Efecto del tratamiento con ácido zoledrónico e hidroxocobalamina sobre la microarquitectura ósea en ratones con periodontitis y osteoporosis inducida: Estudio preclínico / Effect of zoledronic acid and hydroxocobalamin treatment on bone microarchitecture in mice with induced periodontitis and osteoporosis: preclinical study

Objetivo. Evaluar el efecto del tratamiento con ácido zoledrónico e hidroxocobalamina sobre la microarquitectura ósea alveolar en ratones con periodontitis y osteoporosis inducidas. Métodos. Diseño experimental en fase preclínica. Se incluyeron 16 ratones hembras a quienes se les indujo osteoporosis mediante la ovariectomía total y también se indujo la periodontitis por inflamación por ligadura de seda negra 5/0 en el segundo molar maxilar, todos los protocolos fueron sometidos durante anestesia general. Los ratones se distribuyeron en 4 grupos: control, tratamiento con ácido zoledrónico, tratamiento con hidroxocobalamina y tratamiento combinado. A las 16 semanas, se realizó la autanasia, se realizó la disección para la evaluación mediante microtomografía; determinando la densidad mineral ósea (BMD), el volumen de hueso (BV/TV), espesor trabecular (Tb. Th), número de trabéculas (Tb.N), separación trabecular (Tb.Sp); se realizó el análisis descriptivo y bivariado mediante ANOVA de 1 vía considerando un 95% de nivel de confianza. Resultados. El grupo que recibió tratamiento combinado de ácido zoledrónico e hidroxocobalamina presentó mayor densidad mineral ósea (DMO), mayor volumen óseo (BV/TV) y menor separación trabecular (Tb.Sp) en comparación con el grupo de control (p<0,05). Conclusiones. El tratamiento combinado de ácido zoledrónico e hidroxocobalamina mejora las características microarquitectónicas óseas en ratones con osteoporosis y periodontitis inducidas.

Objective. Evaluate the effect of zoledronic acid and hydroxocobalamin treatment on alveolar bone microarchitecture in mice with induced periodontitis and osteoporosis. Methods. Experimental design in preclinical phase. Sixteen female mice were included in which osteoporosis was induced by total ovariectomy and periodontitis was also induced by inflammation by 5/0 black silk ligation of the maxillary second molar, all protocols were performed under general anesthesia. The mice were distributed into 4 groups: control, treatment with zoledronic acid, treatment with hydroxocobalamin and combined treatment. At 16 weeks, euthanasia was performed, dissection was performed for evaluation by microtomography; determining bone mineral density (BMD), bone volume (BV/TV), trabecular thickness (Tb.Th), number of trabeculae (Tb.N), trabecular separation (Tb.Sp); descriptive and bivariate analysis was performed using 1-way ANOVA with a 95% confidence level. Results. The group that received combined treatment of zoledronic acid and hydroxocobalamin presented higher bone mineral density (BMD), higher bone volume (BV/TV) and lower trabecular separation (Tb.Sp) compared to the control group (p<0.05). Conclusions. Combined treatment with zoledronic acid and hydroxocobalamin improves bone microarchitectural features in mice with induced osteoporosis and periodontitis.

Exploring the Accessibility by Using the Hydroxycobalamin Preparations of High Concentration in Treating Methylmalonic Acidemia / 罕见病研究

Methylmalonic acidemia(MMA) is one of the common diseases in hereditary organic acid metabolism disorder. The disorder is mainly treated by using vitamin B12 which comes in various forms.The use of the methylcobalamin and adenosylcobalamin in China cannot meet the needs of children with MMA. Parenteral use of hydroxocobalamin of high concentration has significant advantages in the treatment of MMA. But, the accessibility to hydroxocobalamin is challenging now.Through the supervision and adjustment of hydroxocobalamin, we explored the strategy of using the drugs. Meanwhile, we are considering the oral use of the hydroxocobalamin as supplement to treatment. Solving the challenges of the hydrococobalamin is helpful to meet the treatment of MMA and to provide a new possibility for the use of medication for rare diseases. The improvement in policy and supervision measures will facilitate the development, involvement, and production of hydroxocobalamin, so that the patients will have a good chance of access to the treatment.

Correlation Research on Photodegradation Products of Cobamamide / 中国药师

Objective:To research the correlation between the cobamamide photodegradation products in the visible light area at different wavelengths and the photodegradation rate intensity. Methods:The 40-minute illumination experiment was conducted for co-bamamide reference solution respectively at the wavelength of 400 nm,450 nm,500 nm,550 nm,600 nm,650 nm and 700 nm under the illumination of 50 Lx,100 Lx,200 Lx,300 Lx,400 Lx and 500 Lx,respectively. An HPLC method was used to detect the cobam-amide content after the irradiation, the contents and proportions of hydroxocobalamin and adenosine (two photodegradation products) were calculated and the two photodegradation products were confirmed by mass spectrum. Results:The main photodegradation products of cobamamide (impurity 1,adenosine and hydroxocobalamin) had the similar photodegradation tendency. Within the scope of 50 Lx-200 Lx,the illumination intensity affected the concentration ratio of hydroxocobalamin and adenosine obviously. Within the scope of 200 Lx-500 Lx,the illumination intensity showed smaller effect. Under the different wavelengths and photodegradation rate intensity, the content of hydroxocobalamin was higher than that of adenosine under the same experimental condition.Conclusion:This paper re-searched the cobamamide photodegradation products in the optimum dark condition. The method is accurate and reliable,which can be used for the control of photodegradation related substances of cobamamide.

Hemolytic uremic syndrome associated with methylmalonic acidemia / 中华实用儿科临床杂志

Methylmalonic acidemia(MMA) is one of the most common diseases of autosomal recessive inherited organic acid metabolic disorder,which can cause multiple organ involvement.It can be found in infants or even in the neonatal period and be manifested as feeding difficulty,repeated vomiting,convulsions,abnormal muscle tension,mental retardation,hemolytic uremic syndrome(HUS),etc.In which HUS caused by MMA is better and better known by pediatricians when treating renal diseases while the diagnosis rate is increasing year by year.This article reviews the epidemiology,etiology,pathogenesis,clinical manifestations and treatment of HUS associated with MMA.

Antidotes of cyanide intoxication

Cyanide poisoning can occur from industrial disasters, smoke inhalation from fire, food, and multiple other sources. Cyanide inhibits mitochondrial oxidative phosphorylation by blocking mitochondrial cytochrome oxidase, which in turn results in anaerobic metabolism and depletion of adenosine triphosphate in cells. Rapid administration of antidote is crucial for life saving in severe cyanide poisoning. Multiple antidotes are available for cyanide poisoning. The action mechanism of cyanide antidotes include formation of methemoglobin, production of less or no toxic complex, and sulfane sulfur supplementation. At present, the available antidotes are amyl nitrite, sodium nitrite, sodium thiosulfate, hydroxocobalamin, 4-dimethylaminophenol, and dicobalt edetate. Amyl nitrite, sodium nitrite, and 4-dimethylaminophenol induce the formation of methemoglobin. Sodium thiosulfate supplies the sulfane sulfur molecule to rhodanese, allowing formation of thiocyanate and regeneration of native enzymes. Hydroxocobalamin binds cyanide rapidly and irreversibly to form cyanocobalamin. Dicobalt edetate acts as a chelator of cyanide, forming a stable complex. Based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended for cyanide poisoning. Amyl nitrite and sodium nitrite, which induce methemoglobin, should be avoided in victims of smoke inhalation because of serious adverse effects.

Neural compression-induced neuralgias: clinical evaluation of the effect of nucleotides associated with vitamin B12

The use of a combination of uridine triphosphate (UTP), cytidine monophosphate (CMP), and hydroxocobalamin was evaluated in a double-blind, randomized study in the treatment of neuralgia due to degenerative orthopedic alterations with neural compression. Following informed consent, 80 patients were randomized to a 30 day treatment period. The subjects received a thrice-daily oral treatment regimen of either the combination treatment (Group A: total daily dose of 9mg UTP, 15mg CMP, 6 mg hydroxocobalamin) or vitamin B12 alone (Group B: total daily dose of 6 mg hydroxocobalamin). Efficacy measures evaluated global patient condition from the perspective of the subject and the investigating physician pain ? measured by a visual-analog scale and functionality, using a patient-response questionnaire. The safety evaluation took into account physical evaluations and laboratory tests performed at each visit to the study center as well as the incidence and severity of adverse events. At the end of the 30-day treatment period, there were reductions in the pain scale scores in both groups, however there was a significantly larger reduction in the scores of the Group A patients. The Patient Global Evaluation scores improved in both groups but showed greater improvement in Group A, while the Physician Global Evaluation improved significantly only in Group A. A similar finding was observed in the scores of the Patient Functionality Questionnaire. Based on the findings of this clinical trial, we conclude that the combination of UTP, CMP, and vitamin B12 has a positive effect on pain and functionality improvement in the treatment of degenerative orthopedic alterations with neural compression, in the study population evaluated.

Hydoroxocobalamin (Vitamin B12) Effects on Nerve Function Impairments in Leprosy / 나학회지

95 patients in Sorokdo national hospital injected 1-5mg Hydroxocobalamin (5mg/2ml/1ample) in 5-7 days/week, duration 6.4 months, average age 71.6 years old. Effects are 1) softening of hand movement(22/95), early effect, 2) improving of motor function (8/95) 3) sensory function(8/95) 4) sweating (3/95) 5) neuropathic pain and headache(neuralgia-like) (7/95) 6) jaw and hand tremor (7/95) 7) no response (41/95) 8) side effect (1/95) Leprosy is demyelinating peripheral neuropathy, Vitamin B12 effects on myelin, but unkown it's mechnism. Vitamin B12 improve nerve function impairments in leprosy, especially neuropathic pain and tremor, which lead to deformities and disabilities.

Effects of L-NAME, Aminoguanidine and Hydroxocobalamin on Aortic Contractile Responses in Endotoxemic Rats during Halothane Administration / 대한마취과학회지

BACKGROUND: Recent studies demonstrated that volatile anesthetics suppress the NO-cGMP system in the vascular system. It has been known that the hemodynamic changes produced by volatile anesthetics in septic patients are mediated by upregulation of iNOS leading to excessive release of NO. The mechanisms underlying suppression of the NO-cGMP system by anesthetics are still controversial. It has been elucidated that nitric oxide synthase (NOS) plays a major role in the regulatory function in the L-arginine-NO system. So we examined the effects of NOS inhibitor (L-NAME, aminoguanidine) and NO scavenger (hydroxocobalamin) on vascular smooth muscle contractile function in lipopolysaccharide (LPS)-treated rat aorta during halothane administration. METHODS: Aortic ring preparations were obtained from LPS-treated (1.5 mg/kg, ip, for 18 h) rats. We evaluated the effects of hydroxocobalamin, L-NAME and aminoguanidine on contractile responses to phenylephrine during halothane (1 & 2 MAC) administration respectively. Statistical significances (P<0.05) were analyzed according to data characterictics by repeated measures ANOVA test and student's t-test. RESULTS: The contractile responses to phenylephrine in LPS-treated rats aorta were significantly (P<0.05) increased in the presence of hydroxocobalamin and L-NAME. During the halothane (1 and 2 MAC) administration, the contractile responses to phenylephrine in LPS-treated rats aorta were increased significantly (P<0.05) in the presence of hydroxocobalamin and L-NAME. CONCLUSIONS: From these results, it is suggested that hydroxocobalamin and L-NAME may be useful in the therapy of septic shock.