Cyanocobalamin Research Articles

Vitamin B12 Hypersensitivity: A Retrospective Multicenter Study

Vitamin B12 (Vit B12) deficiency affects approximately 20% of those above the age of 60 years in the United Kingdom and United States. If untreated, it leads to detrimental health outcomes. To investigate a cohort of patients with Vit B12 hypersensitivity (VB12H) referred to 3 UK allergy centers and design a pathway for the investigation of VB12H. A total of 29 patients seen between 2014 and 2022 underwent skin prick testing (1 mg/mL) with cyanocobalamin (CC) and hydroxycobalamin (HC) and intradermal testing (0.1 and 0.01 mg/mL). Patients with negative skin tests underwent a Vit B12 drug provocation test (DPT) with either the index or the alternative drug. Of 29 patients, 18 (62%) presented with immediate VB12H. Eight experienced anaphylaxis (4 to HC and 4 to CC) and had positive skin tests to the index drug. One patient reacted to oral and 7 patients to injectable Vit B12. Seven patients sensitized to one form of Vit B12-tolerated DPT with an alternative Vit B12. One patient with immediate VB12H reacted to polyethylene glycol (PEG) in oral cobalamin. Of 29 patients, 8 presented with delayed hypersensitivity reaction; 4 patients tolerated the intramuscular index formulation, whereas 2 patients tolerated the per oral formulation. One patient presented with symptoms consistent with symmetrical drug-related intertriginous and flexural exanthema. Three patients were referred because of cobalt allergy. Confirmed VB12H is rare. We propose a comprehensive evaluation protocol that includes Vit B12 skin tests and considers PEG allergy in patients presenting with VB12H.

Molecular Recognition Patterns between Vitamin B12 and Proteins Explored through STD-NMR and In Silico Studies.

Ligand-receptor molecular recognition is the basis of biological processes. The Saturation Transfer Difference-NMR (STD-NMR) technique has been recently used to gain qualitative and quantitative information about physiological interactions at an atomic resolution. The molecular recognition patterns between the cyanocobalamin (CNBL)/aqua cobalamin (OHBL) and different plant and animal proteins were investigated via STD-NMR supplemented by molecular docking. This study demonstrates that myoglobin has the highest binding affinity and that gluten has the lowest affinity. Casein also shows a higher binding affinity for cyanocobalamin when compared with that of plant-based proteins. STD-NMR results showed the moderate binding capability of casein with both CNBL and OHBL. Computer simulation confirmed the recognition mode in theory and was compared with the experiments. This work is beneficial for understanding the binding affinity and biological action of cyanocobalamin and will attract researchers to use NMR technology to link the chemical and physiological properties of nutrients.

Interfering with Color Response by Porphyrin-Related Compounds in the MTT Tetrazolium-Based Colorimetric Assay.

Porphyrin compounds are widely distributed in various natural products and biological systems. In this study, effects of porphyrin-related compounds including zinc protoporphyrin (ZnPP), protoporphyrin IX (PPIX), cyanocobalamin (CBL), hemin, and zinc phthalocyanine (ZnPC) were analyzed on color response of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) tetrazolium-based assay, a commonly-used method for analyzing cell viability. Color responses of MTT formazan formed in cells treated with ZnPP, PPIX, or ZnPC were significantly reduced even at submicromolar concentrations without affecting cell viability, whereas hemin and CBL did not. ZnPP, PPIX, and ZnPC rapidly induced degradation of MTT formazan already-produced by cells when exposed to light, but not under a dark condition. Photosensitizing properties of the three compounds were also verified through extensive generation of reactive oxygen species under light. The porphyrins did not affect the stability of water-soluble formazans including XTT, WST-1, WST-8, and MTS formazans. Several factors including different light sources and antioxidants modulated the degradation process of MTT formazan by the porphyrins. The results suggest that certain porphyrin compounds could cause a severe artifact in the MTT assay through rapid degradation of formazan dye due to their photosensitizing property, which needs to be considered carefully in the related assays.

Vitamin B12, Folates, and Docosahexaenoic Acid on the Prevention of Neuronal Dysfunction

ObjectivesGlobal aging increases cognitive pathologies; however, some individuals present earlier symptoms with an etiology independent of age. A possible cause is the increased oxidative stress with the formation of amyloid fibrils in the neuronal tissue (in particular Aβ1–40|42). Studies use Aβ25–35 fragment to form β sheet fibrils with a toxicity similar to Aβ1–40|42. Converging studies sustain the idea that B12, B9, and docosahexaenoic may preserve regular neuronal activity. However, the literature is scarce about their synergy effects. The study aims to verify the hypothesis of reducing cellular apoptosis, using B12, B9, and docosahexaenoic acid (DHA) as preventives, isolated or in synergy, on delaying neuronal dysfunction, using “in vitro” assays.MethodsAn In vitro cell model using the SH-SY5Y cell line was analyzed before and after differentiation, induced by trans-retinoic acid and B27 supplement. Fibrillation with Aβ25–35 peptide fragment was carried out after differentiation. Cytotoxicity on undifferentiated cells and neurons was evaluated by reducing the redox potential of the MTT assay. TUNEL assay evaluates cell apoptosis by flow cytometry after B12 vitamers, folic acid, and DHA treatment.ResultsSupplemented cells with DHA (100 to 400 µM) showed an accented decline in cellular viability, below 10% at 400 µM. DHA IC50 at 344 µM was achieved after 24 h, 309 µM at 48 h, and 291 µM at 72 h. For Cyanocobalamin (CNC), dosages of 0.0045 to 0.072 µg/µl were not toxic, with a constant growth from 24 h to 72 h. CNC increase cell viability to 117 ± 3% at 48 h with 0.045 µg/µl and 82 ± 2% at 0.072 µg/µl. Methylcobalamin presents cell viability to 74 ± 6%, at 0.072 µg/µl after 24 h and 94 ± 5% is observed after 48 h. Folic acid concentrations of 0.1 and 0.5 µg/µl reveal cell viability of 94 ± 5% after 24, 48, and 72 h. Preliminary results from the TUNEL assay indicate a reduction in the level of apoptosis with supplementation for all micronutrients.ConclusionsOur results highlight the importance of vitamin B12, folates, and DHA for proper cerebral cell development and renewal. Furthermore, these founds indicate that well-addressed in vitro studies remain valuable tools to confirm if beneficial effects depend on the dose and frequency of intake of these specific nutrients.Funding SourcesNewFood4Thought PTDC/SAUNUT/30,455/2017.

Cyanocobalamin and/or calcitriol mitigate renal damage-mediated by tamoxifen in rats: Implication of caspase-3/NF-κB signaling pathways

AimTamoxifen (TAMO) is a chemotherapeutic drug used for the treatment of breast cancer. Nevertheless, there is a lack of information available in regarding its nephrotoxicity. The purpose of this work was to investigate the impact of cyanocobalamin (COB) and/or calcitriol (CAL) injections on TAMO-induced nephrotoxicity. Main methodsAnimals were allocated into five groups as follows: normal control group; TAMO (45 mg/kg) administered group; TAMO+COB (6mg/kg, i.p) treated group; TAMO+CAL (0.3 μg/kg, i.p) treated group; TAMO+COB+CAL combination groups. Key findingsRenal injury induced by TAMO was confirmed by the alteration in renal function parameters in the serum (urea and creatinine), as well as in the urine (creatinine clearance, total protein and albumin). These results were supported by histopathological examination. Upregulation of renal inflammatory parameters; tumor necrosis factor (TNF)-α, interleukin (IL)-6, C-reactive protein (CRP); and transforming growth factor (TGF)-β1 as well as in protein expression of nuclear factor-kappa B (NF-κB) and cleaved caspase-3 were observed to a greater extent in the TAMO-treated rats compared with the control. Renal fibrosis was also evidenced by a elevation in renal L-hydroxyproline level as well as by histomorphological collagen deposition in TAMO-treated groups compared to the control group. Administration of COB and/or CAL concurrently with TAMO significantly ameliorated the deviation in the above-studied parameters and improved the histopathological renal picture. SignificanceInhibition of NF-κβ-mediated inflammation and caspase-3-induced apoptosis are possible renoprotective mechanisms of COB and/or CAL against TAMO nephrotoxicity, which was more noticeable in the TAMO group treated with the combination of the two vitamins in question.

Temporal dynamics of evapotranspiration in semiarid native forests in Brazil and Spain using remote sensing

AbstractEvapotranspiration (ET) plays an important role in integrated water resource planning, development and management. This process is particularly relevant in semiarid regions. The aim of this study is, hence, to compare spatial and temporal patterns of actual ET, as well as the temporal trends in two different semiarid forests, Caatinga (Brazil) and Tierra de Pinares (Spain). We used the surface energy balance algorithm for land (SEBAL) to assess actual evapotranspiration (ETa) in both areas. In the Brazilian semiarid forest, Caatinga is the main vegetation, while it is Pinares in Spain. For this purpose, 69 Landsat‐5 and 42 Landsat‐8 images (1995–2019) were used. The Mann–Kendall test was applied to assess the occurrence of trends in precipitation, temperature and potential ET data; and the Temporal Stability Index (TSI) to know which areas have greater seasonal ETa. The annual amplitude of the potential evapotranspiration (ET0) is the same in both areas, however, the Caatinga values are higher. In the Caatinga forest, when ET0 presents its highest values throughout the year, ETa presents the lowest, and vice versa. In the Pinares forest, ETa follows the ET0 dynamics during the year, and the difference between ET0 and ETa is maximum during the summer. The Caatinga forest showed a greater spatial variation of ETa than the Pinares forest as well as a greater extension with lower temporal stability of ETa than the Pinares forest. Both the Caatinga forest and the Pinares forest showed significant positive trends in annual ET0 and ETa. We estimate that the value of ETa increases more rapidly in Pinares than in the Brazilian Caatinga. Taking Caatinga as a hydrological mirror, some consequences are expected to Pinares, such as significant changes in the water balance, increase of biodiversity vulnerability, and reduction of water availability in soil and reservoirs.

Identification of priority shorebird conservation areas in the Caribbean.

Despite being geographically central to the Atlantic Americas Flyway for migratory birds, the Caribbean is often overlooked or underappreciated when addressing the conservation of North American shorebirds. To our knowledge, this is the first Caribbean-wide assessment of shorebird use in the region. We analyzed 211,013 shorebird species observations in the insular Caribbean from 2010–2019, representing 78,794 eBird checklists and cumulative total of 2.1 million shorebirds of 45 species. We conclude that priority areas for shorebird conservation include Humedal Sur de Pinar del Río (Humedal Sur de Los Palacios) in Cuba, and Monte Cristi in the Dominican Republic as they each likely support more than 20,000 shorebirds annually, and they host large abundances of geographic populations for particular taxa. Specifically, the former site hosts >10% of Short-billed Dowitchers (Limnodromus griseus griseus/hendersoni), and >1% of Black-bellied Plovers (Pluvialis squatarola cynosurae) and Wilson’s Plovers (Charadrius wilsonia wilsonia), while the latter site supports large numbers of Black-necked Stilts (Himantopus mexicanus). We also identified at least 15 additional sites that likely cross the 1% population threshold for one or more shorebird taxa. These sites may qualify for special international designations such as Important Bird and Biodiversity Areas or as part of the Western Hemisphere Shorebird Reserve Network; 11 of the 17 sites we identified do not hold either of these titles. Data on subspecific or geographic distributions of three species, Snowy Plover (C. nivosus), Black-necked Stilt, and Killdeer (C. vociferous), are insufficient to reveal if the sites with the highest abundances were mostly comprised of Caribbean populations or migrants, but the limited information suggests that they also likely exceed 1% thresholds on several islands. Based on our results, we recommend more extensive systematic surveys of shorebirds in the Caribbean, including research on turnover rates and movements between islands, as well as assimilation of shorebird survey data not yet included in the eBird portal.

El Juego trobado de Pinar: la memoria cultural colectiva de las damas de la corte de la reina Isabel de Castilla en el año 1496

El Juego trobado de Jerónimo de Pinar ofrece a sus lectores acceso a la mentalidad y a la memoria colectiva de un grupo de damas educadas de la corte de la reina Isabel la Católica en el año 1496, revelando su conocimiento de refranes, de poesía y de ficciones sentimentales, su capacidad de interpretar el simbolismo de las aves y de los árboles, y muchos hechos que no se encuentran en los documentos oficiales. Voy a concentrarme aquí en la dimensión literaria de esta herencia cultural.

Masculinity of Women in RED Cobex, a Comedy Genre

Visualisasi dalam film memiliki pengaruh besar dalam pikiran penonton. Penonton film secara tidak sadar membentuk persepsi tertentu terhadap gambaran pokok dalam konstruksi gender. Dalam hal ini gambaran yang akan diteliti dalam film ini adalah perbedaan visualisasi perempuan dalam sinema dengan genre komedi khususnya maskulinitas perempuan dalam film “Red Cobex” yang diproduksi pada tahun 2010. Konstruksi visual tertentu akan menciptakan makna pada pikiran audiens akan membuat konstruksi stereotype tertentu atas gender. Metode penelitian yang digunakan adalah analisa konten sebagai model untuk menjabarkan perbedaan visualisasi gender yang mempengaruhi persepsi audiens.

El Juego Trobado de Jerónimo de Pinar: Datación del poema e identificación de los miembros de la Casa Real

El presente artículo pretende establecer la identificación de los miembros de la Casa Real castellana mencionados por Jerónimo de Pinar en su conocido poema Juego Trobado (Dutton ID 6637), así como establecer lo más ajustadamente posible la probable fecha de composición y representación de este divertimento áulico. Además de prestar atención a las rúbricas, se indaga cómo la duración del luto en el reino de Castilla es clave para certificar ambas cosas, la datación del poema y la identificación de los protagonistas, habida cuenta de la cadena de muertes sufrida por los Trastámara en los años finales del siglo XV.

Mujeres rurales y desarrollo sostenible en Pueblo Nuevo de Pinares, Mayarí, Cuba

The work recognizes the woman participation as an important indicator to qualify the economic, social and environmental transformation in rural communities. The work show the roll carried out by the women in the agropecuarian project development in the mountain communities of Pinares de Mayari, as well as their place in the community of Pueblo Nuevo de Pinares and the way in which education and culture have turned it into an organized community with a high level of education and technical qualification. All this, however, have not guaranteed women a full participation in the social economic and environmental life of the territory. In the last years, there are a greater participation of women in social innovations like communitarian and local diagnosis, and in the creation and implementation of communitarian strategies and projects promoted by the research station. The work recognises the woman active participation as a key element in the creation of truly sustainable development of the social subject. Keywords: rural women, mountain communities, sustainable development, participation.

Folic acid causes higher prevalence of detectable unmetabolized folic acid in serum than B-complex: a randomized trial.

Unmetabolized folic acid (UMFA) is common in serum of elderly individuals receiving folic acid (FA)-fortified foods or supplements. We studied the effect of supplementing FA or B-complex on serum concentrations of (6S)-5-methyltetrahydropteroylglutamate [(6S)-5-CH3-H4Pte] and UMFA in elderly people and explored factors associated with detectable UMFA post-supplementation. This is a randomized single-blind non-controlled trial on 58 elderly people using daily 400 µg FA (n = 31) or 400 µg FA, 10 µg cyanocob(III)alamin and 8 mg pyridoxine (n = 27) for a median of 23 days. Main outcome includes changes in concentrations of serum (6S)-5-CH3-H4Pte and UMFA. Total homocysteine declined by a median of 1.6 (p = 0.074) in the FA and 1.3 µmol/L (p = 0.009) in the B-complex arms (p = 0.66 between the arms). Serum (6S)-5-CH3-H4Pte significantly (p < 0.001 vs. baseline) increased by a median of 9.2 and 6.5 nmol/L in the FA and B-complex groups, respectively (p = 0.152 between the groups). Compared to FA, B-complex reduced cystathionine and caused lower post-intervention serum UMFA, percentage of UMFA to (6S)-5-CH3-H4Pte and prevalence of UMFA ≥ 0.21 nmol/L. Higher serum cystathionine and whole-blood folate predicted higher post-intervention serum UMFA. FA caused higher UMFA as compared to B-complex. Pyridoxine appears to improve folate recycling. Data on serum UMFA should be interpreted in relation to other vitamins involved in folate metabolism. Serum UMFA is suggested to play a sensory role through which the cell recognizes FA available for metabolism via dihydrofolate reductase.

METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS ESTIMATION OF NICOTINIC ACID, FOLIC ACID AND CYANOCOBALAMIN USING RP-HPLC

A simple Re verse phase liquid chromatographic method has been developed and subsequently validated for simultaneous determination of nic otinic acid, folic acid and cyanocobalamin in combination. The separation was carried out using a mobile phase consisting of sodium acetate buffer of pH 2.5 and Acetonitrile in the ratio of 90 : 10. The column used was phenomenex Luna 5 µ c18 (2) 250x4.6 mm, 100 A with flow rat e of 1.5 ml/min, and the detection was done at 278 nm. The retention times of nicotinic acid, folic acid and cyanocobalamin were found to be 3.79, 6.01 and 14.54 min respectively. The method was validated for linearity, accuracy, precision, limit of detection, limit of quantification and ru ggedness. The limit of detection for nicotinic acid, folic acid and cyanoc obalamin was found to be 100 ng/ml, 1 µg/ml and 10 µg/ml and the limit of Quantification was found to be 1 µg/ml, 10 µg/ml and 100 µg/ml respectively. Linearity for nicotinic acid, folic acid and cyanocobalamin has bee n observed in the range of 1 - 5 µg/ml, 10 - 50 µg/ml and 100 - 500 µg/ml and the respective R 2 values are observed at 0.996, 0.997 and 0.99 respectively. The relative standard deviation for intra and interday precision were <5%. Hence the proposed RP - HPLC method wa s sensitive, rapid, cost - effective and accurate for the simultaneous determination of nicotinic acid, folic acid and cyanocobalamin in both bulk materials and pharmaceutical dosage forms.

Effect of Riboflavin on the Photolysis of Cyanocobolamin in Aqueous Solution

The kinetics of photolysis of cyanocobalamin (CC) by visible radiation in the presence of riboflavin (RF) at pH 2.0-12.0 has been studied. A specific two-component spectrophotometric method has been used for the simultaneous assay of CC and its photoproduct, hydroxocobalamin (HC), at 525 and 550 nm, without any interference from RF. The apparent first-order rate constants for the photolysis of CC in the presence of 1-5 � 10 -5 M concentrations of RF at pH 2.0- 12.0 range from 0.46 (pH 7.0) to 4.22 � 10 -3 min -1 (pH 3.5). The second-order rate constants for the bimolecular interaction of these vitamins are in the range of 8.66 (pH 7.5) to 45.20 M -1 min -1 (pH 2.0). The rate-pH profile indicates a gradual decrease in rate in the acid pH range followed by the slowest rate and maximum stability around pH 7-8. Thus the cationic form of CC is more susceptible to photolysis compared to the neutral form. The increase in rate in the alkaline region is probably due to the hydrolysis of the amide groups. The kinetic results indicate that RF acts as a sensitizer in the photolysis of CC and in this way promotes the degradation of the molecule. Thus the presence of RF in CC solutions adversely affects the stability of vitamin B12.

Fuego festivo, humo sagrado: Las luminarias de San Antón en Tierra de Pinares (Ávila)

The feast-day of Anthony the Abbot, better known simply as St Anthony, is still celebrated in many Spanish towns and villages on 17 January every year. In the depths of winter, traditionally a period of rest from agricultural labour, people light bonfires in a renewal and purification ritual whose origins lie in the religious practices of Ancient Rome. In the village of San Bartolome de Pinares, in the province of Avila, the St Anthony celebrations have not only survived, but have seen a resurgence of interest in recent years. Information gathered from interviews carried out in 2008 gives greater insight into the primitive aspects of the feast-day (“setting the village free from the forces of evil”) as well as into its gradual secularisation.

Spectroscopic and Electrochemical Studies on Cobaloximes and Alkylcobaloximes in Aqueous Surfactant Micelles as Models of Vitamin B 12

Various synthetic models of VitaminB 12 are prepared using dimethylglyoxime, pyridine, imidazole and methyliodide as ligands and their spectroscopic and electrochemical results are compared with the natural analogues methylcobalamin and cyanocobalamin. The spectroscopic and electrochemical results of these compounds are studied in hydrophobic membrane mimicking systems such as aqueous systems of Sodium dodecyl sulfate (SDS), Cetyl trimethyl ammonium bromide (CTAB). The hydrophobic environment of aqueous surfactant micellar solutions around the metal complexes at the active site of the metalloproteins under physiological pH has considerable effect on the electronic spectrum of the model compounds. Platinum working electrode gives a more reliable result for vitamin B 12 showing a reversible couple in the range from -0.3 to -0.6 V. Cobaloxime complexes show reversible couple in the range from -0.6 to -0.8 V with glassy carbon electrode whereas methylcobalamin shows positive redox potential values with glassy carbon electrode. Micellar systems stabilize the organometallic derivatives in aqueous solutions.

Nutritional and chemical evaluation of Momordica charantia

Momordica charantia is used for some medicinal purposes in traditional medicine. The nutritional and chemical compositions of M. charantia were investigated using standard analytical methods. The proximate composition showed the percentage moisture, ash, crude lipid, crude fibre, crude protein and carbohydrate content of the plant materials. The calorific values for leaf, fruit and seed were 213.26, 241.66 and 176.61 Kcal/100 g respectively. The elemental analysis of M. charantia leaf revealed the presence of potassium (413 ppm), sodium (2200 ppm), calcium (20510 ppm) as well as zinc (120 ppm). Other elements found present in the leaf include magnesium, iron, manganese and copper. Vitamin A (β-carotene) (0.03 ppm), vitamin E (α-tocopherol) (800 ppm), folic acid (20600 ppm), cyanocobalamin (5355 ppm) and ascorbic acid (66000 ppm) were present. Trace amount of some other vitamins such as niacin (B3), pyridoxine (B6) cholecalciferol (Vitamin D) and phylloquinone (Vitamin K) were also found present in the methanolic and pet-ether leaf extract of M. charantia. Phytochemicals like alkaloids, tannins, flavonoids, saponins and glycosides were also found present. The study indicates the presence of nutritional and chemical components that are beneficial in addition to the purported numerous medicinal values of the plant. Key words: Atomic absorption spectrophotometry, Momordica charantia, nutrition, phytochemicals, vitamins.

On the Identity of Vitamin B12 and the Animal Protein Factor

On the Identity of Vitamin B12 and the Animal Protein Factor

Assay of “Animal Protein Factor” Using Mice

Journal Article Assay of “Animal Protein Factor” Using Mice Get access Nutrition Reviews, Volume 7, Issue 6, June 1949, Pages 167–169, https://doi.org/10.1111/j.1753-4887.1949.tb02226.x Published: 01 June 1949

Permian 40Ar/39Ar ages for post-Variscan minor intrusions in the Iberian Range and Spanish Central System

40Ar/39Ar dating of biotite from a calc-alkaline gabbro stock NW of Loscos in the Iberian Range yielded a slightly disturbed gas release spectrum. It has an early Permian, 288.5 ± 1.4 Ma total gas age, interpreted as the minimum emplacement age. The 40Ar/39Ar apparent age of the gabbro agrees with the Autunian stratigraphic age of related volcanic rocks. 40Ar/39Ar step-heating dating of amphibole phenocrysts from an alkaline camptonite dyke ca. 4 km SE of El Hoyo de Pinares in the Sierra Guadarrama sector of the Spanish Central System yielded a mid-Permian 264 ± 3 Ma plateau age, interpreted as the emplacement age. The age is indistinguishable from published 40Ar/39Ar amphibole ages for N-S trending camptonite dykes from the western, Sierra de Gredos segment of the Central System. This suggests that the camptonite dykes from both sectors belong to the same generation.