Showing papers in "Acta vitaminologica et enzymologica in 1982"

Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children.

Abstract: In 1973 Rimland reported that some autistic children responded favorably to high doses of vitamin B6. Since this finding, different studies were performed to identify apparently B6 responsive subjects and to critically evaluate clinical and biological B6 responsiveness. Magnesium was included because large doses of B6 might increase irritability. 44 patients (mean age 9.3 years) were examined. All selected children had marked autistic symptoms. The children received a complete diagnostic work-up, including psychiatric, psychological, neurological and medical evaluation. Clinical data were scored using an estimate of global clinical state and numerical rating on a 18 item scale (Behavior Summarized Evaluation). In a first open trial 15 out of 44 children exhibited moderate clinical improvement with worsening on termination of the trial. Thirteen responders and 8 non responders were re-tested in a 2-week crossover, double-blind trial and the responses to the open trial were confirmed. Biochemical data analysis revealed that a significant decrease in urinary homovanillic acid (HVA) levels was observed during B6-Mg administration. During B6-Mg treatment, middle latency evoked potentials exhibited a significant increase of amplitude.

Dexpanthenol (Ro 01-4709) in the treatment of constipation.

Abstract: Functional constipation is not a life-threatening disease, but as a chronic state it worries the patient and causes him discomfort and often leads him to self-medication with potentially dangerous drugs. Ro 01-4709 contains as active substance dexpanthenol, which is the alcohol of pantothenic acid, a vitamin of the B-complex. In the cells, dexpanthenol is readily oxidized to pantothenic acid, which stimulates peristalsis when administered in therapeutically effective doses. Ro 01-4709 has already proven its efficacy in the prevention and treatment of adynamic ileus. Recently, several open and two double-blind studies have been carried out, investigating the efficacy of oral Ro 01-4709 in the treatment of chronic functional constipation. The two double-blind studies showed Ro 01-4709 to be superior to placebo in all parameters measured. The studies with an open design also demonstrated a favourable effect of Ro 01-4709 in the treatment of chronic functional constipation. Owing to its physiological action-which is in a favourable contrast to that of normal laxatives. Ro 01-4709 can be recommended for the treatment of functional constipation in pregnant women, children and the elderly.

The potential use of thiamine in patients with cardiac insufficiency.

Abstract: Incremental doses of vitamin B1 were injected into patients with myocardial and pulmonary insufficiency treated in the post-operative period in the ICU (intensive care unit) after repairment of abdominal aneurysm Compared to the control situation thiamine in a total dose of 50 mg/Kg induced a rise of blood pressure by at least 20 mmHg and a moderate elevation of central venous pressure by 3 mmHg Heart rate was not affected and the EEG exhibited arousal effects after B1 treatment It is suggested that in the failing heart with increased sympathetic tone thiamine acts as a mild peripheral vasodilator followed by a diminished pump outflow impedance and a resultant increase in systolic blood pressure The redistribution of volume to the low pressure side is associated with a rise in central venous pressure Effects of B1 on the EEG suggest an arousal reaction probably due to an interaction with a neurotransmitter system such as acethylcholine

Vitamins and immunity: II. Influence of L-carnitine on the immune system.

Abstract: Vitamin A affects the antibody responses and may affect phagocytic function and properdin levels. Pyridoxine deficiency impairs nucleic acid synthesis and depresses antibody formation, delayed hypersensitivity reactions and the ability of phagocytes to kill bacteria. Pantothenic acid deficiency impairs antibody formation. Vitamin C deficiency increases the incidence of infection, primary by a negative influence on reparative processes. Deficiencies of other vitamins either have not been sufficiently studied or have a variable effect. Moreover, even substances which for their biosynthesis require an adequate vitamin supplementation may exert immunomodulatory influences. With this respect the authors report their results on the influence of L-carnitine on the immune system. L-carnitine increases the proliferative responses of both murine and human lymphocyte following mitogenic stimulation and increase polymorphonuclear chemotaxis. Furthermore, L-carnitine, even at minimal concentrations, neutralizes the lipid induced immunosuppression.

alpha-Tocopherol level in liver diseases.

Abstract: Serum levels of alpha-tocopherol (vitamin E) were determined in various types of liver diseases, and as a results, it was revealed that serum alpha-tocopherol was significantly depressed in acute hepatitis (p less than 0.01, n = 22), alcoholic hepatitis (p less than 0.001, n = 9) and fulminant hepatitis (p less than 0.001, n = 6). There was a significant correlation between serum levels of alpha-tocopherol and beta-lipoprotein (r = 0.92, p less than 0.001, n = 17). Though there was no correlation between serum levels of alpha-tocopherol and triglyceride, there was a significant correlation between alpha-tocopherol and cholesterol (r = 0.57, p less than 0.01, n = 21), and phospholipid (r = 0.49, p less than 0.05, n = 18). There was no correlation between serum levels of alpha-tocopherol and other liver function tests. These facts suggested that the diminished serum vitamin E in patients with liver diseases is ascribable to the depression in blood level of beta-lipoprotein that results from liver disorders, because the liver is the major supply source of beta-lipoprotein.

Vitamin E in beta-thalassemia.

Abstract: In homozygous beta-thalassemia low serum level of alpha-tocopherol have been found. The administration of high doses of the vitamin increased the serum level, decreased lipid peroxidation and, in some case, prolonged red blood cell survival; no significant change in transfusion requirement was obtained. Only few data are available about the vitamin E in heterozygous beta-thalassemia. We have studied 131 patients aged 1 to 72 years with thalassemic trait and 218 age-matched controls. Serum level of alpha-tocopherol was statistically lower in the former. We have studied the effect of vitamin E on 10 patients. In each subject the subsequent parameters were determined before and after a three month treatment (vitamin E 400-600 mg/day) glutathione peroxidase, pyruvate kinase and creatine in erythrocytes serum vitamin E and red blood cell count. Hematological values were unchanged in all patients. In half of them biochemical parameters showed reduction of lipid peroxidation and increased erythrocyte survival.

Vitamins and lipid metabolism.

Abstract: Vitamins play an essential role in lipid metabolism reactions and their presence is therefore absolutely necessary for these reaction to occur. The effect of pantothenic acid, niacin and riboflavin is here described. By transformation into coenzymes these vitamins are involved in fatty acid synthesis and oxidation reactions. Other vitamins, like vitamin B12, folic acid, vitamin C, and essential fatty acids influence lipid metabolism by different mechanisms. Coenzyme B12 and folate coenzyme provide to balance, by methionine synthesis, the pool of methyl radicals necessary for phospholipid biosynthesis. By its involvement in the microsomal respiratory chain, vitamin C promotes cholesterol transformation into bile acids. The essential fatty acids, mainly linoleic acid, are directly connected with cholesterol transport and plasma cholesterol decrease. It is suggested that many lipid metabolism disorders may be due to primary and secondary hypovitaminosis. Nicotinic acid and its derivatives have a particular pharmacological effect since they cause a HDL increase with LDL decrease and improve cholesterol transfer from LDL to HDL. Results of several experiments on the influence of pantothenic acid on polyunsaturated fatty acid metabolism are eventually reported, and these data are related to the effect of the administration of vitamin C at high doses on total cholesterol, triglyceride, lipoprotein, vitamin C and fatty acids of the different plasma lipid fractions.

Therapy of side effects of oral contraceptive agents with vitamin B6.

Abstract: Studies carried out in different countries during the last 15 years have provided evidence that supplementation with (or excess of) estro-progestational hormones may be accompanied by an increased urinary excretion of tryptophan metabolites, as happens in pyridoxine deficiency. Further methods of assessment of vitamin B6 in humans have confirmed an impaired status in women using hormonal contraception. Disturbances in the metabolism of tryptophan have been shown to be responsible for such symptoms as depression, anxiety, decrease of libido and impairment of glucose tolerance occurring in some of the OCA users. Administration of 40 mg of vitamin B6 daily not only restores normal biochemical values but also relieves the clinical symptoms in those vitamin B6 deficient women taking OCA's. Further studies are justified to clarify whether vitamin B6 supplementation may contribute to improving depression also in other situations with hyperoestrogenism (pregnancy, puerperium, estro-progestational treatments, etc.), as well as correcting metabolic impairments, such as a minor alteration of glucose tolerance.

Metabolism of thiamin and its phosphoric esters in different regions of the nervous system: a new approach.

Abstract: In the nervous system thiamin could have two main functions: coenzymatic, as thiamin pyrophosphate, and/or non-coenzymatic, but related to the nervous activity. In order to investigate the thiamin role we studied the turnover and metabolism of thiamin and its phosphoesters (mono-, pyro-, and tri-phosphate) in different regions (cerebellum, brain stem, cerebral cortex and sciatic nerve) of the nervous system, in a steady state condition. Practically, we determined the regional radioactivity of thiamin and its phosphoesters at different times (up to 240 hrs) from labeled thiamin administration, analyzing the obtained data by suitable compartmental models. From the results of two different types of experiment and from their mathematical elaboration, the cerebellum, with the highest thiamin compound content, appeared to be the most active region of the brain in different steps of thiamin metabolism (phosphorylation, dephosphorylation, uptake and release). The sciatic nerve, however, stood out for only thiamin and thiamin monophosphate metabolism, in spite of its very low total thiamin content.

The modulating influence of vitamin E in biological membrane unsaturated phospholipid metabolism.

Abstract: A tissue culture system in which the composition of the medium, with respect to vitamin E, linoleic acid, and cholesterol, can be manipulated at will, was used to study the effect of vitamin E on the fatty acid profiles of fibroblast membrane phospholipids. The effect was studied of alpha-tocopherol, and of butylated hydroxytoluene, on the uptake of isotopically labeled linoleic acid and cholesterol, and of the effect of these antioxidants on the metabolic interconversion of linoleic acid with other unsaturated fatty acids. Butylated hydroxytoluene was without effect on any of the parameters measured, alpha-tocopherol caused a large enhancement in the content and radioactivity of the arachidonyl residues of phosphatidyl choline, phosphatidyl serine, and phosphatidyl ethanolamine, generally at the expense of linoleic acid in the same phospholipids. There was no effect of alpha-tocopherol on the unsaturated fatty acids of the neutral lipids, suggesting that there was no general effect on the chain elongation and desaturation of linoleic acid. The results are thought to demonstrate a specific effect of alpha-tocopherol upon the architecture of membrane phospholipids by controlling the profiles of their unsaturated fatty acid components. The uptake of radioactive cholesterol, and the content of cholesterol and cholesterylesters in cultured cells was also significantly increased by the presence of alpha-tocopherol in the medium.

Effects of ascorbic acid on neutrophil function. Studies on normal and chronic granulomatous disease neutrophils.

Abstract: Ascorbic acid is able to stimulate neutrophil oxidative metabolism in normal neutrophils, as well as other several functions of these cells, either in the normal state or in the defective one. In the present study, we have investigated the effects of ascorbic acid on the hexose monophosphate shunt (HMPS) and on the bactericidal activity of neutrophils from Chronic Granulomatous Disease (CGD) patients. Furthermore, we have investigated the effects of ascorbic acid on the antibody dependent cell cytotoxicity (ADCC) of normal neutrophils. Ascorbic acid in vitro was able to significantly improve both HMPS activity and bacterial killing of CGD neutrophils. Its prolonged administration to such patients led to consistent clinical improvement, possibly related to the enhancement of chemotaxis, although the effects on HMPS and bacterial killing seen in vitro could not be confirmed. Ascorbic acid was also able to interfere with neutrophil ADCC with different results depending on its concentration and the experimental conditions.

Protective effect of L-ascorbic acid in lindane intoxicated rats.

Abstract: Administration of lindane at a dose of 20 mg/kg body weight/day for 15 days to male rats brought about marked growth retardation. Succinic dehydrogenase, Mg2+-ATPase and glucose-6-phosphatase activities were inhibited in different fractions of liver tissues. Mg2+-ATPase, alkaline phosphatase and NADH-dehydrogenase activities were also inhibited in the liver plasma membranes of the lindane treated animals. Stimulation of 5'-nucleotidase activity in liver plasma membrane was observed under lindane intoxication. Supplementation of L-ascorbic acid by separate oral administration to the lindane intoxicated rats neutralized the growth retardation and maintained almost normal values of all the enzymes studied.

Vitamins E and A in vascular diseases.

Abstract: The major pathogenetic factors of the atherosclerotic diseases are: a) vasal endothelium distress; b) rheological disturbs; c) alterations in plasma lipid pattern; d) dietary intake of saturated and polyunsaturated fatty acids; e) alteration of mitochondrial and microsomal membranes; f) vascular injury induced by immune complexes; g) increased lipid peroxidations. Many well documented reports state a positive effect of vitamins A and E on some of the factors previously considered. Vitamins A and E have an endothelium-protective activity and an antiperoxidative effect; they act as antiaggregant factors, affect O2 transport and utilization processes, increase HDL-cholesterol, potentiate the hypolipidemic action of the nicotinic acid.

Vitamin D and its metabolites. Advances in the diagnosis and treatment of rickets.

Abstract: Diagnostic and therapeutical uses of vitamin D3 and its metabolites are reviewed. Special emphasis is dedicated to the fetomaternal relationships of 1,25 (OH)2 D3 and 25-OH-D3 at term. The serum levels of 1,25 (OH)2 D3 have been found to be higher in the maternal serum then in the corresponding fetus (85.3 pg/ml and 50.9 pg/ml, respectively). The highest serum levels of 1,25 (OH)2 D3 were found in October and the lowest ones in January showing that there is a dependence on the ultraviolet light. It has been found that there is a correlation between the fetomaternal serum levels of 1,25 (OH)2 D3 and 25-OHD. However, there is no correlation between the serum levels of 1,25 (OH)2 D3 and 25-OHD3, neither in the fetus nor in the mother.

Biological actions and possible uses of vitamin E.

Abstract: Symptoms of Vitamin E deficiency can be generally attributed to derangement of processes depending upon the integrity of cellular and subcellular membranes, following the formation of tissue-damaging products of lipid peroxidation. Antioxidants modulate also the formation of products derived from long-chain polyunsaturated fatty acids, such as arachidonic acid--which are structural components of biological membranes--through oxidative reactions involving the cyclooxygenase and lipoxygenase systems. Vitamin E inhibits the aggregatory responses of blood platelets to aggregating agents "in vitro", after a preincubation period required for the uptake of the compound by the cells. The antiaggregatory activity of alpha-tocopherol, however, does not appear to be strictly dependent upon inhibition of the formation of thromboxane, the proaggregatory compound derived from arachidonic acid through be cyclooxgenase system. The effects of Vitamin E on platelet function may be of relevance in the control of thromboembolic processes of clinical importance.

Study of blood vitamin C in lung and bladder cancer patients before and after treatment with ascorbic acid. A preliminary report.

Abstract: A systematic study of vitamin C blood levels in patients with cancer and an evaluation of their modifications when the patients were orally treated with daily large doses of ascorbic acid (5g/day) have been carried out. For excluding any interference on intestinal vitamin C absorption, all patients with digestive tract cancer have been excluded. Our first results concern 24 lung cancer and 35 bladder cancer patients, operable or not, of different sex and age. The study has shown hypovitaminosis C subclinic conditions for the greater part of subjects: in fact the average haematic rate of ascorbic acid approaches to lower level of physiologic range, appearing very low particularly for the younger patients. Periodic haematic dosages of vitamin C of unoperable and operated patients treated with large doses of ascorbic acid, have shown a rapid increase of its blood concentration which frequently has been very over 1500 micrograms%, the higher level of normal range. These high vitamin haematic levels, generally constant during the time, appear usefull in increasing the defence reactions of the cancerous patient.

Vitamin A palmitate decreases intravenous glucose tolerance in man.

Abstract: We tested retinyl palmitate for in vivo effects in man and in vitro effects on the IM-9 lymphocyte insulin receptor. Intravenous glucose tolerance tests (IVGTT) with 25 g glucose were performed on 10 healthy subjects before and after two intramuscular injections of retinyl palmitate (25,000 IU) 18 hours apart. In 9 of 10 subjects, glucose disposition was impaired after treatment with retinyl palmitate. In vitro, retinyl palmitate 10(-4) - 10(-6) M did not affect the binding or displacement of insulin 125I from lymphocyte receptors. We conclude that retinyl palmitate decreases glucose tolerance without demonstrable effects on insulin release or insulin binding to receptors.

Vitamin C in normal human mononuclear and polymorphonuclear leukocytes.

Abstract: Human peripheral leukocytes from healthy donors have been isolated by means of a suitable separation method to obtain a high yield of lymphocytes and granulocytes with a very low contamination of platelets and red blood cells. Mononuclear cells so purified contain more than double amounts of vitamin C than polymorphonuclear cells. The difference between lymphocytes and granulocytes content also tends to be larger at increasing vitamin concentrations in total leukocytes. A higher level of vitamin C is displayed by the mononuclear cells obtained from women in respect to men, while no significant difference is found in the polymorphonuclear cells.

Pellagra: "A Reappraisal"

Abstract: A brief review of the epidemiological history of pellagra is attempted. In Europe and North America Pellagra is practically eradicated at the present time. However, in mediterranean countries, with much sunlight, cases of the disease are sporadically seen. Nevertheless, in countries with a low nutritional level Pellagra still exists as endemic form. In Athens, Greece, the last decade 1971-1981, 56 new cases of Pellagra were studied. A short analysis of the above cases concerning mainly the real cause of the disease is presented. Moreover, the more recent aspects concerning the aetiological factors responsible for the appearance of Pellagra, with special emphasis to vitamins, is reported.

Pyridine nucleotide metabolism in the erythrocyte of South African blacks with primary hepatoma.

Abstract: Erthrocytes from African blacks with primary hepatoma were incubated with physiological amounts (1.64 microM) of nicotinamide-14C (NM-14C) and it was found that these erythrocytes could synthesize NAD from NM. After 3-hr incubation with NM-14C, a large percentage of the 14C was found in NMN, nicotinamide riboside (NR) and NAD, but was undetectable in nicotinic acid nucleotides (NAMN and NAAD). This suggested that the NAD synthesized from NM was not through the Preiss-Handler pathway. After 6-plus hr incubation, the 14C found in NAMN and NAAD suggested the NAD synthesized was being broken down and reutilized through Preiss-Handler pathway for synthesis of NAD. This reutilization pathway was confirmed by incubating nicotinic acid-14C (NA-14C) with erythrocytes. Apparently the metabolites from the breakdown of NAD were deaminated. The metabolism of NM-14C was slower than NA-14C. However, after 24 hr incubation with NM-14C, 72.26% of 14C was found in NAD. A high percentage of 14C in NR at the initial incubation and a later drop suggested that NR was another intermediate in the pathway.

Alterations of the tryptophan--nicotinic acid metabolism in vitiligo.

Abstract: Tryptophan metabolism "via kynurenine" is altered in vitiligo: after a load of the amino acid the urinary excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid is decreased, whereas that of xanthurenic acid and its 8-methyl ether is increased. The excretory values of the metabolites suggest a deficiency of the activity of kynurenine hydroxylase and kynunerinase, the enzymes involved in the metabolism of 3-hydroxykynurenine and 3-hydroxyanthranilic acid. The reduced excretion of 3-hydroxykynurenine, a tryptophan metabolite involved in melanin biosynthesis, may indicate a smaller utilization of tryptophan in the biogenesis of the melanins.

Protection of essential fatty acids by vitamin E

Abstract: The protective role of vitamin E against free-radical-mediated oxidations is discussed. In spite of the presence of vitamin E in cell membranes, as structural complex with polyunsaturated fatty acids (PUFA) of phospholipids, the question arises whether high PUFA containing diets, producing high deposition of PUFA in the tissues, can nevertheless lead to peroxidations in the body. It has been suggested that large amounts of dietary PUFA increase the requirement for vitamin E and deplete its tissue stores, particularly when PUFA are discontinued in the diet, also because of their longer half-life time than tocopherols. However, in physiological conditions, linoleic acid up to 10% of caloric intake seems to have no effects on vitamin E requirement. In contrast, in essential fatty acid (EFA) deficient animals, also the addition of small amounts of dietary EFA, by resulting in a proportional increase in PUFA content of membrane structural lipids, is associated with an increased need for vitamin E. This becomes particularly important in the case of dietary fish oils or other poorly protected fats.

Pyridoxine and depression: neuroendocrine aspects.

Abstract: Plasma prolactin levels (PRL) were determined in 5 male depressed patients and in 5 controls, after injection of TRH (200 mg i.v.) (first phase), TRH following oral L-DOPA (500 mg) given 90 minutes before (second phase), TRH plus pyridoxine (300 mg i.v.) after same pretreatment with L-Dopa (third phase). L-Dopa induced a statistically significant suppression of TRH, caused PRL release; such suppression appears to be lower when TRH plus pyridoxine were administered simultaneously. PRL profile was not significantly different in the two groups.

Vitamin deficiencies during the Spanish Civil War in Madrid: a reminiscence.

Abstract: During the second winter of the war (1937-38) most of the patients showed a picture of classic pellagra, with a number of neurological disorders which in same cases appeared with no other manifestations of Pellagra. The clinical picture was dominated by the appearance of famine edema, with less manifestations of specific vitamin deficiencies, with neurological manifestations called similar to those "burning feet" syndrome and described by us as Paresthetic and Paresthetic-causalgic syndrome. The prominent features were: acroparesthesia, dysestesia dolorosa, sensation of cold, sensation of wetness, hyperpathia and causalgic pain. Treatment with nicotinic acid was very effective for the classical manifestations of Pellagra (dermatitis, diarrhea and dementia), but had no significant effect on the neurological manifestations. No effect of vitamin B1 was observed, but some improvement following the administration of autoclaved brewers yeast. It was concluded that the neurological manifestations often associated with the classical picture of Pellagra are not due to nicotinic acid deficiency, but to the deficiency of some component of the vitamin B complex which was neither vitamin B1, nor vitamin B2.

Vitamin E and cholestasis in children

Abstract: The mechanisms and consequences of Vitamin E deficiency were studied in 12 children presenting with chronic cholestasis. Preliminary results indicate that: (1) Vitamin E serum levels are lowest in children with the long-lasting cholestasis and in children in whom fat malabsorption is deepest. (2) Signs of neurologic dysfunction involving peripheral nerves, cerebellum, eye movements and retina were present in 7 children. (3) In vitro study of RBC showed increased hemolysis with oxidating agents and in physiological saline. Degree of hemolysis was inversely related to the serum level of vitamin E. (4) Increased platelet aggregation was observed in 8 patients; 6 of these also had low levels of serum Vitamin E.