凋亡抑制蛋白XIAP与肿瘤多药耐药

XIAP(X-linked inhibitor of apoptosis protein)是凋亡抑制蛋白(inhibitors of apoptosis protein,IAP)家族中最有效的内源性凋亡抑制因子,可以通过直接抑制caspases或者参与信号转导途径抑制细胞凋亡。研究发现,XIAP与肿瘤多药耐药有密切关系,并且有可能成为逆转肿瘤多药耐药提高化疗效果的治疗新靶点。     

经尿道前列腺汽化电切术后后尿道狭窄的防治(附19例报告)

目的探讨经尿道前列腺汽化电切(TVP)术后后尿道狭窄的防治。方法结合文献,回顾分析19例TVP术后并发后尿道狭窄患者诊治经过。结果19例患者中13例经尿道扩张术治愈,5例行冷刀内切开术 电切术治愈,1例腔内手术失败改开放手术治愈。结论后尿道狭窄为TVP术后常见并发症,多数可用尿道扩张术治愈,对尿道扩张失败者应进行冷刀内切开术 电切术,早期及时处理效果好。     

17 β雌二醇通过丝裂原活化蛋白激酶抑制前列腺癌细胞系PC3增殖

目的探讨丝裂原活化蛋白激酶在17β雌二醇(E2)抑制前列腺癌PC3细胞生长中的作用。方法检测不同浓度E2作用不同时间后PC3细胞生长抑制率。流式细胞仪分析细胞周期分布,TUNEL染色检测凋亡。Western blot检测ERK1/2,JNK和p38活性。RT-PCR法检测雌激素受体(ER)α、ERβ、P21WAF1和cyclinD1的表达。结果E2抑制PC3细胞增殖,并且可以激活ERK1/2、JNK和p38。处理因素作用48h后,对照组、E2、E2 PD98059、E2 SP600125、E2 SB203580组细胞的凋亡率分别为(0.9±0.1)%;(23.0±1.4)%;(30.0±1.2)%;(10.6±0.8)%和(14.6±0.7)%,(P<0.05)。E2使细胞阻滞在G1期,PD98059、SP600125、SB203580分别预处理1h后细胞分别进一步阻滞在G1期;轻度阻滞在G1期和进入S期。RT-PCR发现PC3细胞表达ERα和ERβ,E2、E2 PD98059、E2 SP600125、E2 SB203580组中cyclinD1、P21WAF1基因表达分别为对照组的(0.42±0.03)、(3.13±0.02)倍;(0.21±0.03)、(3.08±0.05)倍;(0.43±0.01)、(1.31±0.04)倍;(2.81±0.02)、(3.14±0.02)倍(P<0.05)。结论E2激活JNK增加P21WAF1基因表达,并激活p38抑制cyclinD1表达,使细胞阻滞在G1期,JNK和p38通路还介导E2引起PC3细胞凋亡。同时E2又可激活ERK1/2,轻度拮抗上述作用。     

ING4基因与肿瘤研究新进展

ING4基因是肿瘤抑制因子家族的新成员,近来研究发现,ING基因在正常组织中表达丰富,但在多种恶性肿瘤组织,如乳腺癌、胶质瘤、肺癌等中表达明显下调,ING4可通过增强p53基因的活性、恢复细胞间接触抑制、抑制肿瘤血管生成、抑制HIF的活性而抑制肿瘤的生长,还能诱导细胞凋亡,增加肿瘤细胞对放化疗的敏感性,本研究对ING4基因与肿瘤研究的新进展进行综述。     

慢性肾功能损伤的肝移植受者转换为西罗莫司治疗的疗效观察

目的 观察慢性肾功能损伤的肝移植受者转换为西罗莫司治疗的疗效.方法 应用钙调磷酸酶抑制剂(CNI)并伴有慢性肾功能损伤的肝移植受者23例(其中19例应用他克莫司,4例应用环孢素A)转换为西罗莫司(SRL)治疗.SRL的起始剂量为4mg/d,次日为2 mg/d,应用高压液相色谱法测定全血SRL浓度,当血SRL浓度达5～8 μg/L后,停用CNI类药物,同时服用吗替麦考酚酯,1 g/d.记录受者入组前的基础血清肌酐(Cr)、肌酐清除率、肾小球滤过率(GFR),并分别于用药后第1、3、6、12和24个月时监测血SRL浓度、Cr、肌酐清除率、GFR,同时监测受者体重、血压、血细胞计数、肝功能和肝脏生化指标、血脂、尿蛋白.于用药后12个月时行肝脏穿刺活检确认有无排斥反应.结果 23例平均随访29.4个月,随访期内死亡2例,另21例于用药后1、3、6、12和24月时的Cr分别为(147.40±23.36)、(152.60±20.08)、(150.20±22.64)、(137.60±18.09)、(138.30±17.04)μmol/L,与Cr的基础值[(158.91±29.13)μmol/L]相比较,1、12、24个月时的差异有统计学意义(P＜0.05).用药后1、3、6、12和24月时的肌酐清除率分别为(0.97±0.18)、(0.99±0.14)、(1.00±0.17)、(1.07±0.29)、(1.14±0.12)ml/s,与基础肌酐清除率[(0.91±0.14)ml/s]相比较,1、12、24个月时的差异有统计学意义(P＜0.05).用药后1、3、6、12和24月时的GFR分别为(0.80±0.15)、(0.78±0.11)、(0.75±0.12)、(0.84±0.10)、(0.94±0.13),与基础GFR[(0.71±0.11)ml/s]相比较,1、12、24个月时的差异有统计学意义(P＜0.05).应用SRL后第1、3、6、12和24个月时,Cr≤123μmol/L者所占的比例分别为38.1％、33.3％、28.6％、47.6％和52.4％.随访期内无受者发生排斥反应.结论 慢性肾功能损伤的肝移植受者转换为西罗莫司治疗可改善其肾功能.转换治疗未增加排斥反应的发生率.     

特发性肾出血36例诊治分析

目的：探讨特发性肾出血的诊断与治疗,提高其诊治水平。方法：回顾性分析2000年1月～2010年8月我科收治的特发性肾出血36例。结果：36例患者中肾动静脉瘘28例,微小肾盂及。肾盏癌4例,肾动脉瘤3例,肾假性动脉瘤1例。其中29例行选择性肾动脉栓塞术,2例行肾切除术,4例行肾盂癌根治术,所有治疗后患者血尿均消失;1例因肾动静脉瘘多处,未进行治疗。结论：外科常见的特发性肾出血病例以肾血管疾病最为常见,选择性肾动脉造影及肾动脉栓塞术对特发性肾出血的诊治有重要意义。对于难以确诊的特发性肾出血患者,要考虑到微小肾盂肾盏癌的可能,输尿管软镜检查对其诊断有一定帮助。     

预先注射瑞芬太尼预防小儿静注罗库溴铵时的回避反应

目的:评估在儿童患者中预先注射瑞芬太尼预防静注罗库溴铵时的回避反应的效能.方法:选择40例施行全麻的择期手术患者,年龄在3-10岁,ASAⅠ-Ⅱ级,患儿随机分为两组:瑞芬组,静注瑞芬1ug/kg,(20例患儿);盐水组,静注盐水5ml(20例患儿).用5mg/kg的硫喷妥钠进行麻醉诱导,患者意识丧失并且停止呼吸后10秒,注射实验药物,注射时间超过30秒,实验药物注射后1分钟以后,1%的罗库溴铵0.6mg/kg静注,注射时间超过5秒钟.结果:总的回避反应发生率在盐水组(19人,95%)明显高于瑞芬组(5人,25%),在瑞芬组没有患者出现全身反应,而在盐水组全身反应的发生率为55%.瑞芬太尼还能防止在插管过程中平均动脉压的升高.讨论:这个实验表明了在儿童患者中预先注射1ug/kg瑞芬对减少注射罗库溴铵时的回避的发生一个安全简单的方法,并且提供了一个稳定的血液动力学环境.     

Angiotensin II receptors modulate muscle microvascular and metabolic responses to insulin in vivo

OBJECTIVE

Angiotensin (ANG) II interacts with insulin-signaling pathways to regulate insulin sensitivity. The type 1 (AT₁R) and type 2 (AT₂R) receptors reciprocally regulate basal perfusion of muscle microvasculature. Unopposed AT₂R activity increases muscle microvascular blood volume (MBV) and glucose extraction, whereas unopposed AT₁R activity decreases both. The current study examined whether ANG II receptors modulate muscle insulin delivery and sensitivity.

RESEARCH DESIGN AND METHODS

Overnight-fasted rats were studied. In protocol 1, rats received a 2-h infusion of saline, insulin (3 mU/kg/min), insulin plus PD123319 (AT₂R blocker), or insulin plus losartan (AT₁R blocker, intravenously). Muscle MBV, microvascular flow velocity, and microvascular blood flow (MBF) were determined. In protocol 2, rats received ¹²⁵I-insulin with or without PD123319, and muscle insulin uptake was determined.

RESULTS

Insulin significantly increased muscle MBV and MBF. AT₂R blockade abolished insulin-mediated increases in muscle MBV and MBF and decreased insulin-stimulated glucose disposal by ~30%. In contrast, losartan plus insulin increased muscle MBV by two- to threefold without further increasing insulin-stimulated glucose disposal. Plasma nitric oxide increased by >50% with insulin and insulin plus losartan but not with insulin plus PD123319. PD123319 markedly decreased muscle insulin uptake and insulin-stimulated Akt phosphorylation.

CONCLUSIONS

We conclude that both AT₁Rs and AT₂Rs regulate insulin’s microvascular and metabolic action in muscle. Although AT₁R activity restrains muscle metabolic responses to insulin via decreased microvascular recruitment and insulin delivery, AT₂R activity is required for normal microvascular responses to insulin. Thus, pharmacologic manipulation aimed at increasing the AT₂R-to-AT₁R activity ratio may afford the potential to improve muscle insulin sensitivity and glucose metabolism.Skeletal muscle microvascular perfusion distribution is determined by precapillary terminal arteriolar tone. Dilating these arterioles increases microvascular perfusion and expands the capillary exchange surface area, whereas constriction leads to the opposite (1,2). Microvascular insulin resistance and dysfunction are closely related with metabolic insulin resistance in diabetes (2–4). Insulin-mediated microvascular recruitment precedes insulin-stimulated glucose uptake in skeletal muscle (5), and blockade of insulin’s microvascular action with N^ω-nitro-l-arginine methyl ester (l-NAME) decreases steady-state insulin-stimulated glucose disposal by ~40% (5,6).To act on muscle, insulin must first traverse the microvasculature perfusing the muscle and then be transported through the vascular endothelium into muscle interstitium. Recent evidence suggests that altered muscle microvascular perfusion profoundly affects insulin delivery and action in muscle (2). Many physiological factors regulate muscle microvascular perfusion in vivo, including insulin, mixed meals, and muscle contraction (7–12). Increased muscle microvascular recruitment induced by muscle contraction is associated with increased muscle insulin uptake (11).The renin-angiotensin system (RAS) plays a central role in maintaining hemodynamic stability (13,14), and angiotensin (ANG) II can interact with the insulin-signaling pathways to regulate insulin sensitivity. In cultured cells, ANG II acts via the ANG II type 1 receptor (AT₁R) to impair insulin actions (15–17). On the other hand, acutely raising ANG II systemically improves insulin-stimulated muscle glucose utilization in humans (18–20) and increases muscle microvascular recruitment independent of blood pressure changes in rodents (21). Both the AT₁R and ANG II type 2 receptor (AT₂R) are present on endothelial cells, vascular smooth-muscle cells, and other vessel-associated cells throughout skeletal muscle microcirculation (13,22,23). ANG II stimulates cell proliferation and vasoconstriction via the AT₁Rs and promotes vasodilation through the AT₂R (24,25). We recently have reported that both the AT₁Rs and the AT₂Rs significantly regulate basal microvascular tone and glucose use by muscle (21). Although basal AT₂R activity increases muscle microvascular blood volume (MBV) (an index of microvascular surface area and perfusion) and glucose extraction, basal AT₁R activity decreases both (21).In the current study, we assessed whether ANG II receptors modulate muscle insulin delivery and sensitivity in vivo. Our results indicate that both AT₁Rs and AT₂Rs regulate insulin’s microvascular and metabolic action in muscle. Although AT₁R activity restrains muscle metabolic responses to insulin via decreased microvascular recruitment and insulin delivery, AT₂R activity is required for normal microvascular responses to insulin.     

肝素标记SPIO增强MRI诊断大鼠肝癌病灶

目的:探讨肝素标记超顺磁氧化铁粒子(HepSPIO) 对大鼠肝癌灶的增强作用。材料和方法:应用Gouys 法测定磁化率;应用二乙基亚硝胺建立大鼠化学诱导性肝癌模型;观察静注Hepspio 前后大鼠肝癌的显示情况,并与病理检查对照分析。结果:HepSPIO 的磁化率为201-5 ×10 - 3/g(25 ℃) ;4 只大鼠肝癌模型共有27 个瘤结,平均直径2-4 ±1-3m m 。增强后质子加权像癌灶检出率由平扫的33-3 % (9/27) 提高到74-1 % (20/27) ,病灶对比度/ 噪声比(CNR) 由0-7±1-9 提高至4-2 ±4-0 ;T2 加权像癌灶检出率由平扫的59-3 % (18/27) 提高到77-8 % (22/27) ,CNR 由2-8 ±2-1 上升至3-9 ±3-3 。结论:HEPSPIO 是一种新型磁共振肝网状内皮系统显影剂,对提高肝脏微小病灶的检出率有重要帮助。