BACKGROUND: Endotoxins play important roles in the pathophysiologic alterations associated with sepsis so the authors examined the effects of hydroxocobalamin, NW-nitro-L-arginine-metyl ester (L-NAME) and aminoguanidine on thiopental-induced contractile responses of lipopolysaccharide (LPS)-treated and control rat aortic rings. METHODS: Aortic ring preparation was obtained from LPS-treated (1.5mg/kg, i.p. for 18h) rats. Cumulative doses of thiopental (10-4~3x10- 3M) were added to construct contraction response curves. Hydroxocobalamin (10-5M), L-NAME (10-6M) or aminoguanidine (10-6M) were added as NO scavenger or as NOS inhibitors. Contraction curves by cumulative doses of thiopental (10-4~3x10-3M) were remeasured after treatment of NO scavenger or NOS inhibitors. Statistical significances (p<00.05) were analyzed according to data characteristics by Student's t-test, paired t-test or ANOVA. RESULTS: The vascular responses of cumulative thiopental (10-4~3x10 3M) administration were dose- dependent contraction and LPS-treated rat was less contracted (p<00.05). There was significant increment on vascular contraction induced by thiopental after hydroxocobalamin pretreatment in LPS-treated rat (p<0.05), in spite of L-NAME, aminoguanidine pretreatment was failed to increase contractile forces in control and LPS-treated rats. CONCLUSIONS: From these results, viewed from maintenance of vasomotor tone in septic state, it is suggested that hydroxocobalamin may be candidate for vasopressor during usual induction of general anesthesia.
Anesthesia, General ; Animals ; Aorta, Thoracic* ; Endotoxins ; Hydroxocobalamin* ; NG-Nitroarginine Methyl Ester ; Rats* ; Sepsis ; Thiopental

Obtaining a complete and accurate history is one of the most crucial steps in the initial diagnosis and subsequent management of the poisoned patients. This information can then be integrated with physical evidence, clinical examination, laboratory and toxicological data in designing a therapeutic approach. Such information may include patient data, product information, and nature of exposure. The basic treatment for acute poisoning, whether of drug or chemical, is mainly symptomatic and supportive. The four cardinal principles of good management are ① identification of the causative drug or chemical as quickly as possible, ② evacuation of the poison from the stomach, except when contraindicated, ③ administration of an antidote if available, and ④ symptomatic and supportive therapy as indicated. Management in most cases of toxicity consists of supportive care, symptomatic treatment, and avoidance of exposure to the toxic material. In cases of life-threatening toxicity, maintenance of cardiopulmonary function and fluid and electrolyte balance are important. There are limited specific methods of treatment, or "antidotes". Use of oxygen counters the foxic effect and enhances the elimination of carbon monoxide. In cases acute cyanide of hydrogen sulfide poisoning, nitrites may be used to generate formation of cyanmethemoglobin or sulfmethemoglobin. Hydroxocobalamin can also be used as an antidote for cyanide. Atropine and pralidoxime can be life-saying in reversing the acute cholinesterase-inhibiting effects of organophosphate pesticides. Chelating agents may reverse acute toxicity caused by some metals.
Atropine ; Carbon Monoxide ; Chelating Agents ; Diagnosis ; Humans ; Hydrogen Sulfide ; Hydroxocobalamin ; Metals ; Nitrites ; Oxygen ; Pesticides ; Poisoning* ; Stomach ; Water-Electrolyte Balance

PURPOSE: Antidotes for toxicological emergencies can be life-saving. However, there is no nationwide stocking and delivery system for emergency antidotes in Korea. We report on a two-year experience of a nationwide stocking and delivery trial for emergency antidotes at emergency departments in Korea. METHODS: An expert panel of clinical toxicologists reviewed and made a list of 15 stocked antidote. These antidotes were purchased or imported from other countries and delivered from 14 antidote stocking hospitals nationwide 24 hours per day, seven days per week. RESULTS: From August 1, 2011 to April 30, 2013, 177 patients with acute poisoning, with a median age of 48.5 years, were administered emergency antidotes. The causes of poisoning were intentional in 52.0% and 88.0% were intentional as a suicide attempt. Regarding clinical severity, using the poisoning severity score, 40.7% of patients had severe to fatal poisoning and 39.0% had moderate poisoning according to clinical severity. The most frequent presenting symptom was neurologic deficit, such as altered mentality (62.7%). alerted mentality (62.7%). Emergency antidotes were administered as follows: methylene blue (49 cases), flumazenil (31), N-acetylcysteine (25), glucagon (17), 100% ethanol (15), cyanide antidote kit (12), anti-venin immunoglobulin (5), pyridoxine (4), hydroxocobalamine (2), and deferoxamine (1). The median time interval from antidote request to delivery at the patient's bedside was 95 minutes (interquartile range 58.8-125.8). CONCLUSION: Findings of this study demonstrated the possibility of successful operation of the nationwide system of emergency antidotes stocking and delivery in Korea.
Acetylcysteine ; Antidotes ; Deferoxamine ; Emergencies ; Ethanol ; Flumazenil ; Glucagon ; Humans ; Hydroxocobalamin ; Immunoglobulins ; Information Centers ; Korea ; Methylene Blue ; Neurologic Manifestations ; Pyridoxine ; Suicide

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.
Congenital Abnormalities ; Hand ; Humans ; Hydroxocobalamin ; Jaw ; Leprosy ; Myelin Sheath ; Neuralgia ; Peripheral Nervous System Diseases ; Sweat ; Sweating ; Tremor ; Vitamin B 12

Although sodium nitroprusside (SNP) is often used in pediatric intensive care units, cyanide toxicity can occur after SNP treatment. To treat SNP-induced cyanide poisoning, antidotes such as amyl nitrite, sodium nitrite, sodium thiosulfate, and hydroxycobalamin should be administered immediately after diagnosis. Here, we report the first case of a very young infant whose SNP-induced cyanide poisoning was successfully treated by exchange transfusion. The success of this alternative method may be related to the fact that exchange transfusion not only removes the cyanide from the blood but also activates detoxification systems by supplying sulfur-rich plasma. Moreover, exchange transfusion replaces cyanide-contaminated erythrocytes with fresh erythrocytes, thereby improving the blood's oxygen carrying capacity more rapidly than antidote therapy. Therefore, we believe that exchange transfusion might be an effective therapeutic modality for critical cases of cyanide poisoning.
Amyl Nitrite ; Antidotes ; Natural Resources ; Cyanides ; Erythrocytes ; Humans ; Hydroxocobalamin ; Infant ; Intensive Care Units, Pediatric ; Nitroprusside ; Oxygen ; Plasma ; Sodium ; Sodium Nitrite ; Thiosulfates

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.
Anesthetics ; Animals ; Aorta ; Halothane* ; Hemodynamics ; Humans ; Hydroxocobalamin* ; Muscle, Smooth, Vascular ; NG-Nitroarginine Methyl Ester* ; Nitric Oxide Synthase ; Phenylephrine ; Rats* ; Shock, Septic ; Up-Regulation

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.
Adenosine Triphosphate ; Aminophenols ; Amyl Nitrite ; Antidotes* ; Disasters ; Edetic Acid ; Electron Transport Complex IV ; Equipment and Supplies ; Fires ; Hydroxocobalamin ; Inhalation ; Metabolism ; Methemoglobin ; Oxidative Phosphorylation ; Oxygen ; Poisoning ; Polyphosphates ; Regeneration ; Smoke ; Sodium ; Sodium Nitrite ; Sulfur ; Thiocyanates ; Thiosulfate Sulfurtransferase ; Thiosulfates ; Vitamin B 12

Adult ; Age of Onset ; Amino Acid Metabolism, Inborn Errors ; complications ; diagnosis ; genetics ; therapy ; Betaine ; administration & dosage ; therapeutic use ; Carrier Proteins ; genetics ; metabolism ; Child ; China ; epidemiology ; DNA Mutational Analysis ; Gas Chromatography-Mass Spectrometry ; Genotype ; Homocysteine ; urine ; Humans ; Hydroxocobalamin ; administration & dosage ; therapeutic use ; Hyperhomocysteinemia ; complications ; diagnosis ; genetics ; therapy ; Infant ; Methylmalonic Acid ; blood ; urine ; Mutation ; Vitamin B 12 ; metabolism

OBJECTIVECombined methylmalonic acidemia with homocystinuria is a common form of methylmalonic acidemia in China. Patients with this disease can progress to death without timely and effective treatment. This study aimed to analyze the treatment outcomes of patients with combined methylmalonic acidemia and homocystinuria.

METHODFrom September 2004 to April 2012, 58 patients with combined methylmalonic acidemia and homocystinuria (34 males and 24 females) were diagnosed and treated in our hospital. Fifty cases were from clinical patients including 42 early-onset cases and 8 late-onset cases. Their age when they were diagnosed ranged from 18 days to 30.8 years. The other 8 cases were from newborn screening. All the patients were treated with vitamin B12, betaine, folic acid, vitamin B6, and L-carnitine. The physical and neuropsychological development, general laboratory tests, the levels of amino acids, acylcarnitines, and homocysteine in blood, and organic acids in urine were followed up.

RESULTThe follow-up period ranged from 1 month to 7.1 years. Three cases died (all were early-onset cases). In the other patients after treatment, the symptoms such as recurrent vomiting, seizures, lethargy, and poor feeding disappeared, muscle strength and muscle tension were improved, and general biochemical abnormalities such as anemia and metabolic acidosis were corrected. Among the surviving 55 cases, 49 had neurological impairments such as developmental delay and mental retardation. The median levels of blood propionylcarnitine and its ratio with acetylcarnitine, serum homocysteine, and urine methylmalonic acid were significantly decreased (P < 0.01), from 7.73 µmol/L (ranged from 1.5 to 18.61 µmol/L), 0.74 (ranged from 0.29 to 2.06), 97.3 µmol/L (ranged from 25.1 to 250 µmol/L) and 168.55 (ranged from 3.66 to 1032.82) before treatment to 2.74 µmol/L (ranged from 0.47 to 12.09 µmol/L), 0.16 (ranged from 0.03 to 0.62), 43.8 µmol/L (ranged from 17 to 97.8 µmol/L) and 6.81 (ranged from 0 to 95.43) after treatment, respectively.

CONCLUSIONPatients with combined methylmalonic acidemia and homocystinuria respond to a combined treatment consisting of supplementation of hydroxycobalamin, betaine, folic acid, vitamin B6 and L-carnitine with clinical and biochemical improvement. But the long-term outcomes are unsatisfactory, with neurological sequelae in most patients.

Adolescent ; Adult ; Amino Acid Metabolism, Inborn Errors ; blood ; diagnosis ; therapy ; Betaine ; administration & dosage ; therapeutic use ; Carnitine ; analogs & derivatives ; blood ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Homocystine ; blood ; Homocystinuria ; blood ; diagnosis ; therapy ; Humans ; Hydroxocobalamin ; administration & dosage ; therapeutic use ; Infant ; Infant, Newborn ; Male ; Methylmalonic Acid ; urine ; Neonatal Screening ; Treatment Outcome ; Vitamin B 12 ; administration & dosage ; therapeutic use ; Vitamin B 12 Deficiency ; congenital ; Young Adult