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PubMed1971

Associations between drugs administered during pregnancy and congenital abnormalities of the fetus.

In a retrospective study to compare the drug consumption during pregnancy of mothers of infants with congenital abnormalities and of those without, over 97% of 1,369 mothers took prescribed drugs and 65% self-administered drugs. Significantly more mothers of infants with congenital abnormalities took aspirin, antacids, dextroamphetamine, phenobarbitone, sodium amytal, other barbiturates, cough medicines, iron, sulphonamides, and nicotinamide than mothers in the control group. However, most mothers taking analgesics, antacids, appetite suppressants, barbiturates, cough medicines, iron, sulphonamides, and vitamins produced normal infants. Any teratogenic effect of these drugs is therefore one of low potency. On the other hand, deficiencies such as those of ascorbic acid and folic acid may have a teratogenic effect. There is need for caution in presuming teratogenic effects on the basis of the associations shown here. During pregnancy, however, it would appear wise to avoid the administration of any drug which carries a suspicion of teratogenicity unless that drug is specifically indicated, and self-medication with common household remedies such as aspirin and antacids should be avoided. These recommendations would also apply to any woman of childbearing age in whom conception is likely.

Abnormalities, Drug-Induced↗
PubMed1975

The absorption of iron, with or without supplements of single amino acids and of ascorbic acid, in healthy and Fe-deficient children.

1. Studies were done on the effect of ascorbic acid and five amino acids (histidine, cystine, cysteine, valine and glutamic acid) on intestinal iron absorption in a group of ninety Egyptian infants and young children, of which fifty-seven were healthy controls and thirty-three were suffering from Fe-deficiency anaemia. 2. Supplements tested promoted Fe absorption in healthy controls in the following order: valine larger than histidine larger than ascorbic acid. Cysteine, glutamic acid and cystine were found to have no significant effect. 3. Supplementation with valine, ascorbic acid and histidine also increased intestinal Fe absorption in anaemic subjects, but to a lesser extent than in controls. 4. Supplementation of haematinic therapy with these compounds is recommended. Their use is also suggested to improve the availability of the Fe content of everday diets.

Amino Acids↗
PubMed1976

Ascorbic acid levels in stored blood and in patients undergoing surgery after blood transfusion.

Blood was obtained from 11 healthy voluteers, mixed with two standard types of anticoagulant used in blood transfusion centres and stored for 21-28 days at 4 degrees C. Leucocyte ascorbic acid (LAA) fell to deficient levels after 7 days in all cases. There were no corresponding changes in plasma ascorbic acid (PAA) levels. LAA and PAA were measured before, during and after surgery in 5 control patients who underwent definitive operations for benign peptic ulceration and in 4 patients under-going surgery for bleeding peptic ulceration. The average amount of blood administered to the latter group was 10 units. There was a fall in LAA and PAA in both groups of patients after operation. This fall had returned to normal by 7 days in the controls, but the LAA remained at a deficient level at 7 days in the patients who had bled. Deficient ascorbic acid in stored blood may contribute to low leucocyte ascorbic acid levels in patients after blood transfusion and may contribute to the increased complication rate when surgery is undertaken in these patients.

Adult↗
PubMed2001

Micronutrient interactions: effects on absorption and bioavailability.

A potential risk of interactions between micronutrients affecting absorption and bioavailability has to be considered in any supplementation or fortification strategy. At levels of essential micronutrients present in foods, most micronutrients appear to utilise specific absorptive mechanisms and not be vulnerable to interactions. In aqueous solutions and at higher intake levels competition between elements with similar chemical characteristics and uptake by non-regulated processes can take place. These interactions have clearly been demonstrated in experimental absorption studies and to some extent have been confirmed in supplementation studies. Negative effects of iron supplementation on indices of zinc and copper status and of zinc supplementation on iron and copper status have been reported. In contrast, the negative effect of calcium on iron absorption has not been confirmed in long-term supplementation studies. Ascorbic acid has a strong iron absorption promoting potential and in iron deficient populations ascorbic acid supplementation improves iron status. Thus, ascorbic acid supplements or an increased intake of ascorbic acid rich foods could have important public health implications, especially in populations subsisting on a mainly plant food based diet. The effect of poor status of a given micronutrient on absorption and utilisation of other micronutrients should also be considered while developing strategies to improve micronutrient status in a population. Awareness of these interactions, combined with a balanced evaluation of the dietary intake of the population with regard to absorption promoting and inhibiting substances and the risk for multiple deficiencies, could lead to more effective strategies to improve micronutrient status.

Ascorbic Acid↗
PubMed1970

Autonomic reflexes and vascular reactivity in experimental scurvy in man.

Ascorbic acid is a required cofactor in the conversion of dopamine to norepinephrine in vitro, and the deficiency of this vitamin in guinea pigs is associated with degeneration of autonomic ganglion cells and with cardiac supersensitivity to norepinephrine. Because of these findings, we tested the hypothesis that ascorbic acid deficiency in man alters autonomic cardiovascular reflexes and vasomotor responses to adrenergic stimuli. We studied five normal volunteers who had been deprived of ascorbic acid for a period of 3 months; they had developed symptoms and signs of scurvy and their plasma levels of ascorbic acid averaged 0.178 +/-SE 0.07 mg/100 ml. We repeated the studies after giving the subjects vitamin C for a period of 4 months; they had become asymptomatic and their plasma ascorbic acid had increased to an average of 1.68 +/-0.151 mg/100 ml. Blood flow to the left forearm (plethysmograph), arterial and central venous pressures, and heart rate were measured before and after exposure of the lower half of the body to subatmospheric levels of pressure and before and after intravenous and intra-arterial (left brachial artery) infusions of norepinephrine and tyramine. Average values of blood flow (7.9 +/-1.4 ml/min per 100 ml), arterial pressure (91.2 +/-4.6 mm Hg), heart rate (68 +/-4.4 beats/min), central venous pressure (6.1 +/-1.1 mm Hg), and plasma catecholamines (0.68 +/-0.20 mug/liter) obtained during ascorbic acid deficiency were not altered significantly after correction of the deficiency. Vasoconstrictor responses to intra-arterial norepinephrine and tyramine were augmented after vitamin repletion. During ascorbic acid deficiency, four subjects had reduced responsiveness of resistance vessels of the forearm to lower body negative pressure as compared to the responsiveness observed after vitamin repletion. Reflex tachycardia during lower body negative pressure and reflex bradycardia during the pressor responses to intravenous tyramine and norepinephrine were similar during the two studies. The results suggest that the decreased vascular responsiveness to intra-arterial norepinephrine and tyramine and to lower body negative pressure during ascorbic acid deficiency is caused by a defect in the ability of resistance vessels to constrict in response to adrenergic stimuli. Ascorbic acid deficiency in man does not interrupt autonomic reflexes and does not appear to cause significant depletion of endogenous norepinephrine.

Ascorbic Acid↗
PubMed1982

Feasibility of using an isolated intestinal segment as an artificial organ for enzyme replacement therapy.

Guinea pigs fed an ascorbic acid-deficient diet develop scurvy because of the absence of the enzyme L-gulonolactone oxidase. In theory if this enzyme is provided and its substrate L-gulonolactone is present at adequate concentrations ascorbic acid will be synthesized and the development of scurvy prevented. Using this model we tested whether a viable segment of intestine could be used to contain the administered enzyme and act as an artificial organ for the production of ascorbic acid. A surgical procedure was developed to prepare an externalized pouch of intestine with its circulation left intact. When enzyme is inserted in this intestinal bag it is not toxic and not antigenic in some animals, whereas, enzyme injected intraperitoneally is clearly antigenic. Synthesis of ascorbic acid by this artificial organ could not, however, be detected by elevation of plasma concentrations of the vitamin.

Animals↗
PubMed1991

Production of corticosterone and testosterone in scorbutic mutant rats: difference of in vivo production between adrenal gland and testis.

Effects of deficiency in ascorbic acid on in vivo production of corticosterone and testosterone were examined using a mutant strain of rats unable to synthesize ascorbic acid. The adrenal weight of scorbutic rats was larger, and corticosterone levels in plasma and adrenal tissues were higher than those of ascorbic acid-supplied (ascorbutic) rats. Acute and chronic stimulation with ACTH increased corticosterone levels in both ascorbutic and scorbutic rats. In contrast, weights of seminal vesicles and ventral prostates in unstimulated scorbutic rats were smaller, and testosterone levels in plasma and testicular tissues were lower than those in ascorbutic rats. Acute stimulation with hCG increased testosterone levels only slightly in plasma and not in testicular tissues of scorbutic rats, when testosterone levels in ascorbutic rats reached a maximum. Chronic stimulation with hCG increased testosterone levels remarkably in both ascorbutic and scorbutic rats. These findings seem to indicate that ascorbic acid is not essential for the synthesis of steroid hormones. The scurvy seems to increase plasma ACTH levels secondary to the stress, resulting in the stimulation of the adrenals. In contrast, a prolonged deficiency in ascorbic acid appears to decrease plasma gonadotropin levels, and may reduce the sensitivity of testes to gonadotropins.

Adrenal Glands↗
PubMed1988

Adverse effects of high dietary iron and ascorbic acid on copper status in copper-deficient and copper-adequate rats.

The effects of elevated dietary ascorbic acid and iron on copper utilization were examined. Male Sprague-Dawley rats were fed one of two levels of Cu (deficient, 0.42 microgram Cu/g, or adequate, 5.74 micrograms Cu/g), Fe (moderate, 38 micrograms Fe/g or high, 191 micrograms Fe/g), and ascorbic acid (low, 0% or high, 1% of the diet) for 20 d. High Fe decreased (p less than 0.05) Cu absorption only in Cu-deficient rats. High ascorbic acid significantly decreased tissue Cu levels in Cu-adequate rats. High Fe with ascorbic acid caused severe anemia in Cu-deficient rats and decreased plasma ceruloplasmin by 44% in Cu-adequate rats. Cu,Zn-superoxide dismutase activity in erythrocytes was decreased (p less than 0.05) by 14% during Cu deficiency but was not affected by Fe or ascorbic acid. These results may be important to individuals with high intakes of Fe and ascorbic acid.

Absorption↗
PubMed1976

Extracellular ascorbic acid in lung.

Fifty percent of the ascorbic acid content of sliced rat lung was released from the tissue to the media within a few minutes by either washing or incubating the slices with Krebs-phosphate solution. Measurement of the lactate dehydrogenase and potassium content of the medium after incubating lung slices for 5 min showed that about 20% of the cells were damaged by slicing. Sephadex chromatography of tissue extracts prepared from washed lung slices showed that none of the ascorbic acid in these slices were bound to protein. Also, metabolic poisons were shown to deplete the ascorbic acid content of washed lung slices. Approx. 57% of the lung ascorbic acid of guinea pigs that had been supplemented with ascorbic acid and 78% of the lung ascorbic acid of ascorbic acid-deficient guinea pigs were found in the medium when lung slices from these animals were incubated with Krebs-phosphate solution. These results were taken to indicate the presence of an extracellular pool of ascorbic acid in lung which is maintained even during scurvy.

Animals↗
PubMed1986

Interaction of dietary carbohydrate, ascorbic acid and copper with the development of copper deficiency in rats.

The effects of dietary carbohydrate and ascorbic acid on the development of copper deficiency were investigated. Male Sprague-Dawley rats (n = 48) were fed one of eight diets in a 2 X 2 X 2 factorial design for 21 d. These diets varied in copper (1.11 or 8.96 micrograms Cu/g diet), carbohydrate (sucrose or cornstarch, 62.3%) and ascorbic acid (0 or 1%). Compared to controls, copper-deficient rats had lower hematocrit and ceruloplasmin levels, lower levels of copper and iron in several tissues, higher heart weights and lower spleen weights. During copper deficiency, liver iron levels were higher than control levels when cornstarch, but not sucrose, was the carbohydrate source, while liver and gastrointestinal tract weights were higher with sucrose compared to cornstarch. Copper-deficient rats fed ascorbic acid had significantly (P less than 0.05) lower hematocrits when fed sucrose compared to starch [29.6 +/- 1.2 vs. 36.8 +/- 1.2 g/dl (mean +/- SEM), respectively]. In copper-deficient rats, sucrose tended to lower the apparent absorption of copper compared to cornstarch, while ascorbic acid reduced the apparent absorption of iron. Thus, sucrose and ascorbic acid appeared to reduce hematocrit levels through effects on mineral absorption.

Absorption↗
PubMed1964

METABOLISM OF COLLAGEN IN MAMMALIAN TISSUES.

The amino acid composition of collagen is described and the status of knowledge about the synthesis of its unique amino acids, hydroxyproline and hydroxylysine, presented. This is followed by a schematic overview of collagen metabolism. Scurvy and lathyrism, the only two abnormalities of collagen metabolism which can now be reasonably elucidated at a molecular level, are then discussed in some detail. The paper concludes by stressing the importance of recognizing the role of histoarchitecture and of interactions of collagen with other compounds when studying collagen or its metabolism in the whole animal.

Amino Acids↗