调控miR-181d-5p表达对宫颈癌细胞增殖、凋亡、侵袭的影响

目的 探究miR-181d-5p对宫颈癌细胞增殖、凋亡、侵袭影响及对细胞硫酰化限速酶(sulfation rate-limiting enzyme, PAPSS2)/蛋白聚糖(proteoglycans, VCAN)信号通路的影响。方法 细胞学实验：人宫颈癌细胞Hela细胞分为对照组、NC组和miR-181d-5p组,MTT、流式细胞技术及Transwell实验分别检测各组细胞增殖、凋亡和侵袭能力,Western blot检测各组PAPSS2和VCAN蛋白表达水平。裸鼠荷瘤实验：20只SPF级裸鼠随机分为对照组(n=10)和miR-181d-5p组(n=10),分别接种野生型细胞和转染miR-181d-5p细胞,模型建立后每3 d测量1次小鼠肿瘤体积,连续测量21 d,于实验终点测量肿瘤质量和体积。结果 细胞学实验表明：与对照组和NC组比较,miR-181d-5p组细胞增殖能力显著降低、细胞凋亡比例显著增加、细胞侵袭能力显著降低、PAPSS2,VCAN表达水平显著下调(P<0.05),NC组与对照组差异无统计学意义(P>0.05)。裸鼠荷瘤实验表明：miR-181d-5p组...     

Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in cell culture and in a cotton rat model

DAS181 is a novel drug in development for the treatment of influenza as well as human parainfluenza viruses (hPIVs). Previous studies demonstrated that DAS181 inhibited laboratory strains of hPIV, but no tests were conducted with primary clinical isolates of hPIV. To fill this gap, we studied six primary isolates including hPIV-2 and hPIV-3. First tests showed that the amplification of all viruses in vitro was reproducibly inhibited with DAS181 drug concentrations ranging between 0.1 and 1 nM. An hPIV-3 primary clinical isolate was then tested in a cotton rat model for sensitivity to 0.3–1 mg/kg drug treatments. Results showed that virus amplification in the lower respiratory tract was significantly and reproducibly inhibited by drug. Together, experiments demonstrated that DAS181 inhibited primary clinical isolates of hPIV in vitro and in vivo at doses similar to those previously described for inhibition of laboratory hPIV and influenza virus isolates.     

A pH-triggered delayed-release chronotherapeutic drug delivery system of aceclofenac for effective management of early morning symptoms of rheumatoid arthritis

Abstract

Context: Rheumatoid arthritis (RA) is differentiated as an early morning exacerbation of the core arthritis condition associated with increase in pain and stiffness in joints and necessitate for medication. Objective: The aim of the present work was to develop and optimise a pH-triggered delayed-release colon-specific aceclofenac microspheres and to accomplish chronotherapy of RA. Methods: A 3-factor, 3-level Box–Behnken design (BBD) was used to optimise selected variables. Developed formulation was evaluated for in vivo delayed response and anti-arthritis activity in rats. Results: The particle size and encapsulation efficacy of these microspheres were 117.36?±?10.54?µm and 85.06?±?5.85%, respectively. Optimised formulation was analysed by SEM, DSC, X-RPD and FTIR. The in vivo evaluation reveled delayed anti-inflammatory activity in carrageenan-induced rats and anti-arthritic activity in freund’s adjuvant-induced arthritis rats. Conclusion: The optimised aceclofenac microspheres formulation is potential for the chronotherapy of early morning symptoms of RA.     

Platelet function studies in coronary artery disease. X. Effect of dipyridamole

To evaluate the effects of dipyridamole on blood platelet function in patients with coronary artery disease, platelet counts and aggregation were examined in aortic and coronary venous blood. Before administration of dipyridamole, platelet counts and aggregation in response to adenosine diphosphate were less (p <0.02) in coronary venous than in aortic blood. Dipyridamole administration (100 mg) resulted in an increase in platelet counts and platelet aggregation in coronary venous blood so that the differences in aortic and coronary venous blood values were eliminated. These phenomena were probably related to inhibitory actions of dipyridamole. on platelet adhesion to atherosclerotic vessels. To further study the mechanism of action, the direct effects of dipyridamole on in vitro platelet aggregation were evaluated. Although dipyridamole, in the concentrations used, had no effect on in vitro platelet aggregation, it greatly potentiated the aggregation inhibitory actions of exogenous prostacyclin. In vivo potentiation of endogenous prostacyclin and inhibitory actions on platelet adhesion are the most likely mechanisms of the potentially beneficial actions of dipyridamole.     

Reduction in antibiotic costs by restricting use of an oral cephalosporin

Antibiotic cost control programs are important; however, they may be difficult to Implement if they include intensive involvement of infectious diseases specialists. In a large municipal hospital, review of antibiotic cost data indicated that 31 percent of the total antibiotic expenditure was for an oral cephalosporin, cephalexin. The requirement that an antibiotic justification form be completed did not decrease use of the drug. However, the requirement that the prescribing physician telephone an infectious diseases specialist resulted in marked restriction of the oral cephalosporin and was accompanied by a 29 percent reduction (adjusted for inflation) in total antibiotic costs. Since comparatively few telephone requests were made and since the decision process to use an oral cephalosporin is comparatively simple, marked reduction in antibiotic costs was achieved with relatively little effort by the infectious diseases expert.     

Resting and exercise left ventricular function in patients with hypertrophic cardiomyopathy

Left ventricular ejection fraction (EF) at rest and during exercise was measured in 19 patients with hypertrophic cardiomyopathy (HCM) by means of radionuclide angiography. The results were compared to those in 20 normal subjects. Based on hemodynamic data, patients with HCM were divided into three groups. In group I, no demonstrable left ventricular outflow obstruction, there were five patients; their mean EF increased from 68% +/- 8.9 (+/- SD) at rest to 74% +/- 9.2 during exercise (p less than 0.05). In group II, latent obstruction, there were six patients; their mean EF at rest (75.2% +/- 8.2) and at peak exercise (78.7% +/- 6.7) was not statistically different (p greater than 0.05). Group III, obstruction present at rest, consisted of eight patients; EF at rest (82.6% +/- 8.5) decreased significantly during exercise (75.6% +/- 7.7, p less than 0.01). In normal subjects resting EF was 66.3% +/- 7.6; it increased to 76.4% +/- 7 (p less than 0.001). Exercise duration and heart rate-blood pressure product were lower in groups II and III. Thus there are significant differences in left ventricular systolic function both at rest and during exercise between these three major hemodynamic subgroups. These findings emphasize the importance of such a hemodynamic classification of HCM.     

A prospective clinical, scintigraphic, angiographic and functional evaluation of patients after inferior myocardial infarction with and without right ventricular dysfunction

To elucidate the functional and prognostic significance of right ventricular dysfunction after acute inferior wall myocardial infarction, 74 consecutive patients with inferior infarction were prospectively evaluated with gated equilibrium blood pool imaging at rest, submaximal exercise thallium-201 scintigraphy and coronary angiography before hospital discharge. In addition, symptom-limited stress thallium-201 scintigraphy was performed in 61 patients at 3 months, and all patients were followed up clinically for 23 +/- 15 months. Utilizing predetermined radionuclide angiographic criteria, 47 patients (Group I) had normal right ventricular function, 12 patients (Group II) had mild to moderate dysfunction and 15 patients (Group III) had severe right ventricular dysfunction. There were no significant differences among the groups with regard to age, history of prior myocardial infarction, peak creatine kinase values, maximal Killip functional class, number or type of in-hospital complications, left ventricular ejection fraction, prevalence of multivessel disease or the distribution and severity of disease affecting the infarct-related vessel. Exercise tolerance as assessed by treadmill time, blood pressure-heart rate product and peak work load in METS was comparable among the three groups, both before hospital discharge and at 3 month follow-up. No differences in indicators of exercise-induced ischemia were noted among the groups, including the prevalence of redistribution thallium-201 defects, ST segment depression or symptoms of chest pain. Finally, cardiac mortality, reinfarction rate and the incidence of medically refractory angina pectoris were similar in the three groups. Thus, right ventricular dysfunction after acute inferior wall myocardial infarction does not appear to limit exercise tolerance or identify a subgroup of patients at higher risk for recurrent cardiac events.     

Maximal revascularization (reperfusion) in intact conscious dogs after 2 to 5 hours of coronary occlusion.

Acute infarction was produced in intact conscious dogs by inflating a previously implanted balloon cuff around the left anterior descending coronary artery was occluded in 26 control dogs and reperfused by deflating the balloon cuff after 2 hours of occlusion in 19 dogs (group II) and after 5 hours in 11 dogs (group III). Serial studies were performed and repeated after 48 hours and 7 days. All three groups revealed hemodynamic and metabolic deterioration with coronary occlusion and infarct production. Immediately after reperfusion, arrhythmias developed in groups II and III and persistent ventricular tachycardia was present 2 to 3 hours after reperfusion in 74 percent of animals in group II and 82 percent of those in group III compared with 6 percent and 13 percent incidence rates at corresponding times in control dogs. Q waves developed in 83 percent of animals in group II and 100 percent of those in group III but in only 12 and 27 percent of control animals at corresponding times. Hemodynamic deterioration was accelerated in the postreperfusion period in both groups II and III. Angiographic assessment revealed improvement in 42 percent of dogs in group II, but in none of those in group III after reperfusion. Myocardial oxygen extraction diminished to subnormal levels after reperfusion, indicating either reactive hyperemia or shunting effect. Mortality was not significantly influenced by reperfusion. Infarct size was more than 15 percent of ventricular mass in 92 percent of control dogs and in 100 percent of dogs in group III, but in only 50 percent of those in group II. The data indicate that reperfusion in conscious dogs representing early, noninvasive maximal revascularization under ideal circumstances fails to prevent deterioration or death; instead it hastens the development of arrhythmias and myocardial injury. Reperfusion, although deleterious in the first hours, can reduce infarct size if performed after 2 hours, but not after 5 hours, of occlusion.