CELLULAR SYNTHESIS OF COLLAGEN: RIBOSOMAL AGGREGATES IN HYPERTHYROIDISM, HYPOTHYROIDISM, AND ASCORBIC ACID DEPLETION.
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A dietary deficiency of vitamin B12 was produced in the baboon by use of an artificial diet. Deficiency was further aggravated by feeding propionate or ampicillin, as judged by serum, liver and brain vitamin B12 levels, and urinary excretion of methyl malonic acid. Reduced glutathione levels in the blood and liver increased during deficiency, while ascorbic acid levels were not affected, Brain and liver nucleic acids did not change significantly. Blood pyruvate and serum lipid factors were affected more in the group fed propionate. These results are compared with the work on vitamin B12 deficient rats and pernicious anaemia in humans.
1. This study tested the hypothesis that black death, the ascorbic acid (AsA) related disease of penaeid shrimp, is related to collagen underhydroxylation. 2. Collagen measured as hydroxyproline (HYP) in healthy Penaeus californiensis (Holmes) and P. stylirostris (Stimpson) of a wide range of masses were determined. The results revealed a logarithmic relationship between total body collagen HYP and body weight fitting the equation y = 90x1.18 where y = total collagenous HYP (microgram) and x = body weight (g). 3. Shrimp tissues most subject to mechanical trauma (subcutis, hindgut and gills) had the highest collagenous HYP levels and were most consistently and severely affected by an ascorbic acid (AsA) deficiency disease. 4. Prolyl hydroxylase (PH) activity was demonstrated in tissues of P. californiensis and P. stylirostris by hydroxylation of [3,4-3H]proline. 5. AsA was required for shrimp PH activity using a chicken embryo substrate. 6. Nutritional trials revealed that dietary AsA was required for proline hydroxylation in collagen formation in P. californiensis.
OBJECTIVE: To investigate the possibility that micronutrient antioxidant status is an important factor in determining the severity of Raynaud's phenomenon (RP) and in differentiating between patients with primary Raynaud's phenomenon (PRP) and those in whom Raynaud's is secondary to systemic sclerosis (SSc). METHODS: Four micronutrient antioxidants (selenium, vitamin E, beta-carotene and ascorbic acid) and 2 "markers" of free radical associated activity were assayed in peripheral blood from 10 patients with PRP, 9 with limited cutaneous SSc (ISSc), 9 with diffuse SSc (dSSc) and 15 healthy control subjects. RESULTS: Plasma ascorbic acid was reduced in all 3 groups of patients: median level 10.6 mg/l in controls, 4.8 mg/l in PRP (p < 0.01), 2.5 mg/l in ISSc (p < 0.01) and 6.8 mg/l in dSSc (p < 0.05). A reduction in serum selenium was especially found in dSSc (median 75 micrograms/l compared to 100 micrograms/l in controls, p < 0.05). In keeping with these deficiencies, the serum concentration of 9, 11, linoleic acid was elevated in RP patients: median values for the molar ratio of the isomer to the parent fatty acid were 1.91% in controls, 3.70% in ISSc (p < 0.05) and 3.85% in dSSc (p < 0.01). Smoking patients showed lower levels of ascorbic acid and higher levels of the linoleic isomer than nonsmokers. CONCLUSION: Deficiencies of ascorbic acid and selenium may predispose towards irreversible tissue injury in RP patients and cigarette smoke may be an independent risk factor. Micronutrient antioxidant supplements may be of therapeutic value.
Some aspects of adrenocortical function were investigated in young male guinea pigs fed an ascorbic acid (AsA)-deficient diet for 7 days, followed by 0.1 mg AsA/100 g body weight/day for 4 days; pair-fed guinea pigs served as controls. Ninety minutes prior to killine, all guinea pigs received either an adrenocorticotropic hormone (ACTH) or saline injection, and 30 minutes prior to killing, all were injected with 20 muCi 45Ca/100 g body weight intraperitoneally. AsA restriction alone caused an 89% reduction in adrenal AsA concentration, but growth rate, adrenal weight and plasma ACTH were not different from those of pair-fed controls. Adrenal radiocalcium uptake, adrenal calcium content and plasma corticosteroids were similar in saline-treated guinea pigs restricted in AsA and the ACTH-treated controls, all of which were significantly higher than the values observed in saline-injected controls. Similar responses of the ACTH-treated controls and the saline-treated mildly deficient guinea pigs indicated that, at the adrenal AsA levels achieved (4.45 to 7.02 mg/100 g tissue), adrenal calcium and plasma corticosteroids increased significantly without the mediation of ACTH.
An 91 years old woman was hospitalized because of lethargy, shortness of breath and diffuse subcutaneous hemorrhage of legs. Clinical features were consistent with the diagnosis of vasculitis with systemic involvement. However dermatologic characteristics of the legs, in association with malnutrition, suggested vitamin C deficiency which was confirmed by laboratory test. Ascorbic acid supplement dramatically improved her clinical symptoms. This case remarks how scurvy may mimmick a systemic vasculitis.
Scurvy has been known since ancient times, but the discovery of the link between the dietary deficiency of ascorbic acid and scurvy has dramatically reduced its incidence over the past half-century. Sporadic reports of scurvy still occur, primarily in elderly, isolated individuals with alcoholism. The incidence of scurvy in the pediatric population is very uncommon, and it is usually seen in children with severely restricted diets attributable to psychiatric or developmental problems. The condition is characterized by perifollicular petechiae and bruising, gingival inflammation and bleeding, and, in children, bone disease. We describe a case of scurvy in a 9-year-old developmentally delayed girl who had a diet markedly deficient in vitamin C resulting from extremely limited food preferences. She presented with debilitating bone pain, inflammatory gingival disease, perifollicular hyperkeratosis, and purpura. Severe hypertension without another apparent secondary cause was also present, which has been previously undescribed. The signs of scurvy and hypertension resolved after treatment with vitamin C. The diagnosis of scurvy is made on clinical and radiographic grounds, and may be supported by finding reduced levels of vitamin C in serum or buffy-coat leukocytes. The response to vitamin C is dramatic. Clinicians should be aware of this potentially fatal but easily curable condition that is still occasionally encountered among children.
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The effects of ascorbic acid (AsA)-deficiency on the development of mammary glands were investigated using mutant rats (osteogenic disorder syndrome rats; ODS rats) with hereditary inability to synthesize AsA. Female ODS rats of 21 days old were castrated and divided into two groups. One group was given AsA in their drinking water, and the other was not. All the rats received a daily injection of oestradiol-17 beta and progesterone (EP) from day 28 to day 49 of age. After EP treatment, the concentrations of AsA in the mammary glands of rats not given AsA were less than one tenth of those of rats given AsA and the contents of hydroxyproline in the mammary glands of the former rats were about half of those in the latter. Furthermore, the concentration of serum prolactin in rats not given AsA was reduced to about one third of that in rats given AsA. After EP treatment, whole mounts of mammary glands showed that in rats not given AsA the development of ducts was impaired and there was extensive accumulation of endbuds. Consistent with this finding, EP injections did not increase the area of parenchyma in the mammary glands of rats not given AsA, whereas they increased it about 2-fold in rats given AsA. Moreover, after EP treatment the amount of alpha-lactalbumin was significantly less in the mammary parenchyma of rats not given AsA than in that of rats given AsA. On the other hand, AsA deficiency did not impair the response of the mammary cells to insulin or prolactin in terms of DNA synthesis and alpha-lactalbumin production. These findings indicate that AsA deficiency impaired the development of mammary glands. This effect may be partly attributable to a defect in collagen synthesis in the mammary glands and a decrease in the concentration of serum prolactin.
The hematic level of ascorbic acid was significantly lower with respect to that of healthy subjects in 55 patients with hemorrhagic ocular diseases. Experiments on albino guinea pigs showed that an induced hypovitaminosis C (2 weeks of scorbutigenic diet followed by a maintenance dose of 0,5 mg of ascorbic acid) caused the appearance of widespread retina hemorrhages and a significant decrease of the blood ascorbate levels with respect to the control groups. The present results suggest that a prolonged insufficient dietary intake of ascorbic acid may give rise to hemorrhagic ocular pathologies in humans.
Supply of the Chernobyl NPP staff and Slavutich children with vitamins and minerals has been examined in spring 1992. From 43 to 100% of people have moderate deficiency of vitamin C, B1, B2, B6 and folic acid, 6-61%--deep deficiency of these nutrients. Most of the people have insufficient supply with vitamins in the form of polyhypovitaminosis, i.e. combined deficiency of ascorbic acid and of 2 or 3 vitamins of the B group. Deficiency of 2 vitamins was found in 20% of adults of 3 vitamins in 37%, of 4 vitamins in 29% and of 1 vitamin in 10% of adults. Only 4% of examined adults are sufficiently supplied with all vitamins and none of children. Deficiency of 1 vitamin was found in 11% of children, of 2 vitamins in 15%, of 3 vitamins in 17%, of 4 vitamins in 35%, of 5 vitamins in 20% and of 6 vitamins in 2% of children. Supply of children with all vitamins has been improved when they received combined vitamin-mineral preparation "Duovit" for one month. Universal prophylactic vitaminization by means of administration of ascorbic acid and polyvitamin preparations in doses corresponding to the daily physiological requirement should be recommended as the most reliable, effective and economical measure aimed to improve supply of the population with vitamins.
In previous studies, we found that the ascorbic acid (AsA) deficiency caused changes in the amounts of the various forms of cytochrome P450 (P450) in liver microsomes from guinea pigs in a form-specific manner. Thus, the aim of this study was to clarify whether the changes seen in the protein contents of the various forms of P450 were associated with the levels of the expression of their mRNAs. Prior to determining the mRNA level, we isolated four cDNA clones, encoding CYP1A2, CYP3A14, CYP3A15, and CYP3A17, from guinea pig liver cDNA libraries to use them as probes in further experiments. The amino acid sequence of the guinea pig CYP1A2 showed identity ranging from 73 to 77% with those of other mammalian P450s. The amino acid sequences among guinea pig CYP3As had about 94% identities with each other. The AsA deficiency apparently decreased the expression of mRNA for CYP1A1 and CYP1A2. These results were in agreement with the decrease in the content of CYP1A1 and CYP1A2 proteins. The amount of P450 protein(s) immunochemically cross-reactive with antibodies to human CYP3A4 was likely unaffected while that of human CYP3A7 tended to be decreased by the AsA deficiency. It suggested that the expression of each CYP3A isozyme was regulated differently by AsA. In fact, the level of mRNA for CYP3A14 was unaffected by the AsA deficiency, while those for CYP3A15 and CYP3A17 were significantly decreased by the AsA deficiency, clearly indicating that the expression of each isozyme within the CYP3A subfamily is differently regulated by AsA. These results support the idea that the transcription of P450 is regulated by AsA in guinea pigs.
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