• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.381-388
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• 1996

The hemodynamic changes in septic patients produced by inhalational anesthetics are sufficient to threaten the anesthesiologists. The effect of hydroxocobalamin, a vitamin $B_{12a}$, on contractile responses to phenylephrine during administration of inhalational anesthetics were evaluated in aortic ring preparations obtained from LPS-treated rats. The sepsis was developed by intraperitoneal injection of LPS (1.5 mg/kg for l8h) and confirmed by iNOS expression using RT-PCR. Statistical significances (P<0.05) were analyzed by Student's t-test or paired t-test according to data characteristics. The blood pressure, but not heart rate, was decreased in LPS-treated rats as compared to control rats. The contractile response to phenylephrine were dose-dependently increased from the doses of $10^{-8}\;M$ to that of $10^{-5}$ and were attenuated in LPS-treated rings. Both halothane and enflurane, at the doses of 1 MAC, decreased the contractile responses to phenylephrine while isoflurane did not significantly affect the contractile responses. Hydroxocobalamin ($10^{-5}$ M) significantly potentiated the contractile responses in the LPS-treated aortic ring preparations during administration of each inhalational anesthetic or not. From these results, it is suggested that hydroxocobalamin may improve the hemodynamics of septic patients during inhalational anesthesia. Abbreviations: LPS, lipopolysaccharide; RT-PCR, reverse transcription-polymerase chain reaction; MAC, minimum alveolar concentration; iNOS, inducible nitric oxide synthase; GAPDH, glyceraldehyde 3-phosphate dehydrogenase

• BMB Reports
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• v.44 no.3
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• pp.170-175
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• 2011

We identified a bovine $B_{12}$ trafficking chaperone bCblC in Bos taurus that showed 88% amino acid sequence identity with a human homologue. The protein bCblC was purified from E. coli by over-expression of the encoding gene. bCblC bound cyanocobalamin (CNCbl), methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) in the base-off states and eliminated the upper axial ligands forming aquo/hydroxocobalamin ($OH_2$/OHCbl) under aerobic conditions. A transition of $OH_2$/OHCbl was induced upon binding to bCblC. Interestingly, bCblC-bound $OH_2$/OHCbl did not react with reduced glutathione (GSH), while the reaction of free$OH_2$/OHCbl with GSH resulted in the formation of glutathionylcobalamin (GSCbl) and glutathione disulfide (GSSG). Furthermore we found that bCblC eliminates the GSH ligand of GSCbl forming $OH_2$/OHCbl. The results demonstrated that bCblC is a $B_{12}$ trafficking chaperone that binds cobalamins and protects $OH_2$/OHCbl from GSH, which could be oxidized to GSSG by free $OH_2$/OHCbl.

• Journal of Trauma and Injury
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• v.36 no.4
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• pp.393-398
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• 2023

Patients transported from fire sites may exhibit various injury patterns. Major trauma, skin burn, inhalation burn, and carbon monoxide poisoning are typical injuries. However, most physicians may be unfamiliar that cyanide poisoning can frequently occur due to combustion. Cyanide poisoning is highly significant owing to high mortality and the existence of antidotes. I present a 35-year-old man who was transported from a burning building and suffered severe metabolic acidosis despite no major bleeding as well as mild carbon monoxide poisoning. I suspected cyanide poisoning and administered the antidote; subsequently, the patient showed improvement. The next day, sudden airway obstruction developed, and emergency endotracheal intubation was performed. The inhalation damage was detected only in the lower airway tract and not in the upper airway. Physicians should be aware of cyanide poisoning and inhalation burn to avoid missing treatment opportunities.

• Archives of Pharmacal Research
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• v.22 no.1
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• pp.48-54
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• 1999

These studies were designed to examine the differential effect of nitric oxide (NO) and cGMP on glutamate neurotransmission. In primary cultures of rat cerebellar granule cells, the glutamate receptor agonist N-methyl-D-aspartate (NMDA) stimulates the elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), the release of glutamate, the synthesis of NO and an increase of cGMP. Although NO has been shown to stimulate guanylyl cyclase, it is unclear yet whether NO alters the NMDA-induced glutamate release and ${[Ca^{2+}]}_i$ elevation. We showed that the NO synthase inhibitor, NG-monomethyl-L-arginine (NMMA), partially prevented the NMDA-induced release of glutamate and elevation of ${[Ca^{2+}]}_i$ and completely blocked the elevation of cGMP. These effects of NO on glutamate release and [Ca2+]i elevation were unlikely to be secondary to cGMP as the cGMP analogue, dibutyryl cGMP (dBcGMP), did not suppress the effects of NMDA. Rather, dBcGMP slightly augmented the NMDA-induced elevation of ${[Ca^{2+}]}_i$ with no change in the basal level of glutamate or ${[Ca^{2+}]}_i$. The extracellular NO scavenger hydroxocobalamine prevented the NMDA-induced release of glutamate providing indirect evidence that the effect of NO may act on the NMDA receptor. These results suggest that low concentration of NO has a role in maintaining the NMDA receptor activation in a cGMP-independent manner.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.19 no.1
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• pp.12-19
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• 2019

Purpose: Isolated methylmalonic acidemia (MMA) is an autosomal recessive inherited disorder of propionate metabolism. There are two subtypes of MMUT gene defects. $Mut^0$ represents complete loss of methylmalonyl-CoA mutase (MCM) activity while mut- is associated with residual MCM activity, which can be stimulated by hydroxocobalamin (OHCbl) supplementation. The objective of this study is to investigate cobalamin responsiveness and mutations present in Korean MMA population. Methods: We evaluated 10 MMA patients using somatic cell complementation analysis on their fibroblasts to measure MCM activity and vitamin B12 responsiveness for the optimal treatment. MMUT gene was sequenced to identify the MMA mutations. Results: For all patients, the incorporation of $[^{14}C]-propionate$ was low, and there was no response to OHCbl. The incorporation of $[^{14}C]-methyltetrahydrofolate$ and $[^{57}Co]-CNCbl$ fell within the normal range. There was adequate synthesis of methylcobalamin while the synthesis of adenosylcobalamin was low. The complementation analysis showed all patients were $mut^0$. The sequence analysis identified 12 different MMUT mutations, including 2 novel mutations, p.Gln267Ter and p.Ile697Phe, were identified. All the patients in this study had neonatal onset of symptoms, belonged to $mut^0$ complementation class, and as a result, showed no cobalamin responsiveness. Conclusion: No Korean MMA patient showed cobalamin responsiveness.