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.
Angiography ; Brain ; Contraceptives, Oral ; Dicumarol ; Humans ; Phlebotomy ; Polycythemia* ; Postpartum Period ; Sinus Thrombosis, Intracranial* ; Urokinase-Type Plasminogen Activator ; Venous Thrombosis

Bromadiolone, commonly known as super warfarin, is a long-acting coumarin dicoumarin rodenticide. The mechanism of bromadiolone is mainly to inhibit vitamin K1 epoxide reductase and affect the synthesis of coagulation factors Ⅱ, Ⅶ, Ⅸ and Ⅹ, which causes blood coagulation dysfunction and systemic multiple organ hemorrhage. Here, we report of a case of bromadiolone poisoning patient who had digestive tract, abdominal hemorrhage, as well as secondary paralytic ileus. After blood product transfusion and vitamin K1 supplementation, the patient was discharged after the physical condition was improved. It's suggestied that clinicians should pay attention to rare complications to prevent missed diagnosis when treating other bromadiolone poisoning.
4-Hydroxycoumarins ; Blood Coagulation Factors ; Dicumarol ; Hemorrhage ; Humans ; Intestinal Pseudo-Obstruction/chemically induced* ; Oxidoreductases ; Rodenticides ; Vitamin K 1 ; Warfarin

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.
Aconitate Hydratase ; Benzoquinones ; Biopterin ; Cell Line ; Cytosol ; Dicumarol ; Dopamine ; NAD(P)H Dehydrogenase (Quinone) ; Oxidative Stress ; Parkinson Disease ; Reactive Oxygen Species ; Thiocyanates ; Tyrosine 3-Monooxygenase

The study investigated the effects of different processed products of Polygonati Rhizoma(black bean-processed Polygonati Rhizoma, BBPR; stewed Polygonati Rhizoma, SPR) on the urinary metabolites in a rat model of Alzheimer's disease(AD). Sixty SPF-grade male SD rats were randomized into a control group, a model group, a donepezil group, a BBPR group, and a SPR group, with twelve rats in each group. Other groups except the control group were administrated with D-galactose injection(100 mg·kg~(-1)) once a day for seven weeks. The control group was administrated with an equal volume of normal saline once a day for seven consecutive weeks. After three weeks of D-galactose injection, bilateral hippocampal Aβ_(25-35) injections were performed for modeling. The rats were administrated with corresponding drugs(10 mL·kg~(-1)) by gavage since week 2, and the rats in the model and control group with an equal volume of double distilled water once a day for 35 continuous days. The memory behaviour and pathological changes in the hippocampal tissue were observed. The untargeted metabolites in the urine were detected by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS). Principal component analysis(PCA) and orthogonal partial least square-discriminant analysis(OPLS-DA) were employed to characterize and screen differential metabolites and potential biomarkers, for which the metabolic pathway enrichment analysis was conducted. The results indicated that BBPR and SPR increased the new object recognition index, shortened the escape latency, and increased the times of crossing the platform of AD rats in the Morris water maze test. The results of hematoxylin-eosin(HE) staining showed that the cells in the hippocampal tissue of the drug administration groups were closely arranged. Moreover, the drugs reduced the content of interleukin-6(IL-6, P<0.01) and tumor necrosis factor-α(TNF-α) in the hippocampal tissue, which were more obvious in the BBPR group(P<0.05). After screening, 15 potential biomarkers were identified, involving two metabolic pathways: dicoumarol pathway and piroxicam pathway. BBPR and SPR may alleviate AD by regulating the metabolism of dicoumarol and piroxicam.
Rats ; Male ; Animals ; Alzheimer Disease/drug therapy* ; Chromatography, High Pressure Liquid/methods* ; Rats, Sprague-Dawley ; Dicumarol ; Galactose ; Piroxicam ; Metabolomics/methods* ; Biomarkers/urine*

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.
Antibiotics, Antineoplastic ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Dicumarol ; pharmacology ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; pharmacology ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; metabolism ; Mitomycin ; metabolism

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.
Adenosine Monophosphate ; pharmacology ; Allopurinol ; pharmacology ; Aniline Compounds ; metabolism ; Animals ; Cimetidine ; pharmacology ; Coumarins ; metabolism ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P450 Family 2 ; Cytochrome-B(5) Reductase ; antagonists & inhibitors ; Cytosol ; metabolism ; Dicumarol ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Female ; Humans ; Liver ; cytology ; metabolism ; Male ; Microsomes, Liver ; metabolism ; Mitochondria, Liver ; metabolism ; NAD(P)H Dehydrogenase (Quinone) ; antagonists & inhibitors ; Propylthiouracil ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Steroid 21-Hydroxylase ; antagonists & inhibitors ; Xanthine Oxidase ; antagonists & inhibitors