Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00568 (ascorbate)
 23,072 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rhesus monkeys fed an ascorbic acid-free, purified liquid diet, developed scurvy in 70 to 105 days as evidenced by loss of weight, anemia, bleeding gums, inflamed palate, diarrhea, and inability to stand. Oral administration of either 10 mg/kg body weight of ascorbic acid or an equimolar amount of the magnesium salt of 1-ascorbic acid phosphate cured all symptoms of scurvy. Similarly, oral administration of 1-ascorbic acid phosphate cured all symptoms of scurvy in the guinea pig and resulted in liver ascorbate levels equal to those of animals feed ascorbic acid. It is concluded that ascorbic acid phosphate is a readily available source of ascorbic acid activity in vivo.
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PMID:Antiscorbutic activity of ascorbic acid phosphate in the rhesus monkey and the guinea pig. 10 21

Intestinal absorption of ascorbic acid is believed to be mediated through a sodium-dependent active transport process in man and in the guinea pig, both species having a nutritional requirement for the vitamin. Vitamin C transport was studied in man and in the guinea pig by in vivo intestinal perfusion of concentrations of vitamin C ranging from physiologic to clearly pharmacologic levels. Triple lumen intestinal perfusion of seven human volunteers with vitamin C concentrations ranging from 0.85 to 11.36 mM demonstrated saturation kinetics of absorption with a Km = 5.44 mM. Net secretion of water was observed in three of seven humans with the highest (11.36 mM) concentration of vitamin C. Perfusion of isolated segments of guinea pig intestines with intact blood supply also revealed saturation kinetics (Km = 5.54 mM) in the range of 1.42 to 56.8 mM vitamin C but linear absorption below this range. The phenomenon of decreased water absorption noted with incremental vitamin C dose in human volunteers could not be reproduced in the guinea pig, nor were the intestinal tissue levels of cyclic AMP and GMP increased by high-dose vitamin C in this species. This study suggests that "megavitamin" doses of vitamin C (greater than 1 Gm) are probably not as efficiently absorbed as smaller multiple doses of the vitamin. Intestinal secretion of water may contribute to the diarrhea which is the most common side effect of large doses of vitamin C. The guinea pig is a useful but limited model for vitamin C absorption in man.
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PMID:Demonstration of saturation kinetics in the intestinal absorption of vitamin C in man and the guinea pig. 20 65

A case of watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome due to a pancreatic tumour and identified by VIP plasma level, VIP immunocytochemistry, and ultrastructural analysis of tumour sections, is reported. Since VIP is the mediator of the syndrome and is biologically active under its amidated form, the enzymatic alpha-amidating activity was investigated and characterized in tumour extract; using the synthetic substrate D-Tyr-Val-Gly, the enzyme displayed an optimal activity at pH 7.0, under aerobic conditions and with 35 microM CuSO4 and 3 mM ascorbate as co-factors. The Kmax and Vmax values of the enzymatic activity were 133.7 microM and 26.9 pmol/h/micrograms protein respectively. Its molecular weight, determined by molecular sieving, was close to 36 kDa. Other tumours of the human endocrine pancreas were also investigated for the enzymatic activity. The clinical interest of studying the regulation of the alpha-amidating activity in such tumours is discussed.
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PMID:Characterization of an alpha-amidating activity in a human pancreatic tumour secreting vasoactive intestinal peptide (VIP). 217 16

This study was undertaken with the aim of providing adequate calories for optimal growth in low birth weight (LBW) by fortifying human milk with medium chain triglycerides and sugar. Twenty-one LBW babies with birth weight between 1.0 and 1.75 kg and gestational age 28-36 weeks constituted the study material. They were administered expressed human milk, initially with gavage and then by spoon. Coconut oil and sugar were added to increase the caloric density to (0.8 cal/ml). The aim was to achieve a caloric intake of 200 cal/kg. This was achieved between 6 and 11 days of birth. Additionally, vitamin C (50 mg) and vitamin E (25 IU/kg/day) were administered. Weight was recorded daily to the nearest 50 g. Head circumference was measured weekly using a non-stretch tape measure. Blood urea nitrogen was measured once the neonate started taking high calorie feeds. Stools were examined daily for the presence of fat globules and reducing substances and for the pH. All but one neonate tolerated the feeds well and there were no complications, such as vomiting, diarrhoea, abdominal distension, or necrotizing enterocolitis. The weight gain recorded was 17.29 +/- 5.30 g/day or 13.95 +/- 5.52 g/kg/day. The study demonstrates that optimal growth can be achieved within the metabolic tolerance of low birth weight infants by administering fortified high calorie breast milk.
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PMID:Fortified high calorie human milk for optimal growth of low birth weight babies. 272

I previously described that bowel tolerance (the amount that almost causes diarrhea) to oral ascorbic acid, increases in a person somewhat proportionally to the "toxicity" of his disease. Ascorbic acid ameliorates symptoms and sometimes cures certain diseases at high threshold levels near bowel tolerance. High concentrations of ascorbate cause the redox potential of the redox couple (ascorbate/dehydroascorbate, AA/DHA) to become reducing in diseased tissues. Allergic and sensitivity reactions are frequently ameliorated and sometimes completely blocked by massive doses of ascorbate. I now hypothesize that one mechanism in blocking of allergic symptoms is the reducing of the disulfide bonds between the chains in antibody molecules making their bonding antigen impossible. I further hypothesize that antibodies seek to match antigens only in areas where stray free radicals or a relatively oxidizing redox potential exists. The redox state of normal, healthy tissue does not allow for the bonding of antibodies to antigen. When antioxidant, free radical scavenging systems are overwhelmed, inflammatory, hypersensitivity, and "autoimmune" conditions may result.
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PMID:The vitamin C treatment of allergy and the normally unprimed state of antibodies. 287 12

Colostrum-fed, colostrum-deprived, and colostrum-fed and colostrum-deprived calves fed ascorbic acid (1.75 g/d) in whole, raw milk to 6 wk of age were sampled from 0 to 8 wk of age in order to determine whether ascorbate supplementation would increase plasma Ig concentrations, antibody response to immunization, and disease resistance. Plasma IgG concentrations were lower at 14 and 28 d of age in calves fed ascorbate compared with plasma concentrations in calves not receiving ascorbate supplementation, irrespective of colostrum feeding. Colostrum feeding had no effect on antibody titer to keyhole limpet hemocyanin at any age, but ascorbate-supplemented calves had lower plasma antibody titers to keyhole limpet hemocyanin at 35 and 56 d of age. Calves fed ascorbate had lower clinical scores for diarrhea. Dietary ascorbate does not appear to be immunostimulatory in dairy calves to 56 d of age and appeared to inhibit antibody synthesis. However, at 14 d of age there was an interaction of ascorbate supplementation and colostrum feeding; plasma IgG concentrations were higher in colostrum-deprived calves fed ascorbate then in colostrum-deprived calves not fed ascorbate.
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PMID:Dietary ascorbic acid and immune response in dairy calves. 292 40

It is investigated the calcium, phosphorous and magnesium homeostasis in cows in the dry period, cows in child-birth and calves in connection with the diarrhea in the newborn during the neonatal period, with the respiratory syndrome in the growing up, with the sterility in heifers, with the stillborn, with estrous and postestrous metrorrhagia. It was ascertained a close dependence in the value of Ca, P and Mg in the different physiologic groups of a given farm. It was ascertained that the newborn from mothers with lower serum values of Ca of 2.5 mmol/l, P of 1.8 mmol/l and Mg of 0.70 mmol/l suffer from diarrhea, endotoxic shock, tetany etc. during the neonatal period. Hypocalcemia is registered in the calves with a respiratory syndrome (2.20 mmol/l), sterile heifers (2.39 mmol/l). In all cases is ascertained hypophosphorosis and hypomagnesemia especially in the calves with a respiratory syndrome (P = 1.24 and Mg = 0.46 mmol/l), cows with a still born calves (P = 0.92 and Mg = 0.54 mmol/l) with metrorrhagia (P = 0.93 and Mg = 0.71 mmol/l). The diagnostic value of the product Ca X P X Mg is discussed. A reversible relationship between them is ascertain In comparison with the ideal in which Ca X P X Mg is 11.11 and the ratio--1.09, in the above mentioned diseases the product decreases and the ratio increases. The differences are graded which shows their mutual origin. It was established experimentally that the addition with a medical aim to the ration of the green pea-oats and green rye during spring and summer, such as oats in winter for the pregnant cows has a decisive effect on the living of the newborn. It was ascertained as well that in extra situations a component containing, calcium gluconate, magnesium sulphate, sodium salicylate, analgin, B1 vitamin, vitamin C, sodium phosphate, glucose and sodium chlorate (if necessary sulfathiazole) injected s.c. 5 times to the pregnant cows 15-5 days before childbirth has a positive effect on the new-born calves.
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PMID:[Dynamic aspects of mineral metabolism in dry cows, puerperants and calves]. 345 81

Adoptive immunotherapy of human cancer was investigated in our institution as part of a National Cancer Institute extramural group study. This treatment, for patients with metastatic malignant melanoma, hypernephroma, and colon carcinoma, consisted of three phases: (a) 5 days of i.v. high-dose (10(5) units/kg every 8 h) interleukin 2, (b) 6 1/2 days of rest plus leukapheresis; and (c) 4 days of high-dose interleukin 2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Ascorbic acid is known to be important to cell-mediated immunity, and it has been reported to be depleted during physiologically stressful events. Therefore, we determined plasma ascorbic acid levels in patients (n = 11) before adoptive immunotherapy and before and after Phases 1, 2, and 3 of treatment. Patients entering the trial were not malnourished. Mean plasma ascorbic acid levels were normal (0.64 +/- 0.25 mg/dl) before therapy. Mean levels dropped by 80% after the first phase of treatment with high-dose interleukin 2 alone (0.13 +/- 0.08 mg/dl). Mean plasma ascorbic acid levels remained severely depleted (0.08 to 0.13 mg/dl) throughout the remainder of the treatment, becoming undetectable (less than 0.05 mg/dl) in eight of 11 patients during this time. Values obtained from 24-h urine collections on two of two patients indicated that ascorbate was not excreted in the urine. Plasma ascorbic acid normalized in three of three patients tested 1 mo after the completion of treatment. Unlike the results for ascorbic acid, blood pantothenate and plasma vitamin E remained within normal limits in all 11 patients throughout the phases of therapy. Responders (n = 3) differed from nonresponders (n = 8) in that plasma ascorbate levels in the former recovered to at least 0.1 mg/dl (frank clinical scurvy) during Phases 2 and 3, whereas levels in the latter fell below this level.
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PMID:Severe hypovitaminosis C occurring as the result of adoptive immunotherapy with high-dose interleukin 2 and lymphokine-activated killer cells. 349 58

The amount of oral ascorbic acid that a patient can tolerate without diarrhea, increases somewhat proportionately to the "toxicity" of his disease. Clinically, in a disease ameliorated by ascorbate, there is a suppression of symptoms only with very high doses and approximately to that extent which a nonrate-limited, antioxidant free radical scavenger, might be expected to affect that disease process if all harmful free radicals and highly reactive oxidizing substances were quenched. In most pathologic processes, the rate at which free radicals and highly reactive oxidants are produced, exceeds the rate at which the ordinary rate-limited antioxidant free radical scavenging mechanisms can quench those free radicals and oxidants. When ascorbate acts as a scavenger, dehydroascorbate is formed; but if the ascorbate/dehydroascorbate (AA/DHA) ratio is kept high (the redox potential kept reducing) until the unstable dehydroascorbate undergoes hydrolysis or can be reduced back to ascorbate, the dehydroascorbate will do no harm. Since even at very high doses, ascorbate is virtually nontoxic, it may be given in the enormous doses necessary to quench almost all unwanted free radicals and oxidants. The wide spectrum of infectious diseases ameliorated by massive doses of ascorbate indicates some common pathologic processes in these diseases.
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PMID:Vitamin C: the nontoxic, nonrate-limited, antioxidant free radical scavenger. 406 36

Consensus from individual studies and several review articles is that consumption of supplemental vitamin C leads to no significant adverse health effects to humans in general. Individuals who have a history of kidney stone formation and those who experience iron overload should exercise caution before using supplemental vitamin C. Occasionally, individuals experience diarrhea or mild nausea. There is also the possibility that vitamin C taken simultaneously with other drugs may contribute to adverse health effects and that its interference in clinical laboratory tests will mask diagnosis of disease. Few controlled clinical trials exist that conclusively demonstrate the adverse health effects that humans may experience with supplemental vitamin C usage, and before definite conclusions can be made of the health hazards to humans, more clinical trials are required.
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PMID:Possible adverse health effects of vitamin C and ascorbic acid. 636 56


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