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[The effectiveness of oral and parenteral vitamin A doses in growing cattle with different vitamin A supplies].

The effect of one single oral or parenterally administered dose of 1 million IU vitamin A on the vitamin A depot in the liver and on blood plasma vitamin A concentrations was investigated in 3 individual feeding experiments with involvement of 18 and 24 calves or 24 fattening bulls. 50% of all animals in each of the 3 experiments received feed without any vitamin A through 108 or 112 or 209 days, prior to vitamin A administration, or received 10.000 IU/100 kg live weight and day. Parenteral vitamin A administration in either group yielded rise in blood plasma from 0.06--0.35 to 26.2--30.2 mumol/l, after 1 or 2 days. The maximum value measured after oral administration was 1.9 mumol/l. Most of the plasma values had returned to normal (0.6--12. mumol/l) within 14 days from administration. Oral and parenteral vitamin A doses, after 14 days, caused significant rise in vitamin A concentrations in the liver (from 15.5 to 82.5), with the increase resulting from parenteral administration (from 13.7 to 99.1) being clearly higher than that resulting from oral administration (from 17.3 to 65.9 mumol/kg fresh liver tissue). The same trends were recorded from recovery of vitamin A from the liver (26.8% after parenteral administration versus 15.0% in the wake of oral doses). Storage in and recovery from vitamin-A depleted animals were below values recorded from young cattle with sufficient vitamin A supply. These findings are likely to confirm that one single parenteral vitamin A administration was of clearly higher effectiveness, as compared to oral application.

Administration, Oral↗

R- and S-Warfarin inhibition of vitamin K and vitamin K 2,3-epoxide reductase activities in the rat.

Reduction of vitamin K 2,3-epoxide and vitamin K catalyzed by hepatic microsomal enzymes is required for normal, postribosomal, gamma-carboxyglutamate formation in the prothrombin complex Factors II, VII, IX, and X. The R- and S-warfarin enantiomers differentially inhibit (S-warfarin is 2 to 5 times more active) vitamin K function by mechanisms which have not been unambiguously determined. As a step toward determining the physiologically relevant site(s) of warfarin-antivitamin K activity we investigated in Wistar rats the effects of R- and S-warfarin on vitamin K 2,3-epoxide and vitamin K reductase activities and correlated them with effects on plasma concentrations of the Factors II, VII, and X. Based on the results of these studies we conclude that: 1) warfarin inhibition of the vitamin K 2,3-epoxide and vitamin K reductases is essentially irreversible; 2) S-warfarin stereoselectively inhibits both reductases in vivo but not in vitro; 3) the vitamin K reductase which utilizes dithiothreitol as cofactor in vitro is primarily responsible for vitamin K reduction to vitamin K hydroquinone under physiological conditions; 4) warfarin initially inhibits gamma-carboxyglutamate formation by inhibiting simultaneously the vitamin K 2,3-epoxide and vitamin K reductases; and 5) following enantiomer administration there is an apparent lack of correlation between the restoration of the reductase activities and the reinitiation of coagulation factor synthesis.

Animals↗

Depletion of plasma vitamin C but not of vitamin E in response to cardiac operations.

The whole-body inflammatory response produced by cardiopulmonary bypass is an important cause of perioperative morbidity after cardiac operations. This inflammatory response produces reactive oxygen species and other cytotoxic substances, such as the cytokines. The generation of reactive oxygen species might deplete principal antioxidant micronutrients, that is, vitamins C and E and the carotenoids. Therefore, we have investigated the time course of the plasma concentrations of vitamins C and E and the carotenoids in 18 patients undergoing coronary bypass operations after randomization for previous vitamin E supplementation (300 mg dl-alpha-acetyl-tocopherol 3 times daily for 4 weeks) or placebo. Supplementation with alpha-tocopherol doubled the lipid-standardized plasma vitamin E concentration to 63.7 +/- 14.5 mumol/L when compared with that of the control subjects (31.2 +/- 9.0 mumol/L) before the operation. The plasma concentrations of vitamin C (36.0 +/- 19.0 mumol/L and 44.0 +/- 21.7 mumol/L, respectively) and of the carotenoids were not statistically different between the two groups at baseline. The absolute plasma concentrations of both vitamin E and the carotenoids decreased during and after cardiopulmonary bypass, but after correction for hemodilution the plasma concentrations of vitamin E and the carotenoids showed no decrease. The vitamin E concentrations in the erythrocytes did not change either. In contrast, the plasma concentration of vitamin C decreased in all subjects within 24 hours after the operation by roughly 70%. Correction for hemodilution still revealed a significant decrease in plasma vitamin C that persisted in most patients up to 2 weeks. In conclusion, the vitamin E and the carotenoid plasma concentrations are of no major concern during and after cardiac operations. In contrast, the serious depletion of vitamin C may deteriorate the defense against reactive oxygen species-induced injury during cardiac operations.

Ascorbic Acid↗

Nonsupplemented children of Latino immigrants have low vitamin E intakes and plasma concentrations and normal vitamin C, selenium, and carotenoid intakes and plasma concentrations.

OBJECTIVE: This study sought to determine and evaluate the intakes and plasma concentrations of vitamin E (alpha-tocopherol), gamma-tocopherol, vitamin C, selenium, and carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, and lycopene) of nonsupplemented boys and girls, 4 to 8 years old, of Latino immigrants living in rural Nebraska. DESIGN: Dietary intakes of the Latino children were estimated. Their plasma samples (fasting) were analyzed for vitamin E, vitamin C, selenium, and carotenoid concentrations. Data were evaluated by sex. SUBJECTS: The subjects were a convenience sample of 4- to 8-year-old (n=29), apparently healthy, nonsupplemented children of Latino immigrants living in rural Nebraska. STATISTICAL ANALYSIS: Sex differences in parameter values were determined using general linear models; Pearson r was used for determining correlations. RESULTS: No significant differences in parameter values were observed by sex, with the exception of plasma lutein/zeaxanthin concentration. The majority (69%) had plasma vitamin E (alpha-tocopherol) concentrations<0.516 mg/dL (12 micromol/L), which is indicative of vitamin E inadequacy, and over half (59%) reported consuming less than the Estimated Average Requirement for vitamin E. All subjects had plasma vitamin C and selenium concentrations indicative of adequacy (>0.41 mg/dL or >23 micromol/L, and >6.32 microg/dL or >0.8 micromol/L, respectively), and consumed at least the Recommended Dietary Allowances for these nutrients. The plasma carotenoid concentrations of the children may be useful as norms. CONCLUSIONS: These children of Latino immigrants who did not take supplements had low plasma vitamin E (alpha-tocopherol) concentrations but normal plasma vitamin C and selenium concentrations. IMPLICATIONS: Dietetics professionals and others involved in health care need to work with Latino immigrant parents so that their children consume adequate amounts of vitamin E.

Ascorbic Acid↗

Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination.

OBJECTIVE: Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency. STUDY DESIGN: Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence). RESULTS: Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods. CONCLUSIONS: An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.

Adolescent↗

Vitamin K activity and metabolism of vitamin K-1 epoxide-1,4-diol.

Vitamin K-1 epoxide, the major metabolite of vitamin k-1, has similar activity to vitamin K-1 in inducing prothrombin synthesis and protein carboxylation. The high activity of K-1 epoxide could be due to its conversion to vitamin K-1 hydroquinone without going through vitamin K-1. A logical intermediate in this conversion would be vitamin K-1 epoxide-1,4-diol. The epoxide diol was synthesized and clearly stimulated prothrombin synthesis in vitamin K deficient rats at a minimum dose of 100 micrograms/kg body weight. Since vitamin K-1 produced a similar response at a minimum dose of 1 microgram/kg, the epoxide diol had about 1% of the activity of vitamin K-1. [3H]K-1 or [3H]epoxide could not be detected as metabolites of [3H]epoxide diol indicating that the activity of epoxide diol was probably not due to its conversion to K-1 hydroquinone, since any [3H]hydroquinone formed would be oxidized in air to [3H]K-1 during analysis. Vitamin K-1 epoxide diol represents a new type of structure possessing vitamin K activity. It is probably not active itself but has to be converted to an active compound since there is a delay in the response to the diol and the activity is completely blocked by Warfarin.

Animals↗

Oral mixed micellar vitamin K for prevention of late vitamin K deficiency bleeding.

OBJECTIVE: To determine whether the use of mixed micellar vitamin K improves the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule. DESIGN: Nationwide active surveillance for vitamin K deficiency bleeding (VKDB) complemented with two surveys on the use of the mixed micellar preparation in hospitals and by paediatricians. SETTING AND PATIENTS: Infants in Germany in 1997-2000. INTERVENTION: Prophylaxis with three oral doses of 2 mg mixed micellar vitamin K. MAIN OUTCOME MEASURE: Confirmed VKDB between day 8 and week 12 and no condition requiring specific vitamin K supplementation known before the onset of bleeding. RESULTS: Twenty nine reports met the case definition: seven had not received any vitamin K prophylaxis; for three, vitamin K prophylaxis was unknown; two had insufficient vitamin K prophylaxis for their age; 17 had been given the recommended doses. The mixed micellar preparation had been given to seven, other preparations to nine, and one had been given both. These cases did not differ with respect to the site of bleeding and cholestasis detected at bleeding. Estimates of the use of the mixed micellar preparation in birth hospitals and by paediatricians yielded 1 817 769 newborns exposed to the mixed micellar preparation and 1 320 926 newborns exposed to other preparations. The rate of late VKDB was 0.44/100 000 (95% confidence interval (CI) 0.19 to 0.87) in children given mixed micellar vitamin K compared with 0.76/100 000 (95% CI 0.36 to 1.39) in children given other preparations. CONCLUSION: Mixed micellar vitamin K did not significantly improve the efficacy of the 3 x 2 mg oral vitamin K prophylaxis schedule.

Administration, Oral↗

Intracellular vitamin D binding proteins: novel facilitators of vitamin D-directed transactivation.

Previously recognized intracellular proteins with an affinity for vitamin D metabolites include the vitamin D receptor and the cytochrome P-450-based vitamin D metabolizing mixed-function oxidases. We recently characterized a third set of high-capacity, intracellular vitamin D binding proteins (IDBPs) in the inducible heat shock protein-70 (hsp-70) family. Here we report the cloning and expression of cDNAs coding for two IDBPs. The full-length cDNAs for IDBP-1 and IDBP-2 demonstrated 95% and 94% nucleotide homology, respectively, with the cDNAs for human constitutively expressed heat shock protein 70 (hsc-70) and hsp-70. Transient expression of the IDBP cDNAs in a vitamin D-responsive primate cell line increased extractable 25-hydroxylated vitamin D metabolite-IDBP-binding 25-fold. Transfection experiments also demonstrated that the majority of the constitutively expressed 25-hydroxylated vitamin D metabolite binding activity was attributable to expression of the hsc-70-related IDBP-1 and that metabolite binding activity sublocalized to the highly conserved ATP-binding/ATPase domain of hsp-70s. Stable overexpression of IDBP-1 in wild-type cells enhanced vitamin D-directed responsiveness of endogenous vitamin D-24-hydroxylase, osteopontin, and osteocalcin genes by several-fold over that observed in cells transfected with an empty vector. These results suggest that IDBP-1 facilitates the intracellular localization of active vitamin D metabolites and vitamin D receptor-mediated transactivation.

Amino Acid Sequence↗

Vitamin A toxicity and vitamin E deficiency in a rabbit colony.

Vitamin A toxicosis and vitamin E deficiency was diagnosed in a commercial rabbit-breeding colony and was associated with reproductive abnormalities, abortions, and poor survivability of kits in the breeding colony. Paresis and muscular dystrophy were noted in juvenile rabbits. Another group of New Zealand White rabbits from the same commercial colony was used to assess the effect of vitamin E-based therapy on clinical signs, reproduction, and vitamin A and E serum and liver levels. Blood samples were taken before and after dietary changes and vitamin E therapy. Serum vitamin E remained low after feeding a diet containing the recommended levels of vitamin E. Administration of vitamin E for 2 weeks lowered the serum vitamin A levels and increased the vitamin E serum and liver levels. In conclusion, vitamin E therapy appears to be an effective treatment for hypervitaminosis A.

Abortion, Veterinary↗

[Vitamin disturbances in chronic renal insufficiency. II. Fat soluble vitamins].

Fat soluble vitamins (except vitamin K) are protein bounded with subsequent storage in the body. It is generally accepted that plasma level of vitamin A is increased in majority of patients with chronic renal insufficiency (CRI) including those on continuous ambulatory peritoneal dialysis (CAPD). Thus, there is no need to supplement this vitamin in CRI patients (pts). Plasma level of vitamin E in CRI pts may be elevated, normal or decreased. It seems to be justified to supplement this vitamin, in spite of its normal plasma level, in case platelet aggregation is increased. Both in dialyzed and nondialyzed CRI pts a normal serum level of vitamin K has been observed. Decreased or extremely low serum level of vitamin D following the gradual loss of renal tissue is to be observed in CRI pts. This deficit is regarded as the main factor leading to the decrease in serum level of calcium, the secondary hyperparathyroidism and bone changes. Treatment with 1.25(OH)2D3 (calcitriol) proved to be most successful in alleviation of symptoms resulting from the deficit of vitamin D3 in the body. Intravenous "pulsating" administration of calcitriol results in rapid normalization of serum PTH level. Treatment with 25(OH)D3 (calcidiol) given orally 3 times a week ("pulsating" method) revealed also fairly good results in this respect. During treatment with vitamin D3 hypercalcemia tends to develop, serum alkaline phosphatase normalizes, elevated PTH serum level decreases. Vitamin D metabolites are less active than 1.25(OH)2D3 being less hypercalcemic.

Avitaminosis↗

[The course of vitamin B6 content in growing rats during vitamin B6-free nutrition].

This experiment was designed in two parts. In the first part the vitamin B6 efficiency in response to increasing dietary vitamin B6 intakes was tested in growing rats; in the second part the reaction of rats, originally supplied with the fourfold requirement and then switched on the vitamin-B6-free basal diet was examined. The experimental animals were male Sprague-Dawley rats, of which weight gains, feed intake, and vitamin-B6-concentrations in blood, liver and whole carcass were measured. At the beginning of the trial nine animals were analyzed; 54 additional animals, divided into six groups, were given a vitamin-B6-free semisynthetic diet for three weeks which was supplemented with 0, 1.5, 3, 6, 12, and 24 mg vitamin B6 per kg feed. For the second part the additional 54 animals were given a diet with 24 mg vitamin B6 for three weeks and then switched to the vitamin-B6-free basal diet. Six animals per group were sacrificed after 2, 5, 8, 12, 16, 20, 25, 30, and 35 days of depletion. Efficiency of dietary vitamin B6 decreased from 38% at 1.5 mg vitamin B6 per kg diet to 4% at the 24 mg dietary level. Also, without dietary vitamin B6 the animals gained weight (from 145 to 300 g live weight), the daily feed intake increased from 14 to 19 g and feed efficiency decreased from 2.2 to 4.3 g feed per g gain. Vitamin B6 concentration in tissues reacted differently.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Combinations of low thiamin, riboflavin, vitamin B6 and vitamin C intake among Dutch adults. (Dutch Nutrition Surveillance System).

OBJECTIVE: Clustering of low vitamin intake may entail a greater functional and/or health risk than the summation of separate low intakes may suggest. Therefore, the prevalence of combined low thiamin, riboflavin, vitamin B6 and vitamin C intake in various adult sex-age groups in The Netherlands was estimated. METHODS: Nutritional risks were evaluated by comparing the calculated intakes with the recommendations for each vitamin. For this purpose the data of a subsample of 3353 adults of a nationwide food consumption survey were used, which had been collected in 1987-88 within the framework of the Dutch Nutrition Surveillance System. Food consumption data were obtained through 2-day dietary records. Respondents were segmented into tertiles based on their vitamin intake per 1000 kcal (4.2 MJ) to adjust for energy intake. RESULTS: As compared with the RDAs, mean overall intake was lowest for vitamin B6. Based on tertile analyses, the risk for inadequate intake was relatively high for vitamin C, small for riboflavin and intermediate for thiamin and vitamin B6. Low vitamin densities clustered somewhat since the prevalence of combined low intakes for all four vitamins was higher than expected from probability calculations. This interdependence was mainly the result of a higher consumption of alcoholic beverages and of other food products with a low vitamin density. CONCLUSION: In affluent societies nutritional risk assessment should not be based solely on single vitamins but should also be oriented at combined low intake levels.

Adult↗

Disposition and metabolism of F6-1alpha,25(OH)2 vitamin D3 and 1alpha,25(OH)2 vitamin D3 in the parathyroid glands of rats dosed with tritium-labeled compounds.

26,26,26,27,27,27-Hexafluoro-1alpha,25(OH)2 vitamin D3, a hexafluorinated analog of 1alpha,25(OH)2 vitamin D3, has been reported to be several times more potent than the parent compound with respect to some vitamin D actions. The reason for enhanced biological activity in the bones, kidneys, and small intestine appears to be related to F6-1alpha,25(OH)2 vitamin D3 metabolism to ST-232 (26,26,26,27,27,27-hexafluoro-1alpha,23S,25-trihydroxyvitamin D3), a bioactive 23S-hydroxylated form that is resistant to further metabolism. We compared the disposition and metabolism of [1beta-3H]F6-1alpha,25(OH)2 vitamin D3 and [1beta-3H]1alpha,25(OH)2 vitamin D3 in parathyroid glands of rats intravenously administered with labeled compounds at a dose of 10 microg/kg. In the [1beta-3H]F6-1alpha,25(OH)2 vitamin D3-dosed group, radioactivity was highly detected in the kidneys, parathyroid glands, and the small intestine. The radioactivity in the parathyroid glands remained high until 48 h postdosing, with values of 2.5, 8.4, and 14.6 times higher at 6, 24, and 48 h postdosing than after dosing with [1beta-3H] 1alpha,25(OH)2 vitamin D3. In the group given [1beta-3H]F6-1alpha,25(OH)2 vitamin D3, the unchanged compound was mainly detected with a small amount of ST-232 at 6 h postdosing. At the 24- and 48-h time points, over half of the radioactivity was observed as ST-232, and additionally, ST-233, the 23-oxo form, accounted for a small amount at the 48-h time point. The present study demonstrated local retention of [1beta-3H]F6-1alpha,25(OH)2 vitamin D3 and the bioactive metabolite ST-232 in parathyroid glands after intravenous administration. The findings may indicate one of the reasons for the higher potency of F6-1alpha,25(OH)2 vitamin D3 than 1alpha,25(OH)2 vitamin D3 in parathyroid.

Animals↗

[Determination of vitamins D2, vitamin D3 in cosmetics by high performance liquid chromatography].

OBJECTIVE: A high performance liquid chromatography method was used to detect vitamins D2 and vitamin D3, which is useful to know the use of vitamins D2 and vitamin D3 in cosmetics, prohibit the influx of cosmetics containing vitamins D2 and vitamin D3 to cosmetic market, safeguard the health of consumers. METHODS: A high performance liquid chromatography method was established for determination of vitamins D2 and vitamin D3 in cosmetics. The separation condition was optimized by trying different type of columns and mobile phases. RESULTS: The experiment goes on a Alltima C18 column (250 mm x 4.6 mm I. D., 5 microm)using methanol-acetonitrile (90: 10) as mobile phase at a flow rate of 1.0 ml/min, with the column temperature 25 degrees C and detection wave 265nm. The liner range is from 0.5 mg/L to 100 mg/L with good relationship. The detection limit of vitamin D2 is 0. 12 mg/L, the precision is less than 3.8% and recovery varies from 94.2% to 101.4%, while the detection limit of vitamin D3 is 0.06 mg/L, the precision is less than 3.5% and recovery varies from 91.6% to 97.2%. CONCLUSION: The method is simple, precise and accurate, which is suitable for the determination of vitamins D2 and vitamin D3 in cosmetics.

Cholecalciferol↗

Acute vitamin D3 toxicosis in horses: case reports and experimental studies of the comparative toxicity of vitamins D2 and D3.

Acute vitamin D toxicosis was diagnosed in 2 horses fed a grain ration containing 1,102,311 IU of cholecalciferol (vitamin D3)/kg (500,000 IU/lb) for about 30 days. Horse 1 died acutely with extensive mineralization of cardiovascular and other soft tissues. Horse 2, which had severe clinical signs and clinicopathologic changes of toxicosis, was treated with nonsteroidal antiinflammatory drugs and recovered in about 6 months. In an experimental study, the toxicity of ergocalciferol (vitamin D2) and cholecalciferol was compared in 2 horses (No. 3 and 4) given the respective vitamins at a daily dosage of 33,000 IU/kg of initial (day 0) body weight for 30 days. Except for slight loss in body weight (8%) during the 1st few days of treatment, horse 3 remained clinically normal. Horse 4 developed limb stiffness and tachycardia, became anorectic, weak, and recumbent, lost 29% of body weight, and had polydipsia and polyuria. Horses 2, 3, and 4 developed persistent hyperphosphatemia. Horse 2 remained normocalcemic whereas horses 3 and 4 became hypercalcemic by day 28. In horse 3, serum vitamin D2 metabolite concentrations on days 0, 1, 14, and 26 were: vitamin D2 (ng/ml) = less than 5.0, 5.7, 71.4, and 188.0; 25-hydroxy-vitamin D2 (ng/ml) = less than 5.0, less than 5.0, 43.1, and 117.5; and 1,25-dihydroxy-vitamin D (pg/ml) = 19.7, 23.2, 25.0, and 45.7, respectively. In horse 4, serum vitamin D3 metabolite concentrations on the same days were: vitamin D3 (ng/ml) = less than 5.0, 110.0, 1,049.0, and 887.0; 25-hydroxy-vitamin D3 (ng/ml) = less than 5.0, 18.9, 201.0 and 182.0; and 1,25-dihydroxy-vitamin D (pg/ml) = 21.5, 18.9, 25.2, and 21.6, respectively. Urine of horses 2 and 4 became acidic (pH 6). Horses 2, 3, and 4 became hyposthenuric, but the decrease in urine specific gravity (sp gr) in horse 3 occurred only after 3 weeks of treatment and was only moderate (sp gr, 1.018 to 1.021) and nonprogressive. Hyposthenuria was evident in horse 4 on day 4 (sp gr, 1.028), and was progressive and marked (sp gr, days 28 to 32: 1.006 to 1.009). Urine sp gr of horse 2 ranged from 1.002 to 1.007. Fractures were demonstrated radiographically and histologically in the costochondral junctions of horses 3 and 4. Mineralization of cardiovascular and other soft tissues developed in horses 3 and 4, with lesions being more severe and having a wider tissue distribution in horse 4.

Acute Disease↗

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment.

This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons: i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment; ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS. We assessed the nature of the disease by investigating the clinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows: a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes. b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies. c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS. d) CFS was distinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment. e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS. f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS. g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.

Ambulatory Care Facilities↗

Experimental study of the therapeutic effects of folate, vitamin A, and vitamin B12 on squamous metaplasia of the bronchial epithelium.

BACKGROUND: Vitamin deficiency may be related to carcinogenesis. Cytologic examinations of sputum have already found that the administration of folate and vitamin B12 suppressed the development of squamous metaplasia and atypia in smokers' airways. The authors investigated the effect of folic acid, vitamin B12, and vitamin A on the formation of metaplasia and hyperplasia in methylcholanthrene (MCA)-treated rats. METHODS: The SD strain of rats received 10 mg of MCA intratracheally and was divided into six groups as follows: (1) vitamin A; (2) folic acid; (3) vitamin B12; (4) vitamin B12 with folic acid; (5) a combination of vitamin A, folic acid, and vitamin B12; and (6) no vitamins. The Lower respiratory tract epithelia of the rats were examined histologically 20, 32, and 36 weeks after MCA administration and at the end of the experiment. RESULTS: A clear difference was detected between the group receiving folic acid and that receiving vitamin A. In the former group, metaplasia was found in only one rat, atypia was not found, and hyperplasia with marked changes was present in less than 50% of other groups. In the latter group, atypia was found in all of the metaplastic foci. CONCLUSIONS: It was suggested that the epithelial hyperplasia and metaplasia of respiratory tract induced by MCA can be suppressed by the administration of folic acid.

Animals↗

Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status.

The mechanism of cephalosporin-induced hypoprothrombinemia has been investigated in hospitalized patients, with respect to cephalosporin structure, vitamin K metabolism, and vitamin K status. Cephalosporins containing side chains of N-methylthiotetrazole (latamoxef, cefmenoxime, cefoperazone, cefotetan, cefamandole) or methyl-thiadiazole (cefazolin) all caused the transient plasma appearance of vitamin K1 2,3-epoxide in response to a 10-mg intravenous dose of vitamin K1, whereas two cephalosporins without a heterocyclic side chain (cefotaxime and cefoxitin) did not. The plasma accumulation of vitamin K1 2,3-epoxide was qualitatively similar to, but quantitatively less than, that produced by the oral anticoagulant phenprocoumon. Patients eating normally had plasma vitamin K1 concentrations (176 to 1184 pg/mL) that were within the normal range (150 to 1550 pg/mL) and their clotting tests remained consistently normal for all antibiotics tested. Patients on total parenteral nutrition had lower plasma vitamin K1 concentrations (50 to 790 pg/mL) but normal clotting before starting antibiotic therapy. Of 19 parenterally fed patients, all seven treated with latamoxef developed hypoprothrombinemia, PIVKA-II and a decrease of protein C within four days whereas 12 patients treated with cefotaxime or cefoxitin showed no clotting changes. Latamoxef-associated hypoprothrombinemia was readily reversible by 1 mg of vitamin K1 given intravenously, but hypoprothrombinemia and sub-normal plasma vitamin K1 could recur within two to three days. The data suggest that NMTT-cephalosporins are inhibitors of hepatic vitamin K epoxide reductase and that a lower nutritional-vitamin K status predisposes to hypoprothrombinemia.

Adult↗