Mg Of Cyanocobalamin Research Articles

The Preparation and Evaluation of Cyanocobalamin Mucoadhesive Sublingual Tablets.

Cobalamin (vitamin B12), an essential vitamin with low oral bioavailability, plays a vital role in cellular functions. This research aimed to enhance the absorption of vitamin B12 using sublingual mucoadhesive tablets by increasing the residence time of the drug at the administration site. This research involved the preparation of different 50 mg placebo formulas using different methods. Formulas with disintegration times less than one minute and appropriate physical characteristics were incorporated into 1 mg of cyanocobalamin (S1-S20) using the direct compression method. The tablets obtained were evaluated ex vivo for residence time, and only those remaining for >15 min were included. The final formulas (S5, S8, S11, and S20) were evaluated in several ways, including pre- and post-compression, drug content, mucoadhesive strength, dissolution, and Permeapad® permeation test employed in the Franz diffusion cell. After conducting the evaluation, formula S11 (Eudragit L100-55) emerged as the most favorable formulation. It exhibited a mucoadhesive residence time of 118.2 ± 2.89 min, required a detachment force of 26 ± 1 g, maintained a drug content of 99.124 ± 0.001699%, and achieved a 76.85% drug release over 22 h, fitting well with the Peppas-Sahlin kinetic model (R2: 0.9949). This suggests that the drug release process encompasses the Fickian and non-Fickian kinetic mechanisms. Furthermore, Eudragit L100-55 demonstrated the highest permeability, boasting a flux value of 6.387 ± 1.860 µg/h/cm2; over 6 h. These findings indicate that including this polymer in the formulation leads to an improved residence time, which positively impacts bioavailability.

Use of Butaphosphan with Cyanocobalamin in High Producing Cows and Associations with Milk Yield and Dry Matter Intake

This study aimed to verify the effect of butaphosphan combined with cyanocobalamin (B+C) on dry matter intake (DMI) and milk yield in high producing dairy cows. Eighteen multiparous Holstein cows managed in a compost barn system were enrolled on a calving date and remained under observation until 28 days in milk (DIM). The B+C group administered at 2500 mg of butaphosphan and 1.25 mg of cyanocobalamin (25 mL/cow/day, n = 9), or the control group (NaCl 0.9% administered at 25 mL/cow/day, n = 9,) receiving injections at calving, and at day 3 and 7 post-partum. The DMI, feed efficiency, and DMI/% body weight were evaluated until 21 DIM and the milk yield, rumination, activity, and lying time until 28 DIM. Various metabolites were evaluated at 0, 3, 7, 14, 21, and 28 DIM. DMI did not change with treatment. Milk yield was more significant in the B+C group than in the control group, with an increase of 3.66 kg/milk/d. The maintenance of DMI and the greater milk yield in the B+C group may suggest that the use of B+C can improve feed efficiency. No treatment effect was observed for concentrations of serum glucose, NEFA, BHB, and acetone, however, albumin was higher in B+C than in control. No effect was observed on milk composition. Our results suggest that B+C improves milk yield and feed efficiency by modulating the DMI.

Analysis of cobalt for human sports drug testing purposes using ICP- and LC-ICP-MS.

Due to the current demands in the fight against manipulation of blood and blood components, commonly referred to as "blood doping" in sports drug testing, specific and sensitive detection methods enabling the detection of prohibited substances and methods of doping are required. Similar to illicit blood transfusions, erythropoiesis stimulating agents have been shown to be misused in sport, aiming at improving an athlete's aerobic capacity and endurance performance. Amongst other strategies, the administration of ionic cobalt (Co2+ ) can increase the number of erythrocytes by stimulating the endogenous erythropoietin (EPO) biosynthesis. Conversely, several organic Co-containing compounds such as cyanocobalamin (vitamin B12) are not prohibited in sports, and thus, an analytical differentiation of permitted and banned contributions to urinary Co-concentrations is desirable. An excretion study with daily applications of either 1 mg of CoCl2 or 1 mg of cyanocobalamin was conducted with 20 volunteers over a period of 14 consecutive days. Urine, plasma, and concentrated red blood cells were analyzed for their cobalt content. The samples were collected starting 7 days before the administration until 7 days after. Total Co concentrations were analyzed by using inductively coupled plasma mass spectrometry (ICP-MS), which yielded significantly elevated levels exclusively after inorganic cobalt intake. Furthermore, a liquid chromatography (LC)-ICP-MS approach was established and employed for the simultaneous determination of organically bound and inorganic cobalt by chromatographic separation within one single run. The analytical approach offers the option to further develop detection methods of illegal Co2+ supplementation in sport.

Toxicity induced by multiple high doses of vitamin B12 during pernicious anemia treatment: a case report

Context: The clinical consequences of excess vitamin B12 induced by multiple oral doses of cyanocobalamin are not well-known.Case details: A young woman was treated with multiple daily doses of 1 mg of cyanocobalamin for severe pernicious anemia. After a total dose of 12 mg, she developed acne, palpitations, anxiety, akathisia, facial ruddiness, headache, and insomnia. She improved two weeks after stopping the drug. There were no sequelae nor complications.Discussion: Although these symptoms of cobalamin toxicity were unexpected and unusual, the case reminds us that the administration of any drug is not entirely safe.

NOVA SOLUÇÃO ELETROLÍTICA INTRAVENOSA PARA USO VETERINÁRIO: EFEITOS SOBRE O PERFIL ELETROLÍTICO E ÁCIDO BASE EM BOVINOS ADULTOS HÍGIDOS

Resumo Objetivou-se avaliar os efeitos de uma nova solução hidratante intravenosa sobre os equilíbrios eletrolítico e ácido-base de bovinos. Para tanto, oito animais adultos hígidos, mestiços taurinos foram submetidos a dois tratamentos em delineamento cross-over: solução salina isotônica (SI) e solução teste (ST) composta por 145 mEq de Na+, 5 mEq de K+, 4 mEq de Ca++, 2 mEq de Mg++, 96 mEq de Cl-, 60 mEq de lactato, 50 g de dextrose e 4 mg de cianocobalamina por litro. As soluções foram administradas por via intravenosa, em volume correspondente a 5% do peso corporal, durante três horas de infusão contínua. Amostras de sangue venoso foram colhidas antes da infusão e três, seis, nove e 24 horas após o início da infusão para determinações de glicose, lactato L, Ca, P, Mg, pH, pCO2, HCO3-, BE, Na+, K+, Cl- e Ca++. Os resultados foram analisados por análise de variâncias de medidas repetidas. Ao contrário da SI, que causou hipercloremia e redução da diferença de íons fortes no plasma (SID), determinando efeito acidificante, a ST gerou alcalinização leve e transitória e não provocou alteração das concentrações de Na+ e de Cl-. A hipopotassemia e a hiperglicemia, presentes ao final da infusão da ST, foram transitórias e não determinaram sinais clínicos evidentes. Conclui-se que a ST é uma alternativa segura para a terapia com fluidos em bovinos, tendo a vantagem de provocar alterações iatrogênicas de baixa magnitude.

Effects of a new intravenous electrolyte solution for veterinary therapy on the electrolyte and acid-base balances of healthy horses

ABSTRACT: The effects of a new intravenous electrolyte solution for veterinary therapy on electrolyte and acid-base balances of horses were evaluated, assessing the potential of the use of this solution as a rational alternative in fluid therapy. Eight healthy adult horses, including 4 males and 4 females, received two treatments in a cross-over design: isotonic saline solution (IS) and a test solution (TS) containing 145mEq of Na+, 5mEq of K+, 4mEq of Ca++, 2mEq of Mg++, 96mEq of Cl-, 60mEq of lactate, 50g of dextrose, and 4mg of cyanocobalamin per liter. Solutions were IV infused in a volume corresponding to 5% of BW, over 3 hours. Venous blood samples were taken 5 times before and after the infusion (at 0, 3, 6, 9 e 24h), for pHv, pCO2v, HCO3 -v, BEv, Na+, K+, Cl-, Ca++, Ca, P, Mg, glucose and L-lactate measurements, and AG and SID calculations. The data were analyzed through repeated measures ANOVA. The IS caused mild acidifying effect by increasing Cl- and decreasing plasma SID. In contrast, the TS induced mild and transient hypochloremia without changes in acid-base balance. Hyperglycemia was present at the end of the TS infusion and reversed 6 hours later. The horses did not exhibit any clinical changes. We concluded that TS is an option for fluid therapy in horses.

Effect of butaphosphan and cyanocobalamin on postpartum metabolism and milk production in dairy cows

The aim of this study was to determine the effect of butaphosphan and cyanocobalamin (BTPC) supplementation on plasma metabolites and milk production in postpartum dairy cows. A total of fifty-two Holstein cows were randomly assigned to receive either: (1) 10 ml of saline (NaCl 0.9%, control group); (2) 1000 mg of butaphosphan and 0.5 mg of cyanocobalamin (BTPC1 group); and (3) 2000 mg of butaphosphan and 1.0 mg of cyanocobalamin (BTPC2 group). All cows received injections every 5 days from calving to 20 days in milk (DIM). Blood samples were collected every 15 days from calving until 75 DIM to determine serum concentration of glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), cholesterol, urea, calcium (Ca), phosphorus (P), magnesium (Mg), aminotransferase aspartate (AST) and γ-glutamyltransferase (GGT). The body condition score (BCS) and milk production were evaluated from calving until 90 DIM. Increasing doses of BTPC caused a linear reduction in plasma concentrations of NEFA and cholesterol. Supplementation of BTPC also reduced concentrations of BHB but it did not differ between the two treatment doses. Milk yield and milk protein had a linear increase with increasing doses of BTPC. A quadratic effect was detected for milk fat and total milk solids according to treatment dose, and BTPC1 had the lowest mean values. Concentrations of glucose, urea, P, Mg, AST, GGT, milk lactose and BCS were not affected by treatment. These results indicate that injections of BTPC during the early postpartum period can reduce NEFA and BHB concentrations and increase milk production in Holstein cows.

The effect of injectable butaphosphan and cyanocobalamin on postpartum serum β-hydroxybutyrate, calcium, and phosphorus concentrations in dairy cattle

The objective of this study was to determine the effect of an injection of 10% butaphosphan and cyanocobalamin (Catosal, Bayer, Shawnee Mission, KS) on the day of calving and 1 d later on the prevalence of subclinical ketosis in dairy cattle in the early postpartum period. Cows from 4 herds (n=1,122) were randomized to receive either 25mL of 10% butaphosphan and cyanocobalamin or 25mL of sterile water subcutaneously on both days. Each milliliter of Catosal contained 0.05mg of cyanocobalamin and 100mg of butaphosphan, which provided 17.3mg of P in the form of [1-(butylamino)-1-methylethyl]-phosphonic acid. Serum was sampled for β-hydroxybutyrate (BHBA) concentration at calving (pretreatment) and again between 3 and 10 d in milk. A subset of samples from mature cows was also evaluated for serum Ca and P concentrations. When cows from all age groups were included in the analysis, there was no difference between the median serum BHBA concentrations of cows in the 2 treatment groups, and no difference in the proportion of hyperketonemic cows (serum BHBA ≥1,200μmol/L) during the first week postpartum. When the analysis was restricted to mature cows (lactation ≥3), both the median BHBA concentration and the proportion of hyperketonemic cows were significantly lower in the treatment group than in the placebo group. Serum Ca and P concentrations did not differ between treatment groups. Our results suggest that injection of butaphosphan and cyanocobalamin on the day of calving and 1 d later may decrease the prevalence of subclinical ketosis during the week after calving in mature dairy cows, but not in first- and second-lactation animals.

Urinary excretion of vitamin B12 depends on urine volume in Japanese female university students and elderly

Recent studies have shown that urinary excretion of water-soluble vitamins reflects their intake in humans. However, some have reported that physical characteristics and urine volume may affect the amount of vitamin compounds found in urine. We hypothesized that physical characteristics and urine volume could affect urinary excretion of B-group vitamins. Twenty-four-hour urine samples were collected from 186 free-living Japanese women aged 19 to 21 years and 104 free-living Japanese subjects aged 70 to 84 years. Correlations between urinary output of each B-group vitamin and body height, body weight, body mass index, body surface area, urine volume, and urinary creatinine were determined. Only urinary vitamin B(12) was strongly correlated to urine volume in young (r = 0.683, P < .001) and elderly (r = 0.523, P < .001) subjects. To confirm this finding, 20 Japanese adults were orally administered 1.5 mg of cyanocobalamin (500-fold higher daily intake); and correlations between urinary vitamin B(12) and urine volume were determined. The load of cyanocobalamin increased vitamin B(12) content in the urine by only 1.3-fold. Urinary vitamin B(12) was strongly correlated with urine volume on the day before taking, the day of taking, and the day after taking cyanocobalamin (r = 0.745, P < .001; r = 0.897, P < .0001; and r = 0.855, P < .0001, respectively). We conclude that urinary excretion of vitamin B(12) is dependent upon urine volume, but not on intake of vitamin B(12). Physical characteristics and urine volume are less important for B-group vitamins except for vitamin B(12) as biomarker.

Análisis crítico de un artículo: ¿Sirve reducir los niveles de homocisteinemia en los pacientes con insuficiencia renal avanzada?

Context: High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. Objective: To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. Design, Setting and Participant: Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance 15 micromol/L). Intervention: Participants received a daily capsule containing 40 mg off olic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. Main outcome measures: The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of allow part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. Results: Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < 001) in the vitamin group and 0.4 micromol/L (1.7%; P=.14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs. 436placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 Mis in the vitamin group vs. 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs. 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs. 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = . 38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. Conclusion: Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. Trial registration: clinical trials.gov Identifier: NCT00032435.

Effect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease

High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L). Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. clinicaltrials.gov Identifier: NCT00032435.

Cost-effectiveness of vitamin therapy to lower plasma homocysteine levels for the prevention of coronary heart disease: effect of grain fortification and beyond.

A high homocysteine level has been identified as an independent modifiable risk factor for coronary heart disease (CHD) events and death. Since January 1998, the US Food and Drug Administration has required that all enriched grain products contain 140 microg of folic acid per 100 g, a level considered to decrease homocysteine levels. To examine the potential effect of grain fortification with folic acid on CHD events and to estimate the cost-effectiveness of additional vitamin supplementation (folic acid and cyanocobalamin) for CHD prevention. Cost-effectiveness analysis using the Coronary Heart Disease Policy Model, a validated, state-transition model of CHD events in adults aged 35 through 84 years. Data from the third National Health and Nutrition Examination Survey (NHANES III) were used to estimate age- and sex-specific differences in homocysteine levels. Hypothetical comparison between a diet that includes enriched grain products projected to increase folic acid intake by 100 microg/d with the same diet without folic acid fortification; and a comparison between vitamin therapy that consists of 1 mg of folic acid and 0.5 mg of cyanocobalamin and the diet that includes grains fortified with folic acid. Incidence of myocardial infarction and death from CHD, quality-adjusted life-years (QALYs) saved, and medical costs. Grain fortification with folic acid was predicted to decrease CHD events by 8% in women and 13% in men, with comparable reductions in CHD mortality. The model projected that, compared with grain fortification alone, treating all patients with known CHD with folic acid and cyanocobalamin over a 10-year period would result in 310 000 fewer deaths and lower costs. Over the same 10-year period, providing vitamin supplementation in addition to grain fortification to all men aged 45 years or older without known CHD was projected to save more than 300 000 QALYs, to save more than US $2 billion, and to be the preferred strategy. For women without CHD, the preferred vitamin supplementation strategy would be to treat all women older than 55 years, a strategy projected to save more than 140 000 QALYs over 10 years. Folic acid and cyanocobalamin supplementation may be cost-effective among many population subgroups and could have a major epidemiologic benefit for primary and secondary prevention of CHD if ongoing clinical trials confirm that homocysteine-lowering therapy decreases CHD event rates.

Effective Treatment of Cobalamin Deficiency With Oral Cobalamin

Because cobalamin deficiency is routinely treated with parenteral cobalamin, we investigated the efficacy of oral therapy. We randomly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90 or 2 mg orally on a daily basis for 120 days. Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin (normal, 200 to 900 pg/mL) methylmalonic acid (normal, 73 to 271 nmol/L), and homocysteine (normal, 5.1 to 13.9 μmol/L). Five patients were subsequently found to have folate deficiency, which left 18 evaluable patients in the oral group and 15 in the parenteral group. Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups. The mean pretreatment values for serum cobalamin, methylmalonic acid, and homocysteine were, respectively, 93 pg/mL, 3,850 nmol/L, and 37.2 μmol/L in the oral group and 95 pg/mL, 3,630 nmol/L, and 40.0 μmol/L in the parenteral therapy group. After 4 months of therapy, the respective mean values were 1,005 pg/mL, 169 nmol/L, and 10.6 μmol/L in the oral group and 325 pg/mL, 265 nmol/L, and 12.2 μmol/L in the parenteral group. The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant, with P &lt; .0005 and P &lt; .05, respectively. In cobalamin deficiency, 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior. © 1998 by The American Society of Hematology.

Effective Treatment of Cobalamin Deficiency With Oral Cobalamin

AbstractBecause cobalamin deficiency is routinely treated with parenteral cobalamin, we investigated the efficacy of oral therapy. We randomly assigned 38 newly diagnosed cobalamin deficient patients to receive cyanocobalamin as either 1 mg intramuscularly on days 1, 3, 7, 10, 14, 21, 30, 60, and 90 or 2 mg orally on a daily basis for 120 days. Therapeutic effectiveness was evaluated by measuring hematologic and neurologic improvement and changes in serum levels of cobalamin (normal, 200 to 900 pg/mL) methylmalonic acid (normal, 73 to 271 nmol/L), and homocysteine (normal, 5.1 to 13.9 μmol/L). Five patients were subsequently found to have folate deficiency, which left 18 evaluable patients in the oral group and 15 in the parenteral group. Correction of hematologic and neurologic abnormalities was prompt and indistinguishable between the 2 groups. The mean pretreatment values for serum cobalamin, methylmalonic acid, and homocysteine were, respectively, 93 pg/mL, 3,850 nmol/L, and 37.2 μmol/L in the oral group and 95 pg/mL, 3,630 nmol/L, and 40.0 μmol/L in the parenteral therapy group. After 4 months of therapy, the respective mean values were 1,005 pg/mL, 169 nmol/L, and 10.6 μmol/L in the oral group and 325 pg/mL, 265 nmol/L, and 12.2 μmol/L in the parenteral group. The higher serum cobalamin and lower serum methylmalonic acid levels at 4 months posttreatment in the oral group versus the parenteral group were significant, with P < .0005 and P < .05, respectively. In cobalamin deficiency, 2 mg of cyanocobalamin administered orally on a daily basis was as effective as 1 mg administered intramuscularly on a monthly basis and may be superior.© 1998 by The American Society of Hematology.

Vitamin B2 production by Acetobacterium sp. and its tetrachloromethane-resistant mutants

Abstract A strictly anaerobic, homoacetogenic bacterium strain 69, which produces high amounts of intracellular vitamin B12, was isolated from sea sediment. Taxonomical and physiological studies revealed that the isolate should be classified in the genus Acetobacterium. The isolate grown on methanol produced ca. 11 mg of cyanocobalamin per gram dry cells after 7-d cultivation. Tetrachloromethane (TCM) resistant mutants, strain 67-7 and 69-23, were obtained from the isolate by ethylmethanesulfonate treatment, and produced ca. 23 mg of cyanocobalamin per gram dry cells for strain 69-7 and 20 mg for strain 69-23 in the presence of 10 μM of TCM.

Diffusion permeability of cyanocobalamin in human placenta.

The molecular weight of cyanocobalamin is well suited to distinguish the two patterns of size discrimination found in the hemochorial and epitheliochorial placentas. The concentrations of cyanocobalamin that were used ensured that nondiffusional transport was negligible, and experiments on guinea pigs confirmed that the diffusion permeabilities measured with cyanocobalamin were the same as those expected for inert hydrophilic substances of similar molecular weight. All human studies were performed on volunteers who were scheduled for elective cesarean section under spinal or epidural anesthesia. Endogenous plasma concentrations of cobalamin were measured in 10 pregnant volunteers and their newborns. Ten additional volunteers were given 1 mg of cyanocobalamin by intramuscular injection 44 min before delivery. Placental permeability, calculated as the ratio of fetal uptake and the concentration-time integral between maternal and fetal plasmas, was 14.3 microliter X min-1 X g placental wt-1. The permeability of the human placenta parallels that of the histologically similar guinea pig placenta, at a slightly higher level, up to molecular weights of 1,355.

Transport of Therapeutic Cyanocobalamin in the Congenital Deficiency of Transcobalamin II (TC II)

Cobalamin (Cbl) transport was studied in the circulation of a child deficient in transcobalamin II (TC II) after 1.0 mg of cyanocobalamin (CN-Cbl) either intramuscularly or orally. Pertinent observations include the following: (1) There was no detectable TC II in the serum as measured immunologically or by binding capacities in vivo or in vitro. (2) Transcobalamin I (TC I) was present in at least normal amounts, but, in contrast to the normal, TC I was completely saturated with Cbl. (3) The TC I of the child was qualitatively the same as that of normal persons and there was no evidence that TC I, or any other R-type binder, assumed the functions of the apparently absent TC II. (4) There was, however, an incompletely characterized circulating large molecular sized complex containing R-type binder. (5) After intake of 1.0 mg CN-Cbl orally, the usual daily therapeutic dose and route in this child, free Cbl was present in the serum. HeLa cells in culture took up free Cbl much less efficiently than Cbl bound to TC II, but the free Cbl followed the normal sequence in being bound to an intracellular binder and converted from CN-Cbl to the functioning forms adenosyl and methyl Cbl. Therefore entry to free Cbl into the child's tissues was considered to be a therapeutic possibility.