ABSTRACT
Six patients with factor Ⅴ deficiency were admitted in Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2006 to December 2022. All 6 patients presented with symptoms of coagulation dysfunction, 4 patients had recurrent nose bleeding, gingival bleeding, skin ecchymosis as the main manifestations, 1 patient had lower abdominal pain and ovarian active bleeding, and 1 patient had heavy menstruation. The prothrombin time and activated partial thromboplastin time were significantly prolonged, the factor Ⅴ level was significantly lower than normal, and the thrombin time was basically normal in all patients. Four patients received non-surgical treatment and transfusion of fresh frozen plasma; the bleeding symptoms were significantly relieved during hospitalization, and no aggravation of bleeding symptoms was found during follow-up. One patient with active ovarian hemorrhage underwent emergency surgical suture to stop bleeding, and fresh frozen plasma and prothrombin complex were given perioperatively; and no more bleeding occurred during follow-up. One patients with excessive menstruation underwent curettage plus hysteroscopic endometrial ablation, and the amount of menstruation was significantly reduced. It is suggested that the bleeding symptoms of coagulation factor Ⅴ deficiency vary in severity, which can be effectively alleviated by infusion of the fresh frozen plasma in most cases.
ABSTRACT
Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.
ABSTRACT
Methyl (S)-4-(6-amino-9H-purin-9-yl)-2-hydroxybutanoate (DZ2002) is a potent reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH). Due to its ester structure, DZ2002 is rapidly hydrolyzed in rat blood to 4-(6-amino-9H-purin-9-yl)-2-hydroxybutyric acid (DZA) during and after blood sampling from rats; this hampers accurate determination of the circulating DZ2002 and its acid metabolite DZA in rats. To this end, a method for determining the blood concentrations of DZ2002 and DZA in rats was developed by using methanol to immediately deactivate blood carboxylesterases during sampling. The newly developed bioanalytical assay possessed favorable accuracy and precision with lower limit of quantification of 31 nM for DZ2002 and DZA. This validated assay was applied to a rat pharmacokinetic study of DZ2002. After oral administration, DZ2002 was found to be extensively converted into DZA. The level of systemic exposure to DZ2002 was significantly lower than that of DZA. The apparent oral bioavailability of DZ2002 was 90％–159％. The mean terminal half-lives of DZ2002 and DZA were 0.3–0.9 and 1.3–5.1 h, respectively. The sample preparation method illustrated here may be adopted for de-termination of other circulating ester drugs and their acid metabolites in rodents.
ABSTRACT
[Objective]To investigate the effect of atlanto-axial pedicle screw plate and fusion in treatment of upper cervical injuries. [Methods]Fifty-six cases of upper cervical spine injuries were treated with atlanto-axial pedicle screw plate and internal fixation,with total 200 screws,from March 2000 to September 2007.There were 36 males and 14 females,with an average age of 41.52 years(ranged,20~65 years).There were 23 cases of type II odontoid process fracture,12 cases of odontoid process nonunion,15 cases of transverse ligament injury.[Results]Greater occipital nerve pain occurred in 4 cases postoperatively and fully recovered after treatment 1 month later.The lateral cortical bone was penetrated by screws in 2 cases,without spinal cord or vertebral artery injury.Forty-eight cases were followed up for an average of 27.56 months(ranged,25~60 months).Bone fusion was achieved in all cases,without plate or screw broken.X-ray showed complete replacement of atlas and odontoid process of axis fracture.CT showed good position relation between screw and vertebral artery or spinal cord.According to JOA classification,excellent result was achieved in 34 cases,good in 13 cases,fair in 2 cases,poor in 1 case,with the good-to-excellent rate of 94.00%.[Conclusion]Atlanto-axial pedicle screw combined with plate fixation system is effective in treatment of upper cervical injuries.It can significantly improve the biomechanical stability of atlantoaxial joint,with high bone graft fusion rate.