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Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.
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Objective To understand the clinical features and therapeutic methods for calcineurin inhibitor-induced pain syndrome (CIPS) in kidney transplant recipients. Methods The related articles or abstracts from January 1991 to December 2020 were obtained by searching PubMed, Google Scholar, CNKI, Wanfang and VIP databases. The reviews, duplicate literatures and the articles involved in non-kidney transplant recipients were excluded. 11 full papers were included with 15 case reports. Results The average age of patients at the time of diagnosis of CIPS was (44.6±8.31) years, and the 53.3% of the patients was male. The average appearance time of CIPS was (2.42±3.07) months after kidney transplantation. CIPS mainly affected bilateral hands, elbows, wrists, knees, ankles, feet and back. The patients had normal or elevated trough concentrations of calcineurin inhibitors (CNIs) when CIPS occurred. Some patients had elevated alkaline phosphatase, parathyroid hormone, blood calcium, C-reactive protein levels, and abnormal phosphorus levels, while rheumatoid factor and uric acid levels were normal. CIPS symptoms in most patients disappeared with dose reduction of CNIs, change to different class of CNIs, pamidronate IV injection, pregabalin, calcium channel antagonists, etc. The average recovery time was (4.43±3.31) months. Conclusion The most effective treatment for CIPS is to reduce the dose of CNIs and replace immunosuppressants. Other treatments include GABA analogs, intravenous pamidronate, calcium channel blockers and conservative therapy.
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Objective: To investigate the regulation of CYP3A4 and P-gp by berberine hydrochloride ( BBR) via pregnane X re-ceptor (PXR) pathway. Methods: pLKO. 1-PXR vector, a lentivirus plasmid expressing PXR shRNA, was packaged into 293T cells. Human hepatoma (HepG2) cells were infected with the lentivirus and the cell clones stably expressing PXR shRNA were selected by puromycin according to pLKO. 1 vector characteristics. Real-time RT-PCR and Western blot were used to evaluate CYP3A4 and P-gp mRNA and protein in berberine treated HepG2 cells and PXR-silenced HepG2 cells. Results: The PXR expression in PXR silenced cells significantly decreased (P<0.01) when compared with that in HepG2 cells, while there was no significant difference (P >0. 05) in the expression of CYP3A4 and P-gp between the groups. Compared with that in HepG2 cells, the inhibition of berberine on the mRNA and protein expression of CYP3A4 and P-gp in PXR-silenced HepG2 cells was weakened (P<0. 05 or P<0. 01). Conclu-sion: Berberine can regulate the expression of CYP3A4 and P-gp via PXR signaling pathway, while it is not the only one.
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Objective: To investigate the association between ABCC2 gene polymorphisms and cyclosporine-induced liver injury in re-nal transplant recipients. Methods: The renal transplant recipients were divided into the liver injury group and the control group. Five single nucleotide polymorphisms ( rs4919395, rs2804398, rs4148394, rs4148397 and rs3740065) of ABCC2 were detected by high-throughput technique. The genotypes and haplotypes were analyzed between the groups. Results: There were 35 patients and 182 patients respectively in the liver injury group and the control group. No significant differences in alleles and genotypes were found between the groups (P>0. 05), and the SNP haplotypes showed no significant difference between the groups (P>0. 05). Conclusion: There is no association of ABCC2 polymorphisms (rs4919395, rs2804398, rs4148394, rs4148397 and rs3740065) with the liver injury induced by cy-closporine.
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OBJECTIVE:To investigate the association of synergistic effects of Wuzhi capsules on tacrolimus with CYP3A5*3 (6986A>G,rs776746) gene polymorphisms. METHODS:One hundred and severty patients underwent renal transplantation receiving tacrolimus maintenance therapy after surgery were selected from our hospital during Jan. 1997-Dec. 2015,and then divided into Wuzhi capsules(+)group(74 cases)and Wuzhi capsules(-)group(96 cases)according to the use of Wuzhi capsules. Both groups received tacrolimus+mycophenolate mofetil+prednisone;Wuzhi capsules (+)group was additionally given Wuzhi capsules,one capsule each time,bid,for more than 12 months. Trough concentration of tacrolimus was detected by CMIA 0,1,3,6,12 months after medica-tion,and the blood concentrations(C0/D)were calculated at different time points after correcting daily dose. CYP3A5*3 gene polymor-phisms was detected by PCR-RFLP. The association of C0/D value with gene polymorphism was investigated by analysis of covariance. RESULTS:Among 170 patients,there were 65 cases of CYP3A5 GG genotype,83 cases of AG genotype and 22 cases of AA geno-type;genotype frequencies were 38.2%,48.8% and 12.9%,which was in line with Hardy-Weinberg balance (P>0.05). There was statistical significance in the distribution frequencies of GG,AG+AA genotype between Wuzhi capsules(+)group and Wuzhi capsules (-)group (P0.05). CON-CLUSIONS:Wuzhi capsules can increase C0/D of tacrolimus in CYP3A5*3 AG+AA genotype,but have no significant effect on C0/D of tacrolimus in GG genotype;CYP3A5*3 genotype should be considered when using Wuzhi capsules as synergist of tacrolimus.
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Objective:To investigate the effects of HLA-B?1502 genetic polymorphism on cyclosporine( CsA)-induced liver injury in Chinese renal transplant recipients. Methods:HLA-B?1502 genotypes were determined by polymerase amplification chaln reaction of sequence-specific primers( PCR-SSP) in a total of 339 renal transplant recipients receiving CsA. All the subjects were divided into the CsA-induced liver injury group, non-CsA-induced liver injury group and the control group according to the liver injury occurrence. Results:In the 339 renal transplant recipients, the frequency of HLA-B?1502 mutation allele was 22. 64%. The distribution frequen-cy of HLA-B?1502 mutation allele had no significant difference among the three groups. There were no significant differences in the clinical characteristics of HLA-B?1502 genotypes among three groups(P>0. 05). Conclusion: No association is observed between HLA-B?1502 genetic polymorphism and cyclosporine-induced liver injury in Chinese renal transplant recipients.
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Objective:To discuss the ways to deal with adverse drug reactions in pharmaceutical care. Methods:A case of drug-induced kidney injury was provided to analyze the effect of clinical pharmacist on adverse drug reactions. Results and Conclusion:Good quality of pharmaceutical care, such as reliable drug information, is valuable in clinical practice.
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OBJECTIVE:To investigate the effect of clinical pharmacist intervention on prophylactic application of antibiotics in cardiothoracic surgery. METHODS:Medical records of patients underwent cardiothoracic surgery were collected from our hospi-tal during Mar. to Apr. in 2014 (before intervention) and during Jun. to Jul. in 2014 (after intervention). Those were divided into pre-intervention group(n=115)and post-intervention group(n=119). The prophylactic application effect of antibiotics was com-pared before and after intervention. RESULTS:After intervention,the rates of prophylactic application were decreased significantly from 96.5% to 72.3%;the rationality rate of antibiotics selection was improved significantly from 27.9% to 94.2%;The course of prophylactic medication decreased significantly from(5.4±2.8)days to(2.3±1.8)days;the difference had statistical significance before and after intervention(P<0.01). The postoperative infection rate was decreased from 13.0% to 5.9%,the difference had no statistical significance(P=0.074). The average hospitalization time,average drug costs,and average hospitalization expenses were decreased significantly,the difference had statistical significance(P<0.05 or P<0.01). CONCLUSIONS:Clinical pharmacist inter-vention to prophylactic application of antibiotics in cardiothoracic surgery can control the infection effective and guarantee reason-able and safe use of drugs during perioperative period.
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Objective:To evaluate the effect of continuing intervention on prophylactic application of antibiotics in sterile operation in urology department by clinical pharmacist to provide reference for the clinical prophylactic application of antibiotics. Methods:All cases of discharged patients underwent sterile operation in urology department of our hospital from July 2010 to June 2014 were divided into three groups according to the intervention time and methods: non-intervention group(n=141), stage Ⅰ intervention group(n=139), stage Ⅱ intervention group (n=162) and stage Ⅲ intervention group (n=137). The prophylactic application of antibiotics was statistically analyzed. Results:After the continuing intervention, the prophylactic application rate of antibiotics in the three inter-vention groups was decreased significantly from 100% before the intervention respectively to 34. 5%,18. 5% and 14. 6% after the in-tervention (P<0. 01). The rationality rate of prophylactic application was improved significantly from 36. 9% before the intervention respectively to 58. 3%, 63. 3% and 85. 0% after the intervention (P<0. 01). The course of prophylactic application was decreased significantly from (138.2 ±31.6)h respectively to (89.9 ±48.0)h,(72.8 ±32.5)h and(45.1 ±29.5)h (P<0.01) and the post-operative infection rate was decreased from 2. 8% respectively to 2. 1%,1. 8% and 1. 4%. Conclusion:The pharmaceutical interven-tion is feasible and valid to improve the rational prophylactic use of antibiotics in urological surgery.
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Objective:To explore the breakthrough points of pharmaceutical care in the anti-infection treatment by clinical phar-macists. Methods:Using the pharmaceutical care carried out by clinical pharmacists in the treatment of infected patients as the exam-ple, the breakthrough points of pharmaceutical care in the anti-infection treatment by clinical pharmacists were discussed. Results:Clinical pharmacists should be in accordance with the specific clinical conditions to find out such breakthrough points of pharmaceutical care as judging the indications of antibacterial drugs use, assisting in the development of drug therapeutic regimens ( including the choice of species, dosage and solvent, the optimization of PK/PD parameters and the infusion speed) , paying close attention to bacteri-al culture, concerning on drug interactions, monitoring adverse drug reactions and efficacy, providing patient medication education and so on. Conclusion:Clinical pharmacists can participate in anti-infection treatment and carry out individual pharmaceutical care to en-sure the safety and efficacy of drugs.
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BACKGROUND:Previous studies have found that the susceptibility genes of adiponectin gene and calpain 10 gene of type 2 diabetes are closely related with the incidence of diabetes in Chinese renal transplantation patients. So, are other susceptibility genes of type 2 diabetes also associated with posttransplantation diabetes mel itus? OBJECTIVE:To investigate the association between the zinc transporter solute carrier family 30 member 8 (SLC30A8) gene polymorphism and the posttransplantation diabetes mel itus. METHODS:A total of 97 patients with posttransplantation diabetes mel itus and 301 patents without posttransplantation diabetes mel itus (control group) were selected, and then the SLC30A8 gene rs13266634 genotype was detected with real-time PCR method. The association between gene polymorphism and posttransplantation diabetes mel itus was analyzed with Logistic regression test. RESULTS AND CONCLUSION:There were significant differences in al ele frequencies and genotype distributions of rs13266634 between the patients with and without posttransplantation diabetes mel itus (P<0.05). After adjustments of age, sex, body weight and body mass index, the incidence of posttransplantation diabetes mel itus of the CC genotype patients was 2.108 times to that of the TT genotype patients (odds ratio=2.108, 95%confidence interval:1.075-4.131, P=0.044);and the incidence of posttransplantation diabetes mel itus of the CC+CT genotype patients was 1.862 times to that of the TT genotype patients (odds ratio=1.862, 95%confidence interval:1.049-3.306, P=0.034). The results suggest that the C-al ele in rs13266634 of SLC30A8 gene is the independent risk factor of posttransplantation diabetes mel itus.
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OBJECTIVE:To evaluate the efficacy and safety of Fluvastatin vs. Xuezhikang for hyperlipidemia in patients after renal transplantation. METHODS: 56 hyperlipidemia patients after renal transplantation were enrolled: 32 were assigned to receive Fluvastatin (40～80 mg) po qd for 8 weeks and 24 to receive Xuezhikang (0.6 g) po bid for 8 weeks. Total cholesterol (TC),triglyceride (TG),low-density lipoprotein-cholesterol (LDL),high-density lipoprotein-cholesterol (HDL),liver function and renal function in two groups were measured before and after treatment. RESULTS: In Fluvastatin-treated group,the TC decreased from(7.39?1.98)mmol?L-1 to(5.62?0.93)mmol?L-1,LDL reduced from(3.68?1.13)mmol?L-1 to (2.86?0.83)mmol?L-1;in Xuezhikang-treated group,TC decreased from(6.82?1.29)mmol?L-1 to (5.56?1.19) mmol?L-1 and LDL decreased from (3.26?0.73) mmol?L-1 to (2.78?0.80) mmol?L-1,all showing significant differences as compared with before treatment(P 0.05). No obvious adverse effect was noted in either group during treatment. CONCLUSION: Both Fluvastatin and Xuezhikang are safe and effective for hyperlipidemia in patients after renal transplantation.
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Objective:To study the effect of cyclosporin A based triple immunosuppressive therapy on the plasma glucose in renal transplant recipients.Method:680 renal transplant recipients treated with cyclosporine A combined with prednisone and mycophenolate mofefil from Jan.1996 to May 2007 were analysed.Result:The morbidities of impaired fast- ing glucose,impaired glucose tolerance and post-transplantation diabetes mellitus (PTDM) were 3.97%,5.15% and 8.09%,respectively.The daily doses and concentrations of CsA and the daily doses of prednisone in the impaired glucose tolerance group and PTDM group were significantly higher than those in the normal plasma glucose group.Conclusion:The daily doses and concentrations of CsA and the daily doses of prednisone were closely related to the impaired glucose toler- ance and PTDM of renal transplant recipients.
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Objective:To investigate the therapeutic range of tacrolimus and effects of tacrolimus on liver and re- nal functions and blood routine in renal transplant recipients.Method:The whole blood tacrolimus concentration was meas- ured by micro-particle enzyme immunoassay(MEIA).Blood tacrolimus concentrations in 390 cases of renal transplant re- cipients were analyzed.The effects of tacrolimus on liver and renal function and blood routine were also studied.Result: The blood tacrolimus concentrations in 377 of 390 cases were within the range from 3 to 15?g?L~(-1).Their blood tacrolimus concentration differed greatly in renal transplant recipients within 6 months after transplantation.Their blood tacrolimus concentration was gradually decreased as time went on.Tacrolimus with therapeutic dosage had no effects on liver and renal function and blood routine.Conclusion:The therapeutic ranges of tacrolimus with MEIA were as follows:5 to 15?g?L~(-1) within 3 months after transplantation,5 to 10?g?L~(-1)between 4 to 6 months after transplantation,3 to 10?g?L~(-1)6 months after transplantation.The administration of tacrolimus had no effects on the liver and renal function and blood routine in re- nal transplant recipients.
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Objective:To study the effects of cyclosporine A coadministrated with azathioprine,mycophenolate, mizorihine,rapamycin and/or prednisone on liver function in renal transplant recipients.Method:The drug history records of 600 renal transplant recipients in 1995 to 2005 were retrospectively investigated.Biochemical indexes before and after the treatment with cyclosporine A coadministrated with other immunosuppressants were analyzed.Result:The liver damage was found in 109 cases(18.2%)among 600 cases.The blood concentrations of cyclosporine A in the group with abnormal liver functions were significantly higher than those in the group with normal liver functions(P
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AIM To study the effects of coadministration of berberine chloride(Ber) with cyclosporin (CsA) on liver microsomal cytochrome P450 isoenzyme and multi drug resistance gene in rats. METHODS The activities of liver microsomal erythromycin demethylase(ERD) and aminopyrence N demethylase(ADM) were determined. The levels of mRNA expression of CYP3A1, CYP1A1, CYP2E1, mdr1a and mdr1b were assayed with RT PCR. RESULTS After administration for 6 days, all treatment groups except Ber at 100 mg?kg -1 exhibited inhibitory action on ERD activity in rats. ERD activity markedly decreased in all drug treatment groups after taking drug for 12 days. After administration for 6 days, 45 mg?kg -1 CsA, 100 mg?kg -1 Ber coadministrated with 45 mg?kg -1 CsA and 200 mg?kg -1 Ber plus 45 mg?kg -1 CsA had significant inhibitory effects on ADM activity in rats. All groups except 100 mg?kg -1 Ber and 150 mg?kg -1 ketoconazole had the same effects on ADM activity after treatment for 12 days. Again, after 12 days, all drug treatment groups except 100 mg?kg -1 Ber group was found of remarkable inhibition of the mRNA expression of CYP3A1, CYP2E1, mdr1a and mdr1b. The CYP1A1 gene was not detected in all groups. CONCLUSION The mechanism of Ber to increase CsA concentration is that Ber decreases the expression of CYP3A, mdr1a and mdr1b thereby reduces the metabolism and elimination of CsA by liver.
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Aim To investigate effects of berberine (Ber) on the transport of P-gp substrates including cyclosporine A (CsA) and digoxin across Caco-2 and L-MDR cell monolayers. Methods Permeability coefficients and transport rates of digoxin and CsA across Caco-2 and L-MDR1 monolayers were measured in the presence of Ber(50 ?mol?L-1~5 mmol?L-1). Results The inhibition studies for digoxin transport showed a dose-dependent decrease in basal-to-apical direction across Caco-2 and L-MDR1 monolayers in the presence of Ber (50 ?mol?L-1~5 mmol?L-1). Both a dose-dependent decrease in basal-to-apical direction and an increase in apical-to-basal direction were observed for CsA transport across Caco-2 monolayers with different concentrations of Ber. The IC50 values calculated for Ber-induced inhibition of digoxin transport are 1.44 mmol?L-1 in Caco-2 cells and 1.24 mmol?L-1 in L-MDR1 cells, respectively. The IC50 value for Ber-induced inhibition of CsA transport is 607 ?mol?L-1 in Caco-2 cells. Conclusion It was suggested that the inhibition and saturation of P-gp transport activity might be involved in interactions between Ber and CsA.