Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipient...Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-展开更多
The aim of the research was to investigate the pharmacokinetics(PK) of enteric-coated mycophenolate sodium(EC-MPS) by quantification of the active metabolite of mycophenolic acid(MPA)after multiple escalating oral dos...The aim of the research was to investigate the pharmacokinetics(PK) of enteric-coated mycophenolate sodium(EC-MPS) by quantification of the active metabolite of mycophenolic acid(MPA)after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC–UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to900 mg, C_(max) and AUC_(0–12h) did not increase with dose escalation. The AUC_(0–12h), C_(max), C_0 and T_(max) for the 540 720 and 900 mg doses were not significantly different, respectively(P 40.05). AUC_0–12 h and C_(max) were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_(0–12h), C_(max) and C_0 were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.展开更多
Three new mycophenolic acid derivatives, penicacids E-G(1-3), together with three known analogues, mycophenolic acid(4), 4′-hydroxy-mycophenolic acid(5) and mycophenolic methyl ester(6), were isolated from a marine-d...Three new mycophenolic acid derivatives, penicacids E-G(1-3), together with three known analogues, mycophenolic acid(4), 4′-hydroxy-mycophenolic acid(5) and mycophenolic methyl ester(6), were isolated from a marine-derived fungus Penicillium parvum HDN17-478 from a South China Sea marine sediment sample. The structures of compounds 1-3 were elucidated by HRMS, NMR, and Mosher’s method. Among them, compounds 1 and 2 were the first examples of mycophenolic acid analogs with a double bond at C-3′/C-4′ position. The cytotoxicity of 1-6 was evaluated against the HCT-116, BEL-7402, MGC-803, SH-SY5 Y, HO-8910 and HL-60 cell lines, and compounds 4 and 6 showed potent cytotoxicity with IC50 values ranging from 1.69 to 12.98 μmol·L–1.展开更多
AIM: To investigate the chemical constituents of the cultures of Laetiporus sulphureus(Bull.) Murrill. METHOD: Compounds were isolated and purified by various chromatographic techniques. The structure of the new compo...AIM: To investigate the chemical constituents of the cultures of Laetiporus sulphureus(Bull.) Murrill. METHOD: Compounds were isolated and purified by various chromatographic techniques. The structure of the new compound was determined by interpretation of MS and 1D-, 2D-NMR spectroscopic data, while the known compounds were identified by comparison of their data with those reported. RESULTS: Three mycophenolic acid derivatives, 6-((2E, 6E)-3, 7-dimethyldeca-2, 6-dienyl)-7-hydroxy-5-methoxy-4-methylphtanlan-1-one(1), 6-((2E, 6E)-3, 7, 11-trimethyldedoca-2, 6, 10-trienyl)-5, 7-dihydroxy-4-methylphtanlan-1-one(2), and 6-((2E, 6E)-3, 7, 11-trimethyldedoca-2, 6, 10-trienyl)-7-hydroxy-5-methoxy-4-methylphtanlan-1-one(3) were isolated. CONCLUSION: Among them, compound 1 was new, and compound 2 exhibited moderate cytotoxicity against HL-60, SMMC-7721, A-549, and MCF-7 cells, with IC50 values of 39.1, 31.1, 27.4, and 35.7 μmol·L-1, respectively.展开更多
BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease(MS-IBD). This study hypothesized that as a standard of treatment and the pr...BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease(MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes.AIM To investigate the effectiveness of conventional therapy for MS-IBD.METHODS A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease(CD) and ulcerative colitis(UC). Corticosteroids(prednisone, hydrocortisone, budesonide, prednisolone,dexamethasone), 5-aminosalicylic acid(5-ASA) derivatives(mesalazine and sulfasalazine) and immunosuppressants [azathioprine(AZA), methotrexate(MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine(6-MP)] were considered conventional therapy. The exclusion criteria were sample size below50; narrative reviews; specific subpopulations(e.g., pregnant women,comorbidities); studies on postoperative IBD; and languages other than English,Spanish, French or Portuguese. The primary outcome measures were clinical remission(induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria.RESULTS The search strategy identified 1995 citations, of which 27 were considered eligible(7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected(AZA and 6-MP showed no advantage over placebo,MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus vs placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials(RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing,one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence.CONCLUSION High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.展开更多
The development of chronic kidney disease(CKD)after liver transplantation(LT)exerts a severe effect on the survival of patients.The widespread adoption of the model for end-stage liver disease score strongly impacted ...The development of chronic kidney disease(CKD)after liver transplantation(LT)exerts a severe effect on the survival of patients.The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure,as several patients are transplanted with previously deteriorated renal function.Due to its multifactorial nature,encompassing pre-transplantation conditions,perioperative events,and nephrotoxic immunosuppressor therapies,the accurate identification of patients under risk of renal disease,and the implementation of preventive approaches,are extremely important.Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate,to non-invasive markers,although no option has yet proved efficient in early detection of kidney injury.Considering the nephrotoxicity of calcineurin inhibitors(CNI)as a factor of utmost importance after LT,early nephroprotective strategies are highly recommended.They are based mainly on delaying the application of CNI during the immediate postoperativeperiod,reducing their dosage,and associating them with other less nephrotoxic drugs,such as mycophenolate mofetil and everolimus.This review provides a critical assessment of the causes of renal dysfunction after LT,the methods of its evaluation,and the interventions aimed at preserving renal function early and belatedly after LT.展开更多
文摘Objective To analyze the relationship between genetic polymorphisms of organic anion transporting polypeptide ( SLCO1B1 and SLCO1B3) and mycophenolic acid ( MPA) pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations ( SLCO1B3 T334G,SLCO1B1 A338G) were detected in 68 recipi-
基金supported by the youth fund of The First Affiliated Hospital of Zhengzhou University
文摘The aim of the research was to investigate the pharmacokinetics(PK) of enteric-coated mycophenolate sodium(EC-MPS) by quantification of the active metabolite of mycophenolic acid(MPA)after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC–UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to900 mg, C_(max) and AUC_(0–12h) did not increase with dose escalation. The AUC_(0–12h), C_(max), C_0 and T_(max) for the 540 720 and 900 mg doses were not significantly different, respectively(P 40.05). AUC_0–12 h and C_(max) were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_(0–12h), C_(max) and C_0 were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.
基金supported by the National Key R&D Program of China (No. 2018YFC0310800)the National Science and Technology Major Project for Significant New Drugs Development (No. 2018ZX09735004)+3 种基金the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology (Qingdao)(Nos. 2018SDKJ0401-2 and 2016ASKJ05-04)the NSFC-Shandong Joint Fund (No. U1906212)the Fundamental Research Funds for the Central Universities (No. 201941001)the Taishan Scholar Youth Expert Program in Shandong Province (No. tsqn201812021)。
文摘Three new mycophenolic acid derivatives, penicacids E-G(1-3), together with three known analogues, mycophenolic acid(4), 4′-hydroxy-mycophenolic acid(5) and mycophenolic methyl ester(6), were isolated from a marine-derived fungus Penicillium parvum HDN17-478 from a South China Sea marine sediment sample. The structures of compounds 1-3 were elucidated by HRMS, NMR, and Mosher’s method. Among them, compounds 1 and 2 were the first examples of mycophenolic acid analogs with a double bond at C-3′/C-4′ position. The cytotoxicity of 1-6 was evaluated against the HCT-116, BEL-7402, MGC-803, SH-SY5 Y, HO-8910 and HL-60 cell lines, and compounds 4 and 6 showed potent cytotoxicity with IC50 values ranging from 1.69 to 12.98 μmol·L–1.
基金supported by the National Basic Research Program of China(973 Program,No.2009CB 522300)the National Natural Sciences Foundation of China(Nos.30830113,U1132607)
文摘AIM: To investigate the chemical constituents of the cultures of Laetiporus sulphureus(Bull.) Murrill. METHOD: Compounds were isolated and purified by various chromatographic techniques. The structure of the new compound was determined by interpretation of MS and 1D-, 2D-NMR spectroscopic data, while the known compounds were identified by comparison of their data with those reported. RESULTS: Three mycophenolic acid derivatives, 6-((2E, 6E)-3, 7-dimethyldeca-2, 6-dienyl)-7-hydroxy-5-methoxy-4-methylphtanlan-1-one(1), 6-((2E, 6E)-3, 7, 11-trimethyldedoca-2, 6, 10-trienyl)-5, 7-dihydroxy-4-methylphtanlan-1-one(2), and 6-((2E, 6E)-3, 7, 11-trimethyldedoca-2, 6, 10-trienyl)-7-hydroxy-5-methoxy-4-methylphtanlan-1-one(3) were isolated. CONCLUSION: Among them, compound 1 was new, and compound 2 exhibited moderate cytotoxicity against HL-60, SMMC-7721, A-549, and MCF-7 cells, with IC50 values of 39.1, 31.1, 27.4, and 35.7 μmol·L-1, respectively.
文摘BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease(MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes.AIM To investigate the effectiveness of conventional therapy for MS-IBD.METHODS A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease(CD) and ulcerative colitis(UC). Corticosteroids(prednisone, hydrocortisone, budesonide, prednisolone,dexamethasone), 5-aminosalicylic acid(5-ASA) derivatives(mesalazine and sulfasalazine) and immunosuppressants [azathioprine(AZA), methotrexate(MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine(6-MP)] were considered conventional therapy. The exclusion criteria were sample size below50; narrative reviews; specific subpopulations(e.g., pregnant women,comorbidities); studies on postoperative IBD; and languages other than English,Spanish, French or Portuguese. The primary outcome measures were clinical remission(induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria.RESULTS The search strategy identified 1995 citations, of which 27 were considered eligible(7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected(AZA and 6-MP showed no advantage over placebo,MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus vs placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials(RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing,one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence.CONCLUSION High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.
文摘The development of chronic kidney disease(CKD)after liver transplantation(LT)exerts a severe effect on the survival of patients.The widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure,as several patients are transplanted with previously deteriorated renal function.Due to its multifactorial nature,encompassing pre-transplantation conditions,perioperative events,and nephrotoxic immunosuppressor therapies,the accurate identification of patients under risk of renal disease,and the implementation of preventive approaches,are extremely important.Methods for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate,to non-invasive markers,although no option has yet proved efficient in early detection of kidney injury.Considering the nephrotoxicity of calcineurin inhibitors(CNI)as a factor of utmost importance after LT,early nephroprotective strategies are highly recommended.They are based mainly on delaying the application of CNI during the immediate postoperativeperiod,reducing their dosage,and associating them with other less nephrotoxic drugs,such as mycophenolate mofetil and everolimus.This review provides a critical assessment of the causes of renal dysfunction after LT,the methods of its evaluation,and the interventions aimed at preserving renal function early and belatedly after LT.
