- Assessment of cellular cobalamin metabolism in Gaucher disease. [Journal Article]BMC Med Genet 2020; 21(1):12BM
- CONCLUSIONS: Our results indicate that cobalamin transport and cellular processing pathways are overall protected from lysosomal storage damage in GD fibroblasts. Extending these studies to hepatocytes, macrophages and plasma will shed light on cell- and compartment-specific vitamin B12 metabolism in Gaucher disease.
- A Comparison of Potential Azide Antidotes in a Mouse Model. [Journal Article]Chem Res Toxicol 2020CR
- Three cobalt-containing macrocyclic compounds previously shown to antagonize cyanide toxicity have been comparatively evaluated for the amelioration of sub-lethal azide toxicity in juvenile (7-8 weeks) Swiss-Webster mice. The lowest effective doses were determined for hydroxocobalamin, a cobalt porphyrin and a cobalt-Schiff base macrocycle by giving the antidotes 5 min prior to the toxicant, 27 m…
Three cobalt-containing macrocyclic compounds previously shown to antagonize cyanide toxicity have been comparatively evaluated for the amelioration of sub-lethal azide toxicity in juvenile (7-8 weeks) Swiss-Webster mice. The lowest effective doses were determined for hydroxocobalamin, a cobalt porphyrin and a cobalt-Schiff base macrocycle by giving the antidotes 5 min prior to the toxicant, 27 mg (415 mol) /kg of sodium azide. Both male and female mice were evaluated for their response to the toxicant as well as the antidotes and no significant differences were noted once weight differences were taken into account. Two of the three compounds significantly decreased the recovery time of azide-intoxicated mice at 10 min after the administration of sodium azide as determined by a behavior test (pole climbing). Additionally, azide was determined to cause a several degree drop (~3 °C) in measured tail temperature and warming the mice led to a more rapid recovery. The mice were also shown to recover more rapidly when given sodium nitrite, 24 mg (350 mol)/kg, 5 min after the toxicant; this treatment also suppressed the azide-induced tail temperature decrease. Electron paramagnetic resonance (EPR) measurements of mouse blood treated with sodium azide demonstrated the presence of nitrosylhemoglobin at levels of 10-20 M which persisted for ~300 min. The presence of the methemoglobin azide adduct was also detected by EPR at a maximum level of ~300 M but these signals disappeared around 200 min after the administration of azide. The treatment of mice with 15N sodium azide proved that the nitrosylhemoglobin was a product of the administered azide by the appearance of a two-line hyperfine (due to the 15N) in the EPR spectrum of mouse blood.
- Clinical picture and treatment effects in 5 patients with Methylmalonic aciduria related to MMAA mutations. [Case Reports]Mol Genet Metab Rep 2020; 22:100559MG
- CONCLUSIONS: Patients with a mutation in the MMAA gene are sensitive to treatment with hydroxocobalamine, but the inclusion of appropriate treatment does not protect against neurodevelopmental disorders and chronic kidney disease.
- Vasoplegia During Cardiopulmonary Bypass: Current Literature and Rescue Therapy Options. [Review]J Cardiothorac Vasc Anesth 2019JC
- Vasoplegia syndrome in the cardiac surgical intensive care unit and postoperative period has been an area of interest to clinicians because of its prevalence and effects on morbidity and mortality. However, there is a paucity of evidence regarding the treatment of vasoplegia syndrome during cardiopulmonary bypass (on-CPB VS). This review aims to detail the incidence, outcomes, and possible treatm…
Vasoplegia syndrome in the cardiac surgical intensive care unit and postoperative period has been an area of interest to clinicians because of its prevalence and effects on morbidity and mortality. However, there is a paucity of evidence regarding the treatment of vasoplegia syndrome during cardiopulmonary bypass (on-CPB VS). This review aims to detail the incidence, outcomes, and possible treatment options for patients who develop vasoplegia during bypass. The pharmacologic rescue agents discussed are used in cases in which vasoplegia during CPB is refractory to standard catecholamine agents, such as norepinephrine, epinephrine, and phenylephrine. Methods to improve vasoplegia during CPB can be both pharmacologic and nonpharmacologic. In particular, optimization of CPB parameters plays an important nonpharmacologic role in vasoplegia during CPB. Pharmacologic agents that have been demonstrated as being effective in vasoplegia include vasopressin, terlipressin, methylene blue, hydroxocobalamin, angiotensin II (Giapreza), vitamin C, flurbiprofen (Ropion), and hydrocortisone. Although these agents have not been specifically evaluated for vasoplegia during CPB, they have shown signs of effectiveness for vasoplegia postoperatively to varying degrees. Understanding the evidence for, dosing, and side effects of these agents is crucial for cardiac anesthesiologists when treating vasoplegia during CPB bypass.
- Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft. [Journal Article]J Pharmacol Sci 2019JP
- Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependen…
Cardioprotective abilities of procyanidins, might, at least in part, attribute to their vasodilator properties. The present study was undertaken to assess the vasorelaxant effect of procyanidin B2 on isolated human saphenous vein (HSV) and its underlying mechanisms. Procyanidin B2 relaxed phenylephrine-induced contraction of HSV rings in concentration-dependent manner. The relaxation was dependent on the presence of endothelium and was strongly affected by l-NAME, hydroxocobalamin or ODQ, the inhibitors of NO/cGMP pathway. Indomethacin significantly affected only the relaxation produced by the highest concentrations of procyanidin B2. Apamin and TRAM-34 combination, in the presence of l-NAME and indomethacin, did not additionally decreased procyanidin B2-induced relaxation. In the presence of K+ channel blockers, relaxation induced by procyanidin B2 was partially attenuated by 4-aminopyridine, significantly inhibited by glibenclamide and almost abolished by iberiotoxin. Procyanidin B2 also relaxed the contractions induced by phenylephrine or caffeine in Ca2+-free solution. Finally, nifedipine slightly, while thapsigargin strongly antagonized HSV relaxation. Our results indicate that procyanidin B2 induces endothelium-dependent relaxation of HSV, which results primarily from stimulation of NO production, as well K+ channels opening, especially BKCa, and partially KATP and KV. Regulation of the intracellular Ca2+ release and inhibition of Ca2+ influx probably contribute to procyanidin B2-induced relaxation.
- Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study. [Journal Article]Crit Care 2019; 23(1):421CC
- CONCLUSIONS: Hydroxocobalamin was associated with an increased risk of AKI and severe AKI but was not associated with survival after smoke inhalation.
- Hydroxocobalamin in the treatment of vasodilatory shock. [Letter]J Clin Anesth 2020; 61:109665JC
- Characteristics of emergency department presentations requiring consultation of the national Poisons Information Centre. [Journal Article]Swiss Med Wkly 2019; 149:w20164SM
- CONCLUSIONS: For patients presenting at the emergency department with severe poisoning, contact with the poison information centre can help to implement specific treatment and avoid fatalities. In less severe cases involving more common agents (e.g. paracetamol, benzodiazepines), contact can help to avoid unnecessary treatment and serve as a source of information and/or confirmation.
- Hydroxocobalamin administration for treatment of vasoplegic syndrome associated with cardiopulmonary bypass causes red plasma. [Journal Article]Transfusion 2019T
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- Intranasal treatment of vitamin B12 deficiency in children. [Journal Article]Eur J Pediatr 2019EJ
- CONCLUSIONS: In children, intranasal application of vitamin B12 seems a safe and effective alternative to intramuscular injections, leading to higher compliance and less burden to patients.What is Known:• Children with vitamin B12deficiency are traditionally treated with intramuscular cobalamin injections, which are costly and painful.• Studies in adults showed that intranasal application of hydroxocobalamin leads to normalisation of vitamin B12levels.What is New:• The intranasal application of vitamin B12resulted in a substantial increase of the mean baseline vitamin B12levels without any side effect.• These data encourage a systematic evaluation of intranasal treatment of vitamin B12deficiency in order to define safety, optimal dosage and administration frequency.