Detection of Exogenous γ-Hydroxybutyric Acid in Rat Blood Exosomes / 法医学杂志

OBJECTIVES@#To find a method to distinguish exogenous gamma-hydroxybutyrate (GHB) from endogenous GHB by establishing ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) based on exosome for quantitative detection of GHB in the rat blood.@*METHODS@#Adult male SD rats were divided into 1 h, 5 h, 10 h administration group and control group. After 1 h, 5 h and 10 h of single precursor of GHB gamma-butyrolactone (GBL) intraperitoneal injection in administration groups, 5 mL blood was collected from the abdominal aorta. Meanwhile, the control group was given a same dose of normal saline, and 5 mL blood was collected at 1 h. Among the 5 mL blood, 0.5 mL was directly detected by HPLC-MS after pretreatment, and exosomes were extracted from the remaining blood by differential centrifugation and detected.@*RESULTS@#The concentration of GHB in the control group was (87.36±33.48) ng/mL, and the concentration with administration at 1 h, 5 h and 10 h was (110 400.00±1 766.35) ng/mL, (1 479.00±687.01) ng/mL and (133.60±12.17) ng/mL, respectively. The results of exosome detection showed that no peak GHB signal was detected in the control group and the 10 h administration group, and the concentrations of GHB at 1 h and 5 h administration groups were (91.47±33.44) ng/mL and (49.43±7.05) ng/mL, respectively.@*CONCLUSIONS@#GHB was detected in blood exosome by UPLC-MS, which indicated that exogenous GHB could be detected in plasma exosomes, while endogenous GHB could not be detected, suggesting that this method may be used as a basis to determine whether there is exogenous drug intake.

Pediatric Narcolepsy: Diagnosis and Treatment / 대한소아신경학회지

Narcolepsy is chronic devastating disease that characterized by excessive daytime sleepiness, cataplexy, which often precipitated by intense emotion or excitement, hypnagogic, or hypnapompic hallucinations, sleep paralysis and nocturnal disrupted sleep. In child onset narcolepsy, the presentations of narcolepsy can be very variable, making misdiagnosis as seizure disorders or delaying diagnosis as much as several years after disease onset. For the diagnosis of narcolepsy, overnight polysomnography(PSG) and multiple sleep latency test(MSLT) should be evaluated. Test for Cerebrospinal fluid hypocretin(orexin) concentration and human leukocyte antigens(HLA) would be great helpful to confirm the narcolepsy with cataplexy even in early stage of disease in children. The mainstays of treatment are that reducing the excessive daytime sleepiness, preventing the intrusion of the REM related phenomena including cataplexy and consolidating the nighttime sleep. Central nervous system stimulators such as methylphenidate or amphetamine decrease excessive daytime sleepiness and tricyclic antidepressant(TCA) or selective serotonin reuptake inhibitors(SSRI) can prevent cataplexy. Recently, new therapeutic agents such as modafinil and sodium oxybate are emerging in clinical practice with much effectiveness. Counseling for poor school performance, social isolation and depression should be provided. Early diagnosis and treatment can greatly improve the quality of life. Awareness of excessive daytime sleepiness in children or adolescent will allow pediatricians to effectively identify hypersomnia such as narcolepsy.

Detection of gamma-hydroxybutyrate (GHB) in beverages / 法医学杂志

OBJECTIVE@#To establish an analytical method for the determination of GHB in beverages using GC/MS and LC/MS/MS.@*METHODS@#After beverage samples with GHB-d6 as the internal standard were extracted with ethyl acetate, then the extracts were derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), at last the derivateized extracts analyzed by gas chromatography- mass spectrometry. After beverage samples with GHB-d6 as the internal standard were diluted by mobile phase then directly analyzed by LC/MS/MS. Results The limit of detection was 0.2 microg/mL and both relative standard deviations for between-day and within-day assays were < 8.54% in GC/MS. The limit of detection was 2 microg/mL and both relative standard deviations for between-day and within-day assays were <8.62% in LC/MS/MS. Conclusion These methods of qualitative and quantitative analysis were found to be sensitive, accurate, rapid and suitable for the forensic toxicology to test of GHB in real cases.

Dexmedetomidina para sedación durante intubación difícil con Fibrobroncoscopia / Dexmedetomidina for sedation during intubación difficult with Fibrobroncoscopia

Paciente de 48 años de sexo femenino, con diagnóstico de bocio gigante, valorada en consulta preanestésica que presenta una gran masa en cuello que ya había sido operada previamente y que se extendía al pulmón derecho. Al evaluar la vía aérea se encontró una desviación traqueal importante, con Mallampati III y se programó como intubación difícil con fibrobroncoscopia. El día de la cirugía, se decidió colocar un tubo doble lumen No. 37, previa anestesia tópica con lidocaina spray, 2 mg de midazolam y un bolo de Dexmedetomidina (DXM) 0,7 microgr/kg en 10 minutos, seguido por una infusión continua de 0,25-0,3 microgr/Kg. Se midió el nivel de sedacion mediante la escala de Ramsay, considerando adecuado un nivel 2 y 3 y se procedió a la intubación nasotraqueal con fibrobroncoscopia. Una vez confirmada se le colocó tiopental sódico 3 mg/kg más Rocuronio 0,5 mg/kg y Fentanyl 2 microgr/kg IV. Se continúo con DXM durante todo el procedimiento y se adicionó Isorane a 1 MAC. Se realizó cervicotomía y esternotomía para extraer la masa, se suspendió la DXM 15 minutos antes de finalizar el procedimiento y se extubó a la paciente despierta; hemodinámicamente estable, se llevó a UCI donde evolucionó satisfactoriamente y fue dada de alta a los 3 días...

Interaction of flunarizine with sodium valproate or ethosuximide in gamahydroxybutyrate induced absence seizures in rats.

Sodium valproate(VPA), ethosuximide(ESM), 200 mg/kg ip and flunarizine (FLU) 5 or 10 mg/kg ip were first administered independently to rats in order to study their effects on behavioural and EEG aspects of spike and wave discharges (SWDs) induced by y- hydroxybutyrate (GHB,100 mg/kg ip). GHB treated rats show behavioural changes and concomitant repetitive EEG episodes of 7 to 9 Hz SWDs, mimicking human absence seizures (AS), and can be used as a pharmacological model. The number and duration of SWDs were calculated for 1 hr from the EEG and were parameters for drug evaluation. VPA and ESM at 200 mg/kg, significantly reduced SWD number and duration/hr, while FLU showed significant reduction only at 10 but not at 5 mg/kg. Combination of FLU, 10 mg/kg with either VPA or ESM showed significant reduction of SWD number and duration, suggesting an additive effect of the anti-absence agents with the calcium channel blocker, FLU, on experimental absence seizures in rats.

Comparative profiles of sodium valproate and ethosuximide on electro-behavioural correlates in gamma-hydroxybutyrate and pentylenetetrazol induced absence seizures in rats.

Sodium valproate (VPA) and ethosuximide (ESM) were compared on behavioural and EEG changes in gamma-hydroxybutyrate (GHB) and pentylenetetrazole (PTZ) rat models of Absence Seizures (AS). Both GHB, 100 mg/kg i.p. and PTZ, 20 mg/kg i.p., produced repetitive episodes of staring and immobility with concomitant 6 to 9 Hz spike and wave discharges (SWDs) in the EEG. The parameters used for drug evaluation were the number and duration of SWDs/hour. Though the number of SWDs/hour produced by GHB and PTZ were not significantly different, the duration of SWDs was significantly longer in GHB treated rats (P < 0.001) VPA and ESM, at 200 mg/kg i.p., reduced SWD number and duration in GHB pretreated rats, whereas ESM, 50 mg/kg i.p., was four times more effective than VPA, 200 mg/kg i.p., in the PTZ model. Phenytoin (PHY) 20 and Carbamazepine (CBZ) 10 mg/kg i.p., worsened AS, a feature which has also been reported clinically. Both rat models of experimental AS can be used to defect potential anti-absence activity in new chemical entities.

Acetato de desmopresina en niños enuréticos resistentes a terapias convencionales / Desmopressin acetate in children with conventional therapy resistant enuresis

Se describen los resultados obtenidos con acetato de desmopresina en aerosol por inhalación nasal en 29 niños (15 varones) entre 8 y 10 años de edad, que sufrían enuresis nocturna resistente a tratamiento con imipramina sola y/o asociada a ácido oxibutinino. En todos ellos la anatomía y función vesical eran normales y ninguno sufría enfermedades neurológicas o renales. La desmopresina se suministró en dosis diarias de 10 µg que fueron aumentadas semanalmente, si era necesario, en igual proporción, hasta obtener uno o ningún episodio semanal de enuresis o un máximo de 40 µg diarios del fármaco. La dosis así titulada se mantuvo por 3 meses, al cabo de los cuales se redujo progresivamente en 10 µg semanales hasta suspenderla. Los pacientes fueron seguidos hasta un mes después de la supresión del tratamiento. Se obtuvo buen éxito (uno o menos episodios de enuresis por semana) en 65 por ciento de los casos. Un mes después de suspender la desmopresina se registraban 62,2 por ciento de niñoscon uno o menos episodios semanales de enuresis, sugiriendo una baja proporción de recaídas en plazos cortos. No se anotaron efectos colaterales importantes duarnte el estudio en este grupo de niños, salvo cefalea persistente en un paciente con antecedentes de jaqueca

Avances en el manejo psicofarmacologico del paciente narcoleptico / Advances in the psychopharmacological management of the narcoleptic patient

Se revisan algunos de los conceptos fundamentales de la biologia de la narcolepsia, con énfasis en los aspectos genéticos, neuroquímicos y psicofarmacológicos. Los autores dividen estos últimos en psicofármacos convencionales (antidepresivos y psicoestimulantes) y nuevos enfoques farmacológicos, (propranolol, mazindol, L-Dopa y gamahidroxibutirato), y comentan su experiencia preliminar con uno de ellos; la clonidina