Objective To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease(CKD)stages 3-5 patients with hyperuricemia(HUA).Methods The study was a prospective cohort study...Objective To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease(CKD)stages 3-5 patients with hyperuricemia(HUA).Methods The study was a prospective cohort study.The patients of CKD stages 3-5 with HUA between June 2015 and June 2018 in the Affiliated Hospital of Qingdao University were prospectively analyzed.The patients were assigned to febuxostat(A)group,allopurinol(B)group and non-hyperuricemia(C)group according to the level of serum uric acid and the choice of urate-lowering drugs.Serum uric acid,hypersensitive C-reactive protein(hs-CRP),plasma malondialdehyde(MDA),superoxide dismutase(SOD)and endothelin-1(ET-1)were measured at baseline,1 month and 3 months after treatment and the changes of the values of inflammation and oxidative stress before or after treatment were compared.展开更多
Gout is caused by the deposition of uric acid as monosodium urate(MSU). Chronic hyperuricemia is the necessary condition for MSU deposition, which arises from over-production and/or under-excretion of uric acid. Ren...Gout is caused by the deposition of uric acid as monosodium urate(MSU). Chronic hyperuricemia is the necessary condition for MSU deposition, which arises from over-production and/or under-excretion of uric acid. Renal under-excretion of uric acid accounts for greater than 90% of the patients with hyperuricemia, making URAT1 inhibitors, which act through uricosuric effect a promising class of urate-lowering therapy(ULT). This review aims at the summary and discussion of the latest development of URAT1 inhibitors for the treatment of hyperuricemia and gout and providing an insight into their structure-activity relationship(SAR), which will be helpful to the design of URAT1 inhibitors for both academic research and pharmaceutical industry. The current development pipeline of URAT1 inhibitors is promising and encouraging.展开更多
Despite growing prevalence and incidence,the management of gout remains suboptimal.The intermittent nature of the gout makes the long-term urate-lowering therapy(ULT)particularly important for gout management.However,...Despite growing prevalence and incidence,the management of gout remains suboptimal.The intermittent nature of the gout makes the long-term urate-lowering therapy(ULT)particularly important for gout management.However,patients are reluctant to take medication day after day to manage incurable occasional gout flares,and suffer from possible long-term toxicity.Therefore,a safe and easy-tooperate drug delivery system with simple preparation for the long-term management of gout is very necessary.Here,a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal.This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention.Furthermore,its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models.Besides,the drug co-delivery system could help avoid long-term daily oral colchicine,a drug with a narrow therapeutic index.This system also avoids mass injection of uricase by improving its stability,enhancing the clinical application value of uricase.In general,this two-drug system reduces the dosage of uricase and colchicine and improves the patient’s compliance,which has a strong clinical translation.展开更多
文摘Objective To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease(CKD)stages 3-5 patients with hyperuricemia(HUA).Methods The study was a prospective cohort study.The patients of CKD stages 3-5 with HUA between June 2015 and June 2018 in the Affiliated Hospital of Qingdao University were prospectively analyzed.The patients were assigned to febuxostat(A)group,allopurinol(B)group and non-hyperuricemia(C)group according to the level of serum uric acid and the choice of urate-lowering drugs.Serum uric acid,hypersensitive C-reactive protein(hs-CRP),plasma malondialdehyde(MDA),superoxide dismutase(SOD)and endothelin-1(ET-1)were measured at baseline,1 month and 3 months after treatment and the changes of the values of inflammation and oxidative stress before or after treatment were compared.
基金Supported by Key Projects of Tianjin Science and Technology Support Plan(16YFZCSY00910)Natural Science Foundation of Shandong Province(ZR2015BM028)
文摘Gout is caused by the deposition of uric acid as monosodium urate(MSU). Chronic hyperuricemia is the necessary condition for MSU deposition, which arises from over-production and/or under-excretion of uric acid. Renal under-excretion of uric acid accounts for greater than 90% of the patients with hyperuricemia, making URAT1 inhibitors, which act through uricosuric effect a promising class of urate-lowering therapy(ULT). This review aims at the summary and discussion of the latest development of URAT1 inhibitors for the treatment of hyperuricemia and gout and providing an insight into their structure-activity relationship(SAR), which will be helpful to the design of URAT1 inhibitors for both academic research and pharmaceutical industry. The current development pipeline of URAT1 inhibitors is promising and encouraging.
基金the financial support from the National Natural Science Foundation(NOs.32071342,and 82272154,China)Guangdong Special Support Program(NO.2019TQ05Y209,China)+5 种基金the Natural Science Foundation of Guangdong Province(NO.2023A1515012015,China)Tianjin Science Fund for Distinguished Young Scholars(NO.22JCJQJC00120,China)Natural Science Foundation of Tianjin(The Basic Research Cooperation Special Foundation of Beijing-Tianjin-Hebei Region,NO.22JCZXJC00060,China)the Fundamental Research Funds for the Central Universities(NO.2021-RC310-005,China)Technology&Innovation Commission of Shenzhen Municipality(NOs.JCYJ20220818102810023,JCYJ20190807153601667,and JCYJ20210324124402006,China)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(NOs.2021-I2M-1e058,and 2022-I2M-2-003,China)。
文摘Despite growing prevalence and incidence,the management of gout remains suboptimal.The intermittent nature of the gout makes the long-term urate-lowering therapy(ULT)particularly important for gout management.However,patients are reluctant to take medication day after day to manage incurable occasional gout flares,and suffer from possible long-term toxicity.Therefore,a safe and easy-tooperate drug delivery system with simple preparation for the long-term management of gout is very necessary.Here,a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal.This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention.Furthermore,its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models.Besides,the drug co-delivery system could help avoid long-term daily oral colchicine,a drug with a narrow therapeutic index.This system also avoids mass injection of uricase by improving its stability,enhancing the clinical application value of uricase.In general,this two-drug system reduces the dosage of uricase and colchicine and improves the patient’s compliance,which has a strong clinical translation.