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Gastric emptying in patients with vitamin B(12) deficiency.

The clinical presentation of patients with vitamin B(12) deficiency varies in a spectrum ranging from haematological disorders to neuropsychiatric diseases. In rare cases, orthostatic hypotension, impotence, constipation and urinary retention have been attributed to autonomic nervous system dysfunction due to vitamin B(12) deficiency. The aim of this study was to evaluate the effect of vitamin B(12) deficiency on autonomic nervous system function by studying gastric emptying times ( T(1/2)). Twenty patients with newly diagnosed vitamin B(12) deficiency and 12 control patients with gastritis and normal vitamin B(12) levels were enrolled in this study. Gastroduodenoscopy, endoscopic biopsy, histopathological evaluation of the biopsy specimens and radionuclide gastric emptying studies were performed. After vitamin B(12) replacement therapy for 3 months, radionuclide gastric emptying studies were repeated. Mean gastric emptying T(1/2) in patients before and after treatment and in controls were 103.83+/-48.80 min, 90.00+/-17.29 min and 74.55+/-8.52 min, respectively. The difference in mean gastric emptying T(1/2) between patients before treatment and controls was statistically significant ( P<0.01). The statistically significant difference persisted after vitamin B(12) treatment ( P<0.05), though mean gastric emptying T(1/2) was somewhat shorter. There were no positive or negative correlations between gastric emptying T(1/2) and the following parameters: haemoglobin, vitamin B(12) level and Helicobacter pylori positivity. In conclusion, gastric emptying T(1/2) was prolonged in patients with vitamin B(12) deficiency and this prolongation was not corrected after vitamin B(12) replacement therapy. Although autonomic nervous system dysfunction due to vitamin B(12) deficiency rarely gives rise to clinical manifestations, latent dysfunction demonstrated by laboratory tests seems to be a frequent phenomenon. The level of vitamin B(12) does not correlate with the degree of autonomic nervous system dysfunction measured by radionuclide gastric emptying studies.

Adult↗

Enhanced anaerobic biotransformation of carbon tetrachloride with precursors of vitamin B(12) biosynthesis.

Relatively low concentrations of Vitamin B(12) are known to accelerate the anaerobic biotransformation of carbon tetrachloride (CT) and chloroform (CF). However, the addition of vitamin B(12) for field-scale bioremediation is expected to be costly. The present study considered a strategy to generate vitamin B(12) by addition of biosynthetic precursors. One of the precursors, porphobilinogen (PB) involved in the formation of the corrin ring, significantly increased the CT biotransformation rates by 2.7-, 8.8- and 10.9-fold when supplemented at 160, 500 and 900 microM, respectively. A positive control with 10 microM of vitamin B(12) resulted in a 5.9-fold increase in the CT-bioconversion rate. PB additions provided high molar yields of inorganic chloride (57% of CT organochlorine), comparable to that obtained with vitamin B(12) supplemented cultures. The primary substrate, methanol, known to induce vitamin B(12) production in methanogens and acetogens, was required for PB to have a significant impact on CT conversion. The observation suggests that PB's role was due to stimulating vitamin B(12) biosynthesis. The present study therefore provides insights on how to achieve vitamin B(12) enhanced rates of CT bioremediation through the use of less complex compounds that are precursors of vitamin B(12). Although PB is a costly chemical, its large impact points to corrin ring formation as the rate-limiting step.

Bacteria, Anaerobic↗

Synthesis and biological activity of ribose-5'-carbamate derivatives of vitamin B(12).

Twelve biologically active derivatives of vitamin B(12) (cyanocobalamin) have been synthesized in which spacers were attached to the ribose-5'-hydroxyl group of vitamin B(12). Their potential to act as oral delivery agents for proteins, nanospheres, or immunogens using the vitamin B(12) uptake system was evaluated by determining their affinity for intrinsic factor (IF) and non-IF. The ribose-5'-hydroxyl group of vitamin B(12) was activated through the use of 1,1'-carbonyldiimidazole (CDI), 1,1'-carbonyldi(1,2, 4-triazole) (CDT), or di(1-benzotriazolyl) carbonate (DBTC). Subsequent addition of an aminoalkane, diaminoalkane, or alkane diacid dihydrazide gave rise to vitamin B(12) derivatives suitable for attachment to various proteins, peptides, or nanospheres to enable oral delivery utilizing the vitamin B(12) uptake system. The ribose-5'-carbamate derivatives were found to possess similar affinity for intrinsic factor as that of the e-monocarboxylic acid of vitamin B(12). The affinity for non-IF was similar to cyanocobalamin or even higher for some of the smaller derivatives. Polysciences nanoparticles derivatized with vitamin B(12) 5'-carbamate adipic dihydrazide into CaCo-2 cells showed significantly higher levels of transport of the particles, when compared to unmodified particles.

Adipates↗