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Showing papers on "B vitamins published in 1995"


Journal ArticleDOI
04 Oct 1995-JAMA
TL;DR: Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease and under different assumptions, 13,500 to 50,000 CAD deaths annually could be avoided.
Abstract: Objective. —To determine the risk of elevated total homocysteine (tHcy) levels for arteriosclerotic vascular disease, estimate the reduction of tHcy by folic acid, and calculate the potential reduction of coronary artery disease (CAD) mortality by increasing folic acid intake. Data Sources. —MEDLINE search for meta-analysis of 27 studies relating homocysteine to arteriosclerotic vascular disease and 11 studies of folic acid effects on tHcy levels. Study Selection and Data Extraction. —Studies dealing with CAD, cerebrovascular disease, and peripheral arterial vascular disease were selected. Three prospective and six population-based case-control studies were considered of high quality. Five cross-sectional and 13 other case-control studies were also included. Causality of tHcy's role in the pathogenesis of vascular disease was inferred because of consistency across studies by different investigators using different methods in different populations. Data Synthesis. —Elevations in tHcy were considered an independent graded risk factor for arteriosclerotic vascular diseases. The odds ratio (OR) for CAD of a 5-μmol/L tHcy increment is 1.6(95% confidence interval [Cl], 1.4 to 1.7) for men and 1.8 (95% Cl, 1.3 to 1.9) for women. A total of 10% of the population's CAD risk appears attributable to tHcy. The OR for cerebrovascular disease (5-μmol/L tHcy increment) is 1.5 (95% Cl, 1.3 to 1.9). Peripheral arterial disease also showed a strong association. Increased folic acid intake (approximately 200 μg/d) reduces tHcy levels by approximately 4 μmol/L. Assuming that lower tHcy levels decrease CAD mortality, we calculated the effect of (1) increased dietary folate, (2) supplementation by tablets, and (3) grain fortification. Under different assumptions, 13 500 to 50 000 CAD deaths annually could be avoided; fortification of food had the largest impact. Conclusions. —A 5-μmol/L tHcy increment elevates CAD risk by as much as cholesterol increases of 0.5 mmol/L (20 mg/dL). Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease. Clinical trials are urgently needed. Concerns about masking cobalamin deficiency by folic acid could be lessened by adding 1 mg of cobalamin to folic acid supplements. ( JAMA . 1995;274:1049-1057)

3,722 citations


Journal ArticleDOI
09 Feb 1995-Nature
TL;DR: It is shown that relB expression also correlates with differentiation of DC in autoimmune infiltrates in situ, and that a mutation disrupting the relB gene results in mice with impaired antigen-presenting cell function, and a syndrome of excess production of granulocytes and macrophages.
Abstract: Dendritic cells (DC) derived from bone marrow are critical in the function of the immune system, for they are the primary antigen-presenting cells in the activation of T-lymphocyte response. Their differentiation from precursor cells has not been defined at a molecular level, but recent studies have shown an association between expression of the relB subunit of the NF-kappa B complex and the presence of DC in specific regions of normal unstimulated lymphoid tissues. Here we show that relB expression also correlates with differentiation of DC in autoimmune infiltrates in situ, and that a mutation disrupting the relB gene results in mice with impaired antigen-presenting cell function, and a syndrome of excess production of granulocytes and macrophages. Thymic UEA-1+ medullary epithelial cells from normal mice show striking similarities to DC and, interestingly, these cells are also absent in relB mutant mice. Taken together, these results suggest that relB is critical in the coordinated activation of genes necessary for the differentiation of two unrelated but phenotypically similar cells (DC and thymic UEA-1+ medullary epithelial cells) and is therefore a candidate for a gene determining lineage commitment in the immune system.

773 citations


Journal ArticleDOI
TL;DR: Within the range currently considered to be normal, the risk for coronary disease rises with increasing plasma homocysteine regardless of age and sex, with no threshold effect.
Abstract: Background High plasma homocysteine is associated with premature coronary artery disease in men, but the threshold concentration defining this risk and its importance in women and the elderly are unknown. Furthermore, although low B vitamin status increases homocysteine, the link between these vitamins and coronary disease is unclear. Methods and Results We compared 304 patients with coronary disease with 231 control subjects. Risk factors and concentrations of plasma homocysteine, folate, vitamin B12, and pyridoxal 5′-phosphate were documented. A homocysteine concentration of 14 μmol/L conferred an odds ratio of coronary disease of 4.8 (P<.001), and 5-μmol/L increments across the range of homocysteine conferred an odds ratio of 2.4 (P<.001). Odds ratios of 3.5 in women and of 2.9 in those 65 years or older were seen (P<.05). Homocysteine correlated negatively with all vitamins. Low pyridoxal 5′-phosphate (<20 nmol/L) was seen in 10% of patients but in only 2% of control subjects (P<.01), yielding an odds...

405 citations


Journal ArticleDOI
13 Dec 1995-JAMA
TL;DR: In men with CAD and elevated LDL-C, Lp(a) levels were dominant correlates of baseline disease severity, its progression, and event rate over 2.5 years.
Abstract: Objective. —To determine if lowering elevated low-density lipoprotein cholesterol (LDL-C) levels offsets the adverse effect of raised lipoprotein(a) (Lp[a]) levels on coronary artery disease (CAD) in men. Design. —Randomized, double-blind, placebo-controlled trial of lipid lowering for CAD. Setting. —Post hoc analysis of the Familial Atherosclerosis Treatment Study. Participants. —A total of 146 men aged 62 years or younger with CAD and apolipoprotein B levels of at least 125 mg/dL. Intervention. —Patients received a Step II Diet and lovastatin (40 mg daily) plus colestipol (30 g daily), niacin (4 g daily) plus colestipol, or placebo (plus colestipol if LDL-C >90th percentile) for 2.5 years. They were grouped by their LDL-C responses: "minimal" if LDL-C decreased by 10% or less from baseline (mean [SD] change, +6% [13%]) and "substantial" if LDL-C decreased more than 10% (mean [SD] change, —40% [16%]). Main Outcome Measure. —Impact of lowering elevated LDL-C on the cardiac event rate (death, myocardial infarction, and revascularization for refractory ischemia) and CAD change associated with elevated Lp(a). Results. —In multivariate analyses, the best correlate of baseline CAD severity was Lp(a) (r=0.30;P Conclusions. —In men with CAD and elevated LDL-C, Lp(a) levels were dominant correlates of baseline disease severity, its progression, and event rate over 2.5 years. However, with substantial LDL-C reductions, persistent elevations of Lp(a) were no longer atherogenic or clinically threatening. This provides a possible direction for treatment in such patients with elevated Lp(a) and LDL-C. (JAMA. 1995;274:1771-1774)

300 citations


Journal Article
TL;DR: Tolerance to LPS is not a passive process that occurs in an exhausted cell; rather, it is a well-controlled active response that is orchestrated in order to prevent excessive inflammation.
Abstract: Stimulation with lipopolysaccharide (LPS) will lead to the expression of a variety of genes in CD14+ monocytes/macrophages, but also in CD14- fibroblasts and endothelial cells. Upon secondary LPS stimulation, the expression of many of these genes is only minimal. This applies to several cytokines, most prominent among them tumor necrosis factor (TNF). Induction of tolerance appears to require some degree of activation in the primary exposure, as partial structures of LPS induce tolerance, as long as they are able to activate cells. Studies on the mechanism of unresponsiveness in tolerant cells show that the CD14 LPS receptor is not downregulated but may even increase in number at the cell surface. Furthermore, this receptor appears to be functional in that mobilization of the transcription factor NF-kappa B does still occur. This NF-kappa B complex is composed primarily of p50p50 homodimers, that bind to the respective DNA motif in the promoter region of many proinflammatory genes, thereby blocking transactivation. However, LPS tolerance does not lead to downregulation of all kinds of response, as some genes are even increased in expression upon secondary stimulation; these include p50 of NF-kappa B, TNF receptor type II and interleukin-10 (IL-10). These gene products are involved in the downregulation of proinflammatory cytokines and may thereby be instrumental in the unresponsiveness observed. Hence, tolerance to LPS is not a passive process that occurs in an exhausted cell; rather, it is a well-controlled active response that is orchestrated in order to prevent excessive inflammation. Important modulators of tolerance are glucocorticoids, which result in a general decrease of gene expression, and interferon-gamma (IFN-gamma), which enhances expression of proinflammatory genes. LPS tolerance does occur in some clinical settings, as in hemodialysis, in sepsis and in patients treated repeatedly with LPS or other monocyte activators. In fact, LPS tolerance may be exploited for prophylaxis of severe sepsis in patients at risk.

298 citations


Journal ArticleDOI
K. Fred Gey1
TL;DR: In male Americans, the relative risk of cardiovascular diseases was substantially reduced by daily intake of >130 mg of vitamin C, >100 IU of vitamin E, and by >9 mg of β-carotene, but only in smokers—in comparison with a suboptimal intake that very probably permits only sub optimal plasma levels.
Abstract: The antioxidant hypothesis postulates that suboptimal levels of principal antioxidant micronutrients are hitherto underrated risk factors for cardiovascular diseases. Complementary observational data consistently suggest optimal, i.e., potentially protective plasma levels of approximately >50 μmol/L of vitamin C, >30 μmol/L of lipid-standardized vitamin E (α-tocopherol/cholesterol ratio >5.2 μmol/mmol), and >0.4 μmol/L β (>0.5 μmol/L total)-carotene. Relative risks are doubled at >25 to 50% lower values. Suboptimal levels of each factor increase the risk singly, or in combination risk increases multiplicatively. They can be stronger predictors of coronary heart disease than classical risk factors such as hypercholesterolemia and hypertension, at least in Northern Europe. In male Americans, the relative risk of cardiovascular diseases was substantially reduced by daily intake of >130 mg of vitamin C, >100 IU of vitamin E (100 mg of d,l- or 74 mg of d-α-acetyl-tocopherol) in all subjects, and by >9 mg of β-carotene, but only in smokers—in comparison with a suboptimal intake that very probably permits only suboptimal plasma levels. Antioxidant deficits can be avoided by “prudent diets” rich in fruits/vegetables, and net vitamin E (high vitamin E/polyunsaturated fatty acids ratio) as is common in European communities where premature cardiovascular death is low. These essential antioxidants may be crucial components of such protective diets but other, presumably synergistic constituents await evaluation, e.g., carotenoids other than β-carotene, phenols/bioflavonoids, minerals such as potassium and selenium, fibers, mono- and n-3 polyenic fatty acids, and oxygen-sensitive B vitamins such as folate.

150 citations


Journal Article
TL;DR: The data suggest that distinct allergens represent a new class of so far unknown agents that induce NH-kappa B binding activity that subsequently modulates transcription of cytokine and adhesion molecule genes and include direct effects on other immunocompetent cells such as the endothelium.
Abstract: Nickel chloride (NiCl2) and cobalt chloride (CoCl2), two haptens frequently leading to contact hypersensitivity in industrialized countries, induce gene transcription of adhesion molecules ICAM-1, VCAM-1, and E-selectin in endothelial cells. In search of transcriptional mechanisms underlying their gene-inductive effects, we studied the capacity of both haptens to activate nuclear factor (NF)-kappa B, a transcription factor involved in inducible expression of adhesion molecules. Using electrophoretic mobility shift assays, a strong increase of NF-kappa B DNA binding was detected after stimulation of HUVEC with NiCl2 or CoCl2. Supershift analysis using antisera against p50 and p65 confirmed the authenticity of the induced NF-kappa B complex. Neutralizing Abs against TNF-alpha and IL-1 did not inhibit metal hapten-induced activation of NF-kappa B, thus ruling out action via an indirect autocrine pathway. In addition, NiCl2-induced activation of NF-kappa B and adhesion molecule expression was inhibited by the antioxidant pyrrolidine dithiocarbamate, indicating the involvement of redox-dependent mechanisms. Furthermore, NiCl2 was found to induce dose-dependency mRNA production and protein secretion of the NF-kappa B-controlled proinflammatory cytokine IL-6. Our data suggest that distinct allergens represent a new class of so far unknown agents that induce NH-kappa B binding activity that subsequently modulates transcription of cytokine and adhesion molecule genes. Thus, pathomechanisms leading to contact hypersensitivity to NiCl2 and CoCl2 appear to involve not only Ag-specific Langerhans- and T cell-dependent events but also include direct effects on other immunocompetent cells such as the endothelium.

131 citations


Journal ArticleDOI
TL;DR: The widespread vitamin B-12 deficiency was probably caused by malabsorption, perhaps exacerbated by low dietary intake and, for young children, maternal depletion of the vitamin.

126 citations


Journal ArticleDOI
TL;DR: The results urge caution in the use of herbimycin A as a specific tyrosine kinase inhibitor and suggest that the development of agents that selectively modify p50 may have potential as a means of inhibiting NF-κB-dependent gene transcription.

118 citations


Journal ArticleDOI
TL;DR: Segments in the LHCP polypeptide that are essential for the formation of stable LHCII trimers are identified by analyzing N- and C-terminal deletion mutants of LHCP and mutants carrying point-specific amino acid exchanges.
Abstract: The major light-harvesting complex (LHCII) of photosystem II can be reconstituted in its native, trimeric form starting from its apoprotein light-harvesting chlorophyll a/b-binding protein (LHCP), pigments, and thylakoid lipids. In this paper we identify segments in the LHCP polypeptide that are essential for the formation of stable LHCII trimers by analyzing N- and C-terminal deletion mutants of LHCP and mutants carrying point-specific amino acid exchanges. C-terminal deletions that do not abolish pigment binding to LHCP do not affect trimerization either. By contrast, on the N-terminus of LHCP, where as many as 61 amino acids can be deleted without significant effects on pigment binding, only 15 amino acids are dispensible for LHCII trimer formation. This indicates that structural elements between amino acids 16 and 61 are involved in the stabilization of LHCII trimers but not monomers. Closer inspection of this protein domain in a more detailed mutation analysis revealed that amino acids W16 and/or Y17 as well as R21 are essential for the formation of LHCII trimers. These amino acids are conserved in virtually all known sequences of LHCII apoproteins but only in some of the minor chlorophyll a/b complexes. Possible functions of the crucial residues are discussed.

118 citations


Journal ArticleDOI
TL;DR: A mathematical prediction model is developed that can predict that plasma homocysteine concentrations will approach a normal frequency distribution with a 95% reference range (mean +/- 2 SD) of 4.9-11.7 mumol/L, provided the vitamin status of the study population is improved.
Abstract: Because high plasma concentrations of homocysteine constitute an enhanced risk for premature coronary heart disease, it is necessary to establish a reference range for normal concentrations of plasma homocysteine. The frequency distribution of plasma homocysteine concentrations tails to the right, and the nonparametric approach is unsatisfactory for defining a normal plasma homocysteine reference range. By using subjects' responses to appropriate vitamin supplementation, we developed a mathematical prediction model to calculate the plasma homocysteine concentration that could be expected for each individual treated with a vitamin supplement. With this model, we can predict that plasma homocysteine concentrations will approach a normal frequency distribution with a 95% reference range (mean +/- 2 SD) of 4.9-11.7 mumol/L, provided the vitamin status of the study population is improved.

Journal ArticleDOI
TL;DR: Chronic mild malnutrition appears to be a necessary but insufficient condition for producing behavioral deficits, and suggestions for future research directions include an emphasis on interactions between nutrients and between specific psychosocial and nutritional risk factors.
Abstract: The present review focuses on the relation to human behavior and development of anthropometric or dietary indexes of mild-to-moderate malnutrition. The primary goal of the review is to integrate previous research findings with current findings from correlational studies conducted over the past decade. From this integration, the following conclusions may be drawn: 1) Chronic, mild postnatal malnutrition is associated with a variety of cognitive and behavioral deficits across the life span. The role of prenatal malnutrition in this process is less clear. 2) To understand the role chronic mild malnutrition plays in behavior and development, it is necessary to move beyond protein-calorie deficits to consider the role of intake of animal source foods and specific micronutrients such as iron, zinc and B vitamins. 3) Chronic mild malnutrition is embedded in a host of other biological and psychosocial risk factors. As a result, chronic mild malnutrition appears to be a necessary but insufficient condition for producing behavioral deficits. 4) The salience of chronic mild malnutrition as a risk factor is accentuated when other psychosocial-contextual risk factors are also present or when multiple low-level nutrient deficits are interacting. Suggestions for future research directions include an emphasis on interactions between nutrients and between specific psychosocial and nutritional risk factors; the ways in which individual (e.g., gender) or cultural characteristics can moderate nutrition development relations; and a broader range of populations, such as sibling or elderly caregivers, and outcome variables, such as social-emotional development, temperament and mental health.

Journal ArticleDOI
TL;DR: Thiamine, but none of the other B-vitamins, was effective both in reversal and prevention of the clinical signs and mortality associated with the swim-up syndrome.

Journal ArticleDOI
TL;DR: The results indicate that goldfish oocytes and Xenopus oocytes employ different mechanisms of MPF activation during oocyte maturation, although the final molecular structure of the active MPF (cdc2 bound to cyclin B and phosphorylated on Thr161) is identical.

Journal ArticleDOI
TL;DR: The first mutation that causes profound biotinidase deficiency occurs in a distinct region of the gene that encodes the putative signal peptide, which appears to be a common cause of biotinIDase deficiency in symptomatic children.
Abstract: Biotinidase deficiency is an autosomal recessive inherited disorder that is characterized by neurological and cutaneous symptoms. Biotinidase-deficient children cannot recycle endogenous biotin, an essential water-soluble B vitamin. Biotin is covalently attached to epsilon-amino groups of lysyl residues of four carboxylases. These carboxylases are subsequently degraded to biocytin (biotin-epsilon-lysine). Biotinidase cleaves biocytin to biotin and lysine, thereby completing the biotin cycle. The symptoms of biotinidase deficiency can be resolved or prevented by treatment with biotin. Therefore, it is important that biotinidase deficiency is diagnosed early so that permanent neurological damage can be prevented. Many states and countries currently perform newborn screening for biotinidase deficiency. We have recently isolated and characterized the cDNA for normal human biotinidase and localized the gene to chromosome 3p25 (ref. 9). We have now identified the first mutation that causes profound biotinidase deficiency. It occurs in a distinct region of the gene that encodes the putative signal peptide. Fifty percent of symptomatic children studied have a 7-bp deletion coupled with a 3-bp insertion in at least one of their alleles of the biotinidase gene. This mutation appears to be a common cause of biotinidase deficiency in symptomatic children.

Journal Article
TL;DR: It is demonstrated that triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in HIV-infected human monocytic cells and that enhanced viral replication is associated with C3 receptor-mediated nuclear translocation of the NF-kappa B complex.
Abstract: Monocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time. Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro. The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B (p50/p65), which binds to a specific sequence in the HIV-long terminal repeat. The present study demonstrates that triggering of complement receptors CR1 (CD35) and CR3 (CD11b/CD18) enhances viral replication in HIV-infected human monocytic cells. Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti-CR1 or anti-CR3 Abs or with C3 fragments. Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS. We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50/p65 in infected cells. Translocation of NF-kappa B p50/p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors. The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha. TNF-alpha did not mediate the translocation of NF-kappa B p50/p65 induced by triggering of complement receptors. Taken together, these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor-mediated nuclear translocation of the NF-kappa B complex.

Journal ArticleDOI
TL;DR: Infant anthropometry at 13-17 weeks post- partum was significantly affected by pre-natal weight gain and a number of maternal blood nutrients in pregnancy and post-partum, and nutrition education programmes and enrichment of the staple food with iron, zinc, calcium, and the B vitamins should be considered.
Abstract: OBJECTIVE: To determine by biochemical methods the nutritional status of pre- and post-natal Turkish women and its relationship with offspring anthropometry. DESIGN: Longitudinal study. SETTING: Health centres in Istanbul and Izmit, research department and university hospital laboratories. SUBJECTS: Randomly selected group of women attending health centres at 13-17 weeks gestation (n = 130); same sample of women at 28-32 weeks gestation (n = 88) and 13-17 weeks post-partum (n = 95); offspring at 13-17 weeks post-partum (n = 90). INTERVENTIONS: Blood samples taken from mothers at all three stages and analysed for ferritin, iron, zinc, calcium, alkaline phosphatase, total protein, albumin, vitamins B2, B6, B12, A, E, beta-carotene and folate levels; questionnaire completed for recording medical and socio-demographic background. Anthropometric measurements taken from mothers and offspring. RESULTS: High percentages of subjects were at risk for deficiencies of vitamin B12 (48.8%) and folate (59.7%) in early pregnancy; ferritin (52.3%), zinc (72.3%), vitamin B2 (38.8%), vitamin B12 (80.9%), and folate (76.4%) during late pregnancy; and ferritin (39.0%), vitamins B2 (43.1%), B6 (36.4%), B12 (60.0%), and folate (73.3%) at the post-partum stage. Bone loss was indicated in 55.0% and 80.0% of the subjects in late pregnancy and post-partum respectively. Haematocrit in later pregnancy correlated strongly with prenatal body fat (P < 0.001). Infant anthropometry at 13-17 weeks post-partum was significantly affected by pre-natal weight gain and a number of maternal blood nutrients in pregnancy and post-partum. CONCLUSIONS: Nutrition education programmes and enrichment of the staple food with iron, zinc, calcium, and the B vitamins should be considered.

Journal ArticleDOI
TL;DR: The radical-scavenging ability of BVIT and VLC did not correlate with their effects on microsomal lipid peroxidation, and the stimulation of lipid per oxidation by thiamin, pyridoxine and carnitine suggests that supplementation of large amounts of these compounds may not be desirable.

Journal ArticleDOI
TL;DR: It is concluded that some seaweeds consumed in large amounts can supply adequate amounts of bioavailable vitamin B-12 in the diet of long-term adherents of the "living food diet".
Abstract: The present study examined the vitamin B-12 status in long-term adherents of a strict uncooked vegan diet called the "living food diet." The study was comprised of two parts. In the cross-sectional part, the data on serum vitamin B-12 concentrations and dietary intakes in 21 (1 male, 20 females) long-term adherents (mean 5.2 y, range 0.7-14) of the "living food diet" were compared with those of 21 omnivorous controls matched for sex, age, social status and residence. In the longitudinal part of the study, food consumption data were collected and blood samples were taken from nine "living food eaters" (1 male, 8 females) on two occasions 2 y apart. The cross-sectional study revealed significantly (P < 0.001, paired t test) lower serum vitamin B-12 concentrations in the vegans (mean 193 pmol/L, range 35-408) compared with their matched omnivorous controls (311, 131-482). In the vegan group, total vitamin B-12 intake correlated significantly (r = 0.63, P < 0.01) with serum vitamin B-12 concentration. The vegans consuming Nori and/or Chlorella seaweeds (n = 16) had serum vitamin B-12 concentrations twice as high as those not using these seaweeds (n = 5) (mean 221 pmol/L, range 75-408, vs. 105, 35-252, P = 0.025). In the longitudinal study, six of nine vegans showed slow, but consistent deterioration of vitamin B-12 status over a 2-y observation period. On the basis of these results we conclude that some seaweeds consumed in large amounts can supply adequate amounts of bioavailable vitamin B-12.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: Mitochondrial MMA accumulation secondary to vitamin B-12 deficiency inhibits succinate dehydrogenase and may contribute to various metabolic disorders associated with vitamin B -12 deficiency.
Abstract: Methylmalonic acid (MMA), which accumulates and is excreted in urine in mammals during vitamin B-12 deficiency, has been reported to inhibit succinate dehydrogenase, an enzyme involved in the mitochondrial tricarboxylic acid (TCA) cycle in rat liver. The enzyme inhibition by MMA may lead to various metabolic disorders as well as inhibition of mitochondrial energy generation in vitamin B-12-deficient mammals. To clarify the inhibition of succinate dehydrogenase by MMA in intact rat liver mitochondria, the effect of MMA on mitochondrial respiration was studied. When 6 mmol/L MMA was added to the reaction mixture for measuring mitochondrial respiration with succinate as a substrate, MMA was taken up and accumulated by the mitochondria (34-53 mmol/L). The accumulation of mitochondrial MMA was stimulated by the addition of ADP. Methylmalonic acid competitively inhibited State 3 mitochondrial respiration, and the Ki for the acid was 4.2 +/- 0.4 mmol/L. Although the respiratory control ratio decreased with increasing MMA concentration, the acid did not affect the phosphorus/oxygen ratio. Mitochondrial MMA accumulation secondary to vitamin B-12 deficiency inhibits succinate dehydrogenase and may contribute to various metabolic disorders associated with vitamin B-12 deficiency.

Journal Article
TL;DR: Results indicate a relationship between pyridoxine status and arterial blood pressure in the essential hypertensive patients and suggest vitamin B6 supplementation may be beneficial in these patients.
Abstract: The purpose of this study was to test the effect of vitamin B6 (pyridoxine-HCl, CAS 58-56-0) supplementation on arterial blood pressure in essential hypertension. The trial comprised 9 normotensive subjects (7 men and 2 women, aged between 32-58 years; mean +/- SD, 48 +/- 11) and 20 patients with essential hypertension (16 men and 4 women, aged between 32-69 years; mean +/- SD, 56 +/- 12). The patients were treated during 4 weeks with a single oral dose of pyridoxine (5 mg/kg body weight/day). After a 5-min rest, measurements were made in the supine position. When compared with the normotensive subjects, the hypertensive subject group had a significantly higher systolic and diastolic blood pressure (p < 0.001) and higher level of plasma norepinephrine (NE) (p < 0.01) before pyridoxine treatment. On the other hand, there were no significant differences in plasma epinephrine (E) and heart rates. Treatment of hypertensive patients with pyridoxine significantly reduced systolic (p < 0.01) and diastolic blood pressure (p < 0.005), plasma NE (p < 0.005) and E (p < 0.05) within 4 weeks. However, there was no significant difference in heart rate at the end of pyridoxine treatment. These results indicate a relationship between pyridoxine status and arterial blood pressure in the essential hypertensive patients.

Journal ArticleDOI
TL;DR: The results suggest that the complex formation of cdc2 and cyclin B in response to MIH stimulation at the oocyte surface is a critical step for initiating oocyte maturation in fishes and amphibians, with the exception of Xenopus, in which pre‐MPF already exists in immature oocytes and only its chemical modification is required for MPF activation.
Abstract: Maturation-promoting factor (MPF), a final trigger for initiating oocyte maturation, is activated in the oocyte cytoplasm, in response to maturation-inducing hormone (MIH) secreted from follicle cells surrounding the oocyte. MPF consists of cdc2 and cyclin B. We investigated the state of cdc2 and cyclin B in immature and mature oocytes of fishes (carp, catfish and lamprey) and amphibians (Xenopus, frog [Rana] and toad [Bufo]) using monoclonal antibodies raised against mouse cdc2, which also recognize fish and amphibian cdc2, and monoclonal antibodies against goldfish cyclin B1 and polyclonal antibodies against Xenopus cyclins B1 and B2. Anti-cdc2 and anti-cyclin B immunoblotting of oocyte extracts fractionated by gel filtration chromatography showed that immature oocytes from all of these species with the exception of Xenopus contained only monomeric cdc2. Cyclin B-bound inactive cdc2 (pre-MPF) was present only in immature Xenopus oocytes. Cdc2-cyclin B complex was, however, found in mature oocytes from all the species examined. After the oocyte is induced to mature by MIH, cdc2 should therefore bind to cyclin B in all of these species, except Xenopus. These results suggest that the complex formation of cdc2 and cyclin B in response to MIH stimulation at the oocyte surface is a critical step for initiating oocyte maturation in fishes and amphibians, with the exception of Xenopus, in which pre-MPF already exists in immature oocytes and only its chemical modification is required for MPF activation.

Journal ArticleDOI
01 Feb 1995-Diabetes
TL;DR: It is concluded that standard Nicotinamide offers greater bioavailability than the long-acting formulation tested and that the metabolic clearance pathways of nicotinamide are saturated at the doses currently used in human trials.
Abstract: Nicotinamide, a derivative of the B vitamin niacin, is currently under trial for the prevention of insulin-dependent diabetes mellitus after success in the NOD mouse. However, the dose, route of administration, and formulation of nicotinamide given to humans is quite different from those used successfully in animals, and the aim of this study was to investigate the plasma pharmacokinetics of oral nicotinamide in humans in two doses and in two different formulations (standard and the long-acting Enduramide). There were no significant differences in the kinetics of the low dose of standard nicotinamide (2.5 mg/kg) and low-dose Enduramide (6.7 mg/kg) in young adult men. Nonlinear kinetics were found with both formulations at higher doses, e.g., a 10-fold increase in the dose of the standard nicotinamide produced a 62-fold increase in the area under the plasma concentration-time curve (AUC). The high dose of standard nicotinamide (25 mg/kg body wt) produced a mean peak plasma concentration 75% higher than that achieved with the sustained release nicotinamide preparation given in a dose similar to that currently used in prevention trials (2 g identical to 26.6 mg/kg body wt for a 75-kg subject). The AUC was also significantly greater with the standard formulation, indicating a higher bioavailability. Long-term plasma levels for high doses of both formulations were modeled from the single-dose kinetics by computer program. The AUC for standard nicotinamide was 1.7 times higher than that for Enduramide.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
06 Dec 1995-JAMA
TL;DR: Consumption of supplemental folic acid in addition to folates contained in the usual diet can prevent half to three quarters of cases of spina bifida and anencephaly, two of the most common and severe birth defects.
Abstract: Many Americans do not consume enough of folic acid, a B vitamin. In the last 5 years, it has been shown that increasing folate consumption with folic acid supplements will prevent some birth defects and may reduce the risk of occlusive vascular disease.1-3Consumption of supplemental folic acid in addition to folates contained in the usual diet can prevent half to three quarters of cases of spina bifida and anencephaly (SBA), two of the most common and severe birth defects. Furthermore, for many people increased consumption of folic acid substantially lowers the plasma concentration of homocysteine, an emerging risk factor for occlusive cardiovascular disease. See also p 1698. Folates are a class of compounds with the vitamin properties of folic acid (pteroylmonoglutamic acid). Folic acid is a folate that is used in vitamin supplements, and a number of other folate compounds occur naturally in foods, such as green vegetables.

Journal Article
TL;DR: The combination of a healthy diet supplemented with antioxidants and phytonutrients may be useful in the prevention and promotion of optimum cardiovascular health.
Abstract: The heart is the most susceptible of all the organs to premature aging and free radical oxidative stress. Clinical research has clearly documented the role of free radical damage and the progression of numerous degenerative diseases, particularly cardiovascular disease. This may be the result of acute ischemia-reperfusion injury, endothelial damage of hyperhomocysteinemia, as well as chronic oxidative damage secondary to lipid peroxidation. Fortunately, although highly responsive, and therefore vulnerable to the effects of oxidative stress, the heart is also receptive to the benefits of targeted phytonutrients, antioxidants, and nutritionals. The effects of antioxidant nutrients have been extensively evaluated in epidemiological, population, and clinical studies. Phytonutrients such as the natural flavonoids and carotenoids found in fresh fruits and vegetables or vitamins C, E, and beta-carotene have powerful antioxidant effects. In addition, minerals like selenium and nutrients such as coenzyme Q10 will minimize free radical risk and optimize a favorable outcome from the ubiquitous presence of oxidative stress on the cardiovascular system. The B complex, particularly folic acid, B12, and B6 are also essential in the prevention of hyperhomocysteinemia, another major risk factor for the circulatory system. Measures to minimize accumulation of heavy metals in the body, especially iron and copper, which are capable of initiating adverse free radical reactions, will also help to assuage oxidative stress. Thus, the combination of a healthy diet supplemented with antioxidants and phytonutrients may be useful in the prevention and promotion of optimum cardiovascular health.

Journal ArticleDOI
TL;DR: Data from the present study indicate that plasma B12 and ferritin levels are low in a group of pregnant adolescents and appear to be associated with a high prevalence of hypersegmented neutrophils.

Journal ArticleDOI
TL;DR: The relationship between vitamin status and clinical indices in 13 low-weight patients with anorexia or bulimia nervosa at admission to a treatment program and at discharge was examined.
Abstract: Vitamin abnormalities in eating disorder patients may contribute to altered neuropsychological status and the development of sequelae such as cognitive dysfunction. We examined the relationship between vitamin status and clinical indices in 13 low-weight patients with anorexia or bulimia nervosa at admission to a treatment program. Vitamin status was evaluated again at discharge (2-6 weeks later) in nine of these patients. Four patients (31%) initially had erythrocyte enzyme activity indices suggesting deficiency for riboflavin and for vitamin B-6. Patients with biochemical evidence for riboflavin deficiency had lower relative body weight than those with normal riboflavin status (p 5.69 mmol/L). Plasma retinol concentrations were within the normal range. Plasma alpha-tocopherol concentrations were positively associated with serum albumin (p < .04), cholesterol (p < .0003), and total lipids (p < .0003), and were inversely associated with body mass index (p < .04). At discharge, thiamin, riboflavin and vitamin B-6 status indicators were normal in all cases examined. Suboptimal vitamin status is common in eating disorder patients but is normalized with dietary intervention and nutritional rehabilitation.

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TL;DR: The largely overlooked epidemic of neuropathy observed in Cuba during 1992 and 1993, affecting more than 50 000 patients, was the largest epidemic of neurologic disease in this century and described the symptoms and treatment of patients.
Abstract: Political decisions may cause disease During 1992 and 1993, an epidemic of neuropathy in Cuba--largely overlooked by US physicians--affected more than 50,000 persons and caused optic neuropathy, deafness, myelopathy, and sensory neuropathy Patients with the neurologic disease responded to B group vitamins, and oral vitamin supplementation of the population curbed the epidemic Dietary restrictions and excessive carbohydrate intake were the immediated cause of the epidemic; however, the primary cause might have been political Political changes in eastern Europe had major repercussions on Cuba's economy and food supply In turn, these changes compounded the effects of internal political decisions in the island, leading toward isolationism and economic dependence on the former Soviet Union Also, for more than 30 years, the United States has maintained an economic embargo against Cuba In 1992, the US embargo was tightened by the Torricelli amendment (or the Cuba Democracy Act), which prohibited third-country subsidiaries of US companies from trading with Cuba and prevented food and medicines from reaching the island; this amendment produced a virtual economic blockade Penuries resulting from all these political events resulted in the largest epidemic of neurologic disease in this century Physicians may need to use their influence to modify political decisions when these decisions result in adverse health consequences The American Academy of Neurology has issued a plea to encourage physicians and other health personnel to support efforts leading to lifting of the US embargo against Cuba for humanitarian reasons

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TL;DR: A female infant who presented with developmental delay at 12 months was recognized to have macrocytic anemia and methylmalonicaciduria associated with vitamin B 12 deficiency, and it appears that this deficiency developed after she was exclusively breast-fed by a mother with inadequate breast-milk vitamin B12 levels secondary to gastric bypass surgery and a semivegetarian diet.
Abstract: Vitamin B 12 (cobalamin) deficiency is uncommon in infancy. It may be associated with (1) inadequate dietary intake (eg, breast-fed infants of strict vegetarian [vegan] mothers); (2) congenital defects in intestinal absorption and transportation (eg, absence or malfunction of gastric intrinsic factor, selective ileal transport defect, or transcobalamin II deficiency); or (3) defects in intracellular processing. 1,2 The main clinical feature of vitamin B 12 deficiency is megaloblastic anemia. We herein describe a female infant who presented with developmental delay at 12 months. She was recognized to have macrocytic anemia and methylmalonicaciduria associated with vitamin B 12 deficiency. Her anemia and developmental status improved after parenteral administration of cyanocobalamin. It appears that this deficiency developed after she was exclusively breast-fed by a mother with inadequate breast-milk vitamin B 12 levels secondary to gastric bypass surgery and a semivegetarian diet. Report of a Patient. A 12-month-old female infant was referred for

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TL;DR: Results showed that a PP diet does not elevate the vitamin B-6 requirement over that required for an AP diet given the high amount of dietary protein used in this study, and it was found that 0.015 mg vitaminB-6/g protein intake normalized most biochemical indexes of vitamin B -6 status (including those indicative of functional status), and that0.020 mg/gprotein normalized all biochemical measures except total urinary vitamin B,6.