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PubMed1983

Effect of pharmacological doses of ascorbic acid on the hepatic microsomal haemoproteins in the guinea-pig.

1. Ascorbic acid deficiency results in a reduction in the activity of the hepatic mixed function oxidase systems in the guinea-pig. In this study, male Dunkin-Hartley guinea-pigs were given 0, 50, 100, 200 or 300 mg ascorbic acid/d in two equal doses in buffered sucrose solution (200 g/l) for 4 d. Controls received an equal volume of sucrose solution. 2. A dose of 50 mg ascorbic acid/d resulted in a significant rise in the specific activities of both cytochromes P-450 and b5. At doses of 200 and 300 mg ascorbic acid/d the concentration of both haemoproteins was significantly lower than the control values. These effects were mirrored by total microsomal haem concentration. 3. These results suggest that when given in large doses, ascorbic acid ceases to act simply as a vitamin and should be considered a drug competing for substrates and cofactors with co-administered drugs and endogenous substrates such as cholesterol.

Animals↗
PubMed1983

Leucocyte ascorbic acid levels in Nigerian children with protein-energy malnutrition.

Leucocyte ascorbic acid (LAA) levels were estimated in 26 Nigerian infants and preschool children with protein energy malnutrition (PEM) in order to ascertain their ascorbic acid status. The children included eight with kwashiorkor, 12 with marasmus and six with marasmic kwashiorkor. The mean (SD) LAA level of 13.7 (8.2) micrograms/10(8) leucocytes in the malnourished children did not vary significantly from the mean level of 14.4 (8.8) micrograms/10(8) leucocytes found in 26 age-matched controls, and the values were unrelated to the presence or absence of megaloblastic change in the 14 bone marrows examined. It was concluded that ascorbic acid deficiency was not prevalent amongst children with PEM in Lagos, and was therefore not usually contributory to the anaemia, megaloblastic changes or other features of the syndrome seen in Nigerian children in Lagos.

Ascorbic Acid↗
PubMed1999

The effect of ascorbic acid supplementation on the blood lead levels of smokers.

BACKGROUND: The study subjects were 75 adult men (20 to 30 years of age), who smoked one pack of cigarettes per day (minimum) and had no clinical signs of ascorbic acid deficiency or lead toxicity. None had a history of industrial exposure to lead, and the blood-lead levels were anticipated to be below 1.45 micromol/L, the minimum blood level associated with toxicity symptoms. METHODS: The men were randomly assigned to three study groups of 25, and each group was provided a four-week supply of one level of daily ascorbic acid supplements (placebo, 200 mg or 1000 mg of ascorbic acid). We measured baseline and weekly serum and urine ascorbic-acid levels as well as blood and urine lead levels. The weekly group means and variations of the measured data were statistically compared by means of ANOVA and Pearson's correlation. RESULTS: The serum ascorbic-acid levels of the groups receiving ascorbic acid increased significantly after one week (p< or =.001). There was no effect of placebo or 200 mg ascorbic-acid supplementation on the blood or urine lead levels. However, there was a 81% decrease in blood-lead levels in the 1000 mg ascorbic acid group after one week of supplementation (p< or =.001). CONCLUSIONS: Daily supplementation with 1000 mg of ascorbic acid results in a significant decrease of blood-lead levels associated with the general population. Ascorbic acid supplementation may provide an economical and convenient method of reducing blood-lead levels, possibly by reducing the intestinal absorption of lead.

Adult↗
PubMed1979

Some thoughts on the epidemiology of cardiovascular disease, (with special reference to women "on the pill"). Role of ascorbic acid.

Consideration of nine major factors predisposing to cerebral thrombosis, coronary thrombosis or thrombosis in the deep veins of the calf, reveals that these factors all have one thing in common. Estrogen administration, pregnancy, ageing, smoking, infection, trauma, surgery, soft water and winter season are all associated with a tendency towards decreased plasma ascorbic acid levels. Normally, ascorbic acid deficiency is thought of as causing a tendency towards hemorrhage rather than thrombosis, but it is here suggested that petechial hemorrhages under the endothelium of the blood vessels may precipitate thrombosis on the damaged endothelium. Is not blood coagulation the normal mechanism for the arrest of hemorrhage?

Age Factors↗
PubMed1977

Gonadal and plasma testosterone and cholesterol in scorbutic guinea pigs.

Testes of pre- and post-pubertal guinea pigs were examined histologically and biochemically to see if ascorbic acid deficiency brought about any changes in their structure or function. Apart from a slight but significant fall in gonadal cholesterol there was no apparent change in the histology or testosterone content in scorbutic guinea pigs. Plasma cholesterol and testosterone were also similar in the control and scorbutic animals.

Animals↗
PubMed2006

[Vitamin C].

Vitamin C or ascorbic acid is a hydrosoluble vitamin derived from glucose metabolism. It acts as a reductor agent required for synthesis of collagen fibers through hydroxylation of proline and lysine. It also protects the body against damage caused by the free radicals. Humans cannot synthesize ascorbic acid as they lack an enzyme called gulonolactone oxidase. Concentrations in plasma and leukocytes reflect the levels of the diet and body deposits respectively of this vitamin. Among foods with high vitamin C levels are tomatoes, potatoes, and citrus fruits such as limes, oranges and lemons. The current recommendation of daily intake of vitamin C is 90 mg/d for men and 75 mg/d for women. Patients with chronic diseases such as cancer or diabetes or those who smoke need higher doses in their usual diet. Ascorbic acid deficiency gives rise to the appearance of scurvy. This disease is rarely seen in developed countries. The symptoms develop with plasma levels below 0.15 mg/dL. Scurvy is characterized by the presence of weakness, joint pain or skin lesions in form of petechias, gum bleeding, ease of developing bruises or delay in wound healing. The most characteristic skin manifestations are purpuric perifollicular hyperkeratotic papules and the presence of kinky hair.

Antioxidants↗
PubMed1983

The effect of ascorbic acid on sodium nitrite-induced methemoglobin formation in glucose-6-phosphate dehydrogenase-deficient erythrocytes.

Ascorbic acid significantly reduced the occurrence of sodium nitrite-induced methemoglobin (METHB) formation in a dose-dependent manner in erythrocytes from glucose-6-phosphate dehydrogenase (G-6-PD)-deficient humans in vitro. The ascorbic acid treatment, however, also decreased levels of reduced GSH in a dose-dependent manner, a response indicative of oxidant stress to the erythrocyte membrane. The latter findings are inconsistent with the hypothesis that ascorbic acid supplementation in G-6-PD-deficient humans may help compensate for inherently low levels of erythrocyte GSH. Finally, the ascorbic acid-induced reduction of METHB values, while of statistical significance, does not appear to be of clinical significance.

Ascorbic Acid↗
PubMed1997

Ascorbic acid alters collagen integrins in bone culture.

The effects of ascorbic acid on collagen synthesis, mineralization, and integrins were investigated in a mineralizing organ culture system derived from 20-day fetal rat parietal bones. A significant dose-dependent decrease in calcification at 96 h was demonstrated with decreasing concentrations of ascorbic acid (100-0 microg/ml). No effect on DNA content, [3H]thymidine incorporation, or dry weight was found in control (100 microg/ml ascorbic acid) bones compared with bones treated with decreased ascorbic acid concentrations (10, 1, and 0 microg/ml). Collagen synthesis, measured by [3H]proline incorporation, and alpha1(I) procollagen messenger RNA levels were also unaffected. However, ascorbic acid produced a dose-dependent decrease in the hydroxyproline content, with a maximal 76.8% decrease in bones without ascorbic acid compared with the control bones with 100 microg/ml ascorbic acid. Light microscopy of the ascorbic acid-deficient bones revealed a disruption of the osteoblast layer with misshapen osteoblasts and a decrease in the osteoid seam. The loss of osteoblast organization was also confirmed by analyzing the integrins for collagen by Northern and Western blot and immunofluorescence microscopy. A dose-dependent decrease in alpha2 and beta1 integrin messenger RNA levels and in alpha1, alpha2, and beta1 protein were found in 96-h bone cultures deficient in ascorbic acid. These integrin subunits mediate the binding of osteoblasts to collagen. Immunofluorescence microscopy also demonstrated a dose-dependent decrease in alpha2 and beta1 staining of the osteoblast layer. However, the protein levels of alpha3 and alpha5 subunits were not affected. No beta5 was detected, whereas only bones cultured without ascorbic acid demonstrated a small decrease in alpha(v) and beta3 protein levels. The alpha3, alpha5, alpha(v), and beta3 subunits are involved in cell binding to extracellular matrix proteins other than collagen. Thus, the integrins for collagen are down-regulated, probably in response to the underhydroxylated collagen fibrils, which causes a disruption of osteoblast organization leading to a decrease in mineralization of bone. Integrin assays for specific extracellular proteins may be useful tools in detecting matrix defects in various metabolic bone diseases.

Animals↗
PubMed2003

Vitamin C intake and the risk of preterm delivery.

OBJECTIVE: Ascorbic acid deficiency may lead to premature rupture of the membranes. STUDY DESIGN: The study included a prospective cohort of pregnant women, aged >/=16 years, with singleton gestations who received care at one of four prenatal clinics in central North Carolina from 1995 through 1998. Vitamin C intake preconceptionally and during the second trimester was examined for its association with preterm delivery and subsets of preterm labor, premature rupture of the membranes, and medical induction in 2064 women. RESULTS: Women who had total vitamin C intakes of <10th percentile preconceptionally had twice the risk of preterm delivery because of premature rupture of the membranes (relative risk, 2.2; 95% CI, 1.1, 4.5). This risk was attenuated slightly for second-trimester intake (relative risk, 1.7; 95% CI, 0.8, 3.5). The elevated risk of preterm premature rupture of the membranes was greatest for women with a low vitamin C intake during both time periods. CONCLUSION: Because diet and supplement use are modifiable behaviors, corroboration of these findings would suggest a possible intervention strategy.

Adolescent↗
PubMed1987

Micronutrient deficiencies in the aetiology of anaemia in a rural area in The Gambia.

Early studies in a rural community in The Gambia led to reports of anaemia in certain sections of the population. More recent investigations concerned with identifying micronutrient deficiencies have elaborated these earlier findings. The major determinant of anaemia is an iron deficiency, leading to a microcytic hypochromic haematological picture. However, riboflavin deficiency, which is very widespread, and which leads to clinical signs in some subjects, appears to impose some limitations on absorption and utilization of iron. A subclinical deficiency of ascorbic acid is also observed and this may further compromise iron status. In addition very poor folate status leads to a macrocytosis in some individuals and may limit the haematological response to iron supplementation.

Adolescent↗
PubMed1997

Determination of p-hydroxyphenylpyruvate, p-hydroxyphenyllactate and tyrosine in normal human plasma by gas chromatography-mass spectrometry isotope-dilution assay.

The synthesis and purification of [13C2]p-hydroxyphenyllactic acid from [13C2]p-hydroxyphenylpyruvic acid, the characterization of tert.-butyldimethylsilyl-derivatized tyrosine, p-hydroxyphenylpyruvic acid and p-hydroxyphenyllactic acid, and an isotope-dilution assay for these substances in normal human plasma using gas chromatography-mass spectrometry (GC-MS) are described. Using this method plasma p-hydroxyphenylpyruvate, p-hydroxyphenyllactate and tyrosine levels of 68 +/- 42 ng/ml, 118 +/- 45 ng/ml and 16.6 +/- 6.3 micrograms/ml, respectively, were found in 9 normal adults. Isotope-dilution assays are sensitive enough to determine tyrosine, p-hydroxyphenylpyruvate and p-hydroxyphenyllactate content in normal subjects, and may be useful for studying disorders of tyrosine metabolism, including inborn errors of metabolism, liver disease and ascorbic acid deficiencies.

Carbon Isotopes↗
PubMed2000

Nutritional research in World War 2: the Oxford Nutrition Survey and its research potential 50 years later.

To investigate the nutritional status of the population of the UK during the Second World War, nutritional surveys were commissioned in 1941. These included surveys of two groups of pregnant women: the first comprised 120 working-class women who were studied in the spring of 1942, and a second group of 253 women in 1944. Both groups were followed up until after delivery. Detailed biochemical assessments were performed on each subject. Our statistical analysis of the haematological data showed that nearly 25% of women from the 1942 group were deficient in protein, over 60% were deficient in Fe and vitamin A, and over 70% had severe vitamin C deficiency. The findings were reported to the Ministries of Health and Food who instigated a food supplementation policy at the end of 1942 that entitled pregnant women in the UK to extra rations of fruit, dairy produce and to a supply of cod-liver-oil tablets. A second group of 253 pregnant women were studied 15 months later which enabled the effects of this programme to be investigated. Supplementation reduced the proportion of women with vitamin A concentrations below the normal range from 63% to 38%, and vitamin C from 78% to 20%, but protein and Fe concentrations were not increased but actually declined. These findings continued to exert an influence over government food policy for pregnant women until the abolition of rationing in 1954.

Anemia, Iron-Deficiency↗
PubMed1956

The incorporation of acetate-1-C14 into cholesterol and fatty acids by surviving tissues of normal and scorbutic guinea pigs.

The synthesis of cholesterol and fatty acids from acetate-l-C(14) by the isolated liver, adrenal, and aorta of scorbutic and pair-fed control guinea pigs has been studied. It was found that ascorbic acid deficiency does not affect the rate of incorporation of C(14)-acetate into cholesterol and fatty acids by the tissues investigated, under our experimental conditions. The relatively high metabolic activity of the artery with regard to cholesterogenesis and lipogenesis was noted. The elevation of serum cholesterol and hexosamine in scurvy has been confirmed.

Acetates↗
PubMed2001

Malnutrition in long-term haemodialysis survivors.

BACKGROUND: Long survival is now common in patients with end-stage renal disease owing to improvement in dialysis techniques and kidney transplantation. As malnutrition is commonly reported in dialysis patients, we evaluated the nutritional status of patients treated with haemodialysis (HD) for more than 20 years. METHODS: Ten patients (59.5 years old; 4F/6M; HD treatment for 304 months; group A) underwent an extensive nutritional examination and were compared to a control group of 10 patients treated with HD for an average of 51 months and strictly matched for age (58.6 years old), gender, and height (group B). The patients were treated on a similar basis (long-duration HD, cellulosic membranes, Daugirdas index >2). RESULTS: The body weight (BW) in group A had decreased gradually from the 11th year of HD treatment, whereas it had increased by an average of 1.9+/-4.4% since the beginning of the HD treatment in group B. The body mass index (BMI) was lower in group A (19.3 +/- 2.3 vs 21.4 +/- 2.8 kg/m(2); P = 0.05). The arm-muscle circumference (AMC), the arm-muscle area (AMA), and triceps skinfold (TSF) were lower in group A than in group B. The fat mass assessed with anthropometry (10.8 +/- 4.0 vs 14.8 +/- 4.2 kg) was significantly lower in group A. The deviation of actual BW from ideal BW (IBW) was significantly lower in group A than in group B (80.6 +/- 10.7% vs 89.6 +/- 9.0%; P = 0.028); The deviations of actual BW, TSF, and AMA from standard values of the NHANES II study were more marked in group A than in group B. On the other hand, daily energy and protein intakes (DEI and DPI) were identical in both groups and met the recommendations for dialysis patients when normalized to the actual BW. When normalized to the IBW, the DEI appeared low. Energy expenditure was not different between groups, and not different from the resting metabolism calculated from the Harris and Benedict formula. Average albumin, prealbumin, and IgF-1 were normal and not different between groups. Branched-chain amino acids (BCAA), and especially leucine, were correlated with BMI in group A but not in group B. Serum total and free carnitine were low in both groups. Three patients had ascorbic acid deficiency in group A but none in group B. CONCLUSIONS: Hence, despite adequate dialysis dose and protein intake, patients treated with HD for a long period of time became malnourished, whereas the classical nutritional markers remained in normal ranges. Among the potential causes leading to malnutrition, inadequate energy intake and micronutrient deficiencies were found in these patients.

Aged↗
PubMed1975

Connective tissue cells, cell proliferation and synthesis of extracellular matrix-a review.

The ubiquitous connective tissues contain a wide range of cells including fibroblasts, osteoblasts and chondroblasts. Recently it has been demonstrated that another principal cell of the connective tissue is the smooth muscle cell in several organ systems. These have been shown to be responsible for the synthesis of the connective tissue matrix components of the uterine myometrium and of the arterial system, including collagen, both elastic fibre proteins and glycosaminoglycan. Microtubule inhibitors such as colchicine and vinblastine, and iron chelators such as alpha,alpha -dipyridyl have been used to study their morphologic and chemical effects on collagen synthesis and secretion. Colchicine produces an increase in large Golgi-associated vacuoles, which sometimes contain material reminiscent of aggregates of collagen macromolecules. Vinblastine produces alterations in the endoplasmic reticulum cisternae similar to alterations seen in ascorbic acid deficiency, and alpha,alpha-dipyridyl increases the frequency of regions in cells, interpretable as potential sites of communication of rough endoplasmic reticulum cisternae with the cell surface. Ferritin conjugated anti-procallagen sera were used to localize procollagen in cells and demonstrated procollagen not only in the cisternae of rough endoplasmic reticulum but in all of the elements of the Golgi complex as well. The studies reported in this review have shown that in cell culture arterial smooth muscle will produce not only the microfibrillar protein of the elastic fibre but soluble and/or insoluble elastin as well. Recent studies on serum factors responsible for the proliferation of connective tissue cells have demonstrated that at least one of the principal factors responsible for fibroblast and/or smooth muscle cell proliferation in culture is derived from thrombocytes. Medium containing serum derived from cell-free plasma lacks most of this proliferative effect which can be reinstated when platelets are present during recalcification to form serum. This effect is due to the platelet release reaction as shown by combining supernatant factors derived from platelets exposed to purified thrombin to cell-free, plasma derived serum. Studies with macrophages have also suggested that phagocytic macrophages release factor(s) into a cell culture medium that may also participate in stimulating fibroblasts to proliferate in vitro. The means by which these factors stimulate fibroblast proliferation and connective tissue synthesis remains to be elucidated.

Animals↗
PubMed1972

Chronic gastritis, alcohol, and non-ulcer dyspepsia.

An investigation of 102 men comprising alcoholics, patients with non-ulcer dyspepsia, and healthy controls is reported. It demonstrates that alcohol is a cause of chronic gastritis and the severity of the mucosal lesion is directly related to the duration of excess drinking. Contrary to popular belief, chronic gastritis does not give rise to symptoms. The effect of alcohol on the gastric mucosa is a direct one and is not mediated by malnutrition, hepatic damage, intestinal malabsorption, anaemia, ascorbic acid deficiency, or any disturbance in immune tolerance. The natural history of chronic gastritis is described, involving an initial hypertrophy and hyperfunction of the gastric mucosa, followed by atrophy and hypofunction. Cigarette smoking is confirmed as another cause of chronic gastritis. The non-ulcer dyspepsia syndrome is unrelated to chronic gastritis.

Adolescent↗
PubMed1974

Pharmacology of fibrosis and tissue injury.

Methods controlling tissue fibrosis are classified into those specifically inhibiting various metabolic aspects of collagen selectively in the injured tissue (ascorbic acid deficiency, effect of agent chelating Fe(2+), proline analogs, lathyrogens). The most promising method seems to be the blocking of crosslinks formation among collagen molecules by beta-aminopropionitrile, a competitive inhibitor of a crosslinking enzyme, lysyl oxidase. The second group of methods is called nonspecific, as they affect any stage of inflammatory process preceding the activation of fibroblasts. The importance of activated macrophages in the stimulation of fibroblast is discussed. Finally, a new concept is proposed, indicating the function of zinc ions in the control of the integrity of biomembrances, tissue reactivity to noxious agents. It is suggested that zinc may control NADPH dependent lipid peroxidation at the membrane level by inhibiting NADPH oxidase activity. The implication of these ideas to lung fibrosis induced by silica or asbestos is discussed.

Aminopropionitrile↗