Malabsorption of Crystalline Vitamin B<sub>12</sub>in Cystic Fibrosis

Deren, Julius J.; Arora, B; Toskes, Phillip P.; Hansell, John R.; Sibinga, Maarten S.

doi:10.1056/nejm197305032881808

Cited by 51 publications

(13 citation statements)

References 9 publications

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“…Our hypothesis is supported by the fact that more than 50% of patients with pancreatic exocrine insufficiency malabsorb Cbl based on Schilling tests (5)(6)(7)(8)(9) and by the fact that this abnormality can be corrected by the oral administration of pancreatic proteases (6,(8)(9)(10)(11). The fact that partial correction is obtained with oral bicarbonate (6,9) (12). All in vitro and in vivo studies were performed with the same preparation of Cbi.…”

Section: Introductionmentioning

confidence: 66%

Correction of Cobalamin Malabsorption in Pancreatic Insufficiency with a Cobalamin Analogue that Binds with High Affinity to R Protein but not to Intrinsic Factor

Allen¹,

Seetharam²,

Allen³

et al. 1978

J. Clin. Invest.

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Section: Introductionmentioning

confidence: 66%

Correction of Cobalamin Malabsorption in Pancreatic Insufficiency with a Cobalamin Analogue that Binds with High Affinity to R Protein but not to Intrinsic Factor

Allen¹,

Seetharam²,

Allen³

et al. 1978

J. Clin. Invest.

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“…Mounting evidence has suggested that CF patients suffer from defective vitamin B 12 absorption (7,11,25) Ϫ , an alternative electron acceptor to NO 2 Ϫ , which is further reduced to NO by periplasmic nitrite reductase (NIR). Endogenously accumulated NO intoxicates RNR, which in turn results in decreased synthesis of deoxyribonucleotides (downward-pointing arrow).…”

Section: Fig 7 Microarray Analysis Of Pao1 Grown By Anaerobic Nomentioning

confidence: 99%

“…Abbreviations: RN, ribonucleotide; DeoxyRN, deoxyribonucleotides; RNR, ribonucleotide reductase. absorption can be corrected by administration of pancreatic supplements (7), such malabsorption provides a basis for the frequent occurrence of anemia among CF patients (54). It is not clear how much vitamin B 12 is present in the CF patient mucous airway, which was reported to possess regions with reduced oxygen tension (56,60).…”

Section: Fig 7 Microarray Analysis Of Pao1 Grown By Anaerobic Nomentioning

confidence: 99%

Vitamin B ₁₂ -Mediated Restoration of Defective Anaerobic Growth Leads to Reduced Biofilm Formation in Pseudomonas aeruginosa

Lee

Yoon

et al. 2012

Infect Immun

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ABSTRACTPseudomonas aeruginosaundergoes cell elongation and forms robust biofilms during anaerobic respiratory growth using nitrate (NO3−) as an alternative electron acceptor. Understanding the mechanism of cell shape change induced upon anaerobiosis is crucial to the development of effective treatments againstP. aeruginosabiofilm infection. Here, we uncovered the molecular basis of anaerobiosis-triggered cell elongation and identified vitamin B12to be a molecule that can reinstate defective anaerobic growth ofP. aeruginosa. The ratio of total cellular DNA content to protein content was significantly decreased in the PAO1 strain grown under anaerobic conditions, indicating that DNA replication is impaired during anaerobic growth. Anaerobic growth of PAO1 reached a higher cell density in the presence of vitamin B12, an essential coenzyme of class II ribonucleotide reductase. In addition, cell morphology returned to a normal rod shape and transcription of stress-response genes was downregulated under the same anaerobic growth conditions. These results suggest that vitamin B12, the production of which was suppressed during anaerobic growth, can restore cellular machineries for DNA replication and therefore facilitate better anaerobic growth ofP. aeruginosawith normal cell division. Importantly, biofilm formation was substantially decreased when grown with vitamin B12, further demonstrating that anaerobiosis-induced cell elongation is responsible for robust biofilm formation. Taken together, our data reveal mechanistic details of a morphological change that naturally occurs during anaerobic growth ofP. aeruginosaand illustrates the ability of vitamin B12to modulate the biofilm-forming capacity ofP. aeruginosaunder such condition.

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“…For a long time there were differing opinions as to the effect of the exocrine pancreatic secretions on the absorption of vitamin B~2. Various authors [2,13] believed that the vitamin B12 malabsorption in patients with EPI was based on bicarbonate deficiency since vitamin BI2 absorption could be improved by giving bicarbonate orally. Toskes et al [11,12], however, believed that the absorption-enhancing effect on vitamin B12 was more related to the pancreatic enzymes or to a special undefined factor responsible for vitamin B12 absorption.…”

Section: Discussionmentioning

confidence: 99%

“…This observation has been repeatedly confirmed [7,8,11], although the absorption-enhancing quality of the pancreatic secretion could not be fully explained. In 1973 Deren et al [2] confirmed these findings in children. They found that the absorption of crystalline vitamin B~2 was considerably reduced in 11 children and adolescents with exocrine pancreatic insufficiency due to cystic fibrosis.…”

Section: Introductionmentioning

confidence: 88%

Vitamin B12 absorption and exocrine pancreatic insufficiency in childhood

et al. 1981

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The absorption of vitamin B12, labelled with radioactive 58Co, was measured in 19 patients with cystic fibrosis and one child with the Shwachman-Diamond syndrome using the whole body counting technique. We found vitamin B12 absorption reduced to 7.97 on average, compared to 59.2% for the control group. The low vitamin B12 absorption correlated well with the reduced fat retention coefficients. After adding 0.212 pancreatin to the radioactive vitamin B12 test dose, the absorption quotas improved in all cases, the average being 61%. A meal poor in vitamin B12 tended to increase the absorption of the radioactive test dose to 23% on average. As yet there is no satisfactory explanation for the effect of the diet on the absorption of vitamin B12 in exocrine pancreatic insufficiency. This could be the reason why the malabsorption of vitamin B12 in patients with EPI can go unnoticed for many years and could possibly explain why vitamin B12 malabsorption in exocrine pancreatic insufficiency does not cause symptoms and signs of vitamin B12 deficiency for many years.

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Malabsorption of Crystalline Vitamin B₁₂in Cystic Fibrosis

Cited by 51 publications

References 9 publications

Correction of Cobalamin Malabsorption in Pancreatic Insufficiency with a Cobalamin Analogue that Binds with High Affinity to R Protein but not to Intrinsic Factor

Correction of Cobalamin Malabsorption in Pancreatic Insufficiency with a Cobalamin Analogue that Binds with High Affinity to R Protein but not to Intrinsic Factor

Vitamin B ₁₂ -Mediated Restoration of Defective Anaerobic Growth Leads to Reduced Biofilm Formation in Pseudomonas aeruginosa

Vitamin B12 absorption and exocrine pancreatic insufficiency in childhood

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Malabsorption of Crystalline Vitamin B12in Cystic Fibrosis

Cited by 51 publications

References 9 publications

Correction of Cobalamin Malabsorption in Pancreatic Insufficiency with a Cobalamin Analogue that Binds with High Affinity to R Protein but not to Intrinsic Factor

Correction of Cobalamin Malabsorption in Pancreatic Insufficiency with a Cobalamin Analogue that Binds with High Affinity to R Protein but not to Intrinsic Factor

Vitamin B 12 -Mediated Restoration of Defective Anaerobic Growth Leads to Reduced Biofilm Formation in Pseudomonas aeruginosa

Vitamin B12 absorption and exocrine pancreatic insufficiency in childhood

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Malabsorption of Crystalline Vitamin B₁₂in Cystic Fibrosis

Vitamin B ₁₂ -Mediated Restoration of Defective Anaerobic Growth Leads to Reduced Biofilm Formation in Pseudomonas aeruginosa