Showing papers on "B vitamins published in 1998"
TL;DR: The DRIs represent the new approach adopted by the Food and Nutrition Board to providing quantitative estimates of nutrient intakes for use in a variety of settings, replacing and expanding on the past 50 years of periodic updates and revisions of the Recommended Dietary Allowances.
Abstract: Dietary Reference Intakes (DRIs) represent the new approach adopted by the Food and Nutrition Board to providing quantitative estimates of nutrient intakes for use in a variety of settings, replacing and expanding on the past 50 years of periodic updates and revisions of the Recommended Dietary Allowances (RDAs). The DRI activity is a comprehensive effort undertaken to include current concepts about the role of nutrients and food components in long-term health, going beyond deficiency diseases. The DRIs consist of 4 reference intakes: the RDA, which is to be used as a goal for the individual; the Tolerable Upper Intake Level (UL), which is given to assist in advising individuals what levels of intake may result in adverse effects if habitually exceeded; the Estimated Average Requirement (EAR), the intake level at which the data indicate that the needs for 50% of those consuming it will not be met; and the Adequate Intake (AI), a level judged by the experts developing the reference intakes to meet the needs of all individuals in a group, but which is based on much less data and substantially more judgment than that used in establishing an EAR and subsequently the RDA. When an RDA cannot be set, an AI is given. Both are to be used as goals for an individual. Two reports have been issued providing DRIs for nutrients and food components reviewed to date: these include calcium and its related nutrients: phosphorus, magnesium, vitamin D, and fluoride; and most recently, folate, the B vitamins, and choline. The approaches used to determine the DRIs, the reference values themselves, and the plans for future nutrients and food components are discussed. J Am Diet Assoc. 1998;98: 699–706 .
5,266 citations
01 Jan 1998
TL;DR: The second in a series that presents a comprehensive set of reference values for nutrient intakes for healthy U.S and Canadian populations is presented in this article, which considers evidence concerning the prevention of disease and developmental disorders along with more traditional evidence of sufficient nutrient intake; and examines data about choline, a food component that has not been considered essential in the human diet.
Abstract: This report is the second in a series that presents a comprehensive set of reference values for nutrient intakes for healthy U.S and Canadian populations. It is a product of the Food and Nutrition Board of the Institute of Medicine (IOM) working in cooperation with scientists from Canada.The report establishes a set of reference values for the B vitamins and choline to replace previously published Recommended Dietary Allowances (RDAs) for the United States and Recommended Nutrient Intakes (RNIs) for Canada. It considers evidence concerning the prevention of disease and developmental disorders along with more traditional evidence of sufficient nutrient intake; and examines data about choline, a food component that in the past has not been considered essential in the human diet. Although the reference values are based on data, the data were often scanty or drawn from studies that had limitations in addressing the question. Thus, scientific judgment was required in setting the reference values. The reasoning used is described for each nutrient in Chapters 4 through 12. Evidence concerning the use of these nutrients for the amelioration or cure of disease or disability was not considered because that was beyond the project's scope of work.
1,803 citations
TL;DR: This novel NID DM syndrome with reduced pancreatic insulin stores, which is similar to human NIDDM in that it has a significant response to glucose (although abnormal in kinetics) and preserved sensitivity to tolbutamide, may provide a particularly advantageous tool for pharmacological investigations of new insulinotropic agents.
Abstract: We took advantage of the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create a new experimental diabetic syndrome in adult rats that appears closer to NIDDM than other available animal models with regard to insulin responsiveness to glucose and sulfonylureas. Among the various dosages of nicotinamide tested in 3-month-old Wistar rats (100-350 mg/kg body wt), the dosage of 230 mg/kg, given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded a maximum of animals with moderate and stable nonfasting hyperglycemia (155 +/- 3 vs. 121 +/- 3 mg/dl in controls; P < 0.05) and 40% preservation of pancreatic insulin stores. We also evaluated beta-cell function both in vitro and in vivo 4-9 weeks after inducing diabetes. In the isolated perfused pancreas, insulin response to glucose elevation (5-11 mmol/l) was clearly present, although significantly reduced with respect to controls (P < 0.01). Moreover, the insulin response to tolbutamide (0.19 mmol/l) was similar to that observed in normal pancreases. Perfused pancreases from diabetic animals also exhibited a striking hypersensitivity to arginine infusion (7 mmol/l). In rats administered STZ plus nicotinamide, intravenous glucose tolerance tests revealed clear abnormalities in glucose tolerance and insulin responsiveness, which were interestingly reversed by tolbutamide administration (40 mg/kg i.v.). In conclusion, this novel NIDDM syndrome with reduced pancreatic insulin stores, which is similar to human NIDDM in that it has a significant response to glucose (although abnormal in kinetics) and preserved sensitivity to tolbutamide, may provide a particularly advantageous tool for pharmacological investigations of new insulinotropic agents.
693 citations
TL;DR: The prospective findings add uncertainty to conclusions derived mostly from cross-sectional studies that tHcy is a major, independent, causative risk factor for CHD and point more strongly to the possibility that vitamin B6 offers independent protection.
Abstract: Background—Elevated plasma total homocysteine (tHcy), low B-vitamin intake, and genetic polymorphisms related to tHcy metabolism may play roles in coronary heart disease (CHD). More prospective studies are needed. Methods and Results—We used a prospective case-cohort design to determine whether tHcy-related factors are associated with incidence of CHD over an average of 3.3 years of follow-up in a biracial sample of middle-aged men and women. Age-, race-, and field center–adjusted CHD incidence was associated positively (P<0.05) with tHcy in women but not men, and CHD was associated negatively (P<0.05) with plasma folate (women only), plasma pyridoxal 5′-phosphate (both sexes), and vitamin supplementation (women only). However, after accounting for other risk factors, only plasma pyridoxal 5′-phosphate was associated with CHD incidence; the relative risk for the highest versus lowest quintile of pyridoxal 5′-phosphate was 0.28 (95% CI=0.1 to 0.7). There was no association of CHD with the C677T mutation of...
639 citations
TL;DR: In this paper, the authors explored the interrelationships between homocysteine, B vitamins, and vascular diseases and evaluated the role of these vitamins as risk factors for atherosclerosis.
Abstract: Background—A high plasma homocysteine concentration is a risk factor for atherosclerosis, and circulating concentrations of homocysteine are related to levels of folate and vitamin B6. This study was performed to explore the interrelationships between homocysteine, B vitamins, and vascular diseases and to evaluate the role of these vitamins as risk factors for atherosclerosis. Methods—In a multicenter case-control study in Europe, 750 patients with documented vascular disease and 800 control subjects frequency-matched for age and sex were compared. Plasma levels of total homocysteine (before and after methionine loading) were determined, as were those of red cell folate, vitamin B12, and vitamin B6. Results—In a conditional logistic regression model, homocysteine concentrations greater than the 80th percentile for control subjects either fasting (12.1 μmol/L) or after a methionine load (38.0 μmol/L) were associated with an elevated risk of vascular disease independent of all traditional risk factors. In a...
529 citations
TL;DR: Intervention studies are urgently needed to determine if lowering homocysteine is effective in decreasing the morbidity and mortality of cardiovascular disease.
Abstract: On the basis of recent retrospective and prospective studies, it is now widely accepted that increased total plasma homocysteine is a risk factor for cardiovascular disease. Impaired enzyme function as a result of genetic mutation or deficiency of the essential B vitamins folic acid, B12, and B6 can lead to hyperhomocysteinemia. Oxidized forms of homocysteine account for 98-99% of total plasma homocysteine. Although there is uncertainty as to whether increased homocysteine is causal or merely a proxy for cardiovascular disease, several lines of evidence suggest that it may play a role in atherothrombotic disease. Homocysteine appears to alter the anticoagulant properties of endothelial cells to a procoagulant phenotype. Mildly increased homocysteine causes dysfunction of the vascular endothelium. Folic acid effectively lowers homocysteine concentration in the plasma. Intervention studies are urgently needed to determine if lowering homocysteine is effective in decreasing the morbidity and mortality of cardiovascular disease.
431 citations
TL;DR: Dietary Reference Intakes represent the new approach adopted by the Food and Nutrition Board to providing quantitative estimates of nutrient intakes for use in a variety of settings, replacing and expanding on the past 50 years of periodic updates and revisions of the Recommended Dietary Allowances.
Abstract: Dietary Reference Intakes (DRIs) represent the new approach adopted by the Food and Nutrition Board to providing quantitative estimates of nutrient intakes for use in a variety of settings, replacing and expanding on the past 50 years of periodic updates and revisions of the Recommended Dietary Allowances (RDAs) The DRI activity is a comprehensive effort undertaken to include current concepts about the role of nutrients and food components in long-term health, going beyond deficiency diseases The DRIs consist of 4 reference intakes: the RDA, which is to be used as a goal for the individual; the Tolerable Upper Intake Level (UL), which is given to assist in advising individuals what levels of intake may result in adverse effects if habitually exceeded; the Estimated Average Requirement (EAR), the intake level at which the data indicate that the needs for 50% of those consuming it will not be met; and the Adequate Intake (AI), a level judged by the experts developing the reference intakes to meet the needs of all individuals in a group, but which is based on much less data and substantially more judgment than that used in establishing an EAR and subsequently the RDA When an RDA cannot be set, an AI is given Both are to be used as goals for an individual Two reports have been issued providing DRIs for nutrients and food components reviewed to date: these include calcium and its related nutrients: phosphorus, magnesium, vitamin D, and fluoride; and most recently, folate, the B vitamins, and choline The approaches used to determine the DRIs, the reference values themselves, and the plans for future nutrients and food components are discussed
407 citations
TL;DR: The role of B vitamins in the aetiology and treatment of neuropsychiatric syndromes associated with alcohol misuse, with particular emphasis on the Wernicke Korsakoff syndrome is considered.
Abstract: Alcohol misuse and alcohol withdrawal are associated with a vanety of neuropsychiat ric syndromes, some of which are associated with significant morbidity and mortality B vitamin deficiency is known to contribute to the aetiology of a number of these syndromes, and B vitamin supplementation thus plays a significant part in prophylaxis and treatment. In particular, the Wemicke-Korsakoff syndrome (WKS), due to thiamine deficiency, is a common condition in association with alcohol misuse, and is associated with high morbidity and mortality. Nicotinamide deficiency may result in a rarer condition, alcoholic pellagra encephalopathy, which often has a similar clinical presentation to WKS. This review considers the role of B vitamins in the aetiology and treatment of neuropsychiat ric syndromes associated with alcohol misuse, with particular emphasis on WKS.
257 citations
TL;DR: Niaspan may be an equivalent or better alternative to plain niacin at moderate doses in the management of hyperlipidemia and has comparable efficacy, a lower incidence of flushing, a lesser uric acid rise, and an equivalent hepatic enzyme effect than 500 mg thrice-daily plain niakin inhyperlipidemic subjects.
Abstract: This study compared the efficacy and safety of a once-a-night, time-release niacin formulation, Niaspan (Kos Pharmaceuticals, Miami Lakes, FL), with plain niacin and placebo for the treatment of primary hypercholesterolemia. The study was conducted in nine academic lipid research clinics in a randomized, double-blind design. Niaspan 1.5 g at bedtime was compared with plain niacin 1.5 g/d after 8 weeks and 3.0 g/d after 16 weeks in divided doses and with placebo. A total of 223 hypercholesterolemic adult men and women participated. Compared with placebo at 8 weeks, Niaspan versus plain niacin at 1.5 g/d showed comparable efficacy, comparably lowering total cholesterol (C) (8%/8%), triglycerides (16%/18%), low-density lipoprotein (LDL)-C (12%/12%), apolipoprotein (apo B) (12%/12%), apo E (9%/7%), and lipoprotein(a) [Lp(a)] (15%/11%), and raising high-density lipoprotein (HDL)-C (20%/17%), HDL2-C (37%/33%), HDL3-C (17%/16%), and apo A-I (8%/6%) (P < or = .05 in all instances). After 16 weeks, the Niaspan effect on LDL-C and triglyceride was unchanged while the plain niacin effect approximately doubled. At equal doses of 1.5 g/d of Niapan versus plain niacin, respectively, AST increased 5.0% versus 4.8% (difference not significant [NS]), fasting plasma glucose increased 4.8% versus 4.5% (NS), and uric acid concentrations increased less, 6% versus 16% (P=.0001). Flushing events were more frequent with plain niacin versus Niaspan (1,905 v 576, P < .001). Flushing severity was slightly greater with Niaspan, but still well tolerated. In conclusion, Niaspan 1.5 g hour of sleep (hs) has comparable efficacy, a lower incidence of flushing, a lesser uric acid rise, and an equivalent hepatic enzyme effect than 500 mg thrice-daily plain niacin in hyperlipidemic subjects. Niaspan may be an equivalent or better alternative to plain niacin at moderate doses in the management of hyperlipidemia.
244 citations
TL;DR: Findings indicate that 14-3-3 proteins act as negative regulators of Cdc25 in controlling the G2-M transition.
Abstract: Cdc25, the dual-specificity phosphatase that dephosphorylates the Cdc2-cyclin B complex at mitosis, is highly regulated during the cell cycle. In Xenopus egg extracts, Cdc25 is associated with two isoforms of the 14-3-3 protein. Cdc25 is complexed primarily with 14-3-3epsilon and to a lesser extent with 14-3-3zeta . The association of these 14-3-3 proteins with Cdc25 varies dramatically during the cell cycle: binding is high during interphase but virtually absent at mitosis. Interaction with 14-3-3 is mediated by phosphorylation of Xenopus Cdc25 at Ser-287, which resides in a consensus 14-3-3 binding site. Recombinant Cdc25 with a point mutation at this residue (Cdc25-S287A) is incapable of binding to 14-3-3. Addition of the Cdc25-S287A mutant to Xenopus egg extracts accelerates mitosis and overrides checkpoint-mediated arrests of mitotic entry due to the presence of unreplicated and damaged DNA. These findings indicate that 14-3-3 proteins act as negative regulators of Cdc25 in controlling the G2-M transition.
223 citations
TL;DR: Clinical, electrophysiological, and MRI findings associated with SCD in vitamin B12 deficiency are diverse and should be considered in the differential diagnosis of all spinal cord, peripheral nerve, and neuropsychiatric disorders.
Abstract: OBJECTIVE Vitamin B 12 deficiency is a systemic disease that often affects the nervous system. One of the most prevalent manifestations is subacute combined degeneration (SCD) of the spinal cord. To access the clinical, electrophysiological, and structural abnormalities associated with SCD, a study was conducted in nine patients. METHODS Clinical, electrophysiological (electroneurography, somatosensory and motor evoked potentials), and MRI evaluations were performed in patients before and after treatment. RESULTS The most prominent clinical and electrophysiological findings in all patients were dysfunctions of the posterior column. Corresponding hyperintense lesions in the posterior column of the spinal cord were found in two patients by T2 weighted MRI. Damage to the central motor pathway was identified in four patients. Demyelinating neuropathy was present in one patient and axonal neuropathy in four. All patients showed improvement of their symptoms after treatment with cobalamin. Abnormalities of the spinal cord on MRI disappeared early in recovery. Motor evoked potentials and median somatosensory evoked potentials typically normalised after treatment, whereas tibial somatosensory evoked potentials remained abnormal in most patients. CONCLUSIONS Clinical, electrophysiological, and MRI findings associated with SCD in vitamin B 12 deficiency are diverse. Thus vitamin B 12 deficiency should be considered in the differential diagnosis of all spinal cord, peripheral nerve, and neuropsychiatric disorders.
TL;DR: It is concluded that in this subgroup of diabetes-prone individuals at very high risk and with an assumed rapid disease progression, nicotinamide treatment did not cause a major decrease or delay of diabetes development.
Abstract: On the basis of the positive outcome of animal experiments, several large placebo-controlled trials are underway and aiming for the first time at the prevention of an immune-mediated disease, type 1 diabetes. The first of these trials, The Deutsche Nicotinamide Intervention Study (DENIS), evaluated the clinical efficacy of high doses of nicotinamide in children at high risk for IDDM. Nicotinamide has been shown to protect beta-cells from inflammatory insults and to improve residual beta-cell function in patients after onset of IDDM. Individuals at high risk for developing IDDM within 3 years were identified by screening the siblings (age 3-12 years) of patients with IDDM for the presence of high titer (> or =20 Juvenile Diabetes Foundation [JDF] U) islet cell antibodies. Probands (n = 55) were randomized into placebo and nicotinamide (slow release, 1.2 g x m(-2) x day(-1)) receiving groups and followed prospectively in a controlled clinical trial using a sequential design. Rates of diabetes onset were similar in both groups throughout the observation period (maximum 3.8 years, median 2.1 years). This sequential design provides a 10% probability of a type II error against a reduction of the cumulative diabetes incidence at 3 years from 30 to 6% by nicotinamide. The trial was terminated when the second sequential interim analysis after the eleventh case of diabetes showed that the trial had failed to detect a reduction of the cumulative diabetes incidence at 3 years from 30 to 6% (P = 0.97). The group receiving nicotinamide exhibited decreased first-phase insulin secretion in response to intravenous glucose (P = 0.03). No other side effects were observed. We conclude that in this subgroup of diabetes-prone individuals at very high risk and with an assumed rapid disease progression, nicotinamide treatment did not cause a major decrease or delay of diabetes development. However, the data do not exclude the possibility of a less strong, but potentially meaningful, risk reduction in this cohort, or a major clinical effect of nicotinamide in individuals with less risk of progression to IDDM than studied here.
TL;DR: The high prevalence of mild cobalamin deficiency in healthy, free-living, older Dutch subjects could be explained by inadequate cobalamine intake or severe atrophic gastritis in only 28% of the study population.
TL;DR: Evidence is presented of the importance of homocysteine and suggestive evidence that plasma folate and plasma pyrixodal-l-phosphate (vitamin B6) are protective factors and of the effects on fasting and post–methionine-loading tHcy levels and any independent effects on cardiovascular disease.
Abstract: The list of preventable and reversible risk factors for atherosclerotic cardiovascular disease continues to grow. Cigarette smoking, high blood pressure, physical inactivity, elevated cholesterol, underlying lipoprotein abnormalities, lipoprotein(a), diabetes, overweight, male gender, and age are well-established risk factors. During the 1990s, there have been many reports associating elevated plasma homocysteine levels with arteriosclerotic cardiovascular disease and consistent evidence that dietary and supplemental folic acid can reduce homocysteine levels.1 2
The article by Robinson and colleagues3 in this issue of Circulation presents further evidence of the importance of homocysteine and suggestive evidence that plasma folate and plasma pyrixodal-l-phosphate (vitamin B6) are protective factors. Their study is part of the European Concerted Action Project,4 which examined 750 patients younger than age 60 with diagnoses within the previous 12 months of coronary, cerebrovascular, or peripheral vascular disease and 800 healthy control subjects. The patient groups were young (47 years for cases and 44 years for control subjects) and heterogeneous, with nonfatal clinical events or symptoms of arteriosclerotic cardiovascular disease supported by ECG, angiographic, or Doppler evidence; the study involved 19 centers in nine European countries. Men in the highest quintile for fasting total homocysteine (tHcy), compared with the remainder of the population, had an estimated relative risk of 2.2 (95% confidence interval [CI], 1.6 to 2.9), with a striking dose-response relationship and a more-than-multiplicative interaction with cigarette smoking and high blood pressure on vascular disease risk4 ; the corresponding estimated relative risk for coronary heart disease was similar (2.0; 95% CI 1.6 to 2.8). (tHcy is the sum of homocysteine and homocysteinyl moieties of oxidized disulfides, homocystine, and cysteine- homocysteine.)
Robinson and colleagues3 examined three B vitamins in detail to determine their effects on fasting and post–methionine-loading tHcy levels and any independent effects on cardiovascular disease …
TL;DR: The present molecular and genetic information on human cubilin now provides circumstantial evidence that an impaired synthesis, processing, or ligand binding of cubILin is the molecular background of this hereditary form of megaloblastic anemia.
TL;DR: In this article, the effects of B-group vitamins and antioxidant vitamin supplementation on homocysteine concentrations were evaluated in a randomized, factorial-design, controlled trial with 132 men with mild hyperhomocysteinemia and 5,10-methylene tetrahydrofolate reductase genotype status.
TL;DR: Comparison of the structure of the N15 TCR-VSV8-H-2Kb complex revealed a common docking mode, regardless of TCR specificity or species origin, in which the TCR variable Valpha domain overlie the MHC alpha2 helix and the Vbeta domain overlies the M HC alpha1 helix.
TL;DR: Results indicate that NIMA promotes the nuclear localization of the NIMXCDC2/ NIMECyclin B complex, by a process involving SONA, which may be involved in coordinating the functions of NIMxCDC2 and NimA in the regulation of mitosis.
Abstract: NIMA promotes entry into mitosis in late G2 by some mechanism that is after activation of the Aspergillus nidulans G2 cyclin-dependent kinase, NIMXCDC2/NIMECyclin B. Here we present two independent lines of evidence which indicate that this mechanism involves control of NIMXCDC2/NIMECyclin B localization. First, we found that NIMECyclin B localized to the nucleus and the nucleus-associated organelle, the spindle pole body, in a NIMA-dependent manner. Analysis of cells from asynchronous cultures, synchronous cultures, and cultures arrested in S or G2 showed that NIMECyclin B was predominantly nuclear during interphase, with maximal nuclear accumulation in late G2. NIMXCDC2 colocalized with NIMECyclin B in G2 cells. Although inactivation of NIMA using either the nimA1 or nimA5 temperature-sensitive mutations blocked cells in G2, NIMXCDC2/NIMECyclin B localization was predominantly cytoplasmic rather than nuclear. Second, we found that nimA interacts genetically with sonA, which is a homologue of the yeast nucleocytoplasmic transporter GLE2/RAE1. Mutations in sonA were identified as allele-specific suppressors of nimA1. The sonA1 suppressor alleviated the nuclear division and NIMECyclin B localization defects of nimA1 cells without markedly increasing NIMXCDC2 or NIMA kinase activity. These results indicate that NIMA promotes the nuclear localization of the NIMXCDC2/ NIMECyclin B complex, by a process involving SONA. This mechanism may be involved in coordinating the functions of NIMXCDC2 and NIMA in the regulation of mitosis.
TL;DR: The addition of vitamin B-12 to folic acid supplements or enriched foods maximizes the reduction of homocysteine and may increase the benefits of the proposed measures in the prevention of vascular disease and neural tube defects.
TL;DR: The study aims to examine the effect of vitamin B12 deficiency on older veterans and its relationship to general health and cognitive impairment.
Abstract: OBJECTIVE: To examine the effect of vitamin B12 deficiency on older veterans and its relationship to general health and cognitive impairment.
DESIGN: Cross-sectional study.
SETTING: Oklahoma City Veterans Affairs Medical Center.
PARTICIPANTS: Data for this research were obtained from 303 ambulatory, older veterans who used the outpatient laboratories of the Oklahoma City Department of Veterans Affairs Medical Center. Subjects were included in the study if they were 65 years of age and older and if they had no known diagnosis associated with B12 deficiency. The sample in this study consisted of 301 men and 2 women aged 65 to 89 years.
MEASUREMENTS: This study used two separate measurements of vitamin B12 deficiency: (1) a strict definition of B12 deficiency (serum B12 level < laboratory norm) and (2) a broader definition of B12 deficiency (serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and methyl malonic acid (MMA) or homocysteine (HC) elevated by more than two standard deviations). The laboratory norm is 200 pg/mL. The dependent variables were measures of cognitive impairment and general health. Cognitive impairment was measured using the Folstein Mini-Mental State Examination (MMSE) and general health was measured using the RAND 36–Item Health Survey Version 1.0. The control variables for this study were the subjects' daily alcohol intake, daily intake of a vitamin/mineral supplement, annual income, and level of education.
RESULTS/CONCLUSIONS: Nineteen subjects (6%) were vitamin B12-deficient as measured by the strict definition of B12 deficiency (serum B12 level < laboratory norm), and 49 subjects (16%) were vitamin B12-deficient as measured by the broader definition of B12 deficiency (serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and MMA or HC elevated by more than two standard deviations). Vitamin B12 level decreases as age increases. Of the nine general health outcomes measured by using the RAND 36-Item Health Survey, only bodily pain is associated with vitamin B12 deficiency, and only then when B12 deficiency is measured as serum B12 level < laboratory norm, the strict definition of B12 deficiency. Vitamin B12-deficient subjects experience more bodily pain than those with normal vitamin B12 levels. There is a significant difference between B12-deficient subjects and B12 normal subjects on cognitive impairment, with B12 normal subjects indicating less cognitive impairment, only when B12 deficiency is measured as B12 level < laboratory norm, the strict definition of B12 deficiency. The broader measurement of vitamin B12 deficiency (i.e., serum B12 level < laboratory norm or laboratory norm < B12 < 300 pg/mL and MMA or HC elevated by more than two standard deviations) is not a significant correlate of cognitive impairment and general health.
TL;DR: With avidin pretargeting, accumulation of radioactivity in the liver, kidney, and spleen was reduced to a greater extent than that in the tumor, and tumor to nontumor ratios were increased.
Abstract: Background: Lectins (proteins that bind specific sugar molecules on glycoproteins and glycolipids) are expressed at various levels on the surface of tumor cells. Conjugation of cytotoxic agents to glycoproteins recognized by lectins could be useful in the treatment of tumors. Avidin (a highly glycosylated, positively charged protein found in egg white) contains terminal N-acetylglucosamine and mannose residues that bind to some lectins. In this study, we tested the ability of avidin, labeled through conjugation to radioactive biotin (a B vitamin), to target intraperitoneal tumors. Methods : Biotin was radioactively labeled with 111 In. Four tumor models (one ovarian, one lung, and two colon) were established in nude mice by intraperitoneal injection of cultured cancer cells. The following two approaches were used in the intraperitoneal administration of avidin: 1) radioactive biotin-avidin conjugates were injected and 2) avidin was injected 1-24 hours before the injection of radioactive biotin (avidin pretargeting; avidin-biotin conjugates formed in vivo). The distribution of injected radioactivity in the tissues of treated animals was assessed. Results: Radiolabeled avidin localized highly and rapidly in the tumors. More than 50% of the administered dose of avidin-biotin conjugate accumulated per gram of tumor tissue 2 hours after injection; high tumor uptake of radioactivity was observed up to 24 hours after conjugate injection. In contrast, accumulation of radioactivity in normal tissues was low, yielding high tumor to nontumor ratios. With avidin pretargeting, accumulation of radioactivity in the liver, kidney, and spleen was reduced to a greater extent than that in the tumor, and tumor to nontumor ratios were increased. Conclusions: Avidin may be a promising vehicle for the delivery of radioisotopes, drugs, toxins, or therapeutic genes to intraperitoneal tumors.
TL;DR: Elderly patients respond to cobalamin treatment as fully as younger patients, with complete haematological recovery and complete or good partial resolution of neurological deficits, and should be treated if there is a metabolic deficiency (as indicated by elevated homocysteine and/or MMA levels).
Abstract: Cobalamin (vitamin B12) deficiency is more common in the elderly than in younger patients. This is because of the increased prevalence of cobalamin malabsorption in this age group, which is mainly caused by (autoimmune) atrophic body gastritis. Cobalamin supplementation is affordable and nontoxic, and it may prevent irreversible neurological damage if started early. Elderly individuals with cobalamin deficiency may present with neuropsychiatric or metabolic deficiencies, without frank macrocytic anaemia. An investigation of symptoms and/or signs includes the diagnosis of deficiency as well as any underlying cause. Deficiency states can still exist even when serum cobalamin levels are higher than the traditional lower reference limit. Cobalamin-responsive elevations of serum methylmalonic acid (MMA) and homocysteine are helpful laboratory tools for the diagnosis. The health-related reference ranges for homocysteine and MMA appear to vary with age and gender. Atrophic body gastritis is indirectly diagnosed by measuring serum levels of gastrin and pepsinogens, and it may cause dietary cobalamin malabsorption despite a normal traditional Schilling's test. The use of gastroscopy may also be considered to diagnose dysplasia, bacterial overgrowth and intestinal villous atrophy in healthy patients with atrophic body gastritis or concomitant iron or folic acid deficiency. Elderly patients respond to cobalamin treatment as fully as younger patients, with complete haematological recovery and complete or good partial resolution of neurological deficits. Chronic dementia responds poorly but should, nevertheless, be treated if there is a metabolic deficiency (as indicated by elevated homocysteine and/or MMA levels). Patients who are at risk from cobalamin deficiency include those with a gastrointestinal predisposition (e.g. atrophic body gastritis or previous partial gastrectomy), autoimmune disorders [type 1 (insulin-dependent) diabetes mellitus and thyroid disorders], those receiving long term therapy with gastric acid inhibitors or biguanides, and those undergoing nitrous oxide anaesthesia. To date, inadequate cobalamin intake has not proven to be a major risk factor. Intervention trials of cobalamin, folic acid and pyridoxine (vitamin B6) in unselected elderly populations are currently under way.
TL;DR: Older people who smoke cigarettes are at increased risk of suboptimal antioxidant and other micronutrient intakes and status, but the lower intakes found in cigarette smokers only partly explain their reduced blood indices.
Abstract: OBJECTIVE To examine the relationships between alcohol consumption and a range of nutrient intakes and blood status indices in older people. DESIGN National Diet and Nutrition Survey: cross-sectional survey of nationally representative sample of people aged 65 years or over. SETTING Mainland Britain during 1994/5. SUBJECTS 1198 people (623 males, 575 females) aged 65 years or over, of whom 925 were living in private households and 273 were living in institutions. RESULTS Intermediate alcohol consumption (particularly 0.1-14 units week(-1); 1 unit = 8 g) derived from a 4-day diet diary or a 12-month recall questionnaire, was associated with higher intakes of vitamins C, E, B1, iron, calcium, energy from food, carbohydrate and non-starch polysaccharides than heavy alcohol consumption (28 + units week(-1)) or abstinence, after adjustment for a number of factors (age, sex, domicile, social class, cigarette smoking, self-reported health, grip strength and total energy intake). Intermediate alcohol consumption was also associated with higher blood concentrations (independent of intake) of vitamin C, beta-cryptoxanthin, lutein and calcium, with the lowest concentrations being found in heavy alcohol users. The lowest concentrations of serum ferritin were found in light drinkers and the highest levels in heavier alcohol drinkers. Alcohol consumption ranging from 0.1 to >28 units week(-1) was directly correlated with intakes of B vitamins, total energy and fat, with blood concentrations (independent of intake) of lycopene, high density lipoprotein (HDL)-cholesterol, plasma pyridoxal phosphate and retinol, and with blood pressure and grip strength. CONCLUSIONS Compared with abstinence and heavy drinking, light to moderate alcohol consumption in older people is associated with higher intakes of certain nutrients, and higher blood concentrations (independent of intake) of some micronutrient status indices, including antioxidants. The explanation for the latter associations remains unclear and further investigation is recommended. Heavier alcohol consumption is associated with both beneficial and adverse effects with respect to nutrient intakes and health status.
TL;DR: The data suggest that both the FFQ and 3d-WFR are valid measures of assessing the folate intake of young women, and both appear to be useful in determining vitamin B-12 intake when supplemental users are included.
Abstract: The purpose of this study was to validate a food-frequency questionnaire (FFQ) and a 3-d weighed food record (3d-WFR) by comparing nutrient intakes estimated using these methods with serum folate, RBC folate and serum vitamin B-12 concentrations in 105 females aged 16-19 y. During an early morning clinic visit, subjects completed a self-administered, 116-item FFQ, blood was collected and they were trained to complete a 3d-WFR. Folate intakes as determined by the 3d-WFR (r = 0.65, P < 0.01) exhibited a stronger association with serum folate than did intakes from the FFQ (r = 0.48, P < 0.01) (P = 0.017). The correlations between folate intakes and RBC folate as determined by the FFQ (r = 0.42, P < 0.01) and 3d-WFR (r = 0.50, P < 0.01) methods did not differ. Vitamin B-12 intakes showed only a modest association with serum vitamin B-12 when supplement users were included in the analyses (FFQ, r = 0.25, P < 0.05; 3d-WFR, r = 0.32, P < 0.05). After excluding supplement users from the analyses, the relationship between vitamin B-12 intakes as determined by FFQ and serum vitamin B-12 was no longer significant. Median daily folate intakes (346 vs. 212 microgram) and vitamin B-12 (4.9 vs. 1.9 microgram) estimated from the FFQ were higher than those obtained from the 3d-WFR. In sum, these data suggest that both the FFQ and 3d-WFR are valid measures of assessing the folate intake of young women, and both appear to be useful in determining vitamin B-12 intake when supplemental users are included. The markedly different conclusions about absolute folate and vitamin B-12 intakes obtained using these two dietary methodologies should be taken into consideration when making recommendations about optimal folate intakes in relation to disease prevention.
TL;DR: The presently accepted view that vitamin B6 mainly affects tH Cy after methionine loading, and not fasting tHcy, is contradicted by the findings in referents.
Abstract: Objectives: To investigate the association of status of vitamins B6, B12 and folate with plasma fasting total homocysteine (tHcy) and with risk of coronary atherosclerosis; and to establish whether associations between vitamins and risk of coronary atherosclerosis are mediated by tHcy.Methods: The study population consisted of 131 patients with angiographically-defined severe coronary atherosclerosis and 88 referents with no or minor coronary stenosis. Previous analyses in this study population have shown that fasting tHcy is an independent risk factor for coronary atherosclerosis. In the present analyses, using multiple linear regression, we estimated differences in tHcy concentrations between subjects in the lowest and highest quartiles of concentrations of each of the vitamins, adjusting for age, gender, total:HDL cholesterol ratio, smoking habits, alcohol intake, blood pressure, serum creatinine, body mass index and the two other vitamins. We used logistic regression analysis conditional on the set of...
TL;DR: The initial and follow-up MRI appearances in a patient with subacute combined degeneration of the spinal cord, brain stem and cerebellum, due to vitamin B12 deficiency show the lesions in these structures demonstrated clearly as pathologically high-signal areas on T2-weighted images.
Abstract: Subacute combined degeneration is a rare cause of demyelination of the dorsal and lateral columns of the spinal cord and even more rarely of the pyramidal and spinocerebellar tracts and cerebellum. We present the initial and follow-up MRI appearances in a patient with subacute combined degeneration of the spinal cord, brain stem and cerebellum, due to vitamin B12 deficiency. The lesions in these structures were demonstrated clearly as pathologically high-signal areas on T2-weighted images. These lesions, except those of the brain stem and cerebellum, disappeared 4 months after therapy. MRI 14 months after the patient's discharge on vitamin B12 therapy showed the same picture.
TL;DR: Both achalasia and Hirchsprung's disease arise from defects of innervation of the oesophagus and distal large bowel respectively and their consequences are confined to disorders of motility in the relevant part of the gastrointestinal tract.
Abstract: Both achalasia and Hirchsprung's disease arise from defects of innervation of the oesophagus and distal large bowel respectively. Their consequences are confined to disorders of motility in the relevant part of the gastrointestinal tract. Many neurogenic and primary muscle disorders are associated with abnormalities of gut motility. Stroke, even when unilateral, is commonly associated with dysphagia. Transcranial magnetoelectric stimulation has established that the pharyngeal phase of swallowing tends to receive its innervation principally from one hemisphere. In many neurological disorders, dysphagia is only one part of the clinical picture but in some--for example, the Chiari malformation--dysphagia may be the sole or major feature. Disturbances of small and large bowel motility, when seen in neurogenic disorders, are associated with autonomic neuropathy and are particularly common in diabetes mellitus. Primary muscle disorders can lead to dysphagia (for example, with polymyositis or oculopharyngeal dystrophy) or defects of large bowel motility (for example, with Duchenne's muscular dystrophy). Primary gut disorders particularly associated with neurological disease include pernicious anaemia, nicotinamide and thiamine deficiencies, selective vitamin E deficiency, and coeliac disease. Inflammatory bowel disease is associated with thromboembolic complications which may include the CNS, inflammatory muscle disease, and abnormalities on MRI of the brain of uncertain relevance. Whipple's disease is a rare condition which sometimes is largely or entirely confined to the CNS. In such cases, a particular neurological presentation can indicate the diagnosis.
TL;DR: In this article, a very sensitive, selective, and rapid spectrophotometric method for the determination of vitamin B1 in the presence of vitamins B2, B6, and B12 was carried out in the UV region without performing a previous separation.
Abstract: A very sensitive, selective, and rapid spectrophotometric method for the determination of vitamin B1 in the presence of vitamins B2, B6, and B12 was carried out in the UV region without performing a previous separation. Vitamin B1 was selectively and strongly sorbed on Sephadex CMC-25 ion exchanger at pH 4.80 and its intrinsic absorbance measured directly in the solid phase at 247 and 320 nm. The apparent molar absorptivity ranged from 5.63 × 105 to 2.19 × 107 L mol-1 cm-1, depending on the sample volume used (from 10 to 1000 mL). A procedure (for five different sample volumes) was here proposed. Thiamin could be determined in the concentration ranges 0.5−5.5 μg mL-1 (10-mL sample volume) up to 12 −170 ng mL-1 (1000-mL sample volume) with detection limits ranging from 80.0 to 3.0 μg L-1 and RSDs from 1.5 to 2.6%, respectively. The method showed an excellent selectivity against other compounds of the B complex with similar spectral features and which did not cause interference. The method was satisfactoril...
TL;DR: It is concluded that a high proportion of healthy elderly people may have suboptimal status for these nutrients despite apparently adequate dietary intakes and riboflavin supplementation at physiologic doses corrects biochemical abnormalities of not only EGRAC, but also plasma PLP, confirming the biochemical interdependency of these vitamins and suggesting that rib oflavin is the limiting nutrient.
Journal Article•
TL;DR: The NF-kappa B system is essentially involved in immediate early expression of various immunoregulatory genes and has been demonstrated to represent an important regulatory system of endothelial activation.
Abstract: Although they are considered as destructive agents, free radicals can sometimes become useful. Their presence is intimately coupled with the activity of certain hemal oxydases which insert an atom of oxygen into their substrate by a stereospecific radical mecanism. The cytochromes P450 and the enzymes of the eicosanoide metabolism are some examples. The free radicals can act as second cellular messengers, especially to modulate the metabolism of arachidonic acid and the prostaglandin tract or to infer a myorelaxation. They can even play the role of neurotransmitters such as azote monoxyde. The activation of phagocytes, which is an essential event in the inflammatory reaction, integrates these notions at several levels: in the mechanisms of bacterial death, in the spread of the inflammatory reaction and in the alteration of the extra-cellular matrix. The inflammatory reaction is initiated by interactions between vascular endothelium, platelets and leukocytes including signal exchanges, adhesion molecule expression and secretion of chimiotactic mediators. Activation of vascular endothelium is a key event in the initiation of the phenomenon. The cells intervening in the precocious inflammatory phase were tissular mastocytes and platelet-liberating mediators (histamine) and neutrophile cells responsible for vascular injuries induced by oxygen free radicals and nitric oxide. Reactive oxygen intermediates play a critical role, primarily to limit tissue damage and prevent or inhibit infection, secondary to enhancing and prolonging reaction. The monocytes and platelets liberate cytokines early, which appears to be important in activation and production of an inflammatory response. In fact, cytokines, especially TNF alpha and IL-1, induce synthesis and secretion endothelial adhesion molecules such as ICAM-1, VCAM-1 and E-selectin, which have been demonstrated to mediate leukocyte recruitment to sites of inflammation. The cytokines also activate the fibroblasts and endothelial cells that produce, among others, free radicals and other chimiotactic cytokines of which some (IL-8 and related) can induce neutrophil degranulation and stimulate oxidative stress and formation of free radicals. Furthermore, endothelial cells have been shown to make use of a broad repertoire of cytokines including IL-1, IL-6, IL-8, MCP-1 and gro/MGSA, which may be secreted during an inflammatory response and exercise pro-inflammatory functions. Under the influence of the inflammatory mediators, other enzymes are also activated. The inducible isoforms of cyclo-oxygenase (COX-2) and nitric oxide synthase (iNOS) play an important role in inflammatory reactions via the production respectively of prostaglandins and nitric oxide. The induction of cell adhesion molecules (ICAM-1, VCAM-1 and E-selectin), cytokines, acute phase proteins, growth factors, COX-2 and iNOS expression is mediated by the activation of transcriptional factors, especially the nuclear factor kappa B (NF-kappa B). The NF-kappa B system is essentially involved in immediate early expression of various immunoregulatory genes and has been demonstrated to represent an important regulatory system of endothelial activation. The target genes for NF-kappa B comprise a growing list of genes intrinsically linked to a coordinated inflammatory response. The NF-kappa B is a heterodimer composed of two subunits (p65 and p50). In non-stimulated cells, NF-kappa B resides in the cytoplasm as an inactive complex bound to its inhibitor, I kappa B. Upon stimulation with various agents including cytokines, mitogenes, viruses and reactive oxygen intermediates, I kappa B dissociates from the NF-kappa B-I kappa B complex and translocates to the nucleus, binding with high affinity to specific sites in the promoter regions of target genes and stimulating their transcription. In the case of any weakness of this anti-oxidizing defence or any over-production of radical species, a state of oxidative stress occurs. (ABSTRACT TRUNC