumption was typically found to increase when the one-electron reduction potential E(Q/Q.-) shifted to more positive values. With Q, for which E(Q/Q.-) is less than -100 mV, the rate of oxygen uptake (R(OX)) was found to be directly correlated with the [Q][AscH-] value independent of the concentration of individual reagents, remaining constant for a long period. With mono- and dialkyl-substituted 1,4-BQs, for which E(Q/Q.-) is higher than -100 mV, significant deviations from the above simple kinetic regularities were observed. In particular, R(OX) decreased dramatically with time and critical phenomena (the existence of certain concentrations of Q and/or AscH- above or below which the catalytic oxidation of AscH- ceased completely after a non-stationary period of short duration) were observed. These abnormalities can be explained on the basis of the kinetic scheme which contains, in addition to reactions (1) and (2), several side reactions including that between Q.- and AscH-. Implications of critical phenomena discovered in this study for the problems of Q toxicity and vitamin C avitaminosis are discussed.

Ascorbic Acid↗

PubMed1969

Experimentally induced changes in nasal mucous secretory systems and their effect on virus infection in chickens. I. Effect on mucosal mrphology and function.

The domestic chicken was used as an experimental model in which to demonstrate morphological and functional relationships of nasal organ systems, principally of mucous systems. Mucous secretions of olfactory, respiratory, lacrimal, and accessory areas were found to have clear histochemical differences, yet were sufficiently miscible in normal circumstances to form an unbroken, synchronously moving sheet. Changes induced experimentally in host physiology did not all affect the mucous components of given areas in the same way or to the same degree. Mucosal changes were produced by the following methods: Topically administered cocaine 20%, in a single application, temporarily paralyzed the cilia, and the consequently reduced traction apparently held mucus in the acini and effected a temporary lag in mucus excretion. Three successive applications caused acute acinar depletion and ciliary paralysis. Hexylcaine chloride 5% immediately desquamated all intranasal epithelia, damaged the proximal portion of the acini, and induced acinar exhaustion and mucosal inflammation-effects not overcome within 5(1/2) days. Internal dehydration produced progressively viscous mucus, severe acinar gaping with mucus anchored in the acini, a heavy surface sheet, and deceleration or arrest of mucociliary flow. Avitaminosis A induced reduction in the height (about 50%) of all mucosae and acini, especially the inner lining of the maxillary concha, caused an actual 50% reduction in the number of cells per acinus, and retarded the mucociliary flow rate about 50%. Pilocarpine induced initial hypersecretion, later exhaustion, and, still later, slow production of densely staining mucus in the acinar cells; also acinar gaping. Breeding in a germfree environment produced a greatly reduced mucosal depth throughout the nasal fossa, an extraordinary reduction in the number of cells per acinus, relative reduction in the number of acinar neck cells, and concomitant increase in ciliated cells in that region. Exposure to a temperature of -20 degrees C for 1 hr caused blanching of all secretory cells, acinar gaping, and temporary reduction of mucosal depth.

Amino Alcohols↗

PubMed1978

Nutritional success in a semi-arid land: examination of Tswana agro-pastoralists of the eastern Kalahari, Botswana.

The cultural and environmental factors affecting the food quest and nutritional status of the Moshaweng Tlokwa, a Tswana agro-pastoral society occupying the semi-arid eastern Kalahari Desert of Botswana, are examined. Data are presented on methods of food procurement, storage, preparation, and preservation. Tlokwa diet is based on agriculture horticulture and animal husbandry but a surprising number of wild species are regularly used as food. This pattern is nutritionally protective and viewed by the author as a principal reason for Tlokwa dietary success in their semi-arid environment. Data are presented on food habits, dietary prohibitions, and characteristic diets of infants, children, adolescents, and adults. Many Tlokwa foods are encouraged or prohibited on the basis of the consumers age, sex, and social development. Such patterns reduce competition for dietary resources, assure a more equitable distribution of food, and sustain the nutritional quality of diet. During 1973 to 1975 the Tlokwa appeared healthy and well fed; heavy rain-fall had just broken a 7-year drought. Kwashiorkormarasmus, avitaminosis, or other classical signs of malnutrition were not observed. A trend towards bottle feeding was noted. Children and adolescents are rapidly losing their ability to identify edible wild food resources. The author concludes that the Tlokwa heretofore have coped satisfactorily with drought in their semi-arid territory and recommends continued diversification of their food quest. Diversity is viewed as essential if the Tlokwa are to maintain their nutritional well-being in coming decades.

Adolescent↗

PubMed1982

Effect of vitamin E deficiency on rabbit intramuscular collagen.

The effect of a vitamin E-deficient diet on muscular collagen was studied in young rabbits. Intramuscular collagen content was found to increase in vitamin E-deficient rabbits, both in absolute and relative values, while no changes in urinary hydroxyproline excretion were observed. The overall solubility of intramuscular collagen was higher and the collagen soluble in guanidine hydrochloride was richer in alpha-chains. Such findings would suggest that avitaminosis E induces the production of new intramuscular collagen.

Animals↗