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Aim: Despite being one of common preventable deficiency disorders, vitamin B12 (vit-B12) deficiency can lead to serious health problems both in children and adult. The familiar treatment through parenteral route for vit-B12 deficiency frequently leads to poor adherence, and adequate response to treatment has lead to interest in oral supplementation. This study investigates the efficacy of oral vit-B12 treatment in children with nutritional vit-B12 deficiency. Methods: Forty-seven children (from 1 month to 17 years) with vit-B12 levels below 200 pg/mL were allocated either of two study groups: Group 1 (1-20 months) and Group 2 (6-17 years) which were subdivided according to the duration of treatment (Group 1A&2A: 4 months; Group 1 B&2B: 8 months of 1000 μg oral vit-B12, every day for a week, every other day for 2 weeks, 2 days a week for 2 weeks, then once a week). Results: Vit-B12 levels among all groups were significantly restored following high oral vit-B12 doses (P = 0.013, P = 0.001), the regimen being more effective in Group1 A and Group1 B. Correlation analysis of serum vit-B12 levels and age at the end of treatment revealed a decreasing trend with the increasing patient age (corelation respectively -65.2%, P = 0.08; -35.4%; P = 0.25). Conclusion: Data from this study indicate that oral vit-B12 (1000 μg) for 4 months is effective, giving clinicians more choice, for treatment of children with nutritional vit-B12 deficiency. However, despite this high dose, lower levels were achieved in older children indicating the necessity of dosage adjustment in accordance with body weight. [ABSTRACT FROM AUTHOR]

Childhood brain tumors (CBT) are the second most common childhood cancers, yet their etiology is largely unknown. We investigated whether maternal gestational intake of folate and vitamins B6 and B12 was associated with CBT risk in a nationwide case-control study conducted 2005–2010. Case children 0–14 years were recruited from all 10 Australian pediatric oncology centers. Control children were recruited by national random digit dialing, frequency matched to cases on age, sex, and state of residence. Dietary intake was ascertained using food frequency questionnaires and adjusted for total energy intake. Data from 293 case and 726 control mothers were analyzed using unconditional logistic regression. The odds ratio (OR) for the highest versus lowest tertile of folate intake was 0.70 [95% confidence interval (CI): 0.48, 1.02]. The ORs appeared lower in mothers who drank alcohol during pregnancy (OR = 0.45, 95% CI: 0.22, 0.93), mothers who took folic acid (OR = 0.67, 95% CI: 0.42, 1.06) or B6/B12 supplements (OR = 0.51, 95% CI: 0.25, 1.06) and in children younger than 5 years (OR = 0.50, 95% CI: 0.27, 0.93). These findings are consistent with folate's crucial role in maintenance of genomic integrity and DNA methylation. Dietary intake of B6 and B12 was not associated with risk of CBT. [ABSTRACT FROM AUTHOR]

Background and purpose. Hydrogen sulfide (H2S) is a highly toxic gas for which no effective antidotes exist. It acts, at least in part, by binding to cytochrome c oxidase, causing cellular asphyxiation and anoxia. We investigated the effects of three different ligand forms of cobinamide, a vitamin B12 analog, to reverse sulfide (NaHS) toxicity. Methods. New Zealand white rabbits received a continuous intravenous (IV) infusion of NaHS (3 mg/min) until expiration or a maximum 270 mg dose. Animals received six different treatments, administered at the time when they developed signs of severe toxicity: Group 1-saline (placebo group, N = 9); Group 2-IV hydroxocobalamin ( N = 7); Group 3-IV aquohydroxocobinamide ( N = 6); Group 4-IV sulfitocobinamide ( N = 6); Group 5-intramuscular (IM) sulfitocobinamide ( N = 6); and Group 6-IM dinitrocobinamide ( N = 8). Blood was sampled intermittently, and systemic blood pressure and deoxygenated and oxygenated hemoglobin were measured continuously in peripheral muscle and over the brain region; the latter were measured by diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS). Results. Compared with the saline controls, all cobinamide derivatives significantly increased survival time and the amount of NaHS that was tolerated. Aquohydroxocobinamide was most effective (261.5 ± 2.4 mg NaHS tolerated vs. 93.8 ± 6.2 mg in controls, p < 0.0001). Dinitrocobinamide was more effective than sulfitocobinamide. Hydroxocobalamin was not significantly more effective than the saline control. Conclusions. Cobinamide is an effective agent for inhibiting lethal sulfide exposure in this rabbit model. Further studies are needed to determine the optimal dose and form of cobinamide and route of administration. [ABSTRACT FROM AUTHOR]

Background Pralatrexate (Fotolyn; Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). Patients and methods This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Results Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Conclusions Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted. [ABSTRACT FROM AUTHOR]

Background Long-term haemodialysis patients may be at risk of hydrosoluble vitamin deficiencies. This study aimed to test the hypothesis that in patients with serum B12 < 300 pmol/L, intramuscular hydroxocobalamin reduces erythropoietin requirements whilst maintaining haemoglobin concentrations ( Hb). Methods Study design was prospective, non-randomized, open label, with single group assignment. In 61 patients hydroxocobalamin 1000 μg was given weekly for 3 weeks and erythropoietin dose adjusted to target a Hb of 11-12 g/L. The primary outcome was the change in erythropoietin requirements at 2 years. Secondary outcomes included assessment of change in biochemical or clinical parameters. Results The erythropoietin dose reduced from 11 000 ± 7000 (10 000) IU to 5000 ± 6000 (3000) IU per week ( P < 0.001) with no change in Hb 116 ± 16 (117) g/L before and after 114 ± 15 (113) g/L ( P = 0.488) hydroxocobalamin supplementation. Serum albumin rose from 35 ± 4 (35) g/L to 36 ± 4 (36) g/L ( P = 0.03). A significant rise in red cell folate ( RCF) and serum vitamin B12 levels was observed. Serum ferritin rose despite a reduction in intravenous iron usage and no significant change in c-reactive protein or transferrin saturation. Conclusions In HD patients with B12 < 300 pmol/L, following treatment with hydroxocobalamin there was reduced erythropoietin requirements, maintained Hb and a small but significant rise in the serum albumin. RCF may be low in haemodialysis patients with metabolic cobalamin deficiency and rises significantly after supplementation. Hydroxocobalamin supplementation may have the potential to reduce the cost of anaemia management. [ABSTRACT FROM AUTHOR]

This article presents a history of the dietary cure for pernicious anemia and the role of Vitamin B12 in the treatment of this disease. It discusses the discovery of pernicious anemia and its symptoms in the 19th century, studies conducted by Boston, Massachusetts physicians on this disease and the discovery of the liver therapy for the disease, and the discovery of vitamin B12's effectiveness in treating the disease.

John Scott (1940-2013) was born in Dublin where he was to spend the rest of his career, both as an undergraduate and subsequently Professor of Biochemistry and Nutrition at Trinity College. His research with the talented group of scientists and clinicians that he led has had a substantial impact on our understanding of folate metabolism, mechanisms of its catabolism and deficiency. His research established the leading theory of folate involvement with vitamin B12 in the pathogenesis of vitamin B12 neuropathy. He helped to establish the normal daily intake of folate and the increased requirements needed either in food or as a supplement before and during pregnancy to prevent neural tube defects. He also suggested a dietary supplement of vitamin B12 before and during pregnancy to reduce the risk of neural tube defects. It would be an appropriate epitaph if fortification of food with folic acid became mandatory in the UK and Ireland, as it is in over 70 other countries. [ABSTRACT FROM AUTHOR]

Background and Objective: To assess whether methylcobalamin and alpha lipoic acid (ALA) added to pregabalin provide additional benefit compared to pregabalin alone in type 2 diabetes mellitus associated peripheral neuropathy. Setting and Design: An open label, randomized, controlled parallel-group pilot study. Materials and Methods: Thirty adult patients with type 2 diabetes mellitus with symptoms of peripheral neuropathy for ≥6 months were randomized to receive pregabalin 75 mg, methylcobalamin 750 µg, and ALA 100 mg (PMA, n = 15); or pregabalin 75 mg (PG, n = 15) for 12 weeks. Assessment variables were numeric rating scale (NRS), sleep interference scores (SIS), response rate to pain, and global assessment for the usefulness of therapy. The nerve conduction velocity was assessed for sensory and motor nerves. Safety assessment included adverse events reported by the patients, clinical laboratory, and general medical, neurological examinations. Statistical Analysis: Efficacy analyses were done on per-protocol (PP) population, whereas safety analyses were done on intent-to-treat (ITT) population. Results: Significant improvement was seen in pain and sleep interference in both groups. Mean nerve conduction velocity of left common peroneal nerve (CPN) showed significant improvement in PMA group at week 12 compared to baseline (P = 0.018). For right CPN both groups showed significant improvement. (PMA, P = 0.002, PG, P = 0.007). For sensory testing, at week 12, right superficial peroneal nerve showed reduction in nerve conduction velocity in PG group compared to baseline (P = 0.043). Conclusion: Methylcobalamine, ALA and pregabalin combination provides pain relief and improves sleep interference. Addition of methylcobalamin and ALA to pregabalin improves the nerve function. Due to small sample size, most of the efficacy parameters could not reach significant difference between groups; hence benefit of the 3-drug-combimation should be interpreted with reservation. [ABSTRACT FROM AUTHOR]

Background Cisplatin-based adjuvant chemotherapy provided a significant advantage in the overall survival ( OS) of patients with stage II and III non-small cell lung cancer ( NSCLC). However, the compliance and toxicity in cisplatin-based treatment were not always satisfactory. Pemetrexed plus carboplatin ( PC) had better chemotherapy compliance and efficiency in advanced non-squamous NSCLC patients. The aim of our study was to investigate the feasibility and efficacy of PC as adjuvant chemotherapy in patients with completely resected non-squamous NSCLC. Methods Eighty-two eligible non-squamous NSCLC patients operated on with pathological stage II or IIIA were enrolled in this trial. Adjuvant chemotherapy was initiated between one and four weeks after surgery, and consisted of four cycles of pemetrexed (500 mg/m2) plus carboplatin ( AUC = 5) every three weeks. The primary endpoint was the compliance of the regimen and the second endpoint was disease-free survival ( DFS). Results Patient demographics were median age 58 years (range 32 to 78) and gender ratio 68.3% male/31.7% female. Forty-eight (58.5%) of the patients were at stage II, and the other thirty-four (41.5%) patients were at stage IIIA. Seventy patients (85.4%) received four cycles of therapy over a 12-week period. Reasons for discontinuing therapy included: patient's refusal (n = 10); severe adverse events (n = 1); and surgical complications (n = 1). The primary grade 3 to 4 adverse reaction was hematologic toxicity: neutropenia (13.4%); leucopenia (7.3%); anemia (3.7%); and thrombocytopenia (2.4%). Non-hematological adverse events were mild. No treatment related deaths were observed. Median DFS for stage II and IIIA patients were 38.0 months (95% confidence interval ( CI): 28.1 to 47.9 months) and 21.0 months (95% CI: 13.7 to 28.3 months), respectively. Conclusion Adjuvant PC chemotherapy was an acceptable regimen in resected non-squamous NSCLC patients. [ABSTRACT FROM AUTHOR]

The benefit of isolated vitamins and their role in the prevention and treatment of type 2 diabetes continues to be a focus for research. Evidence suggests that vitamin D deficiency, which is widespread in the UK, is linked to insulin resistance and vitamin D deficiency appears to be particularly prevalent in population groups who are already at high risk of type 2 diabetes. Pharmaceutical doses of vitamins thiamine (B1) and niacin (B3) may be useful to prevent renal and cardiovascular complications in people with type 2 diabetes. A balanced and varied diet containing fruit and vegetables can contribute towards reducing the progression of diabetic complications by providing an adequate intake of antioxidant vitamins. [ABSTRACT FROM AUTHOR]

Nutrition is far more important than most physicians and patients recognize. Maintaining a healthy weight, reducing dietary cholesterol, avoiding egg yolks, and consuming a Cretan Mediterranean diet substantially reduce the risk for stroke. Besides the very high cholesterol content of egg yolks (more than the recommended daily intake of 200 mg of cholesterol in a single large egg yolk), it is now apparent that phosphatidylcholine (lecithin, 250 mg per egg yolk) is converted by intestinal bacteria to trimethylamine, which in turn is oxidized in the liver to trimethylamine n-oxide (TMAO), which is pro-atherosclerotic in animal models and increases the risk for cardiovascular events in patients at risk for coronary disease. Unrecognized metabolic deficiency of vitamin B12 is very common, and frequently missed, because a 'normal' serum B12 is not a reliable test for adequacy of B12. Besides neuropathy, myelopathy, and dementia, B12 deficiency increases the risk for stroke by raising levels of total homocysteine (tHcy). Despite widespread misunderstanding of the complex issues, it is increasingly clear that B vitamin therapy to reduce homocysteine does reduce the risk for stroke. However adequacy of B12 dosing and renal impairment determine the response to B vitamin therapy: cyanocobalamin is beneficial in patients with normal kidney function, but harmful in those with renal impairment (GFR<50). Methylcobalamin should be used in patients with renal impairment. [ABSTRACT FROM AUTHOR]

Background: Spinal motoneuron neuroprotection by vitaminB12 was previously reported; the present study was carried out to evaluate neuroprotectivity in the dorsal root ganglion sensory neuron. Methods: In present study thirty-six Wister-Albino rats (aged 8–9 weeks and weighing 200–250 g) were tested. The animals were randomly divided into 6 groups which every group contained 6 rats. Group A: received normal saline (for 42 days); Group B: vitamin B12 was administered (0.5 mg/kg/day for 21 days); Group C: received vitamin B12 (1 mg/kg/day for 21days); Group D: received vitamin B12 (0.5 mg/kg/day for 42 days); Group E; received vitamin B12 (1 mg/kg/day for 42 days); Group F; received no treatment. The L5 Dorsal Root Ganglion (DRG) neurons count compared to the number of left and right neurons .Furthermore, DRG sensory neurons for regeneration were evaluated 21 or 42 days after injury (each group was analyzed by One-Way ANOVA test). Results: (1): The comparison of left crushed neurons (LCN) number with right non-crushed neurons in all experimental groups (B, C, D and C), indicating a significant decline in their neurons enumeration (p<0/05). (2): The comparison of test group’s LCN with the control group’s LCN revealed a significant rise in the number of experimental group neurons (p<0/05). (3): Moreover, comparing the number of right neurons in experimental groups with the number of neurons in crushed neurons indicated that the average number of right neurons showed a significant increase in experimental groups (p<0/05). Conclusion: Consequently, the probability of nerve regeneration will be increased by the increment of the administered drug dosage and duration. On the other hand, the regeneration and healing in Dorsal Spinal Ganglion will be improved by increase of administration time and vitamin B12 dose, indicating that such vitamin was able to progress recovery process of peripheral nerves damage in experimental rats. Finally, our results have important implications for elucidating the mechanisms of nerve regeneration. Moreover, the results showed that vitaminB12 had a proliferative effect on the dorsal root ganglion sensory neuron. [ABSTRACT FROM AUTHOR]

Abstract: Recently, poly(acrylic acid)-cysteine (PAA-cys) based formulations have shown to modulate vitamin B12 absorption across Caco-2 cells monolayers and rat intestinal mucosa. The aim of the present study was to provide a proof-of-principle for a delivery system based on PAA-cys in vivo by administering vitamin B12 to Sprague Dawley rats. In vitro, the permeation enhancing effect of unmodified and thiolated PAA was evaluated using rat intestinal mucosa mounted on Ussing type chambers and was compared to that of verapamil and reduced glutathione (GSH). Vitamin B12 transport in the presence of 0.5% (m/v) PAA-cys was 3.96-fold improved compared to buffer, while 91.5% and 56.5% increased compared to verapamil and GSH, respectively. In vivo, the oral administration of minitablets based on 0.5mg vitamin B12 with 4.5mg PAA or PAA-cys resulted in a significant improvement of vitamin B12 absolute bioavailability. The area under the serum concentration–time curve (AUC0–8) of vitamin B12 after administration of PAA and PAA-cys minitablets was 1.74-fold and 2.92-fold higher in comparison with oral solution, respectively. Thiolated formulations provided an absolute bioavailability of 0.89%. According to the achieved results, PAA-cys can be considered a valuable tool for improving the oral bioavailability of vitamin B12. [Copyright &y& Elsevier]

Muscle strength plays an important role in determining risk for falls, which result in fractures and other injuries. While bone loss has long been recognized as an inevitable consequence of aging, sarcopenia-the gradual loss of skeletal muscle mass and strength that occurs with advancing age-has recently received increased attention. A review of the literature was undertaken to identify nutritional factors that contribute to loss of muscle mass. The role of protein, acid-base balance, vitamin D/calcium, and other minor nutrients like B vitamins was reviewed. Muscle wasting is a multifactorial process involving intrinsic and extrinsic alterations. A loss of fast twitch fibers, glycation of proteins, and insulin resistance may play an important role in the loss of muscle strength and development of sarcopenia. Protein intake plays an integral part in muscle health and an intake of 1.0-1.2 g/kg of body weight per day is probably optimal for older adults. There is a moderate inverse relationship between vitamin D status and muscle strength. Chronic ingestion of acid-producing diets appears to have a negative impact on muscle performance, and decreases in vitamin B and folic acid intake may also impair muscle function through their action on homocysteine. An adequate nutritional intake and an optimal dietary acid-base balance are important elements of any strategy to preserve muscle mass and strength during aging. [ABSTRACT FROM AUTHOR]

Phenolyl cobamides are unique members of a class of cobalt-containing cofactors that includes vitamin B12 (cobalamin) Cobamide cofactors facilitate diverse reactions in prokaryotes and eukaryotes. Phenolyl cobamides are structurally and chemically distinct from the more commonly used benzimidazolyl cobamides such as cobalamin, as the lower axial ligand is a phenolic group rather than a benzimidazole. The functional significance of this difference is not well understood. Here we show that in the bacterium Sporomusa ovata, the only organism known to synthesize phenolyl cobamides, several cobamide-dependent acetogenic metabolisms have a requirement or preference for phenolyl cobamides. The addition of benzimidazoles to S. ovata cultures results in a decrease in growth rate when grown on methanol, 3,4-dimethoxybenzoate, H2 plus CO2, or betaine. Suppression of native p-cresolyl cobamide synthesis and production of benzimidazolyl cobamides occur upon the addition of benzimidazoles, indicating that benzimidazolyl cobamides are not functionally equivalent to the phenolyl cobamide cofactors produced by S. ovata. We further show that S. ovata is capable of incorporating other phenolic compounds into cobamides that function in methanol metabolism. These results demonstrate that S. ovata can incorporate a wide range of compounds as cobamide lower ligands, despite its preference for phenolyl cobamides in the metabolism of certain energy substrates. To our knowledge, S. ovata is unique among cobamide-dependent organisms in its preferential utilization of phenolyl cobamides. [ABSTRACT FROM AUTHOR]

Imerslund-Gräsbeck syndrome is a rare autosomal recessive disorder, characterized by vitamin B12 deficiency due to selective malabsorption of the vitamin and usually results in megaloblastic anemia appearing in childhood. It is responsive to parenteral vitamin B12 therapy. The estimated prevalence (calculated based on Scandinavian data) is less than 6:1,000,000. However, many cases may be misdiagnosed. When there is reasonable evidence to suspect that a patient suffers from IGS, a new and straightforward approach to diagnosis is mutational analysis of the appropriate genes. We report for the first time the case of a girl of Italian ancestry with IGS genetically confirmed by the detection of a homozygous missense mutation in the AMN gene (c.208-2 A > G). [ABSTRACT FROM AUTHOR]

The article discusses the functions of vitamin B12 and whether supplements would be of any help. It also lists ways on identifying vitamin B12 deficiency including a triad of glossitis, ascending paresthesias, and weakness, and suggests radioassay and nonradioisotopic assay for measuring vitamin B12 levels. It concludes that there is no concrete evidence suggesting that vitamin B12 injections reduce fatigue and increase energy, thus necessitating more studies on the issue.

Several studies suggest that the vitamin B12 (B12) transport system can be used for the cellular delivery of B12-conjugated drugs, also in long-term treatment Whether this strategy will affect the endogenous metabolism of B12 is not known. To study the effect of treatment with excess B12 or an inert derivative, we established a mouse model using implanted osmotic minipumps to deliver saline, cobinamide (Cbi) (4.25 nmol/h), or B12 (1.75 nmol/h) for 27 days (n = 7 in each group). B12 content and markers of B12 metabolism were analysed in plasma, urine, kidney, liver, and salivary glands. Both Cbi and B12 treatment saturated the transcobalamin protein in mouse plasma. Cbi decreased the content of B12 in tissues to 33-50% of the level in control animals but did not influence any of the markers examined. B12 treatment increased the tissue B12 level up to 350%. In addition, the transcript levels for methylenetetrahydrofolate reductase in kidneys and for transcobalamin and transcobalamin receptor in the salivary glands were reduced. Our study confirms the feasibility of delivering drugs through the B12 transport system but emphasises that B12 status should be monitored because there is a risk of decreasing the transport of endogenous B12. This risk may lead to B12 deficiency during prolonged treatment. [ABSTRACT FROM AUTHOR]

Abstract: Exocrine pancreatic insufficiency (EPI) is a syndrome caused by an insufficient amount of pancreatic digestive enzymes in the small intestine. Clinical signs most commonly reported in cats with EPI are weight loss, loose and voluminous stools, steatorrhea, polyphagia, and in some cases a greasy soiling of the hair coat in the perianal region. Serum feline trypsin-like immunoreactivity concentration is the diagnostic test of choice for the diagnosis of affected cats. Treatment of cats with EPI consists of enzyme supplementation with either a powdered pancreatic extract or raw pancreas. Most cats with EPI also have severely decreased serum cobalamin concentrations and may require lifelong parenteral cobalamin supplementation. Most cats respond well to therapy and can have a normal life expectancy and quality of life. [Copyright &y& Elsevier]

Cyanide poisoning is uncommon, but generates interest because of the presumed utility of an antidote immediately available in those areas with a high risk of cyanide exposure. As part of its regular review of guidelines, the Australian Resuscitation Council conducted a systematic review of the human evidence for the use of various proposed cyanide antidotes, and a narrative review of the relevant pharmacological and animal studies. There have been no relevant comparative or placebo-controlled human trials. Nine case series were identified. Treatment with hydroxocobalamin was reported in a total of 361 cases. No serious adverse effects of hydroxocobalamin were reported, and many patients with otherwise presumably fatal poisoning survived. Sodium thiosulphate use was reported in two case series, similarly with no adverse effects. Treatment with a combination of sodium nitrite, amyl nitrite and sodium thiosulphate was reported in 74 patients, with results indistinguishable from those of hydroxocobalamin and sodium thiosulphate. No case series using dicobalt edetate or 4-dimethylaminophenol were identified, but successful use in single cases has been reported. Hydroxocobalamin and sodium thiosulphate differ from alternatives in having negligible adverse effects, and on the basis of current evidence are the antidotes of choice. The indications for the use of an antidote, the requirements for supportive care and a recommended approach for workplaces where there is a risk of cyanide poisoning are presented. [ABSTRACT FROM AUTHOR]

Objective: Vegetarians are more vascular-healthy but those with subnormal vitamin B-12 status have impaired arterial endothelial function and increased intima-media thickness. We aimed to study the impact of vitamin B-12 supplementation on these markers, in the vegetarians. Design: Double-blind, placebo controlled, randomised crossover study. Setting: Community dwelling vegetarians. Participants: Fifty healthy vegetarians (vegetarian diet for at least 6 years) were recruited. Intervention: Vitamin B-12 (500µg/day) or identical placebo were given for 12 weeks with 10 weeks of placebo-washout before crossover (n=43), and then open label vitamin B-12 for additional 24 weeks (n=41). Measurement: How-mediated dilation of brachial artery (FMD) and intima-media thickness (IMT) of carotid artery were measured by ultrasound. Results: The mean age of the subjects was 45+9 years and 22 (44%) were male. Thirty-five subjects (70%) had serum B-12 levels <150pmol/l. Vitamin B-12 supplementation significantly increased serum vitamin B-12 levels (p<0.0001) and lowered plasma homocysteine (p<0.05). After vitamin B-12 supplementation but not placebo, significant improvement of brachial FMD (6.3±1.8% to 6.9±1.9%; p<0.0001) and in carotid IMT (0.69±0.09mm to 0.67±0.09 mm, p<0.05) were found, with further improvement in FMD (to 7.4±1.7%; p<0.0001) and IMT (to 0.65±0.09mm; p<0.001) after 24 weeks open label vitamin B-12. There were no significant changes in blood pressures or lipid profiles. On multivariate analysis, changes in B-12 (β=0.25; p=0.02) but not homocysteine were related to changes in FMD, (R=0.32; F value=3.19; p=0.028). Conclusions: Vitamin B-12 supplementation improved arterial function in vegetarians with subnormal vitamin B-12 levels, proposing a novel strategy for atherosclerosis prevention. [ABSTRACT FROM AUTHOR]

Earlier, we proposed that the ability of folic acid and vitamin B12 to preserve systemic and mitochondrial function after short-term exposure to arsenic may prevent further progression to more permanent injury and pathological changes leading to cell death. To elucidate its mechanism, the present study examined the antiapoptotic efficacy of folic acid and vitamin B12 against short-term arsenic exposure-induced hepatic mitochondria oxidative stress and dysfunction. Sixteen to eighteen weeks old male albino rats weighing 140-150 × g were divided into five groups: Control (A), Arsenic-treated (B), Arsenic + folic acid (C), Arsenic +vitamin B12 (D), and Arsenic + folic acid + vitamin B12 (E). Data generated indicated that folic acid and vitamin B12 separately or in combination can give significant protection against alterations in oxidative stress and apoptotic marker parameters and downstream changes in mitochondria, namely pro-oxidative (NO, TBARS, OH−) and antioxidative defense (SOD, CAT, GSH) markers, iNOS protein expression, mitochondrial swelling, cytochrome c oxidase and Ca2+-ATPase activity, Ca2+ content, caspase-3 activity. Additionally, results of hepatic cell DNA fragmentation, arsenic load of blood, hepatic tissue and urine, and histological observations, all strongly support that both these supplements have efficacy in preventing apoptotic changes and cellular damage. As the mechanisms of actions of both of these supplements are methylation related, a combined application was more effective. Results further reveal new molecular targets through which folic acid and vitamin B12 separately or in combination work to alleviate one critical component of arsenic-induced liver injury: mitochondria dysfunction. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012. [ABSTRACT FROM AUTHOR]

Background: Hyperhomocysteinemia is a new risk factor for cardiovascular disease. It is a sensitive marker of the vitamin B12 and folate insufficiency. Folate and vitamin B12 may be a protective effect on cardiovascular disease. According to limited data about role of vitamin B12 and folate in coronary artery disease (CAD), we conducted this study to measure these factors in patients with coronary artery disease and in control subjects. Methods: This case-control study was performed on 139 subjects who underwent coronary angiography in Shiraz. Plasma vitamin B12 and folate level were measured and compared between patients with CAD and control subjects. Results: 139 individuals with a mean age 56.99±11.93 were enrolled in this study. 31.2% of them had a normal coronary angiography. Mean plasma level of folate in patients with CAD was lower than control subjects (4.46±1.28 ng/ml versus 5.00±1.81 ng/ml, P = 0.04). Also mean plasma level of vitamin B12 in patients CAD and control subjects were 451.43±138.90 and 503.60±199.35 pg/ml respectively. Although mean level of vitamin B12 in patients with CAD was lower than control group, but it was not statistically significant (P = 0.07). Conclusion: Mean plasma level of vitamin B12 and folate were lower in patients with CAD than control group. It seems that supplementation with this vitamins may be useful in patients with CAD. [ABSTRACT FROM AUTHOR]

The article explores the effect of folic acid supplementation on total plasma homocysteine (tHcy) concentrations in sedentary adult men, used to educe homocysteine levels found to be associated with an increased risk of cardiovascular disease. The study covered a period of 90 days of an oral liquid supplement containing folic acid and vitamin B12 following the recommended dosage set by the supplier. A comparison of homocysteine levels between a control group taking a placebo and the group taking the supplement are compared.

Background: Vitamin B12 deficiency leads to myriad hematological and neurological changes leading to megaloblastic anemia and disorders of the nervous system like subacute combined degeneration of the spinal cord, cognitive impairment, peripheral neuropathy, etc. In this case series, an attempt was made to investigate the neurological manifestations of patients with diagnosed vitamin B12-deficient megaloblastic anemia, determine the cause of vitamin deficiency in these cases, and monitor their response to vitamin B12 therapy. Materials and Methods: The study was conducted in a tertiary care referral teaching hospital in New Delhi during a period of over 2 years from August 2007 to December 2009. Eighty-five consecutive patients with megaloblastic anemia (MA) due to vitamin B12 deficiency were screened and a total of 28 patients with neurological and psychiatric symptoms were selected for the study. In addition to bone marrow examination, blood counts, red cell indices, and biochemical tests, assays of serum vitamin B-12, folate, and homocysteine were done. Neuroimaging by magnetic resonance studies and nerve conduction studies (NCS) was done where clinically applicable. Follow-up was done at least twice at 3 months and 6 months to assess clinical, neurological, and hematological response to vitamin B12 therapy. Results: The primary study group of MA with B12 deficiency had 85 patients. Of these, only 28 (32.9%) patients had neurological and/or psychiatric features. There were 18 male and 10 female subjects (M: F ratio being 1.8:1). The mean age was 32.80 years with a range of 18-68 years. Though the majority of MA patients (77.6%) were vegetarian, a good 22% consumed a nonvegetarian diet. Neurological manifestations included peripheral neuropathy in 14 (50%), myelopathy in 2 (7.14%), myeloneuropathy in 2 (7.14%), acute confusional state in 4 (14.28%), and cognitive impairment in 20 (71.42%) patients. Mood disturbances, anxiety, and irritability were also seen. NCS was done in 18 cases and showed demyelinating peripheral neuropathy in 12 cases and both axonal and demyelinating changes in two cases. Magnetic resonance imaging (MRI) showed four cases with the classical demyelination on spinal MRI with white matter hyper intense lesions in the posterior tracts on T2 weighted images. At 6-month follow-up with B12 therapy, 10/14 patients with neuropathy recovered completely, 2/14 had partial recovery, and 2 had poor recovery. While the cases of myelopathy had only partial recovery at 6 months, all four cases with acute confusional state recovered completely in response to B12 therapy. Conclusion: The electrodiagnostic and neuroimaging changes in vitamin B12 deficiency are consistent with focal demyelination of white matter tracts in the brain, the spinal cord, and peripheral nerves. In this case series of B12 deficiency MA, we found demyelinating peripheral neuropathy to be the predominant presenting neurological disease. However, cognitive impairment with behavioral changes was found to be common on neurological and psychiatric examination. Many of these features were found to be reversible with B12 therapy. [ABSTRACT FROM AUTHOR]

Background: DNA damage effects of vitamin B12 deficiency were performed in vitro and in adults. Methods: The study group included 32 children (13 girls, 19 boys) with vitamin B12 deficiency (mean age 44 ± 58 months) and their 27 mothers (mean age 30.4 ± 5.3 years). The control group contained 30 healthy children and 25 mothers. DNA strand breaks in peripheral blood mononuclear leukocytes were assayed by single-cell alkaline gel electrophoresis (comet assay) before and 8 days after the first injection of vitamin B12. Results: Mean DNA damage scores in children with vitamin B12 deficiency and their mothers were significantly higher before treatment than those after treatment. The DNA damage scores of children after treatment were still significantly higher than controls. There were significant negative correlations between the children and their mothers in terms of vitamin B12 levels and DNA damage scores (r = 0.3, P= 0.02; r = 0.58, P= 0.002, respectively). There were correlations between the children's and their mothers' DNA damage and the severity of vitamin B12 deficiency, suggesting that the children and their mothers may play a role in the scarcity of nutritional vitamin B12. Conclusion: DNA damage is increased in children with vitamin B12 deficiency and in their mothers. DNA damage scores were significantly improved through vitamin B12 therapy 8 days after the first injection, however, they were still significantly higher than those of controls. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The purpose of this study was to investigate the protective effects of combined treatment of folate and vitamin B12 against alcoholic liver disease. Methods: Male Wistar rats weighing about 160 g were divided into four groups: an ethanol group fed an ethanol liquid diet; a control group pair-fed an isoenergetic diet without ethanol; an ethanol and vitamin group fed an ethanol-containing diet that was supplemented with folate (10 mg/kg of body weight per day) and vitamin B12 (0.5 mg/kg of body weight per day); and a control and vitamin group fed an isoenergetic diet without ethanol, which was supplemented with folate (10 mg/kg of body weight per day) and vitamin B12 (0.5 mg/kg of body weight per day). Results: After 16 wk, the plasma folate concentration in the ethanol group was significantly lower than in the other three groups. The plasma homocysteine concentration in the ethanol group was significantly higher than in the other three groups. The hepatic matrix metalloproteinase-2 concentration in the ethanol group was significantly higher than in the control and ethanol/vitamin groups. Furthermore, the plasma homocysteine concentration at the 16th week and the hepatic matrix metalloproteinase-2 concentration showed a significant positive correlation in rats of each group. In addition, pathologic evidence of liver fibrosis was observed only in the ethanol group. Furthermore, hepatic cytochrome 2E1 protein expression in group E increased significantly. Conclusion: These results suggest that combined treatment of folate and vitamin B12 can alleviate alcoholic liver injury that may be related to normalization of plasma homocysteine levels. [Copyright &y& Elsevier]

Deficiencies of folate or of vitamin B-12 are widespread and constitute a major global burden of morbidity that affect all age groups. Detecting or confirming the presence of folate or vitamin B-12 deficiency and distinguishing one from the other depends, ultimately, on laboratory testing. Tests to determine the presence of folate or vitamin B-12 deficiency are used singly or in combination to establish the nutritional status and prevalence of deficiencies of the vitamins in various populations. The efficacy of interventions through the use of fortification or supplements is monitored by using the same laboratory tests. Tests currently in use have limitations that can be either technical or have a biological basis. Consequently, each single test cannot attain perfect sensitivity, specificity, or predictive value. Laboratory indicators of vitamin B-12 or folate status involve the measurement of either the total or a physiologically relevant fraction of the vitamin in a compartment such as blood. Thus, assays to measure vitamin B-12 or folate in plasma or serum as well as folate in red blood cells are in widespread use, and more recently, methods to measure vitamin B-12 associated with the plasma binding protein transcobalamin (holotranscobalamin) have been developed. Alternatively, concentrations of surrogate biochemical markers that reflect the metabolic function of the vitamin can be used. Surrogates most commonly used are plasma homocysteine, for detection of either vitamin B-12 or folate deficiency, and methylmalonic acid for detection of vitamin B-12 deficiency. The general methods as well as their uses, indications, and limitations are presented. [ABSTRACT FROM AUTHOR]

Thiamine supplementation may prevent and reverse early-stage diabetic nephropathy. This probably occurs by correcting diabetes-linked increased clearance of thiamine, maintaining activity and expression of thiamine pyrophosphate-dependent enzymes that help counter the adverse effects of high glucose concentrations-particularly transketolase. Evidence from experimental and clinical studies suggests that metabolism and clearance of thiamine is disturbed in diabetes leading to tissue-specific thiamine deficiency in the kidney and other sites of development of vascular complications. Thiamine supplementation prevented the development of early-stage nephropathy in diabetic rats and reversed increased urinary albumin excretion in patients with type 2 diabetes and microalbuminuria in two recent clinical trials. The thiamine monophosphate prodrug, Benfotiamine, whilst preventing early-stage development of diabetic nephropathy experimentally, has failed to produce similar clinical effect. The probable explanations for this are discussed. Further definitive trials for prevention of progression of early-stage diabetic nephropathy by thiamine are now required. [ABSTRACT FROM AUTHOR]

Oral Diseases (2010) , 95-101 The objective of this study was to test the efficacy of three different treatment modalities on the reduction of serum anti-gastric parietal cell autoantibody (GPCA) level in GPCA-positive oral lichen planus (OLP) patients. Of 147 GPCA-positive OLP patients, 100 were treated with levamisole plus vitamin B12, 10 with vitamin B12 only and 37 with levamisole only. The serum GPCA levels in 147 OLP patients were measured at baseline and after treatment. Treatment with levamisole plus vitamin B12 for a period of 2-50 months and treatment with vitamin B12 only for a period of 4-44 months could effectively reduce the high serum GPCA level to undetectable level in 100 and 10 OLP patients, respectively. However, treatment with levamisole only for a period of 2-50 months could not modulate the high mean serum GPCA titer to a significantly lower level in 37 OLP patients. A 92% GPCA recurrence rate was found in 25 OLP patients receiving no further vitamin B12 treatment during the GPCA-negative remission period. For GPCA-positive OLP patients, treatment modality containing vitamin B12 can effectively reduce the high serum GPCA level to undetectable level. OLP patients with underlying autoimmune atrophic gastritis trait should receive a maintenance vitamin B12 treatment for life. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125-200 pM/l is lacking. We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo. Methods: This multicentre (13 general practices, two nursing homes, and one primary care center in western Switzerland), parallel, randomised, controlled, closed-label, observer-blind trial included 50 patients with serum vitamin B12 levels between 125-200 pM/l who were randomized to receive either oral vitamin B12 (1000 μg daily, N = 26) or placebo (N = 24) for four weeks. The institution's pharmacist used simple randomisation to generate a table and allocate treatments. The primary outcome was the change in serum methylmalonic acid (MMA) levels after one month of treatment. Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels. Blood samples were centralised for analysis and adherence to treatment was verified by an electronic device (MEMS; Aardex Europe, Switzerland). Trial registration: ISRCTN 22063938. Results: Baseline characteristics and adherence to treatment were similar in both groups. After one month, one patient in the placebo group was lost to follow-up. Data were evaluated by intention-to-treat analysis. One month of vitamin B12 treatment (N = 26) lowered serum MMA levels by 0.13 μmol/l (95%CI 0.06-0.19) more than the change observed in the placebo group (N = 23). The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 (95% CI 1.7-6.4). A significant change was observed for the B12 serum level, but not for the homocysteine level, hematocrit, or mean corpuscular volume. After three months without active treatment (at four months), significant differences in MMA levels were no longer detected. Conclusions: Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency. However, a one-month daily treatment with1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months, and treatment had no effect on haematological signs of B12 deficiency. [ABSTRACT FROM AUTHOR]

Purpose: Pemetrexed is licensed for use in mesothelioma and non-small-cell lung cancer. Early clinical development indicated that it causes cytotoxicity with dose (efficacy) limiting gastrointestinal (GI) and blood toxic effects. Use of folic acid and vitamin B12 reduced these toxicities. This study was undertaken to assess the effectiveness of a risk minimization program based on administration of folic acid and vitamin B12 to reduce the therapeutic toxicity of pemetrexed and physicians' compliance with these measures. Methods: Lilly Safety Database was searched for reports of GI and blood toxicity associated with pemetrexed. The period of early development was compared with the subsequent period in which risk minimization measures were in place. Reports from the postmarketing period were assessed to determine the percentage reported with appropriate risk minimization supplemention. Results: The proportion of severe GI and blood toxicity in clinical trials was lower after the introduction of supplementation (67.3% vs 84.8%, P < 0.001). A reduction in toxicity was also seen in the individual MedDRA System Organ Classes: hematological toxicity (49.5% to 43%, P-0.015) and GI toxicity (26.5% to 12.9%, P<0.001). In the 4-year postmarketing period, compliance with the risk minimization program as assessed by the percentage of initial reports, which included details of appropriate supplementation, was stable at 70%. This rose to 97.7% on follow-up. Conclusion: Implementation of this risk minimization program demonstrated a significant reduction in adverse drug reaction reports of high-grade blood and GI toxicity together with a high level of compliance with supplementation treatment. It is feasible to verify the success of a risk minimization method by objective demonstration of a reduction in toxicity and, separately, to confirm physicians' compliance with the risk minimization program. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study is to investigate the importance of serum vitamin B12 levels in pregnant women with foetal neural tube defect (NTD). Study design. This study consists of 31 pregnant women having fetuses with NTD. The pregnant women in the study group were selected among cases with normal folate levels. Serum vitamin B12 levels were investigated. Additionally, complete blood count, serum iron level, iron binding capacity, ferritin, folate, free T3, free T4, thyroid stimulating hormone and plasma homocysteine levels were measured. Control group consisted of 32 pregnant women who did not have a history of NTD in previous pregnancies and did not have fetuses with NTD in present pregnancy. NTD was diagnosed between14th and 20th gestational age. The mean gestational age of members of control group was the same as those of NTD group. Results. There was no statistically significant difference between pregnants with NTD and control group according to number of cases with vitamin B12 deficiency. Conclusion. It seems that vitamin B12 deficiency does not play a causative role in the development of foetal NTD. Monitoring maternal homocystein levels might be important in understanding the aetiologies of foetal NTD. [ABSTRACT FROM AUTHOR]

Vitamin B12 (cobalamin) ranks among the most useful, safe and effective orthomolecules when treating a diverse array of neuropsychiatric conditions. However, most clinicians do not consider vitamin B12 important unless the serum level is below laboratory reference ranges. Ten research reports, summarized here, indicate metabolic consequences from low-normal (but not deficient) serum B12 levels, and/or clinical improvements following therapy that markedly increased serum B12 levels. My clinical experience, along with the summarized reports, suggests that (1) serum levels of vitamin B12 not "classically" deficient by current laboratory standards are associated with neuropsychiatric signs and symptoms, and (2) clinical improvement results when serum vitamin B12 levels are optimized or markedly increased following vitamin B12 treatment. Vitamin B12's mechanisms of action are believed to include increased S- adenosylmethionine production, improved methylation, decreased plasma and brain homocysteine, compensation for inborn errors of metabolism, normalized gene expression, correction of long-latency vitamin B12 debt, and anti-inflammatory activity. Clinicians may wish to re-evaluate the importance of lower-than-optimal serum vitamin B12 levels, pursue additional testing such as urinary methylmalonic acid, and consider the potential benefits of vitamin B12 treatment. [ABSTRACT FROM AUTHOR]

Atypical hemolytic uremic syndrome (aHUS) is mostly linked to defects in the regulation of alternative complement pathway, but a rare form is caused by an inherited defect of cobalamin 1 metabolism. Cobalamin C (cblC) deficiency is an autosomal recessive disorder of vitamin B12 metabolism that results from mutations in methylmalonic aciduria and homocysteinuria ( MMACHC). The most severe form of cblC deficiency and the associated high mortality rate are mostly observed in neonates or in infants <6 months of age. Early diagnosis of cblC deficiency leads to early treatment and an improved prognosis. We describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing a study on the overuse of vitamin B12 supplements in French nursing homes.

Abstract: Oxidative stress is a feature of many chronic inflammatory diseases. Such diseases are associated with up-regulation of a vitamin B12 (cobalamin) blood transport protein and its membrane receptor, suggesting a link between cobalamin and the cellular response to inflammation. The ability of cobalamin to regulate inflammatory cytokines suggests that it may have antioxidative properties. Here we show that cobalamins, including the novel thiolatocobalamins N-acetyl-l-cysteinylcobalamin and glutathionylcobalamin, are remarkably effective antioxidants in vitro. We also show that thiolatocobalamins have superior efficacy compared with other cobalamin forms, other cobalamins in combination with N-acetyl-l-cysteine (NAC) or glutathione (GSH), and NAC or GSH alone. Pretreatment of Sk-Hep-1 cells with thiolatocobalamins afforded robust protection (>90% cell survival) against exposure to 30 μM concentrations of the pro-oxidants homocysteine and hydrogen peroxide. The compounds inhibited intracellular peroxide production, maintained intracellular glutathione levels, and prevented apoptotic and necrotic cell death. Moreover, thiolatocobalamins are remarkably nontoxic in vitro at supraphysiological concentrations (>2 mM). Our results demonstrate that thiolatocobalamins act as powerful but benign antioxidants at pharmacological concentrations. Because inflammatory oxidative stress is a component of many conditions, including atherosclerosis, dementia, and trauma, their utility in treating such disorders merits further investigation. [Copyright &y& Elsevier]

Objective: Folic acid and vitamin B12 are essential cofactors in several biochemical pathways that are critical for neurobiological and hematological functions. Vitamin B12 and folate deficiencies are reported in schizophrenia and depression patients but there are only a few studies investigating the effects of the treatment on serum folic acid and vitamin B12 levels. This study aimed to investigate serum folic acid and vitamin B12 levels in patients with depression, schizophrenia and bipolar disorder and the effects of the drug treatment on these vitamin levels. Method: Twenty-six schizophrenia, 16 major depressive, and 47 bipolar (manic, depressive or mixed episode) disorder inpatients diagnosed according to DSM-IV criteria and 21 healthy controls were included in the study. Serum vitamin B12 and folic acid levels were measured before the treatment. The patients received the treatment at therapeutic doses for 5 weeks. Fifteen of the schizophrenic patients were treated with atypical antipsychotics including risperidone, olanzapine, quetiapine and 11 of them with typical antipsychotics (haloperidol or zuclopenthicsole). Bipolar patients received mood stabilizer and antipsychotic and/or antidepressant according to their present episode. The patients with major depressive disorder were treated with various antidepressant drugs. Serum vitamin B12 and folic acid levels were measured again in all patients after five weeks. The same measurements were performed only once in the controls. Results: Serum folic acid and vitamin B12 levels were not significantly different among the patient groups and the controls in pre-treatment. In schizophrenic patients, serum folic acid levels were significantly reduced after typical antipsychotic treatment compared to those in pre-treatment and to those of the controls while they did not change after atypical antipsychotic treatment. Bipolar patients who received lithium had lower serum folic acid levels in post-treatment than in pre-treatment. There was a negative correlation between serum folic acid levels and severity of depression in the patients with major depressive disorder. Conclusion: The results of the study suggest that serum folic acid and vitamin B12 values in schizophrenia, bipolar disorder, and major depressive disorder did not differ from healthy controls. However, it seems that some drug treatments might lead to a decrease in folic acid levels. Nevertheless, further studies are needed to confirm the effects of specific drug treatments on these vitamins. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that increasing methyl-group pools might promote transcriptional repression by other methyl-binding proteins or by mutant methyl-CpG-binding protein 2 with altered affinity, ameliorating the clinical features of Rett syndrome. A 12-month, double-blind, placebo-controlled folate-betaine trial enrolled 73 methyl-CpG-binding protein 2 mutation positive female participants meeting consensus criteria for Rett syndrome. Participants were randomized as young (< age 5 years) or old (≥ age 5 years). Structured clinical assessments occurred at baseline, 3, 6, and 12 months. Primary outcome measures included quantitative evaluation of breathing and hand movements during wakefulness, growth, anthropometry, motor/behavioral function, and qualitative evaluations from electroencephalograms and parent questionnaires. In all, 68 participants completed the study. Objective evidence of improvement was not found. Subjective improvement from parent questionnaires was noted for the <5 years group. This study should inform future treatment trials regarding balancing participants with specific mutations and comparable severity to minimize selection bias. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to compare the sensitivity of three ultrasound phenotypes of carotid atherosclerosis in a longitudinal study of patients with diabetic nephropathy. B-mode ultrasound-derived intima-media thickness (IMT), total plaque area (TPA) as well as three-dimensional ultrasound (3DUS) vessel wall volume (VWV) of the common carotid artery (CCA) (VWVCCA) and internal carotid artery (ICA). (VWVCCA+ICA) were all evaluated in subjects enrolled in a randomized placebo-controlled double blind study of vitamin B therapy. Of 106 subjects randomized, 77 subjects were scanned at baseline and 2.3 ± 1 y later (range: 0.5 to 4.5 y); of these subjects, 71 had images of sufficient quality for complete analysis of all three measurements. Subjects were analyzed according to the two treatment groups (A and B) and the analysis was performed blinded to treatment group description to prevent any potential for bias in future analyses. There were differences in sensitivity to longitudinal changes observed in all the ultrasound measurements. Specifically, there was no difference in IMT change between treatment groups (0.02 ± 0.07 mm/y and 0.02 ± 0.1 mm/y p = 0.15, group A and B, respectively, rates not different from zero [p > 0.05]) or TPA rate between treatment groups (0.09 ± 0.2 cm2/y, significantly different from 0, p = 0.013 and −0.02 ± 0.3 cm2/y in group A and B, respectively). However, the VWVCCA+ICA rate of change was significantly greater than 0 for group B (53 ± 110 mm3/y) (p = 0.008), which was significantly (p = 0.034) higher than the rate of change of VWVCCA+ICA (nonsignificant, p = 0.6) for group A (-12 ± 137 mm3/y). The relationship between ΔVWV and ΔIMT was significant, such that in group A, ΔVWVCCA was positively associated with ΔIMT (r = 0.44, p < 0.05), and in group B, ΔVWVCCA was negatively correlated with ΔIMT (r = −0.44, p < 0.01). These results suggest that 3DUS-derived VWV provides necessary and sufficient sensitivity and specificity to measure longitudinal changes in small numbers of carotid atherosclerosis patients at risk of disease progression and over short periods of time. (E-mail: gep@imaging.robarts.ca) [Copyright &y& Elsevier]

The present study was undertaken to elucidate the toxicity induced by sodium selenite in male quail through in vivo and in vitro studies and the role played by vitamin B12 in alleviating selenium toxicity. Administration of selenite orally for 1 month induced hepatic oxidative damage. Selenite decreased body weight gain and increased relative liver weight. Selenite reduced hemoglobin and iron concentrations and elevated total bilirubin concentration. Serum transaminases and alkaline phosphatase activities were increased in selenium-intoxicated quails. Total protein concentration was decreased associated with the appearance of prealbumin fraction, an increased γ-globulin and a decreased α- and β-globulins. The highest level of selenium was found in liver followed by kidney, testis, faeces and blood. Supplementation of vitamin B12 orally for 1 month simultaneously with selenite caused less marked biological alteration in the investigated parameters. In vitro study using isolated quail hepatocytes incubated with sodium selenite showed a dose-dependent response for toxicity markers. These results suggest that selenosis can be reduced by vitamin B12 supplementation. [Copyright &y& Elsevier]

A letter to the editor is presented regarding a case study of nocturnal enuresis cessation following intervention with methylcobalamin in an 18-year-old patient with childhood autism.

A light-inducible promoter, PB, drives expression of the carB operon in Myxococcus xanthus. Repressed by CarA in the dark, PB is activated when CarS, produced in the light, sequesters CarA to prevent operator-CarA binding. The MerR-type, N-terminal domain of CarA, which mediates interactions with both operator and CarS, is linked to a C-terminal oligomerization module with a predicted cobalamin-binding motif. Here, we show that although CarA does bind vitamin B12, mutating the motif involved has no effect on its ability to repress PB. Intriguingly, PB could be repressed in the dark even with no CarA, so long as B12 and an intact CarA operator were present. We have discovered that this effect of B12 depends on the gene immediately downstream of carA. Its product, CarH, also consists of a MerR-type, N-terminal domain that specifically recognizes the CarA operator and CarS, linked to a predicted B12-binding C-terminal oligomerization module. The B12-mediated repression of PB in the dark is relieved by deleting carH, by mutating the DNA- or B12-binding residues of CarH, or by illumination. Our findings unveil parallel regulatory circuits that control a light-inducible promoter using a transcriptional factor repertoire that includes a paralogous gene pair and vitamin B12. [ABSTRACT FROM AUTHOR]

Objective: To investigate serum levels of folate, B12, and total homocysteine (tHcy) in elderly post-stroke patients, and the possible correlations with radiological markers of neuropathology.Design: Cross-sectional study.Setting: Department of Neurology, Cardinal Tien Hospital.Subjects: Eighty-nine elderly post-stroke patients were enrolled for dietary assessment and blood tests. Neuroradiological assessment was done in 62 of these patients.Main Outcome Measures: Dietary folate and vitamin B12 intakes were evaluated by a 24-h recall system using a semi-quantitative questionnaire. Circulating levels of folate, B12, and tHcy were measured. Magnetic resonance imaging (MRI) or computed tomography (CT) was used for evaluation of brain lesions including infarction and atrophy.Results: Mean folate and B12 intakes of these post-stroke patients were 69% and 261% of the recommended dietary allowances (RDA), respectively. Inadequate folate levels, defined as serum folate < 6 ng/mL, was noted in 68% of these patients. Hyperhomocysteinemia levels (tHcy >or=15 micromol/L) were observed in 48%. According to tertiles of serum tHcy and folate levels, the rate of brain atrophy, but not brain infarctions, are significantly associated with elevated tHcy (P = 0.0126) and decreased folate levels (P = 0.0273). After adjustments for age, sex, disease status, brain infarctions and carotid stenosis, the odds ratio of brain atrophy was 9.8 (95% CI: 1.7-56.4, P = 0.0101) in the hyperhomocysteinemia group and 9.6 (95% CI: 1.1-81.3, P = 0.0377) in the low folate group (serum folate < 3.0 ng/mL) compared with the group with normal tHcy and folate levels. No significant association was noted between vitamin B12 levels and brain lesions.Conclusions: Our data shows that folate deficiency and hyperhomocysteinemia are prevalent in elderly post-stroke patients. These two conditions are strongly and independently associated with the development of brain atrophy. [ABSTRACT FROM AUTHOR]

The article comments on a follow-up study by I. Kvestad and colleagues about the sustainability of benefits of early nutrition interventions to improve cognition in children. Topics discussed include childhood supplementation with vitamin B12 and folate, the assessment of cognitive functions including memory, verbal skills and perceptual reasoning, and the role of nutrition as a predictor of neurodevelopment.

A 64-year-old female underwent cardiopulmonary bypass (CPB) for acute ST-elevation myocardial infarction and received a 5 g dose of intravenous hydroxocobalamin (Cyanokit, Meridian Medical Technologies) for treatment of vasoplegic syndrome. Hydroxocobalamin as a rescue treatment for refractory vasoplegic syndrome after prolonged cardiopulmonary bypass. [Extracted from the article]

Purpose: Determine acceptance of and compliance with intranasal cobalamin (vitamin B12) replacement therapy. Methods: Veteran subjects were recruited from VA Outpatient facilities in Hawai'i. Information was obtained by interview and medical record review. Subjects received the standard dose of intranasal cobalamin of 500 micrograms intranasally, once a week. A follow-up questionnaire was administered at one and three months of therapy. Results: Thirty-four subjects were enrolled in the study. Ages ranged from 29 to 87 years of age, with a mean age of 68. 6. Ninety-seven percent were men, 59% were Caucasian, and 35% were Asian/Pacific Islanders. At the end of three months, 30 patients had completed the study. Ninety percent preferred the gel over injection. In the subset of subjects with a history of depression, only 60% preferred intranasal gel. Conclusion: Veteran patients tolerated intranasal cobalamin gel well. The majority of patients preferred intranasal over intramuscular injection of vitamin B12. [ABSTRACT FROM AUTHOR]

Background: Subacute combined degeneration is an acquired myelopathy caused by vitamin B12 deficiency. Therapy with B12 leads to improvement in most but to complete recovery in only a few patients. Prognostic indicators in subacute combined degeneration are unknown; therefore, predicting complete recovery of neurologic deficits is challenging.Purpose: To identify potential correlates of outcome and to generate hypotheses concerning predictors of complete resolution of neurologic deficits in subacute combined degeneration.Data Source: We searched EMBASE (1974 to October 2005), MEDLINE (1968 to October 2005), and references from identified reports. REPORTS SELECTION: Reports of patients with subacute combined degeneration containing results of magnetic resonance imaging (MRI) and description of outcome and 1 patient treated by the authors.Data Extraction, Synthesis: We extracted data from 45 reports and 57 patients (36 males, 21 females; age range: 10 to 81) with a diagnosis of subacute combined degeneration, and estimated the strength of association between clinical, laboratory, and radiological factors and complete resolution of signs and symptoms.Results: Eight patients (14%) achieved clinical resolution and 49 (86%) improved with B12 therapy. The absence of sensory dermatomal deficit, Romberg, and Babinski signs were associated with a higher complete resolution rate. Patients with MRI lesions in < or = 7 segments and age less than 50 also appear to have higher rates of complete resolution.Conclusions: B12 therapy is reported to stop progression and improve neurologic deficits in most patients with subacute combined degeneration. However, complete resolution only occurs in a small percentage of patients and appears to be associated with factors suggestive of less severe disease at the time of diagnosis. [ABSTRACT FROM AUTHOR]