Inactivation of Aconitase by Tetrahydrobiopterin in DArgic Cells: Relevance to PD

Oxidative damage is thought to be a major cause of the progression of dopamine (DA)rgic neurodegeneration as in Parkinson's disease. We have previously reported that tetrahydrobiopterin (BH4), an endogenous molecule required for DA synthesis, exerts oxidative stress to DA-producing cells and facilitates the production of DA quinone. It is known that aconitase, present in both mitochondrial and cytosolic forms, act as an reactive oxygen species (ROS) sensor, and that their inactivation leads to further generation of ROS. In the present study we investigated whether the BH4-associated vulnerability of DA cells might involve aconitase. In DArgic cell line CATH.a, BH4 treatment caused reduction of activity of both mitochondrial and cytosolic aconitases, and this appeared to be due to direct inactivation of the pre-existing enzyme molecules. Although most of the activity reduced by BH4 was increased upon reactivation reaction under a reducing condition, the restoration was not complete, suggesting that irreversible and covalent modification has occurred. The aconitase inactivation was exacerbated in the presence of DA and attenuated in the presence of tyrosine hydroxylase inhibitor a-methyl-p-tyrosine, suggesting the involvement of DA. The degree of inactivation increased when the cells were treated with the quinone reductase inhibitor dicoumarol and decreased in the presence of quinone reductase inducer sulforaphane. Taken together, BH4 appeared to lead to both reversible and irreversible inactivation of aconitase and that this is facilitated by the presence of DA and accumulation of DA quinone.

Metabolism of nicousamide in rat and human liver in vitro / 药学学报

This paper is aimed to study the metabolic kinetics of nicousamide in rat liver microsomes and cytosol and to identify the major metabolite and drug metabolizing enzymes involved in the metabolism of nicousamide in rat and human liver microsomes by selective inhibitors in vitro. The concentration of nicousamide was determined by HPLC-UV method. The metabolite of nicousamide in rat and human liver microsomes was isolated and identified by LC-MS/MS. The major metabolite of nicousamide in rat and human liver microsomes was identified to be 3-(3'-carboxy-4'-hydroxy-anilino-carbo-)-6-amino-7-hydroxy-8-methyl-coumarin (M1). The metabolite of nicousamide in rat plasma, urine, bile and liver was consistent with M1. The metabolism of nicousamide can be catalyzed by several reductases, including CYP450 reductases, cytochrome b5 reductases and CYP2C6 in rat liver microsomes, as well as xanthine oxidase and DT-diaphorase in rat liver cytosol.

Metabolism of mitomycin C by human liver microsomes in vitro / 药学学报

To provide the profiles of metabolism of mitomycin C (MMC) by human liver microsomes in vitro, MMC was incubated with human liver microsomes, then the supernatant component was isolated and detected by HPLC. Types of metabolic enzymes were estimated by the effect of NADPH or dicumarol (DIC) on metabolism of MMC. Standard, reaction, background control (microsomes was inactivated), negative control (no NADPH), and inhibitor group (adding DIC) were assigned, the results were analyzed by Graphpad Prism 4. 0 software. Reaction group compared with background control and negative control groups, 3 NADPH-dependent absorption peaks were additionally isolated by HPLC after MMC were incubated with human liver microsomes. Their retention times were 10. 0, 14. 0, 14. 8 min ( named as Ml, M2, M3) , respectively. Their formation was kept as Sigmoidal dose-response and their Km were 0. 52 (95% CI, 0. 40 - 0.67) mmol x L(-1), 0. 81 (95% CI, 0. 59 - 1. 10) mmol x L(-1), 0. 54 (95% CI, 0. 41 -0. 71) mmol x L(-1) , respectively. The data indicated that the three absorption peaks isolated by HPLC were metabolites of MMC. DIC can inhibit formation of M2, it' s dose-effect fitted to Sigmoidal curve and it' s IC50 was 59. 68 (95% CI, 40. 66 - 87. 61) micromol x L(-1) , which indicated DT-diaphorase could take part in the formation of M2. MMC can be metabolized by human liver microsomes in vitro, and at least three metabolites of MMC could be isolated by HPLC in the experiment, further study showed DT-diaphorase participated in the formation of M2.

Retropharyngeal hematoma. A complication of anticoagulant therapy

Retropharyngeal hematoma is a fatal condition if clinically missed. The typical presentation of a huge posterior pharyngeal mass pushing the uvula anteriorly and obstructing the airway is described in the following case report. The clinical symptoms, physical findings, and radiological work-up are presented along with a literature review

Dicumarol content in alcoholic herb elixirs: one of the factors at risk induced IVKD-I.

Nine medicinal plants known to be the ingredients of the traditional herbal medicinal elixir, and seven popular commercial alcoholic herb elixirs were investigated for the content of dicumarol by using high pressure liquid chromatography (HPLC) and thin layer chromatography (TLC) methods. Umbelliferae (Conioselinum Univittatum) were the only medicinal plants found to contain dicumarol 0.04 mg/dl. Dicumarol content was also found in three out of seven brands of commercial alcoholic herb elixirs with the concentration of 0.58, 1.86 and 6.00 mg/dl. These findings indicated that the traditional herbal medicinal elixirs containing dicumarol in varying amount may play a role in inducing bleeding diathesis in breast-fed infants of mothers known to consume the elixir.

Pathogenesis of small deep cerebral infarcts

Datos recientes sugieren que el impacto de la Hipertensión Arterial (HTA) ha sido probablemente exagerado y el rol de la enfermedad cardíaca y de la aterosclerosis de grandes vasos subestimado respecto de la patogenia de los pequeños (<1.5 cm) infartos de las arterias penetrantes profundas. En otras palabras, se puede decir que una arteriolopatía primaria local es menos importante de lo que se pensaba en el pasado, y que la embolia puede tener un rol más considerable que el que se le atribuía anteriormente.El tamaño máximo aceptado para un infarto pequeño (o sea "lacunar") ha sido fijado en 1.5 cm. Dentro de ese limite, parece apropiado considerar que las lagunas muy pequeñas (<0,5 cm) --habitualmente asintomáticas--, tienen una fuerte asociación con la arteriolopatia hipertensiva, pero las mas grandes y sintomáticas (0.5-1.5 cm) tienen un origen mucho más diverso. Como ni los sindromes clínicos ni los estudios de TC o RMI diferencian las causas de los diferentes infartos lacunares, parece aconsejable la búsqueda sistemática de enfermedad asociada de grandes vasos (estudios arteriales no invasivos), así como de posible embolia cardiogénica (ECG, ecocardiografía y Holter de ser necesario), tanto como en los infartos cerebrales

Complicaciones intracraneanas de los tratamientos anticoagulantes: implicancias en patología cerebrovascular isquémica / Intracranial complications of anticoagulation and their relation to cerebrovascular ischemic pathology

Las complicaciones mayores de la anticoagulación son actualmente bien conocidas, y todos los resultados de la literatura sugieren que ellas no son despreciables. Por el contrario, las ventajas cerebrovasculares de estos tratamientos todavía no están bien definidas, y la anticoagulación debería ser motivo de más estudios controlados. En este contexto, debido a las complicaciones cerebrales de la anticoagulación, nos parece que la indicación de tal tratamiento es mas una excepción que una regla en el ACV isquémico. Mientras se esperan los resultados de los estudios controlados en curso, las indicaciones de anticoagulación eventual deben ser ponderadas individualmente teniendo en cuenta las características propias del paciente

Medical management of acute cerebral ischemia

El ACV isquémico es una de las causas más frecuentes de muerte e invalidez. A pesar de su alta incidencia, el manejo del ACV agudo sigue siendo controvertido. La mayoría de las formas corrientes de terapéutica están diseñadas para reducir las complicaciones de un ACV reciente o prevenir recidivas.Los datos experimentales sugieren que el tiempo óptimo para la intervención terapéutica debería situarse en las horas inmediatas posteriores a la isquemia cerebral

Multiple Intracranial Dural Sinus Thrombosis associated with Polycythemia: Case Report

Cerebral venous thrombosis is commonly related to infectious processes, trauma, neoplasm, puerperium, and the use of oral contraceptives, etc., but this case was associated with a very rare condition, "polycythemia". This case was confirmed by hematologic study, brain C-T, conventional angiography, and digital subtraction angiography(DSA). The patient was treated by venesection, the use of urokinase and dicumarol, and lumbo-peritoneal shunt(L-P shunt), etc. Post-treatment DSA showed the complete recanalization of all dural sinuses except the left transverse sinus, suggesting normal variant.

The possibility of the native alcoholic drugs as etiological factor of the acquired prothrombin complex deficiency syndrome.

This study was attempted to determine whether the native alcoholic drugs had any significant role in the pathogenesis of the APCD syndrome. The native alcoholic drugs, breast milk and maternal serum were analysed for vitamin K antagonists (dicoumarol, warfarin and coumarin). No vitamin K antagonists were detected from 14 commercial native alcoholic drugs, but one of the two homemade samples had a positive test of coumarin but not dicoumarol and warfarin. Seven breast milk and serum samples from the mothers of APCD infants showed no detectable amount of vitamin K antagonists. Negative results were found in 35 postpartum women who did not consume the drugs and 22 postpartum women who took the drugs. The results suggested that the native alcoholic drugs are unlikely to be the etiological factor of APCD syndrome.