The SLC22 drug transporter family

The SLC22 family comprises organic cation transporters (OCTs), zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). These transporters contain 12 predicted -helical transmembrane domains (TMDs) and one large extracellular loop between TMDs 1 and 2. Transporters of the SLC22 family function in different ways: (1) as uniporters that mediate facilitated diffusion in either direction (OCTs), (2) as anion exchangers (OAT1, OAT3 and URAT1), and (3) as Na⁺/l-carnitine cotransporter (OCTN2). They participate in the absorption and/or excretion of drugs, xenobiotics, and endogenous compounds in intestine, liver and/or kidney, and perform homeostatic functions in brain and heart. The endogenous substrates include monoamine neurotransmitters, choline, l-carnitine, -ketoglutarate, cAMP, cGMP, prostaglandins, and urate. Defect mutations of transporters of the SLC22 family may cause specific diseases such as "primary systemic carnitine deficiency" or "idiopathic renal hypouricemia" or change drug absorption or excretion.     

基于“肠-肾”途径的健脾祛湿中药抗痛风病研究

目的:从“肠-肾”途径探讨健脾祛湿中药防治痛风病作用。方法:10%果糖塑造大鼠高血尿酸模型,高钙高嘌呤食饵并限水诱导鹌鹑尿酸盐沉积模型,以菊苣、参苓白术散为示例药。生化检测大鼠血清尿酸(SUA)、粪便尿酸(FUA)水平,计算肾脏尿酸清除率(RCUA);检测鹌鹑粪尿中尿酸含量,计算尿酸排泄量。免疫组化分析大鼠肠道ABCG2、肾脏URAT1、OAT1,及鹌鹑肠道Occludin、肾脏p-p65表达。六胺银染色分析尿酸盐沉积。结果:1)菊苣可显著降低模型大鼠SUA、增加FUA、RCUA,促进肠道ABCG2表达,减少肾脏URAT1表达。2)参苓白术散可显著减少模型鹌鹑肾脏尿酸盐沉积,增加尿酸排泄量,增加肠道Occludin表达,减少肾脏p-p65表达。结论:痛风病发生发展中存在“肠-肾”途径的病理改变,健脾祛湿中药通过调节“肠-肾”尿酸转运促尿酸排泄、改善肠道屏障功能及肾脏炎症状态以祛除尿酸盐沉积,共同发挥防治痛风病作用。     

痛风患者足踝双能CT尿酸盐结晶沉积特点分析

目的 应用双能CT分析关节周围尿酸盐结晶沉积特点,预测与痛风性关节炎急性发作相关的解剖和形态学特征.方法 选择近期足踝部发作过关节肿和(或)痛患者84例(其中确诊痛风患者68例,无症状高尿酸血症患者1 1例,单纯其他类型关节炎患者5例),入选患者均完成足踝部双能CT检查.应用x2检验及Logistic回归模型分析尿酸盐结晶沉积的解剖、形态学特征与关节炎症急性发作的关系.结果 痛风组共发现278处尿酸盐结晶,最常出现结晶沉积的部位依次为第一趾中远端(18.2％)、第一跖趾关节(16.8％)、跟骨(17.5％)、胫骨下端(11.8％),无症状高尿酸血症组发现34处尿酸盐结晶沉积,分布趋势与痛风组相似.对患者结晶沉积部位与关节炎症急性发作情况进行分析后发现,第一跖趾关节(x2=8.47,P＜0.01)及胫骨下端(x2=3.93,P＜0.05)出现结晶沉积的患者临床上更易出现相应部位关节炎的急性发作.且第一跖趾关节附近的尿酸盐结晶如果沉积于肌腱(x2=5.03,P＜0.05)或软组织(x2=5.19,P＜0.05)中,更易引起痛风性关节炎;而对于踝关节周围的尿酸盐结晶,如果其沉积于踝关节伸面(x2=4.42,P＜0.05)或呈点状(x2=4.76,P＜0.05)或为多个(x2=4.97,P＜0.05)则更易出现关节炎症发作.并且Logistic多元回归分析结果也提示,痛风性关节炎急性发作有潜在的危险因素.结论 双能CT可以清晰显示尿酸盐结晶,有助于痛风的诊断及随防研究.尿酸盐结晶沉积的部位、形状、大小、数量以及受累部位是否伴有软组织肿胀、骨侵蚀等因素,对痛风性关节炎的急性发作有影响.     

三磷酸腺苷结合盒转运蛋白G2与痛风病关联的病理机制研究进展

痛风病是指与高尿酸血症、尿酸盐沉积（关节、肾脏）等尿酸代谢紊乱密切相关的进展性代谢疾病,根据其病理进展特点和临床表现,其病程可分为高尿酸血症阶段、尿酸盐沉积阶段、痛风性炎症阶段。三磷酸腺苷结合盒转运蛋白G2（ABCG2）是高通量的尿酸转运体,既参与了机体尿酸外排的肠-肾途径,又与痛风性炎症密切相关。通过切入ABCG2,对痛风病病理机制研究进展进行综述,以期为临床痛风病的深入研究及防治提供新的见解。     

双源CT双能量成像技术在痛风诊断中的临床应用

目的:通过采用双源CT(dual source computed tomography,DSCT)双能量成像技术检测痛风患者关节部位尿酸盐结晶的沉积状况,探讨DSCT技术在痛风诊断中的临床应用.方法:选择我院临床确诊的痛风患者48例作为试验组,其他关节炎患者30例作为对照组(其中11例类风湿关节炎患者,16例骨关节炎患者及3例系统性红斑狼疮性关节炎),采用双源CT对两组患者行双腕关节、双膝关节、双足踝关节扫描,利用仪器配置的痛风识别软件处理原始图像,由两名临床经验丰富的影像医师对获得的数据进行分析,判断患者检查部位是否有尿酸盐结晶沉积.结果:在48例痛风患者DSCT检查中有46例发现关节内有尿酸盐沉积,痛风诊断的敏感性为46/48(95.8%);在30例对照组患者中,有2例出现伪信号影,诊断特异性为28/30(93.3%);有骨质破坏的痛风患者与无骨质破坏的痛风患者之间的尿酸盐结晶阳性检出率无明显差异(P>0.05);血尿酸水平增高和血尿酸水平正常的痛风患者,其DSCT尿酸盐结晶的检出率差异无统计学意义(P>0.05).结论:采用DSCT双能量成像技术诊断痛风具有较高的敏感性及特异性,并且可以直观无创地显示患者检测部位尿酸盐结晶的沉积情况,提示DSCT可应用于痛风病情的监测,具有较重要的临床推广应用价值.     

256排双源CT对痛风性关节炎的诊断效能及与其他影像学检查的对比

目的 探讨256排双源CT(DECT)对痛风性关节炎(GA)的诊断效能.方法 收集安徽理工大学第一附属医院2019年1月～2020年12月GA住院患者117例的临床资料,其中50例GA行256排DECT检查(GA组),并选取30例同期住院其他类型的关节炎患者为对照组.计算ROC曲线下面积(AUC),评价DECT诊断效能...     

苗药痛风停汤对高尿酸血症大鼠降尿酸机制研究

目的:通过探讨痛风停汤对高尿酸血症大鼠血尿酸水平、血清黄嘌呤氧化酶(XO)浓度、肾小管上皮细胞的尿酸盐转运体(UAT)mRNA和尿酸盐阴离子转运蛋白1(URAT1)mRNA的表达的影响,研究苗药痛风停汤的具体降尿酸作用机制.方法:将56只SD大鼠随机分为苗药痛风停高、中、低组、空白组和模型组、别嘌醇组、苯溴马隆组.除空...     

Juvenile hormone synthesis as related to egg development in neotenic reproductives of the termite Reticulitermes flavipes, with observations on urates in the fat body

The relationship between juvenile hormone (JH) synthesis and egg development, which is well documented in cockroaches, is much less studied in their close relatives, the termites. In this study of neotenic reproductives of the subterranean termite Reticulitermes flavipes, in vitro rates of juvenile hormone (JH) synthesis by corpora allata (CA) are related to vitellogenic egg development and the size of CA. The first study compared brachypterous and apterous neotenics in their first cycle of egg development and a second study compared physogastric and non-physogastric brachypterous and apterous neotenics. In both studies, rates of JH synthesis correlated with the size of CA as indicated by their length. Unlike the cockroach in which all basal oocytes are in the same stage of development, those in termites are in various stages. In brachypterous and apterous in the first cycle of egg development, CA with high rates of JH synthesis were from females with early vitellogenic basal oocytes, whereas CA with low rates of JH synthesis were from females with either pre-vitellogenic or mature basal oocytes. This pattern of JH synthesis is similar to the cycle of JH synthesis correlated with oocyte development in several cockroach species. In later oocyte maturations, CA from physogastric apterous females with ovaries containing mature, as well as growing oocytes, showed a wide range of JH production; the CA with the highest rates of JH synthesis were from females with the highest proportion of early vitellogenic oocytes suggesting that both mature and early vitellogenic oocytes interact to regulate JH synthesis. Rates of JH synthesis were related to the number of vitellogenic ovarioles. Physogastric brachypterous neotenics, compared to the other classes of neotenic females, had CA with 2- to 4-fold higher rates of JH synthesis and ovaries with 2.5- to 8-fold greater number of vitellogenic ovarioles. However, both physogastric brachypterous and apterous neotenics had more vitellogenic basal oocytes and less urate in their fat bodies than the respective non-physogastric neotenics. These results demonstrate the similarities and differences between the classes of neotenic termites and between reproductive females in cockroaches and termites.     

双源双能量CT在痛风性关节炎的诊断应用

目的：评价双源双能量CT在痛风性关节炎尿酸盐结晶检出中的作用。方法选出26例痛风性关节炎患者,行双源双能量CT检查。结果26例痛风性关节炎患者发现36处尿酸盐结晶,第一跖趾关节为最常见沉积部位。结论双源双能量CT能清楚显示尿酸盐结晶,对痛风性关节炎诊断具有特异性。     

双能量CT对痛风的诊断价值

目的 评价双能量CT对痛风的诊断价值.方法 对试验组的25例痛风患者双侧足部、踝关节、膝关节、手部、腕关节及肘关节行双能量CT扫描成像,统计尿酸盐结晶沉积病灶数,对出现临床症状的关节行X线检查.对患者四肢关节进行临床体检,统计临床病灶数目及部位.对照组的20例类风湿关节炎(RA)患者的受累关节及对侧关节行双能量CT扫描成像.同时检测所有患者的血尿酸、血肌酐、总胆固醇及甘油三酯水平.对比2组患者双能量CT检查结果与X线及临床体检之间的差异.统计学处理采用t检验和x2检验.结果 双能量CT检查中各关节发现病灶的病例数及比例分别为足部及踝关节23例(92％),膝关节17例(68％)、手与腕关节3例(12％)及肘关节1例(4％),足部及踝关节受累患者最多(P＜0.05).尿酸盐沉积病灶共184处,其中足与踝关节、膝关节、手与腕关节及肘关节的病灶数分别为107处(58.2％)、72处(39.1％)、4处(2.2％)、1处(0.5％),足部及踝关节中尿酸盐沉积病灶数最多(P＜0.01).临床统计病灶数为64处,仅占双能量CT发现病灶数的34.8％,差异具有统计学意义(P＜0.01).而X线检查仅6例患者发现骨质破坏等非特异性改变.试验组患者血尿酸、血肌酐及甘油三酯水平较对照组明显增高,差异具有统计学意义(P值分别为＜0.01,＜0.05,＜0.05).结论 双能量CT对痛风的诊断有重要的临床价值.