提高尿激酶原治疗急性心肌梗死疗效研究

尿激酶原是新一代特异性溶栓药。为进一步提高该药的安全性和有效性,本文从使用剂量、给药方案、与其他溶栓药伍用,及给药途径等方面提出了意见,供临床医生使用中参考。     

Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Further insight into the task-dependent excitability of motor evoked potentials in first dorsal interosseous muscle in humans

We have reexamined the contradictory evidence in which task-dependent excitation of motor evoked potentials (MEPs) in the first dorsal interosseous (FDI) muscle was stronger with increasingly more complex finger tasks than with individual finger movement tasks. In the first step of the experiment, based on previous findings, we investigated remarkable functional differences between intrinsic and extrinsic hand muscles during complex finger tasks (precision and power grip). During the performance of the tasks, the optimal stimulus intensity of the transcranial magnetic stimulation (TMS) was applied to the contralateral motor cortex. MEPs of the FDI, extensor carpi radialis (ECR), and flexor carpi radialis (FCR) muscles were recorded simultaneously with increased background EMG activity step by step in both tasks. The intensity threshold of TMS was lower in the precision grip. Furthermore, the MEP amplitudes of FDI muscle dependent on the background EMG activity were different between these two tasks, i.e., MEP amplitudes and regression coefficients in a precision grip were larger than those in a power grip. Although our results for MEP amplitude and threshold in the FDI muscle were similar to previous reported evidence, the different contributions of a synergistic muscle (in particular, the ECR muscle) during performance in these tasks was new evidence. Since there were no differences in cutaneous afferent effects on both tasks, corticomotoneuronal (CM) cells connected to FDI motoneurons seemed generally to be more active during precision than power gripping, and there were different contributions from synergistic muscles during the performance of these tasks. In the second part of the experiment, the results obtained from the complex tasks were compared with those from a simple task (isolated index finger flexion). MEP amplitudes, dependent on the background EMG activity during isolated index finger flexion, varied among subjects, i.e., the relationship between the MEP amplitude and the background EMG of the FDI muscle showed individual, strategy-dependent modulation. There were several kinds of individual motor strategies for performing the isolated finger movement. The present results may explain the previous contradictory evidence related to the contribution of the CM system during coordinated finger movement.     

榄香烯与化疗药物联合作用对癌细胞株生长的影响

 用肾透明细胞癌细胞株KCC和红白血病细胞林K562作为靶细胞研究了中药榄香烯和化疗药物的体外协同应用对癌株生长的影响。单独用药情况下，KCC对榄香烯、阿霉素、5氟脲嘧啶均呈不同程度的抵抗，K562则相对较敏感。榄香烯合用阿霉素或5氟脲嘧啶后，对KCC的抑制率明显增强，其中榄香烯加阿霉素组效果要强于合用5-Fu，联合用药后对K562的抑制率也明显增强。经统计学分析：单独用药与联合用药之间差异显著（P＜0.01），实验结果对临床应用榄香烯治疗实质性肿瘤时选择良好的协同药物具有参考意义。     

吸烟与职业性毒物的协同作用

综述了吸烟与职业性毒物对作业工人健康影响的有关资料,提出吸烟与金属和类金属、刺激性气体及其他毒物有协同作用,并与职业性癌症有关,提倡戒烟非常必要.     

In-vitro activity of ceftriaxone combined with newer agents against MRSA

In this study, in vitro synergism in combinations of agents as ceftriaxone/dalbavancin, ceftriaxone/linezolid and ceftriaxone/daptomycin against MRSA strains were investigated. Thirty clinical MRSA strains were tested. The minimum inhibitory concentrations of all antibiotics were determined using reference broth microdilution method. In-vitro activities of antibiotics combined against the strains were tested using two-dimensional checkerboard microdilution method. Results were interpreted as follows: synergy = FICI ≤0.5; ‘no interaction’ effect = FICI ?0.5-≤4; antagonism = FICI ?4. The MIC₅₀, MIC₉₀ and MIC_range of ceftriaxone, daptomycin, dalbavancin and linezolid were found as 128, 1024 and 16-2048 mg/L; 1, 1 and 0.5–1 mg/L; 0.12, 0.12 and 0.03–0.12 mg/L; and 1, 2 and 1–2 mg/L, respectively. Our results showed that the frequency of synergistic effects (FICI: ≤0.5) of three combinations were all at the same rate of 77% (23/30). No in vitro antagonism (FICI >4) was observed.     

Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver,kidney and pancreas tissues of STZ-induced diabetic rats: A mechanistic study

The aim of this study was to investigate the synergistic effects of quercetin (QE) and quinic acid (QA) on a STZ-induced diabetic rat model to determine their potential role in alleviating diabetes and its associated complications. In our study design, diabetic rats were treated with single and combined doses of QE and QA for 45 days to analyse their effects on liver, kidney and pancreas tissues. The study result showed that QE and QA treated groups down-regulated hyperglycaemia and oxidative stress by up-regulating insulin and C-peptide levels. Moreover, histological observations of the liver, kidney and pancreas of diabetic rats treated with single and combined doses of QE and QA showed a significant improvement in the structural degeneration. Interestingly, the combination dose of QE and QA (50 mg/kg) exhibited maximum inhibition of the pro-apoptotic protein Bax expression and demonstrate enhancement of the anti-apoptotic protein Bcl-2 expression in the kidney tissues, suggesting a protective role in the kidneys of diabetic rats. Taken together, these results indicates the synergistic effects of QE and QA in ameliorating hyperglycaemia, hyperlipidemia and insulin resistance in diabetic rats and therefore, open a new window of research on the combinatorial therapy of flavonoids.     

Retinol encapsulated into amorphous Ca2+ polyphosphate nanospheres acts synergistically in MC3T3-E1 cells

Both the quality and quantity of collagen, the major structural component of the skin, decrease in aging skin. We succeeded to encapsulate retinol into amorphous inorganic polyphosphate (polyP) nanoparticles together with calcium ions (“aCa-polyP-NP”), under formation of amorphous Ca-polyP/retinol nanospheres (“retinol/aCa-polyP-NS”). The globular nanospheres are not cytotoxic, show an almost uniform size of ≈45 nm and have a retinol content of around 25%. Both components of those nanospheres, retinol and the aCa-polyP-NP, if administered together, caused a strong increase in proliferation of mouse calvaria MC3T3 cells. The expressions of collagen types I, II and III genes, but not the expression of collagen type V gene, were significantly enhanced if retinol is added together with aCa-polyP-NP. This synergistic effect was especially pronounced for the expression of the collagen type III gene. We propose that the synergistic effect of the retinol/aCa-polyP-NS on cell growth and collagen type III expression is induced via two routes, first through cellular uptake of the 45 nm nanospheres by clathrin-mediated endocytosis and second through extracellular disintegration of the nanospheres resulting in the release of retinol which is then taken up into the cells after binding to the retinal binding protein receptor.     

Combination of Protoporphyrin IX-mediated Sonodynamic Treatment with Doxorubicin Synergistically Induced Apoptotic Cell Death of a Multidrug-Resistant Leukemia K562/DOX Cell Line

The main objective of this study was to evaluate the efficacy of administration of doxorubicin (DOX) in combination with protoporphyrin IX (PpIX)-assisted low-level therapeutic ultrasound (US) in K562/DOX cells as a potential strategy in cancer therapy. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the cytotoxicity of different treatments. Apoptosis was analyzed using annexin V-PE/7-amino-actinomycin D staining. Changes in DNA fragmentation, intracellular reactive oxygen species production, cellular membrane permeability, P-glycoprotein expression and DOX uptake were analyzed with flow cytometry. Under optimal conditions, PpIX-US significantly aggravated DOX-induced K562/DOX cell death, compared with either monotherapy. Synergistic potentiation of DNA damage, generation of reactive oxygen species and P-glycoprotein inhibition were observed. Plasma membrane integrity changed slightly after US exposure, and DOX uptake was notably improved after PpIX-US exposure. The results indicate that PpIX-US could increase the susceptibility of tumors to antineoplastic drugs, suggesting a clinical potential method for sonodynamic therapy-mediated tumor chemotherapy.     

奎宁与三种逆转剂联合对耐药细胞系K562/HHT多药耐药逆转作用的研究

目的：寻找有效的多药耐药联合逆转剂。方法：用ＭＴＴ法、联合效应分析和流式细胞仪测定技术研究奎宁（Ｑｕｉｎ）分别与环孢菌素Ａ（ＣｓＡ）、他莫西酚（Ｔａｍ）、潘生丁（ＤＰＭ）联合逆转耐药细胞系Ｋ５６２／ＨＨＴ对柔红霉素（ＤＮＲ）和高三尖杉酯碱（ＨＨＴ）耐药。结果：逆转倍数是单用药的２～３倍，达到或超过单用２倍剂量的逆转效果，逆转剂间有联合协同作用，其中Ｑｕｉｎ与ＤＰＭ或Ｔａｍ联合的协同作用大于Ｑｕｉｎ与ＣｓＡ联合，可增加细胞内ＤＮＲ浓度。结论：Ｑｕｉｎ与ＣｓＡ、ＤＰＭ或Ｔａｍ联合具有协同作用，不同机制逆转剂联合的协同作用更为显著。