Techn. Universiẗat, Diss., 2005--München.

abstract: Vitamin B12, found only in animal products, is a water-soluble vitamin important for DNA methylation, purine and pyrimidine synthesis, and the myelination of nerves. Symptoms of vitamin B12 deficiency include anemia, gait disturbances, altered vibration proprioception, impaired vision, psychosis, depression, dementia-like illness, and ultimately death. Because vegetarians and vegans consume fewer animal products in their diet than omnivores, they are inherently more at risk for developing these symptoms of vitamin B12 deficiency. Thus, the purpose of this study is to examine the correlation between nervous system markers (balance, dexterity, and vibration sensitivity) and markers of vitamin B12 nutriture (serum B12 and serum holo-transcobalamin II) in a cross-sectional study (n=38). In addition, the impact of daily oral vitamin B12 supplementation on these markers in an 8-week randomized controlled trial was also examined (n=18). The results of the cross-sectional study revealed a moderate correlation (R=-0.351, p=0.031) between serum B12 and left-hand functional dexterity. The results of the intervention study revealed no significant time*group interactions for markers of nervous system functions and biochemical values (after the removal of outliers). In addition, the time*group interaction appeared to be larger for those individuals with a baseline serum B12 of less than 303 pmol/L. These results suggest that vitamin B12 supplementation may have a more pronounced effect on those individuals who are in a state of vitamin B12 depletion (<303 pmol/L serum concentration). In addition, the results also suggest that 8 weeks of oral supplementation is not a long enough period to create significant clinical change, and it is likely that improvements in neurological measures would require long-term supplementation. / Dissertation/Thesis / Doctoral Dissertation Physical Activity, Nutrition and Wellness 2016

Submitted by Giovanna Brasil (1154060@mackenzie.br) on 2017-09-28T17:05:08Z No. of bitstreams: 2 Adriana Brito.pdf: 679131 bytes, checksum: 11bec179ab16d3f624479be7d25c6758 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Paola Damato (repositorio@mackenzie.br) on 2017-10-02T14:19:00Z (GMT) No. of bitstreams: 2 Adriana Brito.pdf: 679131 bytes, checksum: 11bec179ab16d3f624479be7d25c6758 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-10-02T14:19:00Z (GMT). No. of bitstreams: 2 Adriana Brito.pdf: 679131 bytes, checksum: 11bec179ab16d3f624479be7d25c6758 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-08-24 / Depression affects 13% to 20% of the world's population. Vitamin B12 deficiency is related to depression. The lack of this vitamin can be induced in rats by the addition of pectin to the diet. This depletion generates aberrations in base substitutions and DNA methylation. Given the need for animal models with neurobiological fundamentals that best represent depression, the objective of this paper was to validate and characterize an experimental model of depression induced by vitamin B12 deficiency in female rats fed with an added diet pectin. The project was elaborated in two phases and involved 40 Wistar rats, monitored from their weaning to their 133th day of life. In the first phase, the animals were randomly separated into two groups, which differed by the feed offered (ration with or without pectin). At the end of this phase, the animals were submitted to a blood count and tests of positive contrast of sucrose, open field and high cross labyrinth, to evaluate if the vitamin deficiency had altered hematological and behavioral variables. In the second phase, the pectin group was divided into three groups: one group continued with the same diet, another group continued with the same diet but also received antidepressant in the water and a third group started to be fed with the regular feed. The pectin-free fed group was divided into two groups: one continued with the same feed and the other fed with increased pectin feed. At the end of this phase the animals were submitted to the same tests listed above and, after their euthanasia, the brains were removed for analysis of the expression of genes involved in depression in rats in the hippocampus and prefrontal cortex. The dropout times obtained by the groups in the forced swim test (pectin = 108 seconds and standard group = 77 seconds, with p = 0.03), applied at the end of the first phase, indicate that the pectin-fed group was behavior-induced of the depressive type. The output of the other tests confirm that this result did not occur due to locomotor and/ or anxiogenic problems. In the second phase, there was no difference between the times, which indicates that this behavior was not observed at this time of the lives of the animals. It is concluded, then, that pectin intake can induces rats to depression but possibly only within a time window that goes until 11 weeks of age. There are three other hypotheses that may justify the results found: there was a physiological adaptation to pectin consumption; older animals may require increased fiber intake to decrease vitamin uptake or perhaps more intense exhaustion at this stage of life is required to lead to this behavior. / A depressão acomete de 13 a 20% da população mundial. A deficiência de vitamina B12 está relacionada com a depressão. A falta dessa vitamina pode ser induzida em ratos pela adição de pectina à dieta. Esta depleção gera aberrações em substituições de base e metilação de DNA. Dada a necessidade de modelos animais com fundamentos neurobiológicos que melhor representem a depressão, o objetivo deste trabalho foi o de validar e caracterizar um modelo experimental de depressão induzido pela deficiência de vitamina B12 em ratas alimentadas com dieta adicionada de pectina. O projeto foi elaborado em duas fases e contou com 40 ratas Wistar, acompanhadas desde seu desmame até 133 dias de vida. Na primeira, os animais foram separados aleatoriamente em dois grupos, que se diferenciaram pela alimentação oferecida (ração com ou sem pectina). Ao final desta fase os animais foram submetidos a hemograma e aos testes de contraste positivo de sacarose, campo aberto e labirinto em cruz elevado, para avaliar se a ingestão de pectina alterou variáveis hematológicas e comportamentais. Na segunda fase, o grupo com pectina foi dividido em três grupos: um grupo continuou com a mesma alimentação, outro continuou com a mesma alimentação mas passou também a receber antidepressivo na água e um terceiro grupo iniciou alimentação com ração comercial. O grupo com ração sem pectina foi dividido em dois: um continuou com a mesma alimentação e o outro passou a alimentar-se com ração acrescida de pectina. Ao final dessa fase os animais foram submetidos aos mesmos testes elencados acima e, após eutanásia, tiveram o cérebro removido para análise da expressão de genes do hipocampo e do córtex pré-frontal envolvidos em depressão em ratas. Os tempos de desistência obtidos pelos grupos no teste do nado forçado (pectina=108 segundos e grupo padrão=77 segundos, com p=0,03), aplicado no final da primeira fase, indicam que o grupo alimentado com pectina foi induzido a comportamento do tipo depressivo. Os resultados dos outros testes confirmam que esse resultado não ocorreu por problemas de locomotores e/ou ansiogênicos. Na segunda fase não houve diferença entre os tempos, o que indica que esse comportamento não foi observado nessa época da vida dos animais. Conclui-se, então, que a depleção de vitamina B12 pode induzir ratos à depressão mas, possivelmente, apenas dentro de uma janela temporal que vai até a juventude desses animais. Há três outras hipóteses que podem justificar o resultado encontrado: houve uma adaptação fisiológica ao consumo de pectina; animais com mais idade podem necessitar de maior ingestão da fibra para diminuir a absorção da vitamina ou talvez seja necessária uma depleção mais intensa nessa fase da vida para levar a esse comportamento.

Halten näringsämnen i livsmedel varierar bland annat med tillagningsmetod, lagringstid och lagringsförhållanden, som exponering för ljus och syre. Oklarheter finns för mikrovågors inverkan på näringsämnen och framförallt på vitamin B12. Eftersom många äldre drabbas av brist på vitamin B12, är detta av intresse eftersom många hemmaboende äldre människor får hemleverans av färdiga matportioner som är avsedda att värmas, ofta i mikrovågsugn. Syftet med studien var att kunna ge en indikation på om uppvärmning genom mikrovågor påverkar halten vitamin B12 i färdiga kylda måltider. Detta gjordes genom litteratursammanställning om vitamin B12 och mikrovågar samt genom bioassay med Lactobacillus delbrueckii. Vitamin B12 i ouppvärmd lax, lax värmd i mikrovågsugn samt lax värmd i konventionell ugn analyserades. Tillväxten av bakterier uppskattades genom mätning av turbiditet. Högst vitamin B12-halt sågs i mikrovågsvärmd lax, därefter ouppvärmd lax och ugnsvärmd lax. Statistiskt signifikanta skillnader sågs för analyserade vitamin B12-halter mellan ouppvärmt- och ugnsvärmt prov respektive mellan mikrovågsvärmt- och ugnsvärmt prov. De varierande vitaminhalterna kan bero på metodfel, otillräcklig vitaminextraktion eller att bakterierna inte konsumerat allt tillgängligt vitamin vid turbiditetsmätning. Slutsatsen av studien är att halten vitamin B12 i livsmedel inte verkar påverkas negativt av mikrovågor, däremot finns tendenser att halten minskar beroende av temperatur och tillagningstid.

No description available.

Vitamin B12 and folate are necessary for bone marrow progenitor growth and division. Deficiencies are common in lymphoproliferative disorders due to increased demands of rapidly growing malignant cells. Isolated vitamin B12 deficiency is seen in 13% of these patients and may be their only manifestation. We present the case of vitamin B12 deficiency anemia due to an underlying malignancy that was discovered following supplementation. A 77-year-old nonsmoker female with chronic kidney disease and hypothyroidism presented to her internist with dyspnea, tachycardia and unintentional 7-pound weight loss. Age-appropriate cancer screenings were up-to-date. Physical exam was notable for an overweight female with tachycardia and trace ankle edema bilaterally. Electrocardiogram demonstrated sinus tachycardia. Labs were remarkable for hemoglobin 10.3 mg/dL (12.1 mg/dL one year ago) and serum B12/mL. She was started on intramuscular vitamin B12 supplementation. At her one-month follow-up, she reported debilitating gastrointestinal distress, rash, and fatigue lasting 5-6 days with every vitamin B12 injection. Physical exam was notable for 20-pound weight loss. Labs revealed hemoglobin 9.9 mg/dL despite serum B12 750 pg/mL and worsening kidney function with marked proteinuria. Additional work-up by primary team and subsequent Hematology & Oncology referral demonstrated elevated M-spike on urine protein electrophoresis and abnormal bone marrow biopsy suspicious for lymphoid malignancy. CT abdomen and whole body PET scan revealed increased uptake in the T12 vertebrae and multiple nodal basins consistent with stage IV lymphoma. Biopsy of vertebral body confirmed diffuse large B-cell lymphoma. The patient received one cycle of chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Her course was complicated by pathologic hip fracture requiring hospitalization and surgical repair. The patient died following cardiac arrest in the setting of septic shock from sigmoid colon perforation 7 months from initial presentation. Vitamin B12 and folate play critical roles in nucleic acid synthesis for bone marrow progenitors. Vitamin B12 deficiency arrests cell growth and division, leading to macrocytic anemia and various neuropsychiatric manifestations. It is a common diagnosis with numerous causes: autoantibodies to digestive proteins, poor dietary intake, small bowel malabsorption, etc. Diagnose with low hemoglobin (/dL or 13 mg/dL in non-pregnant women or men, respectively) and mean corpuscular volume >100 fL plus low serum B12 or elevated homocysteine and methyl-malonic acid levels. Replacement is given orally or intramuscularly. Vitamin B12 and folate deficiencies are found in lymphoproliferative disorders due to increased demands of rapidly growing malignant cells. Isolated vitamin B12 deficiency is seen in 13% of patients and may be the only clue. Replacement will not resolve their anemia. Physicians should monitor patients receiving supplementation. If anemia fails to improve or patients experience systemic symptoms, further investigation for lymphoid malignancies is warranted. This patient had dramatic deterioration with acceleration of underlying malignancy following vitamin B12 replacement. We believe supplementation enabled malignant lymphoid precursors to resume cell cycle growth and division. Only one report of vitamin B12 supplementation associated with unmasking a lymphoid malignancy exists in literature. Further research is needed to support whether supplementation can accelerate lymphoid malignancies.

Student Number : 0010064D - MSc dissertation - School of Chemistry - Faculty of Science / This dissertation describes the synthesis, physical characterisation and solution chemistry of NAc-CoIIIMP8, a biomimetic model compound of vitamin B12a, synthesised from the haemoctapeptide derived from horse heart cytochrome c. Peptic and tryptic digestion of horse heart cytochrome c removes much of the globular protein encapsulating the iron porphyrin prosthetic group. The resulting haemoctapeptide fragment retains residues 14 to 21 of the parent cytochrome (MP8) via thioether linkages to Cys-14 and Cys-17. Reductive demetalation of MP8 yielded the metal free MP8. This was treated with cobaltous acetate in an aerated aqueous solution to produce CoIIIMP8. CoIIIMP8 was acetylated by treatment with acetic anhydride and yielded N-acetyl-Co(III)- microperoxidase 8 (NAc-CoIIIMP8). It is well established that acetylation reduces aggregation of these haempeptides. The starting materials and products of each step during synthesis were characterised by UV-visible absorption spectroscopy, high performance liquid chromatography (HPLC) and fast atom bombardment-mass spectroscopy (FAB-MS). MP8 free base and Co(III)-MP8 were also analysed using luminescence spectroscopy. The molar extinction coefficients of NAcCoIII-MP8 in aqueous and ionic medium were determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and UV- visible absorption spectroscopy. The extinction coefficient, e, of NAcCoIIIMP8 (? = 420 nm, pH 7.00, 25 ºC) in distilled water and 1.0 M NaClO 4 was 1.80 + 0.01 x 105 M-1 cm-1 and 1.66 + 0.01 x 105 M-1 cm-1, respectively. Beer’s law studies show that NAc-CoIIIMP8 remains monomeric in aqueous solution up to concentrations of at least 35 μM. The spectroscopic changes observed for NAc-CoIIIMP8 during the course of a spectrophotometric titration are very similar to those observed for NAc-FeIIIMP8, with both being consistent with six successive ionisations. By analogy with NAc-FeIIIMP8, we attributed the first (pK1 = 2.0 + 0.3) to the coordination of the c-terminal carboxylate group (Glu-21) of the appended polypeptide. The second acid range transition (pK2 = 2.8 + 0.1) for NAcCoIIIMP8 involved the deprotonation of the cationic His-18 and concomitant replacement of the c-terminal carboxylate by the neutral heterocyclic base. The third and fourth pKa’s are attributed to the ionisation of the haem propanoic acid groups (pK3 = 3.9 + 0.03) and (pK4 = 7.5 + 0.03). Ionisation of the cobalt-bound water molecule above neutal pH was assigned to pK5 = 9.2 + 0.04. Finally, we attributed pK6 (12.1 + 0.03) to the ionisation of the coordinated histidine trans to the OH- to form the histidinate complex (His--CoIII-OH-). A principal aim of this work was to demonstrate that the kinetics and the thermodynamics of the ligand substitution reactions of NAc-CoIIIMP8 can be studied spectrophotometrically; a comprehensive investigation of these reactions will be undertaken by othe rs. Towards this end the formation constants between NAc-CoIIIMP8 and N- methylimidazole and pyridine were determined. We observed the formation of a bis-substituted complex in the reaction of NAc-CoIIIMP8 with the ligands, but only mono-substitution with NAc-FeIIIMP8 and B12a. We attribute this first ligand binding to the replacement of the axial water molecule, and the second replacement of the axial histidine residue. The absence of the second reaction with NAc-FeIIIMP8 and B12a suggest that the CoIII-N(His) bond in NAc-CoIIIMP8 is significantly weaker than the FeIIIN( His) and CoIII-N(dimethylbenzimidazole) bond, respectively. When comparing the formation constants of NAc-FeIIIMP8, NAc-CoIIIMP8 and B12a, we found that the value of log K1 for NAc-CoIIIMP8 for these ligands is significantly higher than that reported for NAc-FeIIIMP8 and B12a. Kinetics studies of NAc-CoIIIMP8 with N-methylimidazole and methylamine were investigated. The data obtained did not follow conventional pseudo-first order kinetics; instead there was some evidence for biphasic kinetics. In the reaction of Nmethylimidazole with NAc-CoIIIMP8, we observed that the rate of reaction is virtually independent of the concentration of the incoming ligand. The results can be explained if the mechanism proceeds through a purely dissociative mechanism, i.e., if the rate of the reaction is controlled by the rate at which, firstly, the water molecule dissociates from the CoIII centre and, secondly, the histidine dissociates from the metal. The second order rate constant, k2, could not be determined since the rate of reaction is independent of Nmethylimidazole concentration. In the reaction of methylamine with NAc-CoIIIMP8, we observed that the rate of reaction is dependent on the concentration and participation of the incoming ligand. We propose that the displacement of water and histidine by methylamine involves an interchange mechanism (Id), where the bond forming and bond breaking occur simultaneously, and thus the rate of reaction becomes dependent on the concentration of the incoming ligand. The results showed that the rate of reaction for methylamine with NAc-CoIIIMP8 was faster than with N-methylimidazole. We attributed these differences in rate constants to the size of the incoming ligands. N-methylimidazole is a secondary amine and is relatively more bulky than methylamine which is a primary amine; therefore it is easier for methylamine to attach to the metal centre compared to N- methylimidazole. For comparison, the rate of reaction of B12a with N-methylimidazole and methylamine was determined. The results show that the rate of the reaction between NAc-CoIIIMP8 and B12a with N-methylimidazole and methylamine are significantly different. Furthermore, we observe only mono -substitution in B12a and bisubstitution in NAc- CoIIIMP8. Overall, the results presented in this work do give a general indication on how thermodynamically stable a CoIII ion is in a porphyrin ring and also to a very limited extent show that a porphyrin does not confer the same kinetic lability on the CoIII ion as the corrin ring.

No description available.

Eine Vielzahl von Patienten mit fortgeschrittener, beziehungsweise dialysepflichtiger Niereninsuffizienz entwickeln eine Polyneuropathie. Die Pathogenese der urämischen Neuropathie (UN) ist nicht geklärt, sodass auf der Suche nach dem Pathomechanismus auch ein Vitamin-B12-Mangel diskutiert werden muss, da dieser ähnliche Symptome wie die UN hervorrufen kann. Ziel dieser Studie war es, den Zusammenhang zwischen den Parametern des Vitamin-B12-Stoffwechsels und der UN darzustellen. In einer prospektiven Studie mit insgesamt 54 teilnehmenden Patienten wurden diese vor und nach einer Vitamin-B12-Substitution laborchemisch untersucht. Zudem erhielten die Patienten neben einer klinischen Untersuchung eine elektroneurographische Diagnostik des N. suralis und des N. tibialis, sowie eine QST-Untersuchung. / Uremic neuropathy (UN) is the most common neurological disorder in end-stage renal disease. The pathophysiology of uremic neuropathy is complex and is not yet fully understood. Vitamin B12 deficiency can cause severe neurological disorders and symptoms are similar to UN. To investigate whether UN is due to Vitamin B12 deficiency, we conducted a study measuring Vitamin B12 Biomarkers on 54 dialysis patients before and after administering Vitamin B12. In addition a full neurological clinical exam, as well as electroneurography and QST were conducted before and after Vitamin B12 supplementation.

No description available.