Risk Factors Analysis of Hypercoagulability in Patients with Chronic Kidney Disease by Thrombelastograph / 中国药师

Objective: To evaluate the risk factors of hypercoagulability in the patients with chronic kidney disease (CKD) by thrombelastograph.Methods:According to the maximal elasticity of thrombus(MA),221 patients with chronic kidney disease under-going thromboelastography were divided into two groups: low coagulation group (MA<69mm, n=139) and high coagulation group (MA≥69mm,n=82). The basic conditions of the two groups were analyzed respectively, including gender, age, height, weight, concomitant diseases such as diabetes mellitus,hyperlipidemia and nephrotic syndrome,medication situation such as recombinant hu-man erythropoietin,anti-platelet drugs and hormones,renal function such as CKD1-3 stages and CKD4-5 stages,clotting parameter re-sponse time(R value),clotting time(K value),angle α,maximum thrombus(MA)and the other coagulation-related indicators such as platelet PLT,and binary logistic regression was used to analyze the risk factors causing hypercoagulability. Results:There were no significant differences in age,gender,height and weight etc(P>0.05)while there were significant differences in concomitant diseases, drug use,renal function, coagulation indicators including thrombus elasticity and blood index between the groups (P<0.05). The risk factors of hypercoagulation mainly included disease factors (diabetes OR 1.895,95% CI 1.082-3.318, nephrotic syndrome OR 2.501,95% CI 1.429-4.379,CKD4-5 stage OR 1.989,95% CI 1.136-3.483),and drug factors(recombinant human erythropoietin rHuEPO)(OR 2.254,95% CI 1.207-4.208). Conclusion: In the patients with CKD, diabetes mellitus, nephrotic syndrome and CKD4-5 stages increase the hypercoagulability of patients,and rHuEPO also increases the risk of hypercoagulability in the patients with renal anemia.

Pharmaceutical Care on a Patient with Cerebral Venous Sinus Thrombosis and Epilepsy / 医药导报

Objective To investigate the role of clinical pharmacist in medical therapy for a patient with cerebrovascular disease and epilepsy.Methods One patient was hospitalized due to headache and twitch.Clinical diagnosis was cerebral venous sinus thrombosis and epilepsy.During the treatment,the clinical pharmacist gave suggestion on drug selection of anti-infection and anti-epileptic therapy,assessed drug interaction between omeprazole-escitalopram and mannitoldexamethasone,monitored the adverse drug reaction of valproate,and provided medication education to the patient.Results Physician adopted clinical pharmacist's suggestion.The patient discharged with stable condition.Conclusion The participation of clinical pharmacists in the medication therapy of patients with cerebrovascular disease can reduce the risk of drug use and promote the efficacy and safety of medication.

Structural characterization of coatomer in its cytosolic state

Studies on coat protein I (COPI) have contributed to a basic understanding of how coat proteins generate vesicles to initiate intracellular transport. The core component of the COPI complex is coatomer, which is a multimeric complex that needs to be recruited from the cytosol to membrane in order to function in membrane bending and cargo sorting. Previous structural studies on the clathrin adaptors have found that membrane recruitment induces a large conformational change in promoting their role in cargo sorting. Here, pursuing negative-stain electron microscopy coupled with single-particle analyses, and also performing CXMS (chemical cross-linking coupled with mass spectrometry) for validation, we have reconstructed the structure of coatomer in its soluble form. When compared to the previously elucidated structure of coatomer in its membrane-bound form we do not observe a large conformational change. Thus, the result uncovers a key difference between how COPI versus clathrin coats are regulated by membrane recruitment.

Flexible interwoven termini determine the thermal stability of thermosomes

Group II chaperonins, which assemble as double-ring complexes, assist in the refolding of nascent peptides or denatured proteins in an ATP-dependent manner. The molecular mechanism of group II chaperonin assembly and thermal stability is yet to be elucidated. Here, we selected the group II chaperonins (cpn-α and cpn-β), also called thermosomes, from Acidianus tengchongensis and investigated their assembly and thermal stability. We found that the binding of ATP or its analogs contributed to the successful assembly of thermosomes and enhanced their thermal stabilities. Cpn-β is more thermally stable than cpn-α, while the thermal stability of the hetero thermosome cpn-αβ is intermediate. Cryo-electron microscopy reconstructions of cpn-α and cpn-β revealed the interwoven densities of their non-conserved flexible N/C-termini around the equatorial planes. The deletion or swapping of their termini and pH-dependent thermal stability assays revealed the key role of the termini electrostatic interactions in the assembly and thermal stability of the thermosomes.

Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature

The mitochondrial respiratory complex II or succinate: ubiquinone oxidoreductase (SQR) is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration. Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography. Crystal structure of the SQR bound with thiabendazole (TBZ) reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role. The obvious inhibitory effect of TBZ based on the biochemical data (IC(50) ~100 μmol/L) and the significant structure-based binding affinity calculation (~94 μmol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.

Soy isoflavones and cardiovascular diseases / 中国临床药理学与治疗学

Cross-cultural comparisons of cardiovascular disease mortality between United States and Japan have shown striking difference. Lower incidence of cardiovascular disease in East Asia compared with the west countries may be related to the consumption of soybean products, which contain soy isoflavones, mainly genistein and daidzein. We reviewed the benefit effects of soy isoflavones on preventing the development of atherosclerosis and subsequent cardiovascular diseases.

Influence of planta medica on the blood concentration of tacrolimus / 中国临床药理学与治疗学

Tacrolimus is an widely used immunosuppressant in organ transplant patients for anti-rejection,and the quality of life and survival rate are greatly enhanced.At present,a growing number of scholars concerned with drug interactions of Western medicine and tacrolimus.However,the impact of planta medica on it was rarely systematically overviewed.This article explored the interaction of planta medica and tacrolimus.