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OBJECTIVE： To optimize prescription audit platform of PIVAS in our hospital， and to provide reference for rational drug use in pediatric department. METHODS： The records of irrational drug use and prescription comment record of physicians were collected and sorted out. Retrieved from drug instruction， China’s National Prescription Collection： Chemicals and Biological Products Volume （Children’s Edition） （2013） and other data， PIVAS prescription audit guideline of our hospital was filed. Based on it， PIVAS prescription audit platform was optimized. The efficiency and accuracy of prescription audit were evaluated using average daily medical order audit time， the number of audit pharmacists， average daily number of telephone communication with clinicians， average daily number of irrational medical orders， the detection rate of irrational medical order as indexes. RESULTS： The revised PIVAS prescription audit guideline is simple and easy to consult. After optimizing and implementing PIVAS prescription auditor platform， average daily medical order audit time， the number of audit pharmacists， average daily number of telephone communication with clinicians， average daily number of irrational medical orders decreased by 33.33 ％， 50.00 ％， 57.89 ％， and 57.14 ％， respectively； the detection rate of irrational medical orders decreased from 1.38％ to 0.54％， with statistical significance （P＜0.05）， which indicated the efficiency and accuracy of prescription audit were improved significantly. CONCLUSIONS： The optimized PIVAS prescription audit platform can significantly improve the standardization of medical order audit and the level of rational drug use， and contribute to rational drug use in pediatric department.
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Objective To investigate the pharmacy practice of clinical pharmacists' attendance in the treatment of adverse reactions caused by drug interactions. Methods Analysis was conducted on the causes and treatment of hypertension in one pedinatric patient with aplastic anemia induced by combined use of cyclosporine and voriconazole. Results Cyclosporine A could lead to prolonged hypertension.Cyclosporine A dosage should be adjusted;antihypertensive drugs should be used in necessity.When choosing antihypertensive drugs,drug interaction with cyclosporine A should be considered. Conclusion Clinical pharmacists could manage adverse drug reactions by analyzing drug interactions,and offer suggestions for ADR patients.
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Objective To investigate the association between single nucleotide polymorphisms (SNPs) of ATP-binding cassette B1 (ABCB1),ATP-binding cassette C2 (ABCC2) and solute carrier organic anion transporter 1B1 (SLCO1 B1) genes with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastic leukemia (ALL).Methods This study was designed as a casecontrol.From September of 2005 to December of 2011,the blood samples were randomly collected from 142ALL patients from Nanjing Children's Hospital,Enzyme-multiplied immunoassay technique (EMIT) was used to measure the plasma concentration of MTX,Seven SNPs in ABCB1 (rs1045642,rs2032582,rs1128503),ABCC2 (rs717620,rs2273697) and SLCO1 B1 (rs4149081,rs11045879) genes were detected by polymerase chain reaction-ligase detection reaction (PCR-LDR).Results A significantly increased risk of MTX-induced toxicity was observed in patients with MTX elimination delay (OR ＝ 2.828,95％ CI:1.217-6.571,P ＜ 0.05).Two SNPs in SLCO1B1,rs4149081 and rs11045879 were linkage disequilibrium (LD) with each other (R2 =0.979,P ＜ 0.05).Multivariate analysis revealed that individuals with SLCO1B1 rs4149081 AA genotype or SLCO1B1 rs11045879 CC genotype showed increased incidence of MTX elimination delay (OR =4.41,95％ CI:1.537-12.654,P =0.042),and the two genotypes were also associated with significantly increased risk of MTX-induced toxicity (OR =4.118,95％ CI:1.135-14.944,P =0.022).No association of MTX elimination delay or MTX-induced toxicity with the other SNPs analyzed was found.Conclusions SLCO1B1 rs4149081 AA or SLCO1B1 rs11045879 CC genotypes might be a risk factor for the susceptibility to MTX-induced toxicity in children with ALL.
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Objective To investigate the influences of the functional polymorphisms of cytochrome P450 isozymes 2A6 (CYP2A6),2B6 (CYP2B6),2C9 (CYP2C9),and 2C19 (CYP2C19) on plasma concentration of sodium valproate.Methods A total of 131 Chinese children with epilepsy receiving sodium valproate after a period of more than 5 half-time were recruited.The genotypes of CYP2A6 were detected by multiplex polymerase chain reaction (PCR),and the genotypes of CYP2B6,CYP2C9,and CYP2C19 were detected by PCR-ligase detection reaction.Enzyme-multiplied immunoassay technique was used to measure the plasma concentration of sodium valproate.The association between the polymorphisms and the plasma concentration of sodium valproate were analyzed by one-way ANOVA or Student' s t-test.Results Patients were divided into 4 groups according to the genotyping results of CYP2C9 and CYP2C19 (G1:extensive metabolizers in both CYP2C9 and CYP2C19; G2:CYP2C19 intermediate metabolizers; G3:CYP2C19 poor metabolizers; G4:CYP2C9 poor metabolizers),the mean normalized steady-state sodium valproate concentrations were significantly higher in G3 (3.70 ± 0.95) and G4 (4.35 ± 1.48) patients when compared to those in G 1 (2.57 ± 1.30,t =3.056,4.490,both P ＜ 0.01) and G2 (2.76 ± 1.19,t =2.827,4.462,both P ＜ 0.01) patients.The daily doses (mg/d) of sodium valproate received by G3 (19.46 ± 5.20) and G4 (19.30 ±7.67) patients were significantly lower than that of G1 patients(24.10 ±6.97,t =2.359,2.297,both P ＜ 0.05).There were no differences in daily doses or normalized steady-state concentrations of sodium valproate among the CYP2A6* 4 or CYP2B6* 6 genotypic groups.Conclusions The CYP2C9 and CYP2C19 polymorphisms have dramatic effects on the plasma concentration of sodium valproate.The daily doses of sodium valproate in G3 and G4 patients should be lower than usual.
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ObjectiveTo study the synergistic effect of p38MAPK and ERK1/2 in bone marrow mesenchymal stem cells (BMSCs), and to explore their influence on osteogenic differentiation in BMSCs cultures. MethodsMouse BMSCs were cultured in phenol red-free α-MEM containing osteogenic supplements (OS) for inducing osteogenic differentiation. The temporal sequence of osteogenic differentiation in BMSCs cultures was assayed by measuring alkaline phosphatase activity (ALP) and calcium deposition gene expression. The activation of p38MAPK and ERK1/2 was detected by western blotting using phospho-specific MAP kinase antibody. BMSCs were treated with the inhibitor of p38MAPK pathway(SB203580) or ERK1/2 pathway (PD98059), and osteogenic differentiation was measured. BMSCs were treated with SB203580 or sodium arsenite(ARS), a strong activator of p38MAPK, and the phosphorylation of ERK 1/2 was measured. BMSCs were treated with PP2A inhibitor, Okadaic acid(OA), the phosphorylation of ERK1/2 and osteogenic differentiation were measured. lmmunoprecipitation was used to test the binding interaction between PP2A and ERK1/2, and the effect of SB203580 on the interaction. ResultsTreatment of BMSCs with osteogenic supplements resulted in activation of p38MAPK and ERK1/2 that coincided with osteogenic differentiation. Inhibition of p38MAPK activation by SB203580, blocked the osteogenic differentiation, whereas inhibition of ERK1/2 activation by PD98059, enhanced the osteogenic differentiation in a dose-dependent manner.SB203580 treatment resulted in increased ERK1/2 phosphorylation. By contrast, ARS treatment resulted in decreased ERK1/2 phosphorylation. Inhibition of PP2A by OA resulted in increased ERK1/2 phosphorylation. OS-induced osteogenic differentiation was also attenuated by PP2A inhibition. Immunoprecipitation confirmed the association of PP2A with ERK1/2 in BMSCs cultures, which was decreased by SB203580 treatment. ConclusionThe present study demonstrates a synergistic effect between p38MAPK and ERK1/2 signaling pathways via PP2A in BMSCs cultures, which may regulate the osteogenic differentiation of BMSCs.
