针对MAGE-1基因RNAi在恶性胶质瘤SHG-44细胞中的作用研究

目的构建抑制黑色素瘤抗原-1(MAGE-1)的siRNA表达载体,鉴定其在人恶性胶质瘤细胞系SHG-44细胞中对MAGE-1基因表达的干涉作用。方法化学合成2对编码短发夹RNA序列的靶向MAGE-1基因寡核苷酸链,克隆到经BglⅡ、HindⅢ双酶切的pSUPER载体上,重组构建RNA干涉(RNAi)质粒载体。利用逆转录多聚酶链反应(RT-PCR)、流式细胞术和荧光显微镜,检测经稳定转染后SHG-44细胞中MAGE-1的表达,以了解siRNA的干扰效果。结果重组构建的pSUPER-MAGE-1载体经双酶切电泳及插入基因片段序列分析,表明寡核苷酸链成功插入到预计位点,并且序列与预期完全一致。稳定转染后G418筛选出的SHG-44多克隆细胞MAGE-1的表达经RT-PCR、流式细胞术和荧光显微镜检测,2对siRNA均有较明显的干涉作用。结论成功构建了针对MAGE-1基因的siRNA表达载体,抑制SHG-44细胞中的MAGE-1分子的表达。     

Tuberculosis trends in Madrid, 1994-2003: impact of immigration and HIV infection.

SETTING: Tuberculosis (TB) cases reported from nine districts of Madrid, where the percentage of immigrant population varied from 1.9% in 1996 to 12.2% in 2003. OBJECTIVE: To describe the trends in TB incidence from 1994 to 2003. DESIGN: Observational study. RESULTS: Between 1994-1995 and 2002-2003, the TB rate decreased from 48.5 (95% CI 45.8-51.1) to 23.3 per 100000 population (95% CI 21.5-25.1) (P < 0.001). The percentage of TB cases co-infected with HIV decreased from 55.9% in 1994 to 14.3% in 2003 (P < 0.001), whereas TB cases in foreigners increased from 2.6% in 1994 to 33.7% in 2003 (P < 0.001). CONCLUSION: Although the TB rates showed a marked decrease in the study period, the increasing impact of immigration contributed to slowing down the trend.     

Dentin enhances the effectiveness of bioactive glass S53P4 against a strain of Enterococcus faecalis.

OBJECTIVE: The aim of the current study was to test the impact of dentin powder on the antimicrobial efficacy of bioactive glass S53P4 (BAG). STUDY DESIGN: BAG was suspended (preincubated) in saline at 37 degrees C for different time periods with or without human dentin powder, hydroxylapatite, or decalcified dentin. Subsequently, Enterococcus faecalis ATCC 29212 cells were added to these suspensions and bacterial recovery measured with and without the use of gentle sonication. Furthermore, survival of bacteria in test and control suspensions was assessed over time. Supernatants of suspensions were analyzed for their element contents using atomic absorption spectrophotometry. The effects of pH, silica, and osmolarity on E faecalis viability were assessed using specifically prepared solutions. RESULTS: BAG preincubated with dentin powder caused a significant (P < .05) decrease in viability compared to pure BAG suspensions. This was not based on adherence of bacteria to solid particles or agglutination of the cells, because sonication did not increase bacterial yields. Hydroxylapatite and decalcified dentin did not increase BAG killing efficacy. The additive effect of BAG + dentin powder was dose dependent, occurred only with solids in suspension, and increased with suspension time. An augmented dissolution of glass components, especially silicon, was measured in BAG + dentin powder compared to pure BAG suspensions or counterparts containing hydroxylapatite or decalcified dentin. High osmolarity per se did not affect E faecalis viability, whereas high pH and silica levels did. CONCLUSION: The observed phenomenon was related to an increased BAG dissolution triggered by dentin powder, causing elevated local pH and silica levels.     

原发性肾上腺皮质癌的诊治分析

目的总结和提高原发性肾上腺皮质癌的诊治水平。方法回顾分析16例肾上腺皮质癌患者的临床资料。根据其临床症状、内分泌功能测定、影像学特点做出诊断，手术治疗并随访。结果16例患者中，内分泌功能紊乱者8例，以库欣征、性征异常、醛固酮增多症为主。超声、CT、MRI测定肿瘤直径为4．8～19．5cm，平均7．8cm。3例有远处转移。行根治性切除术13例，侵及同侧肾脏者做肾和肾上腙切除术2例，肾上腺肿瘤并腔静脉癌栓切除2例，腔静脉部分切除1例。病理结果：Ⅰ其耳2例，Ⅱ期8例，Ⅲ期3例，Ⅳ期3例。随访3-62个月，手术2年以上的11例患者中有6例仍存活，但1例肺转移，1例骨转移；死亡5例，平均存活26个月。结论肾上腺皮质癌患者预后差。影像学检查结合临床症状是早期诊断的关键，根治性手术是惟一有效的治疗方法。     

Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.     

Cognitive function after on or off pump coronary artery bypass grafting.

OBJECTIVE: To investigate cognitive outcome after on and off pump coronary artery bypass grafting. METHODS: Seventy patients between 50 and 80 years with stable angina pectoris, ejection fraction >30%, serum creatinine <150 micromol/l, and lack of tight main stem stenosis were randomized to on or off pump coronary artery bypass grafting. Standardized neuropsychological tests evaluated attention, verbal and visuo-spatial short-term and working memory, verbal learning, delayed recall, visuo-motor speed, and aspects of executive functions. Levels of anxiety and depression were also investigated. Testing was performed before and at 1 week, 1 and 6 months after surgery. RESULTS: There was no difference in cognitive impairment (defined as a 20% reduction in at least 20% of the tests) between groups. The incidence at 1 week post-operatively was 57% in the on pump group and 58% in the off pump group, after 1 month 30% and 12% and after 6 months 19% and 15%, respectively (p for interaction=0.19). There was no difference between groups in anxiety (p=0.18) or depression (p=0.48). CONCLUSIONS: This prospective, randomized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients.     

Spray coated pellets as carrier system for mucoadhesive drug nanocrystals.

High pressure homogenization can be employed to produce drug nanocrystals with a number of advantages, like improved solubility behaviors, better drug targeting or even increased mucoadhesiveness. To obtain a controlled drug delivery system it is necessary to transform the resulting nanosuspension into a solid dosage form. The present study shows the feasibility to use a mucoadhesive nanosuspension of poorly soluble hydrocortisone acetate produced by high pressure homogenization as layering dispersion in a fluidized bed process, followed by the application of an enteric coating to achieve a controlled drug release. To point out the advantages of drug nanocrystals the new fomulation was compared with a formulation containing micronized drug. Both formulations were characterized with regard to their particle size and crystallinity by using laser diffractometry, photon correlation spectroscopy and X-ray diffraction. The pellet morphology was characterized by using the environmental scanning electron microscopy (ESEM). In the in vitro dissolution tests an accelerated dissolution velocity and an increased drug release could be shown for the pellets containing drug nanocrystals.     

Blunted renal dopaminergic system activity in puromycin aminonucleoside-induced nephrotic syndrome.

BACKGROUND: A primary tubular sodium handling abnormality has been implicated in the edema formation of nephrotic syndrome. Dopamine synthesized by renal proximal tubules behaves as an endogenous natriuretic hormone by activating D(1)-like receptors as a paracrine/autocrine substance. METHODS: We examined the time courses of the urinary excretion of sodium, protein and dopamine in puromycin aminonucleoside (PAN)-treated and control rats. The rats were sacrificed during greatest sodium retention (day 7) as well as during negative sodium balance (day 14) for the evaluation of renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine. Also, the influence of volume expansion (VE) and the effects of the D(1)-like agonist fenoldopam (10 microg/kg bw/min) on natriuresis and on proximal tubular Na(+),K(+)-ATPase activity were examined on day 7. RESULTS: The daily urinary excretion of dopamine was decreased in PAN-treated rats, from day 5 and beyond. This was accompanied by a marked decrease in the renal AADC activity, on days 7 and 14. During VE, the fenoldopam-induced decrease in proximal tubular Na(+),K(+)-ATPase activity was more pronounced in PAN-treated rats than in controls. However, the urinary sodium excretion during fenoldopam infusion was markedly increased in control rats but was not altered in PAN-treated animals. CONCLUSION: PAN nephrosis is associated with a blunted renal dopaminergic system activity which may contribute to enhance the proximal tubular Na(+),K(+)-ATPase activity. However, the lack of renal dopamine appears not to be related with the overall renal sodium retention in a state of proteinuria.     

褪黑素对子宫内膜异位症大鼠细胞凋亡相关蛋白的影响

目的观察褪黑素(MT)对大鼠子宫内膜异位症(EM)模型细胞凋亡调控相关蛋白的影响。方法采用手术移植法制备大鼠EM模型,大鼠随机分为正常对照组、模型对照组和MT高、低剂量组,免疫组织化学法检测异位内膜Bcl-2、Fas、细胞间粘附分子(ICAM)-1的表达,同时检测脾脏自然杀伤(NK)细胞活性。结果MT治疗组与模型组比较异位内膜Bcl-2、ICAM-1表达明显下降,Fas表达明显升高,脾脏NK细胞活性显著增加。结论MT具有抑制异位内膜Bcl-2、ICAM-1表达以及增强Fas表达和脾脏NK细胞活性的作用。     

综合性医院抑郁症的特点及疗效分析

目的:了解综合性医院神经内科门诊抑郁症的临床特点及抗抑郁治疗的临床疗效.方法:对46例抑郁症患者的临床特点进行研究分析,同时对其中24例患者给予帕罗西汀治疗,对汉密尔顿抑郁评定表(HAMD)的平均总分数、汉密尔顿4因子及临床总体印象量表(CGI)评分在治疗前后进行比较.结果:46例抑郁症患者均以不同程度的躯体症状为主诉,临床表现多种多样,可涉及全身各系统;其中24例抑郁症患者给予帕罗西汀治疗后,汉密尔顿抑郁评定表的平均总分数、汉密尔顿4因子及临床总体印象量表评分分数在治疗后较治疗前显著减少(P＜0.01).结论:了解抑郁症患者躯体症状的临床特点,对于抑郁症的诊断和治疗至关重要.帕罗西汀对抑郁症患者具有明显的抗焦虑作用及早期改善睡眠的作用且整体抗抑郁疗效好.