Dose reduction for the management of indinavir-related toxicity in human immunodeficiency virus type 1-infected patients in Taiwan: clinical and pharmacokinetic assessment.

This study evaluated the feasibility of reducing the indinavir (IDV) dosage in Taiwanese patients receiving the standard IDV/ritonavir (RTV) dosage of 800/100 mg twice a day who had undetectable plasma human immunodeficiency virus type 1 (HIV-1) RNA but had developed IDV-related toxicities. After dosage reduction to IDV/RTV 600/100 mg twice a day, the dose-related toxicity decreased and plasma HIV RNA remained undetectable at 24 weeks post-switch in all patients. The maximal plasma concentration (Cmax) and area under the plasma concentration-time curve of IDV decreased significantly (median, 6.3 vs 4.3 microg/mL and 1892 vs 1292 microg.min/mL, p=0.01 and 0.001, respectively) but the minimal plasma concentration remained at a similar level (median, 1.0 vs 0.8 microg/mL, p=0.12). This study found that the reduction in the dosage of IDV in HIV-1 infected patients receiving the standard IDV/RTV regimen guided by therapeutic drug monitoring decreased the Cmax, dose-related toxicity and medical cost without compromising viral control.     

Inhibition of the ubiquitin-proteasome system: a new avenue for atherosclerosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) is thought to be functionally active in atherosclerosis (AS) lesions. Aspirin was found to be a potent inhibitor of the UPS in some tumour studies; however, its effect on AS remains to be demonstrated in vivo. METHODS: New Zealand rabbits were placed on a normal diet (N) or on a normal diet with aspirin (NI) or on an atherogenic diet without (H) or with aspirin (HI) for 12 weeks. Proteasome activity, concentrations of plasma lipids and levels of peroxidation were determined. Ubiquitin/ubiquitin-conjugates (Ub), IkappaBalpha, phosphorylated IkappaB (pIkappaBalpha) and p65 were investigated by Western blotting or immunochemistry. RESULTS: Concentrations of plasma lipids and peroxidation levels were higher in H or HI vs. N or NI. Histological analysis showed that atheroma was increased in H. Ub and IkappaBalpha were mainly localised in subendothelium and media vascular smooth muscle cells. Western blots revealed that Ub, IkappaBalpha, and pIkappaBalpha were increased, whereas p65 was lower in HI vs. H. The activity of the 20S proteasome was functionally active in H vs. N, NI or HI, while the 26S proteasome was not affected in any of the groups. CONCLUSIONS: Aspirin can attenuate the pathogenesis of atheroma formation, the degradation of IkappaBalpha and pIkappaBalpha, and lower the expression of p65, indicating that its therapeutic effects on AS may be via inhibition of the UPS.     

大脑中动脉支架内血栓形成1例报告

支架内血栓形成是支架置入术后的一种常见并发症。术后血管内皮损伤、胶原组织暴露和作为异物的支架均为引发血栓形成的可能机制。不能及时识别处理则成为再狭窄的重要原因。我们报告1例发生在大脑中动脉（middle cerebral artery，MCA）支架内的血栓形成，探讨其识别处理过程和可能的机制。     

下肢严重开放性损伤的保肢治疗

高能量损伤导致的下肢严重开放性损伤的保肢治疗，对骨科医生来说是一个挑战。随着修复重建技术的提高和术后辅助治疗的完善，给保肢治疗带来了希望，但总体疗效仍不理想。我院自2003年1月～2004年12月共对32例下肢严重损伤患者行保肢治疗，现结合相关文献进行回顾性分析，旨在探讨保肢的指征、肢体重建的方法与时机及保肢失败的原因。     

Caveolin-1对乳腺癌细胞Hs578T耐药株周期和凋亡影响

目的 探讨Caveolin-1基因对乳腺癌细胞系Hs578T耐药株(Hs578T/Dox)生长和凋亡的影响. 方法在乳腺癌细胞系Hs578T耐药株中转染Caveolin-1基因,构建高表达Caveolin-1蛋白的细胞系(Hs578T/Dox-cav),通过Western Blot方法证实转染成功.将这2种细胞以同样的条件培养96h,应用流式细胞仪检测细胞周期和凋亡的分布.比较转染前后细胞的细胞周期分布的不同.应用软琼脂培养法比较转染前后细胞抛锚生长能力的变化以及对促凋亡剂(staurosporine)的不同反应.结果 转染Caveolin-1后明显促进了所用细胞株由G1期向G2期的转变(P<0.01).自然凋亡率显著下降.抛锚生长能力增加,缓解了对staurosporine的反应.结论 Caveolin-1促进乳腺癌细胞系Hs578T耐药株生长和增殖,抑制凋亡.     

旋转复位配合矫形鞋治疗退变性腰椎侧弯

退变性腰椎侧弯(degenerative lumbar scoliosis,DLS)是继发于腰椎间盘及腰椎骨关节退变的成人脊柱侧弯,较一般典型的腰椎骨性关节炎症状重,同时伴有明显旋转侧弯畸形,常规治疗方法疗效差。2003年9月-2005年9月采用脊柱(定点)旋转复位手法结合矫形鞋治疗77例DLS患者,近期效果满意,总结报告如下。1临床资料本组77例中,男29例,女48例;平均年龄56.5岁(45~76岁)。病程平均6个月(2个月~10年)。所有患者均有腰痛及下肢疼痛,同时伴有明显的腰脊柱侧弯,站立、行走疼痛明显,其中48例(82.3%)需要药物控制疼痛,间歇性跛行者26例(33.8%),直腿抬高试验…     

The changes of the interspace angle after anterior correction and instrumentation in adolescent idiopathic scoliosis patients

Background  

In idiopathic scoliosis patients, after anterior spinal fusion and instrumentation, the discs (interspace angle) between the lowest instrumented vertebra (LIV) and the next caudal vertebra became more wedged. We reviewed these patients and analyzed the changes of the angle.     

FasL基因表达对缺氧状态下直肠癌细胞增殖凋亡的影响

Objective To elucidate the effect of FasL gene expression on the proliferation and apoptosis of hypoxic rectal carcinoma cells. Methods The normoxic expression level of FasL in HR-8348 subtype cells (HR-8348B, HR-8348L, HR-8348F and HR-8348As) with different invasive power were verified by Western blot. Hypoxia models for HR-8348B, HR-8348L, HR-8348F and HR-8348As were constructed with chemical modeling, then the FasL levels in all groups at 12 h after hypoxia were quantitated by Western blot. Distribution of different cell life cycles was determined with flow cytometry. Cell reproductive activities were detected with MTT method, and cell apoptesis was assessed with TUNEL. Results FasL protein was pigmentized at the position of 40 000 by Western blot, and the expression level of FasL was significantly higher in HR-8348F cells than those in HR-8348B, HR-8348L and HR-8348As cells(F=361.149, P<0.01) in normoxia. At 12 h after hypoxia, the FasL level was also significantly higher in HR-8348F cells than those in other groups (F=278.766, P<0.01), but was not markedly different as compared to themselves in normoxia (t=1.762, P>0.05). The proliferation index was significantly higher in HR-8348F (60.43±3.72) than those in HR-8348B (40.01±3.30), HR-8348L (41.30±4.06) and HR-8348As cells (35.87±4.39), respectively (F=39.477, P<0.01). However, both inhibition rate of proliferation and apoptotic index were remarkably lower in HR-8348F (17.30±1.98 and 13.10±1.04) than those in HR-834B (33.70±4.33 and 21.60±1.31), HR-8348L (34.20±3.92 and 20.10±1.15), and HR-8348As (38.00±4.55 and 23.90±1.23), respectively (F=28.811 and 76.462, respectively, P<0.01). Conclusion The expression enhancement of intracellular FasL in rectal carcinoma in hypoxia can lead to accelerated proliferation and reduced apeptosis of cells, which will promote tumor cells to adapt microenvironmental hypoxia.     

Correlation between levels of serum immunoglobulin、complement and immunopathology in glomerular disease

目的 探讨肾小球疾病免疫球蛋白、补体水平与免疫病理的相关性.方法 112 例肾小球疾病患者,14 例健康人测定血清免疫球蛋白及补体,112 例肾小球疾病患者,112 例患者行肾活组织病理检查.结果 112 例肾小球疾病患者 IgG 升高 11 例(9.82%),降低 29 例(25.89%),IgA 升高 33 例(29.46%),降低 2 例(1.79%).IgM 升高 7 例(6.25%),降低 3 例(2.68%),三种免疫球蛋白的变化有显著差异(x2=70.587,P=O.000);C3 减低 29 例(25.89%),C4减低 32 例(28.57%),两者比较无显著差异(X2=0.203,P=0.653).免疫荧光阳性率依次为C3(50%)>lgA(49.11%)>IgG(40.18%)>lgM(21.43%)>C4(14.29%)(x2=49.303,P=0.000);免疫荧光 IgA 阳性者血清 lgA 水平较阴性者高(P=0.042),C3、CA阳性者血清 C3、c4 水平较阴性者低(P=0,P=0.007),IgG、IgM 阳性者血清 IgG、lgM 水平与阴性者比较无差异(P=0.136,P=0.383).结论 肾小球疾病存在体液免疫紊乱,测定血清免疫球蛋白、补体及行肾组织免疫病检有助于了解体液免疫状况,估计疾病活动度,判断疗效,但两种检查之间无明显的相关性,可相互补充,不能相互替代.     

The action of(±)-MDMA on medial prefrontal cortical neurons is mediated through the serotonergic system

The mechanism of action of systemitically administered(±)-MDMA (3, 4-methylenedioxymethamphetamine) on spontaneously active neurons in the medial prefrontal cortex (mPFc) of chloral hydrate anesthetized rats was examined using standard single unit extracellular recording techniques. Intravenously administered MDMA dose-dependently decreased the firing rates of the majority of mPFc neurons in control rats. In contrast, in rats that were pretreated withp-chlorophenylalanine (PCPA), which depletes the brain serotonin (5-hydroxytryptamine, 5-HT) content by inhibiting tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of 5-HT, MDMA was largely ineffective in inhibiting the firing of mPFc cells. In PCPA-treated animals, the administration of 5-hydroxytryptophan (5-HTP), which presumably restored the brain 5-HT content, but notl-DOPA, reinstated MDMA's inhibitory action in PCPA-treated rats. In rats that were pretreated withα-methyl-p-tyrosine (AMPT), which depletes the brain dopamine (DA) content by inhibiting tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of DA, MDMA inhibited the firing of all of the mPFc cells. MDMA's effect on mPFc neurons was reversed by 5-HT receptor antagonists such as granisetron and metergoline. These results strongly suggest that MDMA exerts its action on mPFc cells indirectly by releasing endogenous 5-HT.